90. BMJ. 2016 Dec 5;355:i6188. doi: 10.1136/bmj.i6188.

Chemoprevention of colorectal cancer in individuals with previous colorectal
neoplasia: systematic review and network meta-analysis.

Dulai PS(1), Singh S(2)(3), Marquez E(1), Khera R(4), Prokop LJ(5), Limburg
PJ(6), Gupta S(7)(8), Murad MH(9).

Author information:
(1)Division of Gastroenterology, University of California San Diego, La Jolla,
CA, USA.
(2)Division of Gastroenterology, University of California San Diego, La Jolla,
CA, USA sis040@ucsd.edu.
(3)Division of Biomedical Informatics, University of California San Diego, La
Jolla, CA, USA.
(4)Division of Cardiology, University of Texas Southwestern Medical Center,
Dallas, TX, USA.
(5)Department of Library Services, Mayo Clinic, Rochester, MN, USA.
(6)Divison of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
(7)Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.
(8)Moores Cancer Center, University of San Diego, La Jolla, CA, USA.
(9)Robert D and Patricia E Kern Center for the Science of Health Care Delivery,
Mayo Clinic, Rochester, MN, USA.

OBJECTIVE:  To assess the comparative efficacy and safety of candidate agents
(low and high dose aspirin, non-aspirin non-steroidal anti-inflammatory drugs
(NSAIDs), calcium, vitamin D, folic acid, alone or in combination) for prevention
of advanced metachronous neoplasia (that is, occurring at different times after
resection of initial neoplasia) in individuals with previous colorectal
neoplasia, through a systematic review and network meta-analysis.
DATA SOURCES:  Medline, Embase, Web of Science, from inception to 15 October
2015; clinical trial registries.
STUDY SELECTION:  Randomized controlled trials in adults with previous colorectal
neoplasia, treated with candidate chemoprevention agents, and compared with
placebo or another candidate agent. Primary efficacy outcome was risk of advanced
metachronous neoplasia; safety outcome was serious adverse events.
DATA EXTRACTION:  Two investigators identified studies and abstracted data. A
Bayesian network meta-analysis was performed and relative ranking of agents was
assessed with surface under the cumulative ranking (SUCRA) probabilities (ranging
from 1, indicating that the treatment has a high likelihood to be best, to 0,
indicating the treatment has a high likelihood to be worst). Quality of evidence
was appraised with GRADE criteria.
RESULTS:  15 randomized controlled trials (12 234 patients) comparing 10
different strategies were included. Compared with placebo, non-aspirin NSAIDs
were ranked best for preventing advanced metachronous neoplasia (odds ratio 0.37,
95% credible interval 0.24 to 0.53; SUCRA=0.98; high quality evidence), followed
by low-dose aspirin (0.71, 0.41 to 1.23; SUCRA=0.67; low quality evidence). Low
dose aspirin, however, was ranked the safest among chemoprevention agents (0.78,
0.43 to 1.38; SUCRA=0.84), whereas non-aspirin NSAIDs (1.23, 0.95 to 1.64;
SUCRA=0.26) were ranked low for safety. High dose aspirin was comparable with low
dose aspirin in efficacy (1.12, 0.59 to 2.10; SUCRA=0.58) but had an inferior
safety profile (SUCRA=0.51). Efficacy of agents for reducing metachronous
colorectal cancer could not be estimated.
CONCLUSIONS:  Among individuals with previous colorectal neoplasia, non-aspirin
NSAIDs are the most effective agents for the prevention of advanced metachronous
neoplasia, whereas low dose aspirin has the most favorable risk:benefit profile.
REGISTRATION:  PROSPERO (CRD42015029598).

Published by the BMJ Publishing Group Limited. For permission to use (where not
already granted under a licence) please go to
http://group.bmj.com/group/rights-licensing/permissions.


PMCID: PMC5137632
PMID: 27919915  [Indexed for MEDLINE]

Conflict of interest statement: All authors have completed the ICMJE uniform
disclosure form at www.icmje.org/coi_disclosure.pdf and declare: PSD and EM are
supported by the NIDDK training grant 5T32DK007202. SS is supported by the
NIH/NLM training grant T15LM011271 and the American College of Gastroenterology
junior faculty development award. SG is partly supported by NCI 2
U54CA132379-06A1, as well as merit review award No 1 I01 HX001574-01A1 from the
US Department of Veterans Affairs Health Services Research and Development
Service of the VA Office of Research and Development. The views expressed in this
article are those of the author(s) and do not necessarily represent the views of
the Department of Veterans Affairs.


91. Am J Prev Med. 2016 Dec;51(6):1060-1071. doi: 10.1016/j.amepre.2016.07.011. Epub
2016 Sep 9.

Combination Therapies for Smoking Cessation: A Hierarchical Bayesian
Meta-Analysis.

Windle SB(1), Filion KB(2), Mancini JG(1), Adye-White L(1), Joseph L(3), Gore
GC(4), Habib B(1), Grad R(5), Pilote L(6), Eisenberg MJ(7).

Author information:
(1)Division of Clinical Epidemiology, Lady Davis Institute, Jewish General
Hospital/McGill University, Montreal, Quebec, Canada.
(2)Division of Clinical Epidemiology, Lady Davis Institute, Jewish General
Hospital/McGill University, Montreal, Quebec, Canada; Department of Epidemiology,
Biostatistics, and Occupational Health, McGill University, Montreal, Quebec,
Canada.
(3)Department of Epidemiology, Biostatistics, and Occupational Health, McGill
University, Montreal, Quebec, Canada; Division of Clinical Epidemiology, McGill
University Health Centre, Montreal, Quebec, Canada; Research Institute, McGill
University Health Centre, McGill University, Montreal, Quebec, Canada.
(4)Schulich Library of Science and Engineering, McGill University, Montreal,
Quebec, Canada.
(5)Herzl Family Practice Centre, Jewish General Hospital, Montreal, Quebec,
Canada; Department of Family Medicine, McGill University, Montreal, Quebec,
Canada.
(6)Department of Epidemiology, Biostatistics, and Occupational Health, McGill
University, Montreal, Quebec, Canada; Division of Clinical Epidemiology, McGill
University Health Centre, Montreal, Quebec, Canada; Division of General Internal
Medicine, McGill University Health Centre, Montreal, Quebec, Canada.
(7)Division of Clinical Epidemiology, Lady Davis Institute, Jewish General
Hospital/McGill University, Montreal, Quebec, Canada; Department of Epidemiology,
Biostatistics, and Occupational Health, McGill University, Montreal, Quebec,
Canada; Division of Cardiology, Jewish General Hospital, Montreal, Quebec,
Canada. Electronic address: mark.eisenberg@ladydavis.ca.

CONTEXT: Treatment guidelines recommend the use of combination therapies for
smoking cessation, particularly behavioral therapy (BT) as an adjunct to
pharmacotherapy. However, these guidelines rely on previous reviews with
important limitations. This study's objective was to evaluate the efficacy of
combination therapies compared with monotherapies, using the most rigorous data
available.
EVIDENCE ACQUISITION: A systematic review and meta-analysis of RCTs of
pharmacotherapies, BTs, or both were conducted. The Cochrane Library, Embase,
PsycINFO, and PubMed databases were systematically searched from inception to
July 2015. Inclusion was restricted to RCTs reporting biochemically validated
abstinence at 12 months. Direct and indirect comparisons were made in 2015
between therapies using hierarchical Bayesian models.
EVIDENCE SYNTHESIS: The search identified 123 RCTs meeting inclusion criteria
(60,774 participants), and data from 115 (57,851 participants) were
meta-analyzed. Varenicline with BT increased abstinence more than other
combinations of a pharmacotherapy with BT (varenicline versus bupropion: OR=1.56,
95% credible interval [CrI]=1.07, 2.34; varenicline versus nicotine patch:
OR=1.65, 95% CrI=1.10, 2.51; varenicline versus short-acting nicotine-replacement
therapies: OR=1.68, 95% CrI=1.15, 2.53). Adding BT to any pharmacotherapy
compared with pharmacotherapy alone was inconclusive, owing to wide CrIs
(OR=1.17, CrI=0.60, 2.12). Nicotine patch with short-acting nicotine-replacement
therapy appears safe and increases abstinence versus nicotine-replacement
monotherapy (OR=1.63, CrI=1.06, 3.03). Data are limited concerning other
pharmacotherapy combinations and their safety and tolerability.
CONCLUSIONS: Evidence suggests that combination therapy benefits may be less than
previously thought. Combined with BT, varenicline increases abstinence more than
other pharmacotherapy with BT combinations.

Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier
Inc. All rights reserved.

DOI: 10.1016/j.amepre.2016.07.011
PMID: 27617367  [Indexed for MEDLINE]


92. Cardiovasc Revasc Med. 2016 Dec;17(8):535-545. doi: 10.1016/j.carrev.2016.09.011.
Epub 2016 Sep 30.

Comparison of heparin, bivalirudin, and different glycoprotein IIb/IIIa inhibitor
regimens for anticoagulation during percutaneous coronary intervention: A network
meta-analysis.

Lipinski MJ(1), Lee RC(1), Gaglia MA Jr(1), Torguson R(1), Garcia-Garcia HM(1),
Pichard AD(1), Satler LF(1), Waksman R(2).

Author information:
(1)Section of Interventional Cardiology, MedStar Washington Hospital Center,
Washington, DC, USA.
(2)Section of Interventional Cardiology, MedStar Washington Hospital Center,
Washington, DC, USA. Electronic address: Ron.Waksman@Medstar.net.

Comment in
    Cardiovasc Revasc Med. 2016 Dec;17 (8):491-493.

BACKGROUND/PURPOSE: Numerous GPIs are available for PCI. Although they were
tested in randomized controlled trials, a comparison between the different GPI
strategies is lacking. Thus, we performed a Bayesian network meta-analysis to
compare different glycoprotein IIb/IIIa inhibitor (GPI) strategies with heparin
and bivalirudin for percutaneous coronary intervention (PCI).
METHODS: MEDLINE, Cochrane CENTRAL, and ClinicalTrials.gov were searched by two
independent reviewers for randomized controlled trials comparing high-dose bolus
tirofiban, abciximab, eptifibatide, heparin with provisional glycoprotein
IIb/IIIa inhibitors, and bivalirudin with provisional GPI that reported clinical
outcomes. Mixed treatment comparison model generation was performed to directly
and indirectly compare between different anticoagulation strategies for all-cause
mortality, myocardial infarction, major adverse cardiovascular events, major
bleeding, minor bleeding, need for transfusion, and thrombocytopenia.
RESULTS: A total of 41 randomized controlled trials with 38,645 patients were
included in the analysis, among which 2654 were randomized to high-dose bolus
tirofiban, 6752 to abciximab, 1669 to eptifibatide, 16,500 to heparin, and 11,070
to bivalirudin. Mean age was 64±11years, 75% were male, 91% were treated with
stenting, 71% with clopidogrel, and 74% for acute coronary syndrome. High-dose
bolus tirofiban was associated with a significant reduction in all-cause
mortality compared with heparin (OR 0.57 [credible intervals 0.37, 0.9]) and
eptifibatide (OR 0.44 [credible intervals 0.19, 1.0]). GPI regimens had less
myocardial infarction and major adverse cardiovascular events but greater
bleeding compared with heparin and bivalirudin. There was no difference among the
GPI therapies for other outcomes, including myocardial infarction, major adverse
cardiovascular events, and major bleeding.
CONCLUSIONS: Our network meta-analysis of 38,645 patients demonstrated that GPI
regimens were associated with a reduction in recurrent myocardial infarction or
major adverse cardiovascular events for PCI, while bivalirudin was associated
with the lowest risk of bleeding.

Copyright © 2016. Published by Elsevier Inc.

DOI: 10.1016/j.carrev.2016.09.011
PMID: 27842901  [Indexed for MEDLINE]


93. Heart Rhythm. 2016 Dec;13(12):2340-2347. doi: 10.1016/j.hrthm.2016.09.010. Epub
2016 Sep 8.

Standard dose versus low dose non-vitamin K antagonist oral anticoagulants in
Asian patients with atrial fibrillation: A meta-analysis of contemporary
randomized controlled trials.

Wang KL(1), Giugliano RP(2), Goto S(3), Chiu CC(4), Lin CY(5), Lai EY(6), Chiang
CE(7).

Author information:
(1)General Clinical Research Center, Taipei Veterans General Hospital, Taipei,
Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
(2)Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston,
Massachusetts; Department of Medicine, Harvard Medical School, Boston,
Massachusetts.
(3)Department of Medicine, Tokai University School of Medicine, Kanagawa, Japan.
(4)School of Medicine, National Yang-Ming University, Taipei, Taiwan.
(5)School of Nursing, National Yang-Ming University, Taipei, Taiwan.
(6)Institute of Information Science, Academia Sinica, Taipei, Taiwan.
(7)General Clinical Research Center, Taipei Veterans General Hospital, Taipei,
Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Electronic address: cechiang@vghtpe.gov.tw.

BACKGROUND: Although randomized controlled trials (RCTs) indicated that standard
dose non-vitamin K antagonist oral anticoagulants (NOACs) were more compelling,
low dose NOACs are commonly used in clinical practice in Asia.
OBJECTIVE: The purpose of this study was to assess the relative therapeutic
benefit and risk of standard dose vs low dose NOACs in Asian patients enrolled in
contemporary RCTs.
METHODS: We performed a prespecified meta-analysis of 3155 Asian patients with
NOACs in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy)
and ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation
in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) trials. Efficacy
and safety with standard dose vs low dose NOACs were compared by risk ratios
(RRs) and 95% confidence intervals (CIs) in a random-effects model. An evidence
network incorporating additional Asian patients from ROCKET AF, J- ROCKET AF, and
ARISTOTLE was constructed with the Bayesian method.
RESULTS: Risks of stroke or systemic embolism and ischemic stroke were
significantly reduced with standard dose vs low dose NOACs (RR 0.62, 95% CI
0.45-0.85; and RR 0.55, 95% CI 0.38-0.79, respectively). Rates of major,
intracranial, and life-threatening bleeding with 2 dosing regimens were broadly
similar (RR 1.31, 95% CI 0.74-2.33; RR 1.54, 95% CI 0.72-3.30; and RR 1.49, 95%
CI 0.87-2.55, respectively). Absolute rates of all-cause mortality and the net
clinical outcome with standard dose NOACs were lower but not statistically
significant (absolute reduction 0.4% per year and 1.1% per year, respectively).
Network meta-analyses demonstrated that standard dose NOACs had the most
favorable risk-benefit profile among oral anticoagulants.
CONCLUSION: In Asian patients, standard dose NOACs represent a more appealing
therapeutic option than low dose NOACs, with a significant reduction in ischemic
stroke without an excess of major bleeding.

Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights
reserved.

DOI: 10.1016/j.hrthm.2016.09.010
PMID: 27614026  [Indexed for MEDLINE]


94. J Endovasc Ther. 2016 Dec;23(6):851-863. Epub 2016 Oct 5.

Comparative Effectiveness of Plain Balloon Angioplasty, Bare Metal Stents,
Drug-Coated Balloons, and Drug-Eluting Stents for the Treatment of Infrapopliteal
Artery Disease: Systematic Review and Bayesian Network Meta-analysis of
Randomized Controlled Trials.

Katsanos K(1), Kitrou P(2), Spiliopoulos S(3), Diamantopoulos A(4), Karnabatidis
D(2).

Author information:
(1)Department of Interventional Radiology, Guy's and St. Thomas' Hospitals, NHS
Foundation Trust, King's Health Partners, London, UK katsanos@med.upatras.gr.
(2)Department of Interventional Radiology, Patras University Hospital, School of
Medicine, Rion, Greece.
(3)2nd Department of Radiology, Interventional Radiology Unit, ATTIKO Athens
University Hospital, Athens, Greece.
(4)Department of Interventional Radiology, Guy's and St. Thomas' Hospitals, NHS
Foundation Trust, King's Health Partners, London, UK.

PURPOSE: To report a Bayesian network meta-analysis of randomized controlled
trials (RCTs) comparing bare metal stents (BMS), paclitaxel-coated balloons
(PCBs), and drug-eluting stents (DES) with balloon angioplasty (BA) or with each
other in the infrapopliteal arteries.
METHODS: Sixteen RCTs comprising 1805 patients with 1-year median follow-up were
analyzed. Bayesian random effects binomial models were employed (WinBUGS).
Relative treatment effects were expressed as odds ratios (ORs) with 95% credible
intervals (CrI), and the cumulative rank probabilities were calculated to provide
hierarchies of competing treatments. Quality of evidence (QoE) was assessed with
the GRADE (grading of recommendations assessment, development, and evaluation)
system. Sensitivity, heterogeneity, and consistency analyses were performed.
RESULTS: There was high QoE that infrapopliteal DES significantly reduced
restenosis compared with BMS (OR 0.26, 95% CrI 0.12 to 0.51) and BA (OR 0.22, 95%
CrI 0.11 to 0.45). Likewise, DES significantly reduced target lesion
revascularization (TLR) compared with BA (OR 0.41, 95% CrI 0.22 to 0.75) and BMS
(OR 0.26, 95% CrI 0.15 to 0.45). Paclitaxel-coated balloons also reduced TLR
compared with BA (OR 0.55, 95% CrI 0.34 to 0.90) and BMS (OR 0.35, 95% CrI 0.18
to 0.67), but QoE was low to moderate. BA had lower TLR than BMS (OR 0.63, 95%
CrI 0.40 to 0.99) with high QoE. DES was the only treatment that significantly
reduced limb amputations compared with BA (OR 0.58, 95% CrI 0.35 to 0.96), PCB
(OR 0.51, 95% CrI 0.26 to 0.98), or BMS (OR 0.38, 95% CrI 0.19 to 0.72) with
moderate to high QoE. DES also significantly improved wound healing compared with
BA (OR 2.02, 95% CrI 1.01 to 4.07) or BMS (OR 3.45, 95% CrI 1.41 to 8.73) with
high QoE. Results were stable on sensitivity and meta-regression analyses without
any significant publication bias or inconsistency.
CONCLUSION: Infrapopliteal DES were associated with significantly lower rates of
restenosis, TLR, and amputations and improved wound healing compared to BA and
BMS. DES also significantly reduced amputations compared with PCB.

© The Author(s) 2016.

DOI: 10.1177/1526602816671740
PMID: 27708143  [Indexed for MEDLINE]


95. Medicine (Baltimore). 2016 Dec;95(51):e5464. doi: 10.1097/MD.0000000000005464.

A Bayesian network meta-analysis of three different surgical procedures for the
treatment of humeral shaft fractures.

Qiu H(1), Wei Z, Liu Y, Dong J, Zhou X, Yin L, Zhang M, Lu M.

Author information:
(1)aDepartment of Orthopaedic Surgery, Yongchuan Hospital of Chongqing Medical
University bDepartment of Orthopaedic Surgery, The Children's Hospital of
Chongqing Medical University cDepartment of Endocrinology, The Second Affiliated
Hospital of Chongqing Medical University dDepartment of Endocrinology, Yongchuan
Hospital of Chongqing Medical University eDepartment of Orthopaedic Surgery, The
Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

BACKGROUND: The optimal surgical procedure for humeral shaft fractures remains a
matter of debate. We aimed to establish the optimum procedure by performing a
Bayesian network meta-analysis.
METHODS: PubMed, EMBASE, the Cochrane Library, and Medline were searched for both
randomized controlled trials and prospective studies of surgical treatment for
humeral shaft fractures. The quality of the included studies was assessed
according to the Cochrane Collaboration's "Risk of bias".
RESULTS: Seventeen RCTs or prospective studies were included in the
meta-analysis. The pooled results showed that the occurrence rate of radial nerve
injury was lowest for minimally invasive plate osteosynthesis (MIPO; SUCRA
probability, 95.1%), followed by open reduction and plate osteosynthesis (ORPO;
SUCRA probability, 29.5%), and was highest for intramedullary nailing (IMN; SUCRA
probability, 25.4%). The aggregated results of pairwise meta-analysis showed no
significant difference in radial nerve injury rate when comparing ORPO versus IMN
(OR, 1.92; 95% CI, 0.96 to 3.86), ORPO versus MIPO (OR, 3.38; 95% CI, 0.80 to
14.31), or IMN versus MIPO (OR, 3.19; 95% CI, 0.48 to 21.28). Regarding the
nonunion, SUCRA probabilities were 90.5%, 40.2%, and 19.3% for MIPO, ORPO, and
IMN, respectively. The aggregated results of a pairwise meta-analysis also showed
no significant difference for ORPO versus IMN (OR, 0.83; 95% CI, 0.41 to 1.69),
ORPO versus MIPO (OR, 2.42; 95% CI, 0.45 to 12.95), or IMN versus MIPO (OR, 2.49;
95% CI, 0.35 to 17.64).
CONCLUSION: The current evidence indicates that MIPO is the optimum choice in the
treatment of humeral shaft fractures and that ORPO is superior to IMN.

DOI: 10.1097/MD.0000000000005464
PMCID: PMC5181811
PMID: 28002327  [Indexed for MEDLINE]

Conflict of interest statement: The authors have no conflicts of interest to
disclose.


96. Pharmacol Rep. 2016 Dec;68(6):1237-1243. doi: 10.1016/j.pharep.2016.07.013. Epub
2016 Aug 1.

Safety profile of biologic drugs in the therapy of Crohn disease: A systematic
review and network meta-analysis.

Moćko P(1), Kawalec P(2), Pilc A(3).

Author information:
(1)Drug Management Department, Institute of Public Health, Faculty of Health
Sciences, Jagiellonian University Medical College, Kraków, Poland.
(2)Drug Management Department, Institute of Public Health, Faculty of Health
Sciences, Jagiellonian University Medical College, Kraków, Poland. Electronic
address: pawel.kawalec@uj.edu.pl.
(3)Institute of Pharmacology, Polish Academy of Sciences, Department of
Neurobiology, 31-343 Kraków, Smętna street 12, Poland.

BACKGROUND: Crohn disease (CD) is an inflammatory bowel disease which occurs
especially in developed countries of Western Europe and North America. The aim of
the study was to compare the safety profile of biologic drugs in patients with
CD.
METHODOLOGY: A systematic literature search was performed using PubMed, Embase,
and CENTRAL databases, until April 27, 2016. We included randomized controlled
trials (RCTs) that compared the safety of biologic drugs (infliximab, adalimumab,
vedolizumab, certolizumab pegol, and ustekinumab) with one another or with
placebo in patients with CD. The network meta-analysis (NMA) was conducted for an
induction phase (6-10 weeks) and maintenance phase (52-56 weeks) with a Bayesian
hierarchical random effects model in the ADDIS® software. The PROSPERO
registration number was CRD42016032606.
RESULTS: Ten RCTs were included in the systematic review with NMA. In the case of
the induction phase, the NMA could be conducted for the assessment of the
relative safety profile of adalimumab, vedolizumab, certolizumab pegol, and
ustekinumab, and in the case of the maintenance phase-of infliximab, adalimumab,
and vedolizumab. There were no significant differences in the rate of adverse
events in patients treated with biologics. Statistical analysis revealed that
vedolizumab had the greatest probability of being the safest treatment in most
endpoints in the induction phase and adalimumab-in the maintenance phase.
CONCLUSIONS: No significant differences between the biologics in the relative
safety profile analysis were observed. Further studies are needed to confirm our
findings, including head-to-head comparisons between the analyzed biologics.

Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published
by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

DOI: 10.1016/j.pharep.2016.07.013
PMID: 27686963  [Indexed for MEDLINE]


97. Prev Vet Med. 2016 Dec 1;135:67-73. doi: 10.1016/j.prevetmed.2016.11.006. Epub
2016 Nov 9.

Diagnostic accuracy of clinical illness for bovine respiratory disease (BRD)
diagnosis in beef cattle placed in feedlots: A systematic literature review and
hierarchical Bayesian latent-class meta-analysis.

Timsit E(1), Dendukuri N(2), Schiller I(3), Buczinski S(4).

Author information:
(1)Department of Production Animal Health, Faculty of Veterinary Medicine,
University of Calgary, Calgary, AB, Canada; Feedlot Health Management Services,
Okotoks, AB, Canada. Electronic address: eftimsit@ucalgary.ca.
(2)Division of Clinical Epidemiology, McGill University Health Centre, Montreal,
QC, Canada. Electronic address: nandini.dendukuri@mcgill.ca.
(3)Division of Clinical Epidemiology, McGill University Health Centre, Montreal,
QC, Canada. Electronic address: Ian.Schiller@clinepi.mcgill.ca.
(4)Department of Clinical Science, Faculté de Médecine Vétérinaire, Université de
Montréal, St-Hyacinthe, QC, Canada. Electronic address: s.buczinski@umontreal.ca.

Diagnosis of bovine respiratory disease (BRD) in beef cattle placed in feedlots
is typically based on clinical illness (CI) detected by pen-checkers.
Unfortunately, the accuracy of this diagnostic approach (namely, sensitivity [Se]
and specificity [Sp]) remains poorly understood, in part due to the absence of a
reference test for ante-mortem diagnosis of BRD. Our objective was to pool
available estimates of CI's diagnostic accuracy for BRD diagnosis in feedlot beef
cattle while adjusting for the inaccuracy in the reference test. The presence of
lung lesions (LU) at slaughter was used as the reference test. A systematic
review of the literature was conducted to identify research articles comparing CI
detected by pen-checkers during the feeding period to LU at slaughter. A
hierarchical Bayesian latent-class meta-analysis was used to model test accuracy.
This approach accounted for imperfections of both tests as well as the within and
between study variability in the accuracy of CI. Furthermore, it also predicted
the SeCI and SpCI for future studies. Conditional independence between CI and LU
was assumed, as these two tests are not based on similar biological principles.
Seven studies were included in the meta-analysis. Estimated pooled SeCI and SpCI
were 0.27 (95% Bayesian credible interval: 0.12-0.65) and 0.92 (0.72-0.98),
respectively, whereas estimated pooled SeLU and SpLU were 0.91 (0.82-0.99) and
0.67 (0.64-0.79). Predicted SeCI and SpCI for future studies were 0.27
(0.01-0.96) and 0.92 (0.14-1.00), respectively. The wide credible intervals
around predicted SeCI and SpCI estimates indicated considerable heterogeneity
among studies, which suggests that pooled SeCI and SpCI are not generalizable to
individual studies. In conclusion, CI appeared to have poor Se but high Sp for
BRD diagnosis in feedlots. Furthermore, considerable heterogeneity among studies
highlighted an urgent need to standardize BRD diagnosis in feedlots.

Copyright © 2016 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.prevetmed.2016.11.006
PMID: 27931931  [Indexed for MEDLINE]


98. Nutrients. 2016 Nov 25;8(12). pii: E747.

Effects of Hazelnut Consumption on Blood Lipids and Body Weight: A Systematic
Review and Bayesian Meta-Analysis.

Perna S(1), Giacosa A(2), Bonitta G(3), Bologna C(4), Isu A(5), Guido D(6),
Rondanelli M(7).

Author information:
(1)Department of Public Health, Experimental and Forensic Medicine, Endocrinology
and Nutrition Unit, University of Pavia, Azienda di Servizi alla Persona di
Pavia, Pavia 27100, Italy. simoneperna@hotmail.it.
(2)Department of Gastroenterology, Policlinico di Monza, Monza 20097, Italy.
attilio.giacosa@policlinicodimonza.it.
(3)Department of Biomedical Sciences for Health, Division of General Surgery,
IRCCS Policlinico San Donato, University of Milan, Milan 20097, Italy.
bbonit@icloud.com.
(4)Department of Public Health, Experimental and Forensic Medicine, Endocrinology
and Nutrition Unit, University of Pavia, Azienda di Servizi alla Persona di
Pavia, Pavia 27100, Italy. chiara.bologna02@universitadipavia.it.
(5)Department of Public Health, Experimental and Forensic Medicine, Endocrinology
and Nutrition Unit, University of Pavia, Azienda di Servizi alla Persona di
Pavia, Pavia 27100, Italy. antonio.isu@gmail.com.
(6)Department of Public Health, Experimental and Forensic Medicine, Biostatistics
and Clinical Epidemiology Unit, University of Pavia, Pavia 27100, Italy.
davide.guido@unipv.it.
(7)Department of Public Health, Experimental and Forensic Medicine, Endocrinology
and Nutrition Unit, University of Pavia, Azienda di Servizi alla Persona di
Pavia, Pavia 27100, Italy. mariangela.rondanelli@unipv.it.

Hazelnuts are rich in monounsaturated fatty acids and antioxidant bioactive
substances: their consumption has been associated with a decreased risk of
cardiovascular disease events. A systematic review and a meta-analysis was
performed to combine the results from several trials and to estimate the pooled
(overall) effect of hazelnuts on blood lipids and body weight outcomes.
Specifically, a Bayesian random effect meta-analysis of mean differences of
Δ-changes from baseline across treatment (MDΔ) (i.e., hazelnut-enriched diet vs.
control diet) has been conducted. Nine studies representing 425 participants were
included in the analysis. The intervention diet lasted 28-84 days with a dosage
of hazelnuts ranging from 29 to 69 g/day. Out of nine studies, three randomized
studies have been meta-analyzed showing a significant reduction in low-density
lipoprotein (LDL) cholesterol (pooled MDΔ = -0.150 mmol/L; 95% highest posterior
density interval (95%HPD) = -0.308; -0.003) in favor of a hazelnut-enriched diet.
Total cholesterol showed a marked trend toward a decrease (pooled MDΔ = -0.127
mmol/L; 95%HPD = -0.284; 0.014) and high-density lipoprotein (HDL) cholesterol
remained substantially stable (pooled MDΔ = 0.002 mmol/L; 95%HPD = -0.140;
0.147). No effects on triglycerides (pooled MDΔ = 0.045 mmol/L; 95%HPD = -0.195;
0.269) and body mass index (BMI) (pooled MDΔ = 0.062 kg/m²; 95%HPD = -0.293;
0.469) were found. Hazelnut-enriched diet is associated with a decrease of LDL
and total cholesterol, while HDL cholesterol, triglycerides and BMI remain
substantially unchanged.

DOI: 10.3390/nu8120747
PMCID: PMC5188407
PMID: 27897978  [Indexed for MEDLINE]

Conflict of interest statement: The authors declare that they have no competing
interests.


99. Antimicrob Agents Chemother. 2016 Nov 21;60(12):7035-7042. Print 2016 Dec.

Systematic Review and Meta-analysis of the Pharmacokinetics of Benznidazole in
the Treatment of Chagas Disease.

Wiens MO(1)(2), Kanters S(1), Mills E(1)(3), Peregrina Lucano AA(4), Gold S(5),
Ayers D(1), Ferrero L(5), Krolewiecki A(6).

Author information:
(1)Precision Global Health, Vancouver, British Columbia, Canada.
(2)Department of Medicine, University of British Columbia, Vancouver, British
Columbia, Canada.
(3)Department of Clinical Epidemiology & Biostatistics, McMaster University,
Hamilton, Ontario, Canada.
(4)Departamento de Farmacobiología, Centro Universitario de Ciencias Exactas e
Ingenierías, Universidad de Guadalajara, Guadalajara, Jalisco, México.
(5)Fundación Mundo Sano, Buenos Aires, Argentina.
(6)Instituto de Investigaciones en Enfermedades Tropicales and Instituto de
Patologia Experimental, Universidad Nacional de Salta/CONICET, Salta, Argentina
alekrol@hotmail.com.

Chagas disease is a neglected parasitic illness affecting approximately 8 million
people, predominantly in Latin America. Benznidazole is the drug of choice for
treatment, although its availability has been limited. A paucity of knowledge of
the pharmacokinetic properties of this drug has contributed to its limited
availability in several jurisdictions. The objective of this study was to conduct
a systematic literature review and a Bayesian meta-analysis of pharmacokinetic
studies to improve estimates of the basic pharmacokinetic properties of
benznidazole. A systematic search of the Embase, Medline, LILACS, and SciELO
(Scientific Electronic Library Online) databases was conducted. Eligible studies
reported patient-level data from single-100-mg-dose pharmacokinetic evaluations
of benznidazole in adults or otherwise provided data relevant to the estimation
of pharmacokinetic parameters which could be derived from such studies. A
Bayesian hierarchical model was used for analysis. Secondary data (i.e., data
from studies that did not include patient-level, single-100-mg-dose data) were
used for the generation of empirical priors for the Bayesian analysis. The
systematic search identified nine studies for inclusion. Nine pharmacokinetic
parameters were estimated, including the area under the concentration-time curve
(AUC), the maximum concentration of drug in plasma (Cmax), the time to Cmax, the
elimination rate constant (kel), the absorption rate constant (Ka), the
absorption and elimination half-lives, the apparent oral clearance, and the
apparent oral volume of distribution. The results showed consistency across
studies. AUC and Cmax were 51.31 mg · h/liter (95% credible interval [CrI],
45.01, 60.28 mg · h/liter) and 2.19 mg/liter (95% CrI, 2.06, 2.33 mg/liter),
respectively. Ka and kel were 1.16 h-1 (95% CrI, 0.59, 1.76 h-1) and 0.052 h-1
(95% CrI, 0.045, 0.059 h-1), respectively, with the corresponding absorption and
elimination half-lives being 0.60 h (95% CrI, 0.38, 1.11 h) and 13.27 h (95% CrI,
11.79, 15.42 h), respectively. The oral clearance and volume of distribution were
2.04 liters/h (95% CrI, 1.77, 2.32 liters/h) and 39.19 liters (95% CrI, 36.58,
42.17 liters), respectively. A Bayesian meta-analysis was used to improve the
estimates of the standard pharmacokinetic parameters of benznidazole. These data
can inform clinicians and policy makers as access to this drug increases.

Copyright © 2016, American Society for Microbiology. All Rights Reserved.

DOI: 10.1128/AAC.01567-16
PMCID: PMC5118981
PMID: 27550362  [Indexed for MEDLINE]


100. PLoS One. 2016 Nov 18;11(11):e0166801. doi: 10.1371/journal.pone.0166801.
eCollection 2016.

Effectiveness and Safety of Interventions for Treating Adults with Displaced
Proximal Humeral Fracture: A Network Meta-Analysis and Systematic Review.

Chen L(1)(2), Xing F(1), Xiang Z(1).

Author information:
(1)Department of Orthopedics, West China Hospital, Sichuan University, Chengdu,
Sichuan, China.
(2)Department of Orthopedics, Guizhou Provincial People's Hospital, Guiyang,
Guizhou, China.

PURPOSE: Network meta-analysis (NMA) is a comparatively new evidence-based
technique in medical disciplines which compares the relative benefits associated
with multiple interventions and obtains hierarchies of these interventions for
various treatment options. We evaluated the effectiveness and safety of open
reduction and internal fixation (ORIF), hemiarthroplasty (HA), reverse shoulder
arthroplasty (RSA), intramedullary nailing (IN) and non-operative treatment (NOT)
of displaced proximal humeral fractures in adults using Bayesian NMA of data from
clinical trials.
METHOD: PUBMED, EMBASE and CENTRAL in July 2016 were searched and clinical trials
that evaluated interventions for treating adults with displaced proximal humeral
fractures were identified. Methodological qualities of studies were assessed by
the Newcastle-Ottawa Scale and risk of bias using the Cochrane Collaboration
tool.
RESULT: Thirty-four trials involving 2165 participants were included in the
study. RSA had significantly the highest Constant score and lower total incidence
of complications than ORIF, HA and IN. Moreover, RSA resulted in a lower
incidence of additional surgery than ORIF and IN. The rank of treatments in terms
high Constant score was: RSA, ORIF, IN, NOT and HA. The rank for reduction in
total incidence of complications was: RSA, NOT, HA, IN and ORIF. For lowering the
risk of additional surgery, the rank was: RSA, NOT, HA, IN and ORIF.
CONCLUSION: RSA had the highest probability for improving functional outcome and
reduction in the total incidence of complications and requiring additional
surgery among the five interventions for treating adults with displaced proximal
humeral fracture.

DOI: 10.1371/journal.pone.0166801
PMCID: PMC5115806
PMID: 27861604  [Indexed for MEDLINE]

Conflict of interest statement: The authors have declared that no competing
interests exist.


101. Cochrane Database Syst Rev. 2016 Nov 17;11:CD012437.

Biologic or tofacitinib monotherapy for rheumatoid arthritis in people with
traditional disease-modifying anti-rheumatic drug (DMARD) failure: a Cochrane
Systematic Review and network meta-analysis (NMA).

Singh JA(1), Hossain A, Tanjong Ghogomu E, Mudano AS, Tugwell P, Wells GA.

Author information:
(1)Department of Medicine, Birmingham VA Medical Center, Faculty Office Tower
805B, 510 20th Street South, Birmingham, AL, USA, 35294.

BACKGROUND: We performed a systematic review, a standard meta-analysis and
network meta-analysis (NMA), which updates the 2009 Cochrane Overview, 'Biologics
for rheumatoid arthritis (RA)'. This review is focused on biologic monotherapy in
people with RA in whom treatment with traditional disease-modifying
anti-rheumatic drugs (DMARDs) including methotrexate (MTX) had failed (MTX/other
DMARD-experienced).
OBJECTIVES: To assess the benefits and harms of biologic monotherapy (includes
anti-tumor necrosis factor (TNF) (adalimumab, certolizumab pegol, etanercept,
golimumab, infliximab) or non-TNF (abatacept, anakinra, rituximab, tocilizumab))
or tofacitinib monotherapy (oral small molecule) versus comparator (placebo or
MTX/other DMARDs) in adults with RA who were MTX/other DMARD-experienced.
METHODS: We searched for randomized controlled trials (RCTs) in the Cochrane
Central Register of Controlled Trials (CENTRAL; The Cochrane Library 2015, Issue
6, June), MEDLINE (via OVID 1946 to June 2015), and Embase (via OVID 1947 to June
2015). Article selection, data extraction and risk of bias and GRADE assessments
were done in duplicate. We calculated direct estimates with 95% confidence
intervals (CI) using standard meta-analysis. We used a Bayesian mixed treatment
comparisons (MTC) approach for NMA estimates with 95% credible intervals (CrI).
We converted odds ratios (OR) to risk ratios (RR) for ease of understanding. We
calculated absolute measures as risk difference (RD) and number needed to treat
for an additional beneficial outcome (NNTB).
MAIN RESULTS: This update includes 40 new RCTs for a total of 46 RCTs, of which
41 studies with 14,049 participants provided data. The comparator was placebo in
16 RCTs (4,532 patients), MTX or other DMARD in 13 RCTs (5,602 patients), and
another biologic in 12 RCTs (3,915 patients). Monotherapy versus placeboBased on
moderate-quality direct evidence, biologic monotherapy (without concurrent
MTX/other DMARDs) was associated with a clinically meaningful and statistically
significant improvement in American College of Rheumatology score (ACR50) and
physical function, as measured by the Health Assessment Questionnaire (HAQ)
versus placebo. RR was 4.68 for ACR50 (95% CI, 2.93 to 7.48); absolute benefit RD
23% (95% CI, 18% to 29%); and NNTB = 5 (95% CI, 3 to 8). The mean difference (MD)
was -0.32 for HAQ (95% CI, -0.42 to -0.23; a negative sign represents greater HAQ
improvement); absolute benefit of -10.7% (95% CI, -14% to -7.7%); and NNTB = 4
(95% CI, 3 to 5). Direct and NMA estimates for TNF biologic, non-TNF biologic or
tofacitinib monotherapy showed similar results for ACR50 , downgraded to
moderate-quality evidence. Direct and NMA estimates for TNF biologic, anakinra or
tofacitinib monotherapy showed a similar results for HAQ versus placebo with
mostly moderate quality evidence.Based on moderate-quality direct evidence,
biologic monotherapy was associated with a clinically meaningful and
statistically significant greater proportion of disease remission versus placebo
with RR 1.12 (95% CI 1.03 to 1.22); absolute benefit 10% (95% CI, 3% to 17%; NNTB
= 10 (95% CI, 8 to 21)).Based on low-quality direct evidence, results for
biologic monotherapy for withdrawals due to adverse events and serious adverse
events were inconclusive, with wide confidence intervals encompassing the null
effect and evidence of an important increase. The direct estimate for TNF
monotherapy for withdrawals due to adverse events showed a clinically meaningful
and statistically significant result with RR 2.02 (95% CI, 1.08 to 3.78),
absolute benefit RD 3% (95% CI,1% to 4%), based on moderate-quality evidence. The
NMA estimates for TNF biologic, non-TNF biologic, anakinra, or tofacitinib
monotherapy for withdrawals due to adverse events and for serious adverse events
were all inconclusive and downgraded to low-quality evidence. Monotherapy versus
active comparator (MTX/other DMARDs)Based on direct evidence of moderate quality,
biologic monotherapy (without concurrent MTX/other DMARDs) was associated with a
clinically meaningful and statistically significant improvement in ACR50 and HAQ
scores versus MTX/other DMARDs with a RR of 1.54 (95% CI, 1.14 to 2.08); absolute
benefit 13% (95% CI, 2% to 23%), NNTB = 7 (95% CI, 4 to 26) and a mean difference
in HAQ of -0.27 (95% CI, -0.40 to -0.14); absolute benefit of -9% (95% CI, -13.3%
to -4.7%), NNTB = 2 (95% CI, 2 to 4). Direct and NMA estimates for TNF
monotherapy and NMA estimate for non-TNF biologic monotherapy for ACR50 showed
similar results, based on moderate-quality evidence. Direct and NMA estimates for
non-TNF biologic monotherapy, but not TNF monotherapy, showed similar HAQ
improvements , based on mostly moderate-quality evidence.There were no
statistically significant or clinically meaningful differences for direct
estimates of biologic monotherapy versus active comparator for RA disease
remission. NMA estimates showed a statistically significant and clinically
meaningful difference versus active comparator for TNF monotherapy (absolute
improvement 7% (95% CI, 2% to 14%)) and non-TNF monotherapy (absolute improvement
19% (95% CrI, 7% to 36%)), both downgraded to moderate quality.Based on
moderate-quality direct evidence from a single study, radiographic progression
(scale 0 to 448) was statistically significantly reduced in those on biologic
monotherapy versus active comparator, MD -4.34 (95% CI, -7.56 to -1.12), though
the absolute reduction was small, -0.97% (95% CI, -1.69% to -0.25%). We are not
sure of the clinical relevance of this reduction.Direct and NMA evidence
(downgraded to low quality), showed inconclusive results for withdrawals due to
adverse events, serious adverse events and cancer, with wide confidence intervals
encompassing the null effect and evidence of an important increase.
AUTHORS' CONCLUSIONS: Based mostly on RCTs of six to 12-month duration in people
with RA who had previously experienced and failed treatment with MTX/other
DMARDs, biologic monotherapy improved ACR50, function and RA remission rates
compared to placebo or MTX/other DMARDs.Radiographic progression was reduced
versus active comparator, although the clinical significance was unclear.Results
were inconclusive for whether biologic monotherapy was associated with an
increased risk of withdrawals due to adverse events, serious adverse events or
cancer, versus placebo (no data on cancer) or MTX/other DMARDs.

DOI: 10.1002/14651858.CD012437
PMID: 27855242  [Indexed for MEDLINE]


102. J Affect Disord. 2016 Nov 15;205:335-343. doi: 10.1016/j.jad.2016.08.014. Epub
2016 Aug 16.

Summary diagnostic validity of commonly used maternal major depression disorder
case finding instruments in the United States: A meta-analysis.

Owora AH(1), Carabin H(2), Reese J(3), Garwe T(4).

Author information:
(1)Department of Biostatistics and Epidemiology, College of Public Health,
University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States.
Electronic address: hamieuga@gmail.com.
(2)Department of Biostatistics and Epidemiology, College of Public Health,
University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States.
Electronic address: Helene-Carabin@ouhsc.edu.
(3)Department of Biostatistics and Epidemiology, College of Public Health,
University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States.
Electronic address: Jessica-Reese@ouhsc.edu.
(4)Department of Biostatistics and Epidemiology, College of Public Health,
University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States.
Electronic address: Tabitha-Garwe@ouhsc.edu.

INTRODUCTION: Major Depression Disorder (MDD) is common among mothers of young
children. However, its detection remains low in primary-care and community-based
settings in part due to the uncertainty regarding the validity of existing
case-finding instruments. We conducted meta-analyses to estimate the diagnostic
validity of commonly used maternal MDD case finding instruments in the United
States.
METHODS: We systematically searched three electronic bibliographic databases
PubMed, PsycINFO, and EMBASE from 1994 to 2015 to identify relevant published
literature. Study eligibility and quality were evaluated using the Standards for
the Reporting of Diagnostic Accuracy studies and Quality Assessment of Diagnostic
Accuracy Studies guidelines, respectively. Pooled sensitivity and specificity of
case-finding instruments were generated using Bayesian hierarchical summary
receiver operating models.
RESULTS: Overall, 1130 articles were retrieved and 74 articles were selected for
full-text review. Twelve articles examining six maternal MDD case-finding
instruments met the eligibility criteria and were included in our meta-analyses.
Pooled sensitivity and specificity estimates were highest for the BDI-II (91%;
95% Bayesian Credible Interval (BCI): 68%; 99% and 89%; 95% BCI: 62%; 98%
respectively) and EPDS10 (74%; 95% BCI: 46%; 91% and 97%; 95% BCI: 84%; 99%
respectively) during the antepartum and postpartum periods respectively.
LIMITATION: No meta-regression was conducted to examine the impact of study-level
characteristics on the results.
DISCUSSION: Diagnostic performance varied among instruments and between
peripartum periods. These findings suggest the need for a judicious selection of
maternal MDD case-finding instruments depending on the study population and
target periods of assessment.

Copyright © 2016 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.jad.2016.08.014
PMCID: PMC5568628
PMID: 27566453  [Indexed for MEDLINE]


103. Atherosclerosis. 2016 Nov;254:215-227. doi:
10.1016/j.atherosclerosis.2016.10.025. Epub 2016 Oct 14.

Efficacy and safety of long-term treatment with statins for coronary heart
disease: A Bayesian network meta-analysis.

Lu Y(1), Cheng Z(2), Zhao Y(1), Chang X(1), Chan C(3), Bai Y(1), Cheng N(4).

Author information:
(1)Institute of Epidemiology and Statistics, School of Public Health, Lanzhou
University, Lanzhou, Gansu, PR China.
(2)Center of Evidence-based Medicine of Lanzhou University, Basic Medical
College, Lanzhou University, Lanzhou, Gansu, PR China.
(3)Yale University and US. Fulbright Program, USA.
(4)Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Basic
Medical College, Lanzhou University, Lanzhou, Gansu 730000, PR China. Electronic
address: chengn@lzu.edu.cn.

BACKGROUND AND AIMS: Our study aims to evaluate the efficacy and safety of
long-term treatment of statins for coronary heart disease (CHD).
METHODS: Efficacy outcomes included changes in blood lipids, risk of CHD
mortality and all-cause mortality. Safety outcomes were evaluated by the risk of
adverse events (AE). Bayesian network meta-analysis was used to compare the
direct and indirect effects between different statins.
RESULTS: The systematic review showed that levels of blood lipids decreased
during statin treatment. High dose of atorvastatin was the most obvious treatment
for the reduction of blood lipids. Network meta-analysis showed that statins were
significantly more effective than the control in reducing the risk of CHD
mortality (Odds Ratio (OR) 0.69, 95% CI 0.61-0.77) and all-cause mortality (OR
0.84, 95% CI 0.80-0.87). In terms of reducing the risk of CHD morality,
fluvastatin (77.3%), atorvastatin (72.3%) and lovastatin (68.4%) had higher
cumulative probability than other statins, which were more effective treatments
for the reduction of CHD morality. In terms of reducing all-cause mortality,
atorvastatin (78.6%), fluvastatin (77.1%) and pitavastatin (74.1%) had higher
cumulative probability than other statins, which were more effective treatment
for reducing the all-cause mortality. Compared with placebo, statins increased
the incidence risk of muscle disease (OR 1.05, 95% CI 1.00-1.10) and kidney
disease (OR 1.11, 95% CI 1.05-1.72).
CONCLUSIONS: Statins significantly reduced levels of blood lipids, with a high
dose of atorvastatin being the most effective in blood-lipid level modification.
Statins reduced the risk of CHD mortality and all-cause mortality, with
atorvastatin and fluvastatin being the most effective in reducing the risk of CHD
mortality and all-cause mortality. Statins increased the risk of muscle disease
and kidney damage.

Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

DOI: 10.1016/j.atherosclerosis.2016.10.025
PMID: 27764723  [Indexed for MEDLINE]


104. Int J Hyperthermia. 2016 Nov;32(7):809-21. doi: 10.1080/02656736.2016.1195924.
Epub 2016 Aug 14.

Hyperthermia and radiotherapy with or without chemotherapy in locally advanced
cervical cancer: a systematic review with conventional and network meta-analyses.

Datta NR(1), Rogers S(1), Klingbiel D(2), Gómez S(1), Puric E(1), Bodis S(1)(3).

Author information:
(1)a Centre for Radiation Oncology , KSA-KSB, Kantonsspital Aarau , Aarau ,
Switzerland ;
(2)b Swiss Group for Clinical Cancer Research (SAKK) , Coordinating Centre , Bern
, Switzerland ;
(3)c Department of Radiation Oncology , University Hospital Zurich , Zurich ,
Switzerland.

PURPOSE: A systematic review with conventional and network meta-analyses (NMA)
was conducted to examine the outcomes of loco-regional hyperthermia (HT) with
radiotherapy (RT) and/or chemotherapy (CT) in locally advanced cervix cancer,
IIB-IVA (LACC).
METHODS AND MATERIALS: A total of 217 abstracts were screened from five databases
and reported as per PRISMA guidelines. Only randomised trials with HT and RT ± CT
were considered. The outcomes evaluated were complete response (CR), long-term
loco-regional control (LRC), patients alive, acute and late grade III/IV
toxicities.
RESULTS: Eight articles were finally retained. Six randomised trials with HTRT
(n = 215) vs. RT (n = 212) were subjected to meta-analysis. The risk difference
for achieving CR and LRC was greater by 22% (p < .001) and 23% (p < .001),
respectively, with HTRT compared to RT. A non-significant survival advantage of
8.4% with HTRT was noted with no differences in acute or late toxicities. The
only HTCTRT vs. RT trial documented a CR of 83.3% vs. 46.7% (risk difference:
36.7%, p = .001). No other end points were reported. Bayesian NMA, incorporating
13 studies (n = 1000 patients) for CR and 12 studies for patients alive (n = 807
patients), comparing HTCTRT, HTRT, CTRT and RT alone, was conducted. The pairwise
comparison of various groups showed that HTRTCT was the best option for both CR
and patient survival. This was also evident on ranking treatment modalities based
on the "surface under cumulative ranking" values.
CONCLUSIONS: In LACC, HTRT demonstrates a therapeutic advantage over RT without
significant acute or late morbidities. On NMA, HTCTRT appears promising, but
needs further confirmation through prospective randomised trials.

DOI: 10.1080/02656736.2016.1195924
PMID: 27411568  [Indexed for MEDLINE]


105. Int J Rheum Dis. 2016 Nov;19(11):1103-1111. doi: 10.1111/1756-185X.12822. Epub
2015 Dec 22.

Comparative efficacy and safety of tocilizumab, rituximab, abatacept and
tofacitinib in patients with active rheumatoid arthritis that inadequately
responds to tumor necrosis factor inhibitors: a Bayesian network meta-analysis of
randomized controlled trials.

Lee YH(1), Bae SC(2).

Author information:
(1)Division of Rheumatology, Department of Internal Medicine, Korea University
College of Medicine, Seoul, South Korea.
(2)Department of Rheumatology, Hanyang University Hospital for Rheumatic
Diseases, Seoul, South Korea.

AIMS: This study aimed to assess the relative efficacy and safety of biologics
and tofacitinib in patients with rheumatoid arthritis (RA) showing an inadequate
response to tumor necrosis factor (TNF) inhibitors.
METHODS: We performed a Bayesian network meta-analysis to combine the direct and
indirect evidence from randomized controlled trials (RCTs) examining the efficacy
and safety of tocilizumab, rituximab, abatacept and tofacitinib in patients with
RA that inadequately responds to TNF inhibitors.
RESULTS: Four RCTs including 1796 patients met the inclusion criteria. The
tocilizumab 8 mg group showed a significantly higher American College of
Rheumatology 20% (ACR20) response rate than the abatacept and tofacitinib groups.
Ranking probability based on surface under the cumulative ranking curve (SUCRA)
indicated that tocilizumab 8 mg had the highest probability of being the best
treatment for achieving the ACR20 response rate (SUCRA = 0.9863), followed by
rituximab (SUCRA = 0.6623), abatacept (SUCRA = 0.5428), tocilizumab 4 mg (SUCRA =
0.4956), tofacitinib 10 mg (SUCRA = 0.4715), tofacitinib 5 mg (SUCRA = 0.3415)
and placebo (SUCRA = 0). In contrast, the safety based on the number of
withdrawals due to adverse events did not differ significantly among the
treatment options.
CONCLUSIONS: Tocilizumab 8 mg was the second-line non-TNF biologic with the
highest performance regarding an early good response based on ACR20 response rate
and acceptable safety profile, followed by rituximab, abatacept and tofacitinib
in patients with RA and an inadequate response to anti-TNF therapy, and none of
these treatments were associated with a significant risk of withdrawal due to
adverse events.

© 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing
Asia Pty Ltd.

DOI: 10.1111/1756-185X.12822
PMID: 26692536  [Indexed for MEDLINE]


106. Int J Surg. 2016 Nov;35:111-119. doi: 10.1016/j.ijsu.2016.09.088. Epub 2016 Oct
2.

Cervical disc arthroplasty for symptomatic cervical disc disease: Traditional and
Bayesian meta-analysis with trial sequential analysis.

Kan SL(1), Yuan ZF(2), Ning GZ(1), Liu FF(1), Sun JC(1), Feng SQ(3).

Author information:
(1)Department of Orthopaedics, Tianjin Medical University General Hospital, 154
Anshan Road, Heping District, Tianjin 300052, China.
(2)School of Nursing, Tianjin Medical University, 22 Qixiangtai Road, Heping
District, Tianjin 300070, China.
(3)Department of Orthopaedics, Tianjin Medical University General Hospital, 154
Anshan Road, Heping District, Tianjin 300052, China. Electronic address:
sqfeng@tmu.edu.cn.

OBJECTIVE: Cervical disc arthroplasty (CDA) has been designed as a substitute for
anterior cervical discectomy and fusion (ACDF) in the treatment of symptomatic
cervical disc disease (CDD). Several researchers have compared CDA with ACDF for
the treatment of symptomatic CDD; however, the findings of these studies are
inconclusive. Using recently published evidence, this meta-analysis was conducted
to further verify the benefits and harms of using CDA for treatment of
symptomatic CDD.
METHODS: Relevant trials were identified by searching the PubMed, EMBASE, and
Cochrane Library databases. Outcomes were reported as odds ratio or standardized
mean difference. Both traditional frequentist and Bayesian approaches were used
to synthesize evidence within random-effects models. Trial sequential analysis
(TSA) was applied to test the robustness of our findings and obtain more
conservative estimates.
RESULTS: Nineteen trials were included. The findings of this meta-analysis
demonstrated better overall, neck disability index (NDI), and neurological
success; lower NDI and neck and arm pain scores; higher 36-Item Short Form Health
Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary
(MCS) scores; more patient satisfaction; greater range of motion at the operative
level; and fewer secondary surgical procedures (all P < 0.05) in the CDA group
compared with the ACDF group. CDA was not significantly different from ACDF in
the rate of adverse events (P > 0.05). TSA of overall success suggested that the
cumulative z-curve crossed both the conventional boundary and the trial
sequential monitoring boundary for benefit, indicating sufficient and conclusive
evidence had been ascertained.
CONCLUSIONS: For treating symptomatic CDD, CDA was superior to ACDF in terms of
overall, NDI, and neurological success; NDI and neck and arm pain scores; SF-36
PCS and MCS scores; patient satisfaction; ROM at the operative level; and
secondary surgical procedures rate. Additionally, there was no significant
difference between CDA and ACDF in the rate of adverse events. However, as the
CDA procedure is a relatively newer operative technique, long-term results and
evaluation are necessary before CDA is routinely used in clinical practice.

Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights
reserved.

DOI: 10.1016/j.ijsu.2016.09.088
PMID: 27693477  [Indexed for MEDLINE]


107. J Dairy Sci. 2016 Nov;99(11):9238-9253. doi: 10.3168/jds.2015-10383. Epub 2016
Sep 7.

Prediction of portal and hepatic blood flow from intake level data in cattle.

Ellis JL(1), Reynolds CK(2), Crompton LA(2), Hanigan MD(3), Bannink A(4), France
J(5), Dijkstra J(6).

Author information:
(1)Animal Nutrition Group, Wageningen University, Wageningen, 6708 WD, the
Netherlands; Centre for Nutrition Modeling, Department of Animal Biosciences,
University of Guelph, Guelph, ON, N1G 2W1, Canada. Electronic address:
jen.ellis.stpierre@gmail.com.
(2)School of Agriculture, Policy and Development, University of Reading, PO Box
237, Earley Gate, Reading, RG6 6AR, Berkshire, UK.
(3)College of Agriculture and Life Science, Virginia Tech University, 175 West
Campus Drive, Blacksburg 24061.
(4)Animal Nutrition, Wageningen UR Livestock Research, Wageningen, 6708 WD, the
Netherlands.
(5)Centre for Nutrition Modeling, Department of Animal Biosciences, University of
Guelph, Guelph, ON, N1G 2W1, Canada.
(6)Animal Nutrition Group, Wageningen University, Wageningen, 6708 WD, the
Netherlands.

Interest is growing in developing integrated postabsorptive metabolism models for
dairy cattle. An integral part of linking a multi-organ postabsorptive model is
the prediction of nutrient fluxes between organs, and thus blood flow. The
purpose of this paper was to use a multivariate meta-analysis approach to model
portal blood flow (PORBF) and hepatic venous blood flow (HEPBF) simultaneously,
with evaluation of hepatic arterial blood flow (ARTBF; ARTBF=HEPBF - PORBF) and
PORBF/HEPBF (%) as calculated values. The database used to develop equations
consisted of 296 individual animal observations (lactating and dry dairy cows and
beef cattle) and 55 treatments from 17 studies, and a separate evaluation
database consisted of 34 treatment means (lactating dairy cows and beef cattle)
from 9 studies obtained from the literature. Both databases had information on
dry matter intake (DMI), metabolizable energy intake (MEI), body weight, and a
basic description of the diet including crude protein intake and forage
proportion of the diet (FP; %). Blood flow (L/h or L/kg of BW0.75/h) and either
DMI or MEI (g or MJ/d or g or MJ/kg of BW0.75/d) were examined with linear and
quadratic fits. Equations were developed using cow within experiment and
experiment as random effects, and blood flow location as a repeated effect. Upon
evaluation with the evaluation database, equations based on DMI typically
resulted in lower root mean square prediction errors, expressed as a % of the
observed mean (rMSPE%) and higher concordance correlation coefficient (CCC)
values than equations based on MEI. Quadratic equation terms were frequently
nonsignificant, and the quadratic equations did not outperform their linear
counterparts. The best performing blood flow equations were PORBF (L/h)=202
(±45.6) + 83.6 (±3.11) × DMI (kg/d) and HEPBF (L/h)=186 (±45.4) + 103.8 (±3.10) ×
DMI (kg/d), with rMSPE% values of 17.5 and 16.6 and CCC values of 0.93 and 0.94,
respectively. The residuals (predicted - observed) for PORBF/HEPBF were
significantly related to the forage % of the diet, and thus equations for PORBF
and HEPBF based on forage and concentrate DMI were developed: PORBF (L/h)=210
(±51.0) + 82.9 (±6.43) × forage (kg of DM/d) + 82.9 (±6.04) × concentrate (kg of
DM/d), and HEPBF (L/h)=184 (±50.6) + 92.6 (±6.28) × forage (kg of DM/d) + 114.2
(±5.88) × concentrate (kg of DM/d), where rMSPE% values were 17.5 and 17.6 and
CCC values were 0.93 and 0.94, respectively. Division of DMI into forage and
concentrate fractions improved the joint Bayesian information criterion value for
PORBF and HEPBF (Bayesian information criterion=6,512 vs. 7,303), as well as
slightly improved the rMSPE and CCC for ARTBF and PORBF/HEPBF. This was despite
minimal changes in PORBF and HEPBF predictions. Developed equations predicted
blood flow well and can easily be used within a postabsorptive model of nutrient
metabolism. Results also suggest different sensitivity of PORBF and HEPBF to the
composition of DMI, and accounting for this difference resulted in improved ARTBF
predictions.

Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc.
All rights reserved.

DOI: 10.3168/jds.2015-10383
PMID: 27614843  [Indexed for MEDLINE]


108. J Korean Med Sci. 2016 Nov;31(11):1828-1837. doi: 10.3346/jkms.2016.31.11.1828.

Pharmacological and Mechanical Thromboprophylaxis in Critically Ill Patients: a
Network Meta-Analysis of 12 Trials.

Park J(1), Lee JM(2), Lee JS(3), Cho YJ(4).

Author information:
(1)Department of Internal Medicine and Cardiovascular Center, Seoul National
University Hospital, Seoul, Korea.
(2)Division of Cardiology, Department of Internal Medicine, Heart Vascular Stroke
Institute, Samsung Medical Center, Seoul, Korea.
(3)Department of Internal Medicine, Seoul National University Hospital, Seoul,
Korea.
(4)Division of Pulmonary and Critical Care Medicine, Department of Internal
Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
lungdrcho@gmail.com, lungdrcho@snubh.org.

Thromboprophylaxis for venous thromboembolism is widely used in critically ill
patients. However, only limited evidence exists regarding the efficacy and safety
of the various thromboprophylaxis techniques, especially mechanical
thromboprophylaxis. Therefore, we performed meta-analysis of randomized
controlled trials (RCTs) that compared the overall incidence of deep vein
thrombosis (DVT) for between unfractionated heparin (UFH), low-molecular-weight
heparin (LMWH), and intermittent pneumatic compression (IPC) in critically ill
patients. A Bayesian random effects model for multiple treatment comparisons was
constructed. The primary outcome measure was the overall incidence of DVT at the
longest follow-up. The secondary outcome measure was the incidence of major
bleeding, as defined by the original trials. Our analysis included 8,622 patients
from 12 RCTs. The incidence of DVT was significantly lower in patients treated
with UFH (OR, 0.45; 95% CrI, 0.22-0.83) or LMWH (OR, 0.38; 95% CrI, 0.18-0.72)
than in patients in the control group. IPC was associated with a reduced
incidence of DVT compared to the control group, but the effect was not
statistically significant (OR, 0.50; 95% CrI, 0.20-1.23). The risk of DVT was
similar for patients treated with UFH and LMWH (OR, 1.16; 95% CrI, 0.68-2.11).
The risk of major bleeding was similar between the treatment groups in medical
critically ill patients and also in critically ill patients with a high risk of
bleeding. In critically ill patients, the efficacy of mechanical
thromboprophylaxis in reducing the risk of DVT is not as robust as those of
pharmacological thromboprophylaxis.

DOI: 10.3346/jkms.2016.31.11.1828
PMCID: PMC5056218
PMID: 27709864  [Indexed for MEDLINE]

Conflict of interest statement: The authors have no potential conflicts of
interest to disclose.


109. Lancet HIV. 2016 Nov;3(11):e510-e520. doi: 10.1016/S2352-3018(16)30091-1. Epub
2016 Sep 6.

Comparative efficacy and safety of first-line antiretroviral therapy for the
treatment of HIV infection: a systematic review and network meta-analysis.

Kanters S(1), Vitoria M(2), Doherty M(2), Socias ME(3), Ford N(2), Forrest JI(1),
Popoff E(3), Bansback N(4), Nsanzimana S(5), Thorlund K(3), Mills EJ(6).

Author information:
(1)Precision Global Health, Vancouver, BC, Canada; School of Population and
Public Health, University of British Columbia, Vancouver, BC, Canada.
(2)Department of HIV/AIDS, WHO, Geneva, Switzerland.
(3)Precision Global Health, Vancouver, BC, Canada.
(4)School of Population and Public Health, University of British Columbia,
Vancouver, BC, Canada.
(5)Rwanda Biomedical Centre, Ministry of Health, Kigali, Rwanda.
(6)Precision Global Health, Vancouver, BC, Canada; School of Public Health,
University of Rwanda, Kigali, Rwanda. Electronic address:
ed.mills@precisionglobalhealth.com.

BACKGROUND: New antiretroviral therapy (ART) regimens for HIV could improve
clinical outcomes for patients. To inform global guidelines, we aimed to assess
the comparative effectiveness of recommended ART regimens for HIV in ART-naive
patients.
METHODS: For this systematic review and network meta-analysis, we searched for
randomised clinical trials published up to July 5, 2015, comparing recommended
antiretroviral regimens in treatment-naive adults and adolescents (aged 12 years
or older) with HIV. We extracted data on trial and patient characteristics, and
the following primary outcomes: viral suppression, mortality, AIDS defining
illnesses, discontinuations, discontinuations due to adverse events, and serious
adverse events. We synthesised data using network meta-analyses in a Bayesian
framework and included older treatments, such as indinavir, to serve as
connecting nodes. We defined network nodes in terms of specific antivirals rather
than specific ART regimens. We categorised backbone regimens and adjusted for
them through group-specific meta-regression. We used the GRADE framework to
interpret the strength of inference.
FINDINGS: We identified 5865 citations through database searches and other
sources, of which, 126 articles related to 71 unique trials were included in the
network analysis, including 34 032 patients randomly assigned to 161 treatment
groups. For viral suppression at 48 weeks, compared with efavirenz, the odds
ratio (OR) for viral suppression was 1·87 (95% credible interval [CrI] 1·34-2·64)
with dolutegravir and 1·40 (1·02-1·96) with raltegravir; with respect to viral
suppression, low-dose efavirenz was similar to all other treatments. Both
low-dose efavirenz and integrase strand transfer inhibitors tended to be
protective of discontinuations due to adverse events relative to normal-dose
efavirenz. The most protective effect relative to efavirenz in network
meta-analyses was that of dolutegravir (OR 0·26, 95% CrI 0·14-0·47), followed by
low-dose efavirenz (0·39, 0·16-0·92). Owing to insufficient data, we could make
no conclusions about serious adverse events. Low event rates also limited the
quality of evidence with regard to mortality and AIDS defining illnesses.
INTERPRETATION: The efficacy and safety of ART has substantially improved with
the introduction of newer drug classes of antiretrovirals that are now available
to patients and HIV care providers. Their improved tolerance could be part of a
larger solution to improve retention, which is a challenge, particularly in
low-income and middle-income country settings.
FUNDING: The World Health Organization.

Copyright © 2016 Elsevier Ltd. All rights reserved.

DOI: 10.1016/S2352-3018(16)30091-1
PMID: 27658869  [Indexed for MEDLINE]


110. Cochrane Database Syst Rev. 2016 Oct 31;10:CD010683.

Methods to decrease blood loss during liver resection: a network meta-analysis.

Moggia E(1), Rouse B, Simillis C, Li T, Vaughan J, Davidson BR, Gurusamy KS.

Author information:
(1)Department of General and Digestive Surgery, IRCCS Humanitas Research
Hospital, Via Manzoni 56, 20089 Rozzano, Milan, Italy, Italy, 20089.

Update of
    Cochrane Database Syst Rev. 2014 Apr 02;(4):CD010683.

BACKGROUND: Liver resection is a major surgery with significant mortality and
morbidity. Specialists have tested various methods in attempts to limit blood
loss, transfusion requirements, and morbidity during elective liver resection.
These methods include different approaches (anterior versus conventional
approach), use of autologous blood donation, cardiopulmonary interventions such
as hypoventilation, low central venous pressure, different methods of parenchymal
transection, different methods of management of the raw surface of the liver,
different methods of vascular occlusion, and different pharmacological
interventions. A surgeon typically uses only one of the methods from each of
these seven categories. The optimal method to decrease blood loss and transfusion
requirements in people undergoing liver resection is unknown.
OBJECTIVES: To assess the effects of different interventions for decreasing blood
loss and blood transfusion requirements during elective liver resection.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials
(CENTRAL), MEDLINE, Embase, and Science Citation Index Expanded to September 2015
to identify randomised clinical trials. We also searched trial registers and
handsearched the references lists of identified trials.
SELECTION CRITERIA: We included only randomised clinical trials (irrespective of
language, blinding, or publication status) comparing different methods of
decreasing blood loss and blood transfusion requirements in people undergoing
liver resection.
DATA COLLECTION AND ANALYSIS: Two review authors independently identified trials
and collected data. We assessed the risk of bias using Cochrane domains. We
conducted a Bayesian network meta-analysis using the Markov chain Monte Carlo
method in WinBUGS 1.4, following the guidelines of the National Institute for
Health and Care Excellence Decision Support Unit guidance documents. We
calculated the odds ratios (OR) with 95% credible intervals (CrI) for the binary
outcomes, mean differences (MD) with 95% CrI for continuous outcomes, and rate
ratios with 95% CrI for count outcomes, using a fixed-effect model or
random-effects model according to model-fit. We assessed the evidence with GRADE.
MAIN RESULTS: We identified 67 randomised clinical trials involving a total of
6197 participants. All the trials were at high risk of bias. A total of 5771
participants from 64 trials provided data for one or more outcomes included in
this review. There was no evidence of differences in most of the comparisons, and
where there was, these differences were in single trials, mostly of small sample
size. We summarise only the evidence that was available in more than one trial
below. Of the primary outcomes, the only one with evidence of a difference from
more than one trial under the pair-wise comparison was in the number of adverse
events (complications), which was higher with radiofrequency dissecting sealer
than with the clamp-crush method (rate ratio 1.85, 95% CrI 1.07 to 3.26; 250
participants; 3 studies; very low-quality evidence). Among the secondary
outcomes, the only differences we found from more than one trial under the
pair-wise comparison were the following: blood transfusion (proportion) was
higher in the low central venous pressure group than in the acute normovolemic
haemodilution plus low central venous pressure group (OR 3.19, 95% CrI 1.56 to
6.95; 208 participants; 2 studies; low-quality evidence); blood transfusion
quantity (red blood cells) was lower in the fibrin sealant group than in the
control (MD -0.53 units, 95% CrI -1.00 to -0.07; 122 participants; 2; very
low-quality evidence); blood transfusion quantity (fresh frozen plasma) was
higher in the oxidised cellulose group than in the fibrin sealant group (MD 0.53
units, 95% CrI 0.36 to 0.71; 80 participants; 2 studies; very low-quality
evidence); blood loss (MD -0.34 L, 95% CrI -0.46 to -0.22; 237 participants; 4
studies; very low-quality evidence), total hospital stay (MD -2.42 days, 95% CrI
-3.91 to -0.94; 197 participants; 3 studies; very low-quality evidence), and
operating time (MD -15.32 minutes, 95% CrI -29.03 to -1.69; 192 participants; 4
studies; very low-quality evidence) were lower with low central venous pressure
than with control. For the other comparisons, the evidence for difference was
either based on single small trials or there was no evidence of differences. None
of the trials reported health-related quality of life or time needed to return to
work.
AUTHORS' CONCLUSIONS: Paucity of data meant that we could not assess transitivity
assumptions and inconsistency for most analyses. When direct and indirect
comparisons were available, network meta-analysis provided additional effect
estimates for comparisons where there were no direct comparisons. However, the
paucity of data decreases the confidence in the results of the network
meta-analysis. Low-quality evidence suggests that liver resection using a
radiofrequency dissecting sealer may be associated with more adverse events than
with the clamp-crush method. Low-quality evidence also suggests that the
proportion of people requiring a blood transfusion is higher with low central
venous pressure than with acute normovolemic haemodilution plus low central
venous pressure; very low-quality evidence suggests that blood transfusion
quantity (red blood cells) was lower with fibrin sealant than control; blood
transfusion quantity (fresh frozen plasma) was higher with oxidised cellulose
than with fibrin sealant; and blood loss, total hospital stay, and operating time
were lower with low central venous pressure than with control. There is no
evidence to suggest that using special equipment for liver resection is of any
benefit in decreasing the mortality, morbidity, or blood transfusion requirements
(very low-quality evidence). Radiofrequency dissecting sealer should not be used
outside the clinical trial setting since there is low-quality evidence for
increased harm without any evidence of benefits. In addition, it should be noted
that the sample size was small and the credible intervals were wide, and we
cannot rule out considerable benefit or harm with a specific method of liver
resection.

DOI: 10.1002/14651858.CD010683.pub3
PMID: 27797116  [Indexed for MEDLINE]


111. Adv Ther. 2016 Oct;33(10):1814-1830. Epub 2016 Aug 17.

A Systematic Review and Network Meta-Analysis to Evaluate the Comparative
Efficacy of Interventions for Unfit Patients with Chronic Lymphocytic Leukemia.

Städler N(1), Shang A(2), Bosch F(3), Briggs A(4), Goede V(5), Berthier A(2),
Renaudin C(2), Leblond V(6).

Author information:
(1)F. Hoffmann-La Roche Ltd, Basel, Switzerland. nicolas.staedler@roche.com.
(2)F. Hoffmann-La Roche Ltd, Basel, Switzerland.
(3)Hematology Department, University Hospital Vall d'Hebron, Barcelona, Spain.
(4)Health Economics and Health Technology Assessment, University of Glasgow,
Glasgow, UK.
(5)Department I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn,
University Hospital Cologne, Cologne, Germany.
(6)UPMC GRC11-GRECHY, AP-HP Hôpital Pitié Salpêtrière, Paris, France.

INTRODUCTION: Rituximab plus fludarabine and cyclophosphamide (RFC) is the
standard of care for fit patients with untreated chronic lymphocytic leukemia
(CLL); however, its use is limited in 'unfit' (co-morbid and/or full-dose
F-ineligible) patients due to its toxicity profile. We conducted a systematic
review and Bayesian network meta-analysis (NMA) to determine the relative
efficacy of commercially available interventions for the first-line treatment of
unfit CLL patients.
METHODS: For inclusion in the NMA, studies had to be linked via common treatment
comparators, report progression-free survival (PFS), and/or overall survival
(OS), and meet at least one of the five inclusion criteria: median cumulative
illness score >6, median creatinine clearance ≤70 mL/min, existing
co-morbidities, median age ≥70 years, and no full-dose F in the comparator arm. A
manual review, validated by external experts, of all studies that met at least
one of these criteria was also performed to confirm that they evaluated
first-line therapeutic options for unfit patients with CLL.
RESULTS: In unfit patients, the main NMA (five studies for PFS and four for OS)
demonstrated clear preference in terms of PFS for obinutuzumab + chlorambucil
(G-Clb) versus rituximab + chlorambucil (R-Clb), ofatumumab + chlorambucil
(O-Clb), fludarabine and chlorambucil (median hazard ratios [HRs] 0.43, 0.33,
0.20, and 0.19, respectively), and a trend for better efficacy versus
rituximab + bendamustine (R-Benda) and RFC-Lite (median HR 0.81 and 0.88,
respectively). OS results were generally consistent with PFS data, (median HR
0.48, 0.53, and 0.81, respectively) for G-Clb versus Clb, O-Clb, and R-Clb 0.35
and 0.81 versus F and R-Benda, respectively); however, the OS findings were
associated with higher uncertainty. Treatment ranking reflected improved PFS and
OS with G-Clb over other treatment strategies (median rank of one for both
endpoints).
CONCLUSION: G-Clb is likely to show superior efficacy to other treatment options
selected in our NMA for unfit treatment-naïve patients with CLL.
FUNDING: F. Hoffmann-La Roche Ltd.

DOI: 10.1007/s12325-016-0398-2
PMCID: PMC5055565
PMID: 27535291  [Indexed for MEDLINE]


112. Am J Kidney Dis. 2016 Oct;68(4):554-563. doi: 10.1053/j.ajkd.2016.03.418. Epub
2016 Apr 30.

The Validity of Left Ventricular Mass as a Surrogate End Point for All-Cause and
Cardiovascular Mortality Outcomes in People With CKD: A Systematic Review and
Meta-analysis.

Badve SV(1), Palmer SC(2), Strippoli GFM(3), Roberts MA(4), Teixeira-Pinto A(5),
Boudville N(6), Cass A(7), Hawley CM(8), Hiremath SS(9), Pascoe EM(10), Perkovic
V(11), Whalley GA(12), Craig JC(13), Johnson DW(8).

Author information:
(1)Australasian Kidney Trials Network, Brisbane, Australia; School of Medicine,
The University of Queensland, Brisbane, Australia; Department of Nephrology, St.
George Hospital, Sydney, Australia; The George Institute for Global Health,
University of Sydney, Sydney, Australia. Electronic address:
sbadve@georgeinstitute.org.au.
(2)Australasian Kidney Trials Network, Brisbane, Australia; Department of
Medicine, University of Otago Christchurch, Christchurch, New Zealand.
(3)School of Public Health, University of Sydney, Sydney, Australia; Diaverum
Scientific Office and Diaverum Academy, Lund, Sweden; Department of Emergency and
Organ Transplantation, University of Bari, Italy.
(4)Australasian Kidney Trials Network, Brisbane, Australia; Department of Renal
Medicine, Eastern Health Clinical School, Monash University, Melbourne,
Australia.
(5)School of Public Health, University of Sydney, Sydney, Australia.
(6)Australasian Kidney Trials Network, Brisbane, Australia; School of Medicine
and Pharmacology, University of Western Australia, Perth, Australia.
(7)Australasian Kidney Trials Network, Brisbane, Australia; Menzies School of
Health Research, Charles Darwin University, Darwin, Australia.
(8)Australasian Kidney Trials Network, Brisbane, Australia; School of Medicine,
The University of Queensland, Brisbane, Australia; Department of Nephrology,
Princess Alexandra Hospital, Brisbane, Australia.
(9)Division of Nephrology, University of Ottawa, Ottawa, Canada; Clinical
Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Canada.
(10)Australasian Kidney Trials Network, Brisbane, Australia; School of Medicine,
The University of Queensland, Brisbane, Australia.
(11)Australasian Kidney Trials Network, Brisbane, Australia; The George Institute
for Global Health, University of Sydney, Sydney, Australia.
(12)Unitec Institute of Technology, Auckland, New Zealand.
(13)Australasian Kidney Trials Network, Brisbane, Australia; School of Public
Health, University of Sydney, Sydney, Australia; Cochrane Kidney and Transplant
Group, Sydney, Australia.

BACKGROUND: Left ventricular mass (LVM) is a widely used surrogate end point in
randomized trials involving people with chronic kidney disease (CKD) because
treatment-induced LVM reductions are assumed to lower cardiovascular risk. The
aim of this study was to assess the validity of LVM as a surrogate end point for
all-cause and cardiovascular mortality in CKD.
STUDY DESIGN: Systematic review and meta-analysis.
SETTING & POPULATION: Participants with any stages of CKD.
SELECTION CRITERIA FOR STUDIES: Randomized controlled trials with 3 or more
months' follow-up that reported LVM data.
INTERVENTION: Any pharmacologic or nonpharmacologic intervention.
OUTCOMES: The surrogate outcome of interest was LVM change from baseline to last
measurement, and clinical outcomes of interest were all-cause and cardiovascular
mortality. Standardized mean differences (SMDs) of LVM change and relative risk
for mortality were estimated using pairwise random-effects meta-analysis.
Correlations between surrogate and clinical outcomes were summarized across all
interventions combined using bivariate random-effects Bayesian models, and 95%
credible intervals were computed.
RESULTS: 73 trials (6,732 participants) covering 25 intervention classes were
included in the meta-analysis. Overall, risk of bias was uncertain or high. Only
3 interventions reduced LVM: erythropoiesis-stimulating agents (9 trials;
SMD, -0.13; 95% CI, -0.23 to -0.03), renin-angiotensin-aldosterone system
inhibitors (13 trials; SMD, -0.28; 95% CI, -0.45 to -0.12), and isosorbide
mononitrate (2 trials; SMD, -0.43; 95% CI, -0.72 to -0.14). All interventions had
uncertain effects on all-cause and cardiovascular mortality. There were weak and
imprecise associations between the effects of interventions on LVM change and
all-cause (32 trials; 5,044 participants; correlation coefficient, 0.28; 95%
credible interval, -0.13 to 0.59) and cardiovascular mortality (13 trials; 2,327
participants; correlation coefficient, 0.30; 95% credible interval, -0.54 to
0.76).
LIMITATIONS: Limited long-term data, suboptimal quality of included studies.
CONCLUSIONS: There was no clear and consistent association between
intervention-induced LVM change and mortality. Evidence for LVM as a valid
surrogate end point in CKD is currently lacking.

Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

DOI: 10.1053/j.ajkd.2016.03.418
PMID: 27138469  [Indexed for MEDLINE]


113. Clin Ther. 2016 Oct;38(10):2204-2226. doi: 10.1016/j.clinthera.2016.08.014. Epub
2016 Sep 29.

Comparison of Inhaled Antibiotics for the Treatment of Chronic Pseudomonas
aeruginosa Lung Infection in Patients With Cystic Fibrosis: Systematic Literature
Review and Network Meta-analysis.

Elborn JS(1), Vataire AL(2), Fukushima A(2), Aballea S(2), Khemiri A(2), Moore
C(3), Medic G(4), Hemels ME(5).

Author information:
(1)School of Medicine, Dentistry & Biomedical Sciences, Queen׳s University
Belfast, Belfast, United Kingdom.
(2)Health Economics and Outcomes Research, Creativ-Ceutical, Paris, France.
(3)Raptor Pharmaceuticals, Inc, Novato, California.
(4)Raptor Pharmaceuticals Europe BV, Amsterdam, the Netherlands; Unit of
Pharmacoepidemiology and Pharmacoeconomics, Department of Pharmacy, University of
Groningen, Groningen, the Netherlands.
(5)Raptor Pharmaceuticals Europe BV, Amsterdam, the Netherlands. Electronic
address: mhemels@raptorpharma.com.

PURPOSE: In Europe, 4 inhaled antibiotics (tobramycin, colistimethate sodium,
aztreonam, and levofloxacin) are currently approved for the treatment of chronic
Pseudomonas aeruginosa lung infection in patients with cystic fibrosis (CF).
Levofloxacin inhalation solution (LIS) is the most recently approved inhaled
antibiotic for adult patients with CF. A systematic literature review and
Bayesian network meta-analysis (NMA) was conducted to compare the relative
short-term (4 weeks) and long-term (24 weeks) outcomes of these inhaled
antibiotics versus LIS.
METHODS: A systematic literature search was conducted on February 16, 2016, using
EMBASE and Medline via OvidSP. All randomized controlled trials comparing any of
the aforementioned inhaled antibiotics with 4 or 24 weeks of follow-up were
evaluated. NMA was performed for the following outcomes: relative and absolute
percent changes from baseline in forced expiratory volume in 1 second (FEV1%)
predicted, change in P aeruginosa sputum density, respiratory symptoms score from
the CF questionnaire-revised, hospitalization, additional antibiotics use, and
study withdrawal rates.
RESULTS: Of the 685 articles identified, 7 unique studies were included in the 4
weeks' NMA and 9 unique studies were included in the 24 weeks' NMA. Aztreonam was
predicted to result in the greatest numerically increase in FEV1% predicted at 4
weeks, whereas LIS were predicted to be numerically greater than colistimethate
sodium, tobramycin inhaled solution (TIS), and tobramycin inhaled powder (TIP).
However, all of the 95% credibility intervals (CrIs) of these comparisons
included zero. At 24 weeks, none of the treatments was significantly more
effective than LIS. The estimates for the mean change from baseline to 24 weeks
in relative FEV1% versus LIS was -0.55 (95% CrI, -3.91 to 2.80) for TIS, -2.36
(95% CrI, -7.32 to 2.63) for aztreonam, -2.95 (95% CrI, -10.44 to 4.51) for TIP,
and -9.66 (95% CrI, -15.01 to -4.33) for placebo. Compared with LIS, the odds
ratio for hospitalization at 24 weeks was 1.92 (95% CrI, 1.01-3.30) for TIS, 2.25
(95% CrI, 1.01-4.34) for TIP, and 3.16 (95% CrI, 1.53-5.78) for placebo, all
statistically worse than LIS. P aeruginosa sputum density scores, additional use
of antipseudomonal antibiotics, and study withdrawal rates were comparable among
all inhaled antibiotics at all times.
IMPLICATIONS: Based on this NMA, the analyses for many of the outcomes did not
provide significant evidence to indicate that the other approved inhaled
antibiotics were more effective than LIS for the treatment of chronic P
aeruginosa lung infection in patients with CF. Study withdrawal rates seemed to
be comparable among these inhaled antibiotics.

Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.clinthera.2016.08.014
PMID: 27692977  [Indexed for MEDLINE]


114. Pathol Oncol Res. 2016 Oct;22(4):853-61. doi: 10.1007/s12253-016-0078-1. Epub
2016 May 28.

Fluoropyrimidine-Based Chemotherapy as First-Line Treatment for Advanced Gastric
Cancer: a Bayesian Network Meta-Analysis.

Zhu L(1)(2), Liu J(1)(2), Ma S(3)(4).

Author information:
(1)Department of Oncology, Affiliated Hangzhou Hospital of Nanjing Medical
University, No.261, Huansha Road, Shangcheng District, Hangzhou, 310006, People's
Republic of China.
(2)Department of Oncology, Hangzhou First People's Hospital, Hangzhou, 310006,
People's Republic of China.
(3)Department of Oncology, Affiliated Hangzhou Hospital of Nanjing Medical
University, No.261, Huansha Road, Shangcheng District, Hangzhou, 310006, People's
Republic of China. mashenglin@outlook.com.
(4)Department of Oncology, Hangzhou First People's Hospital, Hangzhou, 310006,
People's Republic of China. mashenglin@outlook.com.

Fluoropyrimidine-based regimens are the most common treatments in advanced
gastric cancer. We used a Bayesian network meta-analysis to identify the optimal
fluoropyrimidine-based chemotherapy by comparing their relative efficacy and
safety. We systematically searched databases and extracted data from randomized
controlled trials, which compared fluoropyrimidine-based regimens as first-line
treatment in AGC. The main outcomes were overall survival (OS), progression-free
survival (PFS), overall response rate (ORR), and grade 3 or 4 adverse events
(AEs). A total of 12 RCTs of 4026 patients were included in our network
meta-analysis. Pooled analysis showed S-1 and capecitabine had a significant OS
benefit over 5-Fu, with hazard ratios of 0.90 (95%CI = 0.81-0.99) and 0.88
(95%CI = 0.80-0.96), respectively. The result also exhibited a trend that S-1 and
capecitabine prolonged PFS in contrast to 5-Fu, with hazard ratios of 0.84
(95%CI = 0.66-1.02) and 0.84 (95%CI = 0.65-1.03), respectively. Additionally, all
the three fluoropyrimidine-based regimens were similar in terms of ORR and grade
3 or 4 AEs. Compared with regimens based on 5-Fu, regimens based on S-1 or
capecitabine demonstrated a significant OS improvement without compromise of AEs
as first-line treatment in AGC in Asian population. S-1 and capecitabine can be
interchangeable according their different emphasis on AEs.

DOI: 10.1007/s12253-016-0078-1
PMID: 27236591  [Indexed for MEDLINE]


115. BMC Med. 2016 Sep 13;14(1):137. doi: 10.1186/s12916-016-0673-8.

Risk of serious infections with immunosuppressive drugs and glucocorticoids for
lupus nephritis: a systematic review and network meta-analysis.

Singh JA(1)(2)(3)(4), Hossain A(5), Kotb A(5), Wells G(5).

Author information:
(1)Medicine Service, VA Medical Center, Birmingham, AL, 35233, USA.
jasvinder.md@gmail.com.
(2)Department of Medicine at the School of Medicine, University of Alabama at
Birmingham, Birmingham, AL, 35294, USA. jasvinder.md@gmail.com.
(3)Division of Epidemiology at the School of Public Health, University of Alabama
at Birmingham, Birmingham, AL, 35294, USA. jasvinder.md@gmail.com.
(4)Department of Orthopedic Surgery, Mayo Clinic College of Medicine, Rochester,
MN, 55905, USA. jasvinder.md@gmail.com.
(5)Ottawa Heart Institute and the University of Ottawa, Ottawa, Ontario, K1Y 4W7,
Canada.

BACKGROUND: To perform a systematic review and network meta-analysis (NMA) to
compare the risk of serious infections with immunosuppressive medications and
glucocorticoids in lupus nephritis.
METHODS: A trained librarian performed two searches: (1) PubMed for all lupus
nephritis trials from the end dates for the systematic review for the 2012
American College of Rheumatology (ACR) lupus nephritis treatment guidelines and
the 2012 Cochrane Systematic Review on treatments for lupus nephritis, to
September 2013; and (2) PubMed and SCOPUS for all lupus trials (excluding lupus
nephritis) from inception to February 2014, to obtain additional trials for harms
data in any lupus patient. The search was updated to May 2016. Duplicate
title/abstract review and duplicate data abstractions by two abstractors
independently was performed for all eligible studies, including those studies
abstracted for the 2012 ACR lupus nephritis treatment guidelines and the 2012
Cochrane Systematic Review on lupus nephritis treatments. We performed
a systematic review and a Bayesian NMA, including randomized controlled trials
(RCTs) of immunosuppressive drugs or glucocorticoids in patients with lupus
nephritis assessing serious infection risk. Markov chain Monte Carlo methods were
used to model 95 % credible intervals (CrI). Sensitivity analyses examined the
robustness of estimates.
RESULTS: A total of 32 RCTs with 2611 patients provided data. There were 26
two-arm, five three-arm, and one four-arm trials. We found that tacrolimus was
associated with significantly lower risk of serious infections compared to
glucocorticoids, cyclophosphamide (CYC), mycophenolate mofetil (MMF), and
azathioprine (AZA) with odds ratios (95 % CrI) of 0.33 (0.12-0.88), 0.37
(0.15-0.87), 0.340 (0.18-0.81), and 0.32 (0.12-0.81), respectively. Conversely,
CYC low dose (LD), CYC high dose (HD), and HD glucocorticoids were associated
with higher odds of serious infections compared to tacrolimus, ranging from 4.84
to 12.83. We also found that MMF followed by AZA (MMF-AZA) was associated with
significantly lower risk of serious infections as compared to CYC LD, CYC HD,
CYC-AZA, or HD glucocorticoids with odds ratios (95 % CrI) of 0.09 (0.01-0.76),
0.07 (0.01-0.54), 0.14 (0.02-0.71), and 0.03 (0.00-0.56), respectively. Estimates
were similar to pair-wise meta-analyses. Sensitivity analyses that varied
estimate (odds ratio vs. Peto's odds ratio), method (random vs. fixed effects
model), data (sepsis vs. serious infection data; exclusion of observational
studies), treatment grouping (CYC and CYC HD as a combined treatment group vs.
separate), made little/no difference to these estimates.
CONCLUSIONS: Tacrolimus and MMF-AZA combination were associated with lower risk
of serious infections compared to other immunosuppressive drugs or
glucocorticoids for lupus nephritis. In conjunction with comparative efficacy
data, these data can help patients make informed decisions about treatment
options for lupus nephritis.
PROSPERO REGISTRATION: CRD42016032965.

DOI: 10.1186/s12916-016-0673-8
PMCID: PMC5022202
PMID: 27623861  [Indexed for MEDLINE]


116. Am J Gastroenterol. 2016 Sep;111(9):1230-43. doi: 10.1038/ajg.2016.287. Epub 2016
Jul 12.

Comparison of Efficacy of Prophylactic Endoscopic Therapies for Postpolypectomy
Bleeding in the Colorectum: A Systematic Review and Network Meta-Analysis.

Park CH(1), Jung YS(2), Nam E(3), Eun CS(1), Park DI(2), Han DS(1).

Author information:
(1)Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang
University College of Medicine, Guri, Korea.
(2)Department of Internal Medicine, Division of Gastroenterology, Kangbuk Samsung
Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
(3)Biostatistical Consulting and Research Lab, Medical Research Coordinating
Center, Hanyang University, Seoul, Korea.

OBJECTIVES: Although various endoscopic therapies have been suggested for
preventing bleeding after colorectal polypectomy, the optimal therapy has yet to
be fully clarified. We assessed the comparative efficacy of prophylactic
therapies for postpolypectomy bleeding through a network meta-analysis combining
direct and indirect comparisons.
METHODS: We searched for all relevant randomized controlled trials published up
until January 2016 examining the effects of prophylactic therapy for bleeding
after colorectal polypectomy. The types of prophylactic therapy were classified
as mechanical therapy, epinephrine-saline injection therapy, coagulation therapy,
combined therapy, or no prophylactic therapy. Combined therapy was defined as a
combination of two or more types of therapy including mechanical therapy,
epinephrine-saline injection therapy, and coagulation therapy. We performed a
Bayesian network meta-analysis for all prophylactic therapies.
RESULTS: Fifteen studies with 3,462 patients were included in the meta-analysis.
Compared with no prophylactic therapy, both epinephrine-saline injection and
mechanical therapy showed superiority for preventing early postpolypectomy
bleeding with a moderate quality of evidence (injection therapy, risk ratio (RR;
95% credible interval (CrI))=0.32 (0.11-0.67); mechanical therapy, RR (95%
CrI)=0.13 (0.03-0.37)). Combined therapy did not show a statistically significant
difference for decreasing the risk of early bleeding compared with injection or
mechanical therapies, respectively (combined vs. injection therapy: RR (95%
CrI)=0.35 (0.10-1.00); combined vs. mechanical therapy: RR (95% CrI)=0.88
(0.23-3.00)). In cases of delayed bleeding, no type of prophylactic therapy
decreased the risk of bleeding compared with no prophylactic therapy.
CONCLUSIONS: Either mechanical therapy or injection therapy reduced the risk of
early postpolypectomy bleeding. As for delayed bleeding, none of the prophylactic
therapies was associated with a lower risk of bleeding compared with no
prophylactic therapy.

DOI: 10.1038/ajg.2016.287
PMID: 27402502  [Indexed for MEDLINE]


117. Am J Kidney Dis. 2016 Sep;68(3):392-401. doi: 10.1053/j.ajkd.2016.02.042. Epub
2016 Mar 29.

Early Change in Urine Protein as a Surrogate End Point in Studies of IgA
Nephropathy: An Individual-Patient Meta-analysis.

Inker LA(1), Mondal H(2), Greene T(3), Masaschi T(2), Locatelli F(4), Schena
FP(5), Katafuchi R(6), Appel GB(7), Maes BD(8), Li PK(9), Praga M(10), Del
Vecchio L(4), Andrulli S(4), Manno C(5), Gutierrez E(10), Mercer A(11), Carroll
KJ(12), Schmid CH(13), Levey AS(2).

Author information:
(1)Division of Nephrology, Tufts Medical Center, Boston, MA. Electronic address:
linker@tuftsmedicalcenter.org.
(2)Division of Nephrology, Tufts Medical Center, Boston, MA.
(3)Division of Epidemiology, University of Utah, Salt Lake City, UT.
(4)Department of Nephrology and Dialysis, Alessandro Manzoni Hospital, Lecco,
Italy.
(5)Renal, Dialysis & Transplant Unit, University of Bari, Bari, Italy.
(6)National Fukuoka Higashi Medical Center, Koga City, Fukuoka, Japan.
(7)The Glomerular Kidney Disease Center, Columbia University College of
Physicians and Surgeons, New York, NY.
(8)Department of Nephrology, AZ Delta, Roeselare, Belgium.
(9)Department of Medicine, Prince of Wales Hospital, Chinese University of Hong
Kong, Shatin, Hong Kong, China.
(10)Nephrology, Department of Medicine, Hospital Universitario 12 de Octubre,
Complutense University, Madrid, Spain.
(11)Pharmalink AB, Stockholm, Sweden.
(12)KJC Statistics Ltd and University of Sheffield, Sheffield, United Kingdom.
(13)Department of Biostatistics and Center for Evidence Based Medicine, Brown
University School of Public Health, Providence, RI.

BACKGROUND: The role of change in proteinuria as a surrogate end point for
randomized trials in immunoglobulin A nephropathy (IgAN) has previously not been
thoroughly evaluated.
STUDY DESIGN: Individual patient-level meta-analysis.
SETTING & POPULATION: Individual-patient data for 830 patients from 11 randomized
trials evaluating 4 intervention types (renin-angiotensin system [RAS] blockade,
fish oil, immunosuppression, and steroids) examining associations between changes
in urine protein and clinical end points at the individual and trial levels.
SELECTION CRITERIA FOR STUDIES: Randomized controlled trials of IgAN with
measurements of proteinuria at baseline and a median of 9 (range, 5-12) months
follow-up, with at least 1 further year of follow-up for the clinical outcome.
PREDICTOR: 9-month change in proteinuria.
OUTCOME: Doubling of serum creatinine level, end-stage renal disease, or death.
RESULTS: Early decline in proteinuria at 9 months was associated with lower risk
for the clinical outcome (HR per 50% reduction in proteinuria, 0.40; 95% CI,
0.32-0.48) and was consistent across studies. Proportions of treatment effect on
the clinical outcome explained by early decline in proteinuria were estimated at
11% (95% CI, -19% to 41%) for RAS blockade and 29% (95% CI, 6% to 53%) for
steroid therapy. The direction of the pooled treatment effect on early change in
proteinuria was in accord with the direction of the treatment effect on the
clinical outcome for steroids and RAS blockade. Trial-level analyses estimated
that the slope for the regression line for the association of treatment effects
on the clinical end points and for the treatment effect on proteinuria was 2.15
(95% Bayesian credible interval, 0.10-4.32).
LIMITATIONS: Study population restricted to 11 trials, all having fewer than 200
patients each with a limited number of clinical events.
CONCLUSIONS: Results of this analysis offer novel evidence supporting the use of
an early reduction in proteinuria as a surrogate end point for clinical end
points in IgAN in selected settings.

Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All
rights reserved.

DOI: 10.1053/j.ajkd.2016.02.042
PMID: 27032886  [Indexed for MEDLINE]


118. J Interv Card Electrophysiol. 2016 Sep;46(3):213-24. doi:
10.1007/s10840-016-0126-5. Epub 2016 Mar 21.

Network meta-analysis of efficacy and safety of competitive oral anticoagulants
in patients undergoing radiofrequency catheter ablation of atrial fibrillation.

Li PJ(1), Xiao J(2), Yang Q(3), Feng Y(3), Wang T(1), Liu GJ(4), Liang ZA(5).

Author information:
(1)Department of Respiratory and Critical Care Medicine, West China Hospital,
Sichuan University, 37 Guoxue Road, Chengdu, Sichuan, People's Republic of China,
610041.
(2)Department of Intensive Care Unit, West China Hospital, Sichuan University, 37
Guoxue Road, Chengdu, 610041, People's Republic of China.
(3)Department of Cardiology, West China Hospital, Sichuan University, 37 Guoxue
Road, Chengdu, 610041, People's Republic of China.
(4)Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan
University, 37 Guoxue Road, Chengdu, 610041, People's Republic of China.
(5)Department of Respiratory and Critical Care Medicine, West China Hospital,
Sichuan University, 37 Guoxue Road, Chengdu, Sichuan, People's Republic of China,
610041. za_liang319@163.com.

PURPOSE: The aim of this network meta-analysis was to evaluate the comparative
efficacy and safety of dabigatran, rivaroxaban, apixaban, interrupted vitamin K
antagonist (I-VKA), and continuous VKA (C-VKA) in patients undergoing
radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF).
METHODS: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials
were searched to identify clinical trials comparing dabigatran, rivaroxaban, or
apixaban with I-VKA or C-VKA, or against each other, in AF patients undergoing
RFCA. A network meta-analysis was conducted to directly and indirectly compare
the efficacy and safety of competitive anticoagulation regimens with a Bayesian
random-effects model.
RESULTS: A total of 39 studies enrolling 27,766 patients were included. C-VKA
demonstrated significant superiority over I-VKA in reducing thromboembolic events
(risk difference [RD] -0.0068, 95 % confidence interval [CI] -0.0106 to -0.0032)
and major bleeding complications (RD -0.0044, 95 % CI -0.0098 to -0.0006).
Rivaroxaban compared with I-VKA was associated with a lower risk of
thromboembolism (RD -0.0073, 95 % CI -0.0134 to -0.0012), being at the best
ranking position among all of the compared anticoagulation regimens in terms of
both the efficacy and safety. None of the remaining comparisons reached
statistically significant difference in the rate of thromboembolism or major
bleeding.
CONCLUSIONS: The present study suggests that C-VKA is superior to I-VKA for AF
patients undergoing RFCA. Rivaroxaban is the highest probability to be the
optimal alternative to C-VKA among the three non-VKA oral anticoagulants in AF
ablation.

DOI: 10.1007/s10840-016-0126-5
PMID: 27001171  [Indexed for MEDLINE]


119. Mult Scler Relat Disord. 2016 Sep;9:23-30. doi: 10.1016/j.msard.2016.06.001. Epub
2016 Jun 8.

Comparative efficacy of disease-modifying therapies for patients with relapsing
remitting multiple sclerosis: Systematic review and network meta-analysis.

Fogarty E(1), Schmitz S(2), Tubridy N(3), Walsh C(4), Barry M(5).

Author information:
(1)National Centre for Pharmacoeconomics, Dublin, Ireland. Electronic address:
efogarty@stjames.ie.
(2)Health Economics and Evidence Synthesis Research Unit, Department of
Population Health, Luxembourg Institute of Health, Luxembourg.
(3)Department of Neurology, St. Vincent's University Hospital, Dublin, Ireland.
(4)Department of Mathematics and Statistics, University of Limerick, Ireland.
(5)National Centre for Pharmacoeconomics, Dublin, Ireland.

INTRODUCTION: Randomised studies have demonstrated efficacy of disease-modifying
therapies in relapsing remitting multiple sclerosis (RRMS). However it is unclear
how the magnitude of treatment efficacy varies across all currently available
therapies.
OBJECTIVE: To perform a systematic review and network meta-analysis to evaluate
the comparative efficacy of available therapies in reducing relapses and
disability progression in RRMS.
METHODS: A systematic review identified 28 randomised, placebo-controlled and
direct comparative trials. A network meta-analysis was conducted within a
Bayesian framework to estimate comparative annualised relapse rates (ARR) and
risks of disability progression (defined by both a 3-month, and 6-month
confirmation interval). Potential sources of treatment-effect modification from
study-level covariates and baseline risk were evaluated through meta-regression
methods. The Surface Under the Cumulative RAnking curve (SUCRA) method was used
to provide a ranking of treatments for each outcome.
RESULTS: The magnitude of ARR reduction varied between 15-36% for all
interferon-beta products, glatiramer acetate and teriflunomide, and from 50 to
69% for alemtuzumab, dimethyl fumarate, fingolimod and natalizumab. The risk of
disability progression (3-month) was reduced by 19-28% with interferon-beta
products, glatiramer acetate, fingolimod and teriflunomide, by 38-45% for
pegylated interferon-beta, dimethyl fumarate and natalizumab and by 68% with
alemtuzumab. Broadly similar estimates for the risk of disability progression
(6-month), with the exception of interferon-beta-1b 250mcg which was much more
efficacious based on this definition. Alemtuzumab and natalizumab had the highest
SUCRA scores (97% and 95% respectively) for ARR, while ranking for disability
progression varied depending on the definition of the outcome. Interferon-beta-1b
250mcg ranked among the most efficacious treatments for disability progression
confirmed after six months (92%) and among the least efficacious when the outcome
was confirmed after three months (30%). No significant modification of relative
treatment effects was identified from study-level covariates or baseline risk.
CONCLUSION: Compared with placebo, clear reductions in ARR with disease-modifying
therapies were accompanied by more uncertain changes in disability progression.
The magnitude of the reduction and the uncertainty associated with treatment
effects varied between DMTs. While natalizumab and alemtuzumab demonstrated
consistently high ranking across outcomes, with older interferon-beta and
glatiramer acetate products ranking lowest, variation in disability progression
definitions lead to variation in the relative ranking of treatments. Rigorously
conducted comparative studies are required to fully evaluate the comparative
treatment effects of disease modifying therapies for RRMS.

Copyright © 2016 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.msard.2016.06.001
PMID: 27645339  [Indexed for MEDLINE]


120. Cochrane Database Syst Rev. 2016 Aug 29;(8):CD010227. doi:
10.1002/14651858.CD010227.pub2.

Methotrexate monotherapy and methotrexate combination therapy with traditional
and biologic disease modifying anti-rheumatic drugs for rheumatoid arthritis: A
network meta-analysis.

Hazlewood GS(1), Barnabe C, Tomlinson G, Marshall D, Devoe DJ, Bombardier C.

Author information:
(1)Department of Medicine and Department of Community Health Sciences, University
of Calgary, 3330 Hospital Drive NW, Calgary, ON, Canada, T2N 1N1.

BACKGROUND: Methotrexate is considered the preferred disease-modifying
anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis, but
controversy exists on the additional benefits and harms of combining methotrexate
with other DMARDs.
OBJECTIVES: To compare methotrexate and methotrexate-based DMARD combinations for
rheumatoid arthritis in patients naïve to or with an inadequate response (IR) to
methotrexate.
METHODS: We systematically identified all randomised controlled trials with
methotrexate monotherapy or in combination with any currently used conventional
synthetic DMARD , biologic DMARDs, or tofacitinib. Three major outcomes (ACR50
response, radiographic progression and withdrawals due to adverse events) and
multiple minor outcomes were evaluated. Treatment effects were summarized using
Bayesian random-effects network meta-analyses, separately for methotrexate-naïve
and methotrexate-IR trials. Heterogeneity was explored through meta-regression
and subgroup analyses. The risk of bias of each trial was assessed using the
Cochrane risk of bias tool, and trials at high risk of bias were excluded from
the main analysis. The quality of evidence was evaluated using the GRADE
approach. A comparison between two treatments was considered statistically
significant if its credible interval excluded the null effect, indicating >97.5%
probability that one treatment was superior.
MAIN RESULTS: 158 trials with over 37,000 patients were included.
Methotrexate-naïve: Several treatment combinations with methotrexate were
statistically superior to oral methotrexate for ACR50 response: methotrexate +
sulfasalazine + hydroxychloroquine ("triple therapy"), methotrexate + several
biologics (abatacept, adalimumab, etanercept, infliximab, rituximab,
tocilizumab), and tofacitinib. The estimated probability of ACR50 response was
similar between these treatments (range 56-67%, moderate to high quality
evidence), compared with 41% for methotrexate. Methotrexate combined with
adalimumab, etanercept, certolizumab, or infliximab was statistically superior to
oral methotrexate for inhibiting radiographic progression (moderate to high
quality evidence) but the estimated mean change over one year with all treatments
was less than the minimal clinically important difference of five units on the
Sharp-van der Heijde scale. Methotrexate + azathioprine had statistically more
withdrawals due to adverse events than oral methotrexate, and triple therapy had
statistically fewer withdrawals due to adverse events than methotrexate +
infliximab (rate ratio 0.26, 95% credible interval: 0.06 to 0.91).
Methotrexate-inadequate response: In patients with an inadequate response to
methotrexate, several treatments were statistically significantly superior to
oral methotrexate for ACR50 response: triple therapy (moderate quality evidence),
methotrexate + hydroxychloroquine (low quality evidence), methotrexate +
leflunomide (moderate quality evidence), methotrexate + intramuscular gold (very
low quality evidence), methotrexate + most biologics (moderate to high quality
evidence), and methotrexate + tofacitinib (high quality evidence). There was a
61% probability of an ACR50 response with triple therapy, compared to a range of
27% to 64% for the combinations of methotrexate + biologic DMARDs that were
statistically significantly superior to oral methotrexate. No treatment was
statistically significantly superior to oral methotrexate for inhibiting
radiographic progression. Methotrexate + cyclosporine and methotrexate +
tocilizumab (8 mg/kg) had a statistically higher rate of withdrawals due to
adverse events than oral methotrexate and methotrexate + abatacept had a
statistically lower rate of withdrawals due to adverse events than several
treatments.
AUTHORS' CONCLUSIONS: We found moderate to high quality evidence that combination
therapy with methotrexate + sulfasalazine+ hydroxychloroquine (triple therapy) or
methotrexate + most biologic DMARDs or tofacitinib were similarly effective in
controlling disease activity and generally well tolerated in methotrexate-naïve
patients or after an inadequate response to methotrexate. Methotrexate + some
biologic DMARDs were superior to methotrexate in preventing joint damage in
methotrexate-naïve patients, but the magnitude of these effects was small over
one year.

DOI: 10.1002/14651858.CD010227.pub2
PMID: 27571502  [Indexed for MEDLINE]


121. Lancet. 2016 Aug 27;388(10047):881-90. doi: 10.1016/S0140-6736(16)30385-3. Epub
2016 Jun 8.

Comparative efficacy and tolerability of antidepressants for major depressive
disorder in children and adolescents: a network meta-analysis.

Cipriani A(1), Zhou X(2), Del Giovane C(3), Hetrick SE(4), Qin B(2), Whittington
C(5), Coghill D(6), Zhang Y(2), Hazell P(7), Leucht S(8), Cuijpers P(9), Pu J(2),
Cohen D(10), Ravindran AV(11), Liu Y(2), Michael KD(12), Yang L(2), Liu L(2), Xie
P(13).

Author information:
(1)Department of Psychiatry, University of Oxford, Oxford, UK. Electronic
address: andrea.cipriani@psych.ox.ac.uk.
(2)Department of Neurology and Psychiatry, The First Affiliated Hospital of
Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the
Collaborative Innovation Center for Brain Science, Chongqing Medical University,
Chongqing, China.
(3)Department of Diagnostic, Clinical and Public Health Medicine, University of
Modena and Reggio Emilia, Modena, Italy.
(4)Orygen, The National Centre of Excellence in Youth Mental Health, University
of Melbourne, Melbourne, VIC, Australia.
(5)Doctor Evidence, Santa Monica, CA, USA.
(6)Division of Neuroscience, School of Medicine, University of Dundee, Dundee,
UK; Department of Paediatrics, and Department of Psychiatry, Faculty of Medicine,
Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC,
Australia.
(7)Discipline of Psychiatry, Sydney Medical School, Concord West, NSW, Australia.
(8)Department of Psychiatry and Psychotherapy, Technische Universität München,
Munich, Germany.
(9)Department of Clinical, Neuro- and Developmental Psychology, VU University
Amsterdam, Amsterdam, Netherlands.
(10)Department of Child and Adolescent Psychiatry, Hôpital Pitié-Salpétrière,
Institut des Systèmes Intelligents et Robotiques, Université Pierre et Marie
Curie, Paris, France.
(11)Department of Psychiatry, University of Toronto, Toronto, ON, Canada;
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental
Health, Toronto, ON, Canada.
(12)Department of Psychology, Appalachian State University, Boone, NC, USA.
(13)Department of Neurology and Psychiatry, The First Affiliated Hospital of
Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the
Collaborative Innovation Center for Brain Science, Chongqing Medical University,
Chongqing, China; South Australian Health and Medical Research Institute,
Adelaide, South Australia, Australia. Electronic address: xiepeng973@126.com.

Comment in
    Lancet. 2016 Aug 27;388(10047):844-5.
    Pediatrics. 2017 Sep;140(3):null.

BACKGROUND: Major depressive disorder is one of the most common mental disorders
in children and adolescents. However, whether to use pharmacological
interventions in this population and which drug should be preferred are still
matters of controversy. Consequently, we aimed to compare and rank
antidepressants and placebo for major depressive disorder in young people.
METHODS: We did a network meta-analysis to identify both direct and indirect
evidence from relevant trials. We searched PubMed, the Cochrane Library, Web of
Science, Embase, CINAHL, PsycINFO, LiLACS, regulatory agencies' websites, and
international registers for published and unpublished, double-blind randomised
controlled trials up to May 31, 2015, for the acute treatment of major depressive
disorder in children and adolescents. We included trials of amitriptyline,
citalopram, clomipramine, desipramine, duloxetine, escitalopram, fluoxetine,
imipramine, mirtazapine, nefazodone, nortriptyline, paroxetine, sertraline, and
venlafaxine. Trials recruiting participants with treatment-resistant depression,
treatment duration of less than 4 weeks, or an overall sample size of less than
ten patients were excluded. We extracted the relevant information from the
published reports with a predefined data extraction sheet, and assessed the risk
of bias with the Cochrane risk of bias tool. The primary outcomes were efficacy
(change in depressive symptoms) and tolerability (discontinuations due to adverse
events). We did pair-wise meta-analyses using the random-effects model and then
did a random-effects network meta-analysis within a Bayesian framework. We
assessed the quality of evidence contributing to each network estimate using the
GRADE framework. This study is registered with PROSPERO, number CRD42015016023.
FINDINGS: We deemed 34 trials eligible, including 5260 participants and 14
antidepressant treatments. The quality of evidence was rated as very low in most
comparisons. For efficacy, only fluoxetine was statistically significantly more
effective than placebo (standardised mean difference -0·51, 95% credible interval
[CrI] -0·99 to -0·03). In terms of tolerability, fluoxetine was also better than
duloxetine (odds ratio [OR] 0·31, 95% CrI 0·13 to 0·95) and imipramine (0·23,
0·04 to 0·78). Patients given imipramine, venlafaxine, and duloxetine had more
discontinuations due to adverse events than did those given placebo (5·49, 1·96
to 20·86; 3·19, 1·01 to 18·70; and 2·80, 1·20 to 9·42, respectively). In terms of
heterogeneity, the global I(2) values were 33·21% for efficacy and 0% for
tolerability.
INTERPRETATION: When considering the risk-benefit profile of antidepressants in
the acute treatment of major depressive disorder, these drugs do not seem to
offer a clear advantage for children and adolescents. Fluoxetine is probably the
best option to consider when a pharmacological treatment is indicated.
FUNDING: National Basic Research Program of China (973 Program).

Copyright © 2016 Elsevier Ltd. All rights reserved.

DOI: 10.1016/S0140-6736(16)30385-3
PMID: 27289172  [Indexed for MEDLINE]


122. JACC Cardiovasc Interv. 2016 Aug 22;9(16):1731-42. doi:
10.1016/j.jcin.2016.06.008.

Drug-Coated Balloon Versus Plain Balloon Angioplasty for the Treatment
of Femoropopliteal Artery Disease: An Updated Systematic Review and Meta-Analysis
of Randomized Clinical Trials.

Giacoppo D(1), Cassese S(1), Harada Y(1), Colleran R(1), Michel J(1), Fusaro
M(1), Kastrati A(2), Byrne RA(3).

Author information:
(1)Deutsches Herzzentrum München, Technische Universität München, Munich,
Germany.
(2)Deutsches Herzzentrum München, Technische Universität München, Munich,
Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich
Heart Alliance, Munich, Germany.
(3)Deutsches Herzzentrum München, Technische Universität München, Munich,
Germany. Electronic address: byrne@dhm.mhn.de.

OBJECTIVES: This study sought to assess the risk of target lesion
revascularization (TLR) and all-cause death at 12 months and at the maximum
available follow-up. Secondary objectives included the identification of factors
which could have influenced general findings.
BACKGROUND: Recently several randomized trials comparing drug-coated balloon
(DCB) with conventional plain balloon (PB) for the treatment of femoropopliteal
artery disease have been reported, but no updated meta-analyses are available and
questions remain surrounding the long-term antirestenotic effectiveness of the 2
therapies.
METHODS: We searched main electronic databases for randomized trials comparing
DCB and PB for femoropopliteal artery disease. Random effects models were used to
estimate the risk of TLR and all-cause death at 12 months, whereas long-term TLR
and death risk were assessed by mixed effects Poisson regression models and
incident rates of each outcome per patient-year. Main analyses were supplemented
by sensitivity analyses, Bayesian estimates, and trial sequential analysis.
RESULTS: A total of 8 eligible trials were identified. DCB was associated with a
marked 12-month TLR risk reduction as compared with PB (risk ratio: 0.33; 95%
confidence interval [CI]: 0.19 to 0.57). The risk of death was similar between
groups (risk ratio: 0.96; 95% CI: 0.47 to 1.95). Long-term outcomes assessment
showed a reduced incidence of TLR with DCB (0.35; 95% CI: 0.24 to 0.51) and a
similar incidence of all-cause death (incidence rate ratio: 1.13; 95% CI: 0.60 to
2.15). Similar findings were observed in Bayesian analyses. Significant
heterogeneity was present with evidence of differential efficacy across devices.
Trial sequential analysis indicated that available evidence is sufficient to
prove superior antirestenotic efficacy of DCB over PB.
CONCLUSIONS: DCB significantly reduces the risk of TLR as compared with PB
without any effect on all-cause death. Evidence exists for differential efficacy
according to the type of device used. Future trials investigating DCB angioplasty
should include potentially more effective comparator therapies.

Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier
Inc. All rights reserved.

DOI: 10.1016/j.jcin.2016.06.008
PMID: 27539695  [Indexed for MEDLINE]


123. Int J Cardiol. 2016 Aug 15;217:128-34. doi: 10.1016/j.ijcard.2016.04.132. Epub
2016 Apr 29.

ACE-inhibitors versus angiotensin receptor blockers for prevention of events in
cardiovascular patients without heart failure - A network meta-analysis.

Ricci F(1), Di Castelnuovo A(2), Savarese G(3), Perrone Filardi P(3), De Caterina
R(1).

Author information:
(1)University Cardiology Division, G. d'Annunzio University, Chieti, Italy.
(2)Department of Epidemiology and Prevention, IRCCS-Istituto Neurologico
Mediterraneo Neuromed, Pozzilli, (IS), Italy.
(3)Cardiology Division, Federico II University, Naples, Italy.

BACKGROUND: Angiotensin receptor blockers (ARBs) are a valuable option to reduce
cardiovascular (CV) mortality and morbidity in cardiac patients in whom
ACE-inhibitors (ACE-Is) cannot be used. However, clinical outcome data from
direct comparisons between ACE-Is and ARBs are scarce, and some data have
recently suggested superiority of ACE-Is over ARBs.
METHODS: We performed a Bayesian network-meta-analysis, with data from both
direct and indirect comparisons, from 27 randomized controlled trials (RCTs),
including a total population of 125,330 patients, to assess the effects of ACE-Is
and ARBs on the composite endpoint of CV death, myocardial infarction (MI) and
stroke, and on all-cause death, new-onset heart failure (HF) and new-onset
diabetes mellitus (DM) in high CV risk patients without HF.
RESULTS: Using placebo as a common comparator, we found no significant
differences between ACE-Is and ARBs in preventing the composite endpoint of CV
death, MI and stroke (RR: 0.92; 95% CI 0.78-1.08). When components of the
composite outcome were analysed separately, ACEi and ARBs were associated with a
similar risk of CV death (RR: 0.92; 95% CI 0.73-1.10), MI (RR: 0.91; 95% CI
0.78-1.07) and stroke (RR: 0.97; 95% CI 0.79-1.19), as well as a similar incident
risk of all-cause death (RR: 0.94; 95% CI 0.85-1.05), new-onset HF (RR: 0.92; 95%
CI 0.77-1.15) and new-onset DM (RR: 99; 95% CI 0.81-1.21).
CONCLUSIONS: With the limitations of indirect comparisons, we found that in
patients at high CV risk without HF, ARBs were similar to ACE-Is in preventing
the composite endpoint of CV death, MI and stroke. Compared with ARBs, we found
no evidence of statistical superiority for ACE-Is, as a class, in preventing
incident risk of all-cause death, CV death, MI, stroke, new-onset DM and
new-onset HF.

Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

DOI: 10.1016/j.ijcard.2016.04.132
PMID: 27179902  [Indexed for MEDLINE]


124. BMJ. 2016 Aug 9;354:i3857. doi: 10.1136/bmj.i3857.

Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic
heart disease, and ischemic stroke events: systematic review and dose-response
meta-analysis for the Global Burden of Disease Study 2013.

Kyu HH(1), Bachman VF(2), Alexander LT(1), Mumford JE(1), Afshin A(1), Estep
K(1), Veerman JL(3), Delwiche K(4), Iannarone ML(1), Moyer ML(1), Cercy K(1), Vos
T(1), Murray CJ(1), Forouzanfar MH(5).

Author information:
(1)Institute for Health Metrics and Evaluation, University of Washington, 2301
5th Avenue, Suite 600, Seattle, WA 98121, USA.
(2)School of Medicine, University of Washington, Seattle, WA 98105, USA.
(3)School of Public Health, Faculty of Medicine and Biomedical Sciences,
University of Queensland, Herston, QLD 4006, Australia.
(4)Geisel School of Medicine, Dartmouth College, Hanover, NH 03755-1404, USA.
(5)Institute for Health Metrics and Evaluation, University of Washington, 2301
5th Avenue, Suite 600, Seattle, WA 98121, USA forouzan@uw.edu.

OBJECTIVE:  To quantify the dose-response associations between total physical
activity and risk of breast cancer, colon cancer, diabetes, ischemic heart
disease, and ischemic stroke events.
DESIGN:  Systematic review and Bayesian dose-response meta-analysis.
DATA SOURCES:  PubMed and Embase from 1980 to 27 February 2016, and references
from relevant systematic reviews. Data from the Study on Global AGEing and Adult
Health conducted in China, Ghana, India, Mexico, Russia, and South Africa from
2007 to 2010 and the US National Health and Nutrition Examination Surveys from
1999 to 2011 were used to map domain specific physical activity (reported in
included studies) to total activity.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES:  Prospective cohort studies examining
the associations between physical activity (any domain) and at least one of the
five diseases studied.
RESULTS:  174 articles were identified: 35 for breast cancer, 19 for colon
cancer, 55 for diabetes, 43 for ischemic heart disease, and 26 for ischemic
stroke (some articles included multiple outcomes). Although higher levels of
total physical activity were significantly associated with lower risk for all
outcomes, major gains occurred at lower levels of activity (up to 3000-4000
metabolic equivalent (MET) minutes/week). For example, individuals with a total
activity level of 600 MET minutes/week (the minimum recommended level) had a 2%
lower risk of diabetes compared with those reporting no physical activity. An
increase from 600 to 3600 MET minutes/week reduced the risk by an additional 19%.
The same amount of increase yielded much smaller returns at higher levels of
activity: an increase of total activity from 9000 to 12 000 MET minutes/week
reduced the risk of diabetes by only 0.6%. Compared with insufficiently active
individuals (total activity <600 MET minutes/week), the risk reduction for those
in the highly active category (≥8000 MET minutes/week) was 14% (relative risk
0.863, 95% uncertainty interval 0.829 to 0.900) for breast cancer; 21% (0.789,
0.735 to 0.850) for colon cancer; 28% (0.722, 0.678 to 0.768) for diabetes; 25%
(0.754, 0.704 to 0.809) for ischemic heart disease; and 26% (0.736, 0.659 to
0.811) for ischemic stroke.
CONCLUSIONS:  People who achieve total physical activity levels several times
higher than the current recommended minimum level have a significant reduction in
the risk of the five diseases studied. More studies with detailed quantification
of total physical activity will help to find more precise relative risk estimates
for different levels of activity.

Published by the BMJ Publishing Group Limited. For permission to use (where not
already granted under a licence) please go to
http://group.bmj.com/group/rights-licensing/permissions.


PMCID: PMC4979358
PMID: 27510511  [Indexed for MEDLINE]

Conflict of interest statement: All authors have completed the ICMJE uniform
disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from
any organisation for the submitted work; no financial relationships with any
organisations that might have an interest in the submitted work in the previous
three years; no other relationships or activities that could appear to have
influenced the submitted work.


125. JAMA. 2016 Aug 9;316(6):611-24. doi: 10.1001/jama.2016.10708.

Association of Noninvasive Ventilation Strategies With Mortality and
Bronchopulmonary Dysplasia Among Preterm Infants: A Systematic Review and
Meta-analysis.

Isayama T(1), Iwami H(2), McDonald S(3), Beyene J(4).

Author information:
(1)Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Ontario,
Canada2Department of Newborn and Developmental Paediatrics, Sunnybrook Health
Sciences Centre, Toronto, Ontario, Canada.
(2)Department of Neonatology, Osaka City General Hospital, Osaka, Japan.
(3)Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Ontario,
Canada4Department of Obstetrics & Gynecology, McMaster University, Hamilton,
Ontario, Canada5Department of Radiology, McMaster University, Hamilton, Ontario,
Canada.
(4)Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, Ontario,
Canada.

Erratum in
    JAMA. 2016 Sep 13;316(10):1116.

IMPORTANCE: Various noninvasive ventilation strategies are used to prevent
bronchopulmonary dysplasia (BPD) of preterm infants; however, the best mode is
uncertain.
OBJECTIVE: To compare 7 ventilation strategies for preterm infants including
nasal continuous positive airway pressure (CPAP) alone, intubation and surfactant
administration followed by immediate extubation (INSURE), less invasive
surfactant administration (LISA), noninvasive intermittent positive pressure
ventilation, nebulized surfactant administration, surfactant administration via
laryngeal mask airway, and mechanical ventilation.
DATA SOURCES: MEDLINE, EMBASE, CINAHL, and Cochrane CENTRAL from their inceptions
to June 2016.
STUDY SELECTION: Randomized clinical trials comparing ventilation strategies for
infants younger than 33 weeks' gestational age within 24 hours of birth who had
not been intubated.
DATA EXTRACTION AND SYNTHESIS: Data were independently extracted by 2 reviewers
and synthesized with Bayesian random-effects network meta-analyses.
MAIN OUTCOMES AND MEASURES: A composite of death or BPD at 36 weeks'
postmenstrual age was the primary outcome. Death, BPD, severe intraventricular
hemorrhage, and air leak by discharge were the main secondary outcomes.
RESULTS: Among 5598 infants involved in 30 trials, the incidence of the primary
outcome was 33% (1665 of 4987; including 505 deaths and 1160 cases of BPD). The
secondary outcomes ranged from 6% (314 of 5587) for air leak to 26% (1160 of
4455) for BPD . Compared with mechanical ventilation, LISA had a lower odds of
the primary outcome (odds ratio [OR], 0.49; 95% credible interval [CrI],
0.30-0.79; absolute risk difference [RD], 164 fewer per 1000 infants; 57-253
fewer per 1000 infants; moderate quality of evidence), BPD(OR, 0.53; 95% CrI,
0.27-0.96; absolute RD, 133 fewer per 1000 infants; 95% CrI, 9-234 fewer per 1000
infants; moderate-quality), and severe intraventricular hemorrhage (OR, 0.44; 95%
CrI, 0.19-0.99; absolute RD, 58 fewer per 1000 births; 95% CrI, 1-86 fewer per
1000 births; moderate-quality). Compared with nasal CPAP alone, LISA had a lower
odds of the primary outcome (OR, 0.58; 95% CrI, 0.35-0.93; absolute RD, 112 fewer
per 1000 births; 95% CrI, 16-190 fewer per 1000 births; moderate quality), and
air leak (OR, 0.24; 95% CrI, 0.05-0.96; absolute RD, 47 fewer per 1000 births;
95% CrI, 2-59 fewer per 1000 births; very low quality). Ranking probabilities
indicated that LISA was the best strategy with a surface under the cumulative
ranking curve of 0.85 to 0.94, but this finding was not robust for death when
limited to higher-quality evidence.
CONCLUSIONS AND RELEVANCE: Among preterm infants, the use of LISA was associated
with the lowest likelihood of the composite outcome of death or BPD at 36 weeks'
postmenstrual age. These findings were limited by the overall low quality of
evidence and lack of robustness in higher-quality trials.

DOI: 10.1001/jama.2016.10708
PMID: 27532916  [Indexed for MEDLINE]


126. PLoS One. 2016 Aug 3;11(8):e0160064. doi: 10.1371/journal.pone.0160064.
eCollection 2016.

Comparison of the Non-VKA Oral Anticoagulants Apixaban, Dabigatran, and
Rivaroxaban in the Extended Treatment and Prevention of Venous Thromboembolism:
Systematic Review and Network Meta-Analysis.

Cohen AT(1), Hamilton M(2), Bird A(3), Mitchell SA(4), Li S(2), Horblyuk R(5),
Batson S(4).

Author information:
(1)Guy's and St Thomas' Hospitals, King's College, London, United Kingdom.
(2)BMS, Princeton, United States of America.
(3)Pfizer, Walton Oaks, United Kingdom.
(4)Abacus International, Bicester, United Kingdom.
(5)Pfizer, New York, United States of America.

Erratum in
    PLoS One. 2016;11(9):e0163386.

BACKGROUND: Historically, warfarin or aspirin have been the recommended
therapeutic options for the extended treatment (>3 months) of VTE. Data from
Phase III randomised controlled trials (RCTs) are now available for non-VKA oral
anticoagulants (NOACs) in this indication. The current systematic review and
network meta-analysis (NMA) were conducted to compare the efficacy and safety of
anticoagulants for the extended treatment of VTE.
METHODS: Electronic databases (accessed July 2014 and updated April 2016) were
systematically searched to identify RCTs evaluating apixaban, aspirin,
dabigatran, edoxaban, rivaroxaban, and warfarin for the extended treatment of
VTE. Eligible studies included adults with an objectively confirmed deep vein
thrombosis, pulmonary embolism or both. A fixed-effect Bayesian NMA was
conducted, and results were presented as relative risks (RRs). Sensitivity
analyses examining (i) the dataset employed according to the time frame for
outcome assessment (ii) the model used for the NMA were conducted.
RESULTS: Eleven Phase III RCTs (examining apixaban, aspirin, dabigatran,
rivaroxaban, warfarin and placebo) were included. The risk of the composite
efficacy outcome (VTE and VTE-related death) was statistically significantly
lower with the NOACs and warfarin INR 2.0-3.0 compared with aspirin, with no
significant differences between the NOACs. Treatment with apixaban (RR 0.23, 95%
CrI 0.10, 0.55) or dabigatran (RR 0.55, 95% Crl 0.43, 0.71) was associated with a
statistically significantly reduced risk of 'major or clinically relevant
non-major bleed' compared with warfarin INR 2.0-3.0. Apixaban also showed a
significantly reduced risk compared with dabigatran (RR 0.42, 95% Crl 0.18, 0.97)
and rivaroxaban (RR 0.23, 95% Crl 0.09, 0.59). Sensitivity analyses indicate that
results were dependent on the dataset, but not on the type of NMA model employed.
CONCLUSIONS: Results from the NMA indicate that NOACs are an effective treatment
for prevention of VTE or VTE-related death) in the extended treatment setting.
However, bleeding risk differs between potential treatments, with apixaban
reporting the most favourable profile compared with other NOACs, warfarin INR
2.0-3.0, and aspirin.

DOI: 10.1371/journal.pone.0160064
PMCID: PMC4972314
PMID: 27487187  [Indexed for MEDLINE]


127. Br J Sports Med. 2016 Aug;50(15):900-8. doi: 10.1136/bjsports-2014-094387. Epub
2015 Sep 21.

Injection therapies for lateral epicondylalgia: a systematic review and Bayesian
network meta-analysis.

Dong W(1), Goost H(2), Lin XB(3), Burger C(4), Paul C(5), Wang ZL(1), Kong FL(1),
Welle K(4), Jiang ZC(6), Kabir K(4).

Author information:
(1)Department of Orthopedic and Trauma Surgery, Central Hospital of PetroChina,
Langfang, China.
(2)Department of Orthopedic and Trauma Surgery, Hospital Wermelskirchen,
Wermelskirchen, Germany.
(3)Department of Orthopedic and Trauma Surgery, Rizhao People's Hospital, Rizhao,
China.
(4)Department of Orthopedic and Trauma Surgery, University Hospital Bonn, Bonn,
Germany.
(5)Department of Orthopedic and Trauma Surgery, Evangelic Wald-Krankenhaus, Bonn,
Germany.
(6)Department of Fundamental Science, North China Institute of Aerospace
Engineering, Langfang, China.

BACKGROUND: There are many injection therapies for lateral epicondylalgia but
there has been no previous comprehensive comparison, based on the Bayesian
method.
METHODS: The MEDLINE, EMBASE and the Cochrane Central Register of Controlled
Trials (CENTRAL) databases were searched for appropriate literature. The outcome
measurement was the pain score. Direct comparisons were performed using the
pairwise meta-analysis, and network meta-analysis, based on a Bayesian model, was
used to calculate the results of all of the potentially possible comparisons and
rank probabilities. A sensitivity analysis was performed by excluding low-quality
studies. The inconsistency of the model was assessed by means of the
node-splitting method. Metaregression was used to assess the relationship between
the sample size and the treatment effect.
RESULTS: All of the injection treatments showed a trend towards better effects
than placebo. Additionally, the peppering technique did not add additional
benefits when combined with other treatments. No significant changes were
observed by excluding low-quality studies in the sensitivity analysis. No
significant inconsistencies were found according to the inconsistency analysis,
and metaregression revealed that the sample size was not associated with the
treatment effects.
CONCLUSIONS: Some commonly used injection therapies can be considered treatment
candidates for lateral epicondylalgia, such as botulinum toxin, platelet-rich
plasma and autologous blood injection, but corticosteroid is not recommended.
Hyaluronate injection and prolotherapy might be more effective, but their
superiority must be confirmed by more research. The peppering technique is not
helpful in injection therapies.

Published by the BMJ Publishing Group Limited. For permission to use (where not
already granted under a licence) please go to
http://www.bmj.com/company/products-services/rights-and-licensing/

DOI: 10.1136/bjsports-2014-094387
PMID: 26392595  [Indexed for MEDLINE]


128. Int J Clin Oncol. 2016 Aug;21(4):668-675. doi: 10.1007/s10147-015-0938-9. Epub
2016 Jan 5.

Meta-analysis supporting noninferiority of oxaliplatin plus S-1 to cisplatin plus
S-1 in first-line treatment of advanced gastric cancer (G-SOX study): indirect
comparison with S-1 alone.

Hamada C(1), Yamada Y(2), Azuma M(3), Nishikawa K(4), Gotoh M(5), Bando H(6),
Sugimoto N(7), Nishina T(8), Amagai K(9), Chin K(10), Niwa Y(11), Tsuji A(12),
Imamura H(13), Tsuda M(14), Yasui H(15), Fujii H(16), Yamaguchi K(17), Yasui
H(18), Hironaka S(19), Shimada K(20), Miwa H(21), Hyodo I(22).

Author information:
(1)Faculty of Engineering, Tokyo University of Science, 1-3, Kagurazaka,
Shinjuku-ku, Tokyo, 162-8601, Japan. hamada@ms.kagu.tus.ac.jp.
(2)Gastrointestinal Oncology Division, National Cancer Center Hospital, 5-1-1,
Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
(3)Department of Gastroenterology, Kitasato University East Hospital, 2-1-1,
Asamizodai, Minami-ku, Sagamihara, 252-0380, Japan.
(4)Department of Surgery, Osaka General Medical Center, 3-1-56, Bandaihigashi,
Sumiyoshi-ku, Osaka, 558-0056, Japan.
(5)Cancer Chemotherapy Center, Osaka Medical College Hospital, 2-7, Daigakumachi,
Takatsuki, 569-8686, Japan.
(6)Division of Gastrointestinal Oncology and Digestive Endoscopy, National Cancer
Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, 277-0882, Japan.
(7)Department of Clinical Oncology, Osaka Medical Center for Cancer and
Cardiovascular Diseases, 1-3-3, Nakamichi, Higashinari-ku, Osaka, 537-8511,
Japan.
(8)Department of Gastrointestinal Medical Oncology, National Hospital
Organization Shikoku Cancer Center, 160, Minamiumemotomachi, Matsuyama, 791-0280,
Japan.
(9)Department of Gastroenterology, Ibaraki Prefectural Central Hospital, 6528,
Koibuchi, Kasama, 309-1703, Japan.
(10)Department of Gastroenterology, Cancer Institute Hospital of JFCR, 3-8-31,
Ariake, Tokyo, 135-8550, Japan.
(11)Department of Endoscopy, Aichi Cancer Center Hospital, 1-1, Kanokoden,
Chikusa-ku, Nagoya, 464-8681, Japan.
(12)Department of Medical Oncology, Kochi Health Sciences Center, 2125-1, Ike,
Kochi, 781-8555, Japan.
(13)Department of Surgery, Sakai City Hospital, 1-1-1, Minamiyasui-cho, Sakai,
590-0064, Japan.
(14)Department of Gastroenterological Oncology, Hyogo Cancer Center, 13-70,
Kitaoji-cho, Akashi, 673-0021, Japan.
(15)Division of Gastrointestinal Oncology, Shizuoka Cancer Center, 1007,
Nagaizumi-cho, Shimonagakubo, Sunto-gun, 411-8777, Japan.
(16)Division of Clinical Oncology, Jichi Medical University, 3311-1, Yakushiji,
Shimotsuke, 329-0498, Japan.
(17)Division of Gastroenterology, Saitama Cancer Center, 780, Inamachi, Oaza
Komuro, Kita-adachi-gun, 362-0806, Japan.
(18)Department of Medical Oncology, National Hospital Organization Kyoto Medical
Center, 1-1, Fukakusamukaihata-cho, Fushimi-ku, Kyoto, 612-0861, Japan.
(19)Clinical Trial Promotion Department, Chiba Cancer Center, 666-2, Nitona-cho,
Chuo-ku, Chiba, 260-0801, Japan.
(20)Department of Internal Medicine, Showa University Northern Yokohama Hospital,
Chigasakichuo, Tsuzuki-ku, Yokohama, 224-0032, Japan.
(21)Division of Gastroenterology, Department of Internal Medicine, Hyogo College
of Medicine, 1-1, Mukogawa-cho, Nishinomiya, 663-8131, Japan.
(22)Division of Gastroenterology, University of Tsukuba, 1-1-1, Tennodai,
Tsukuba, 305-8577, Japan.

BACKGROUND: The Randomized Phase III Study Comparing Oxaliplatin plus S-1 with
Cisplatin plus S-1 in Chemotherapy-naïve Patients with Advanced Gastric Cancer
(G-SOX) showed the noninferiority of S-1 (an oral fluoropyrimidine-derivative
dihydropyrimidine dehydrogenase inhibitor) plus oxaliplatin combination therapy
(SOX) to S-1 plus cisplatin therapy (CS) in overall survival [hazard ratio (HR)
from proportional hazard model 0.958, 95 % confidence interval (CI) 0.803-1.142;
noninferiority margin 1.15]. To further clarify the clinical position of SOX in
advanced gastric cancer (AGC), a meta-analysis including information from other
reported studies was conducted.
METHODS: In addition to G-SOX, Japanese phase III clinical trials including S-1
monotherapy were included in the analyses. Individual patient data for SOX (318
patients) and CS (324 patients) from G-SOX, as well as those for S-1 (160
patients) from the Randomized Phase III Study Comparing the Efficacy and Safety
of Irinotecan plus S-1 with S-1 Alone as First-line Treatment for Advanced
Gastric Cancer (GC0301/TOP-002), were available. Published clinical information
for S-1 from other studies (total 705 patients) was also collected. A Weibull
distribution was assumed for overall survival time, and parameters for SOX, CS,
and S-1 were estimated parametrically. Posterior HR distributions were obtained
with a Bayesian approach.
RESULTS: The HR of SOX to S-1 was 0.817 (95 % credible interval 0.704-0.939), and
the probability of the HR <1.00 was 99.8 %. The HR of CS to S-1 was 0.871 (95 %
credible interval; 0.754-0.998), and the probability of the HR <1.00 was 97.6 %.
The HR of SOX to CS in G-SOX was 0.942 (95 % credible interval; 0.789-1.117), and
the probability of HR <1.15 was 98.9 %.
CONCLUSION: This meta-analysis indicates that SOX was superior to S-1 and
noninferior to CS in AGC.

DOI: 10.1007/s10147-015-0938-9
PMID: 26733020  [Indexed for MEDLINE]


129. Int J Geriatr Psychiatry. 2016 Aug;31(8):892-904. doi: 10.1002/gps.4405. Epub
2015 Dec 17.

The comparative efficacy and safety of cholinesterase inhibitors in patients with
mild-to-moderate Alzheimer's disease: a Bayesian network meta-analysis.

Kobayashi H(1), Ohnishi T(1), Nakagawa R(1), Yoshizawa K(1).

Author information:
(1)Evidence Generation Department, Medical Affairs Division, Janssen
Pharmaceutical K.K., Tokyo, Japan.

BACKGROUND: Comparative evidence for efficacy and safety of second-generation
cholinesterase inhibitors (ChEIs) is still sparse.
OBJECTIVES: The purpose of this research is to compare three ChEIs, donepezil,
galantamine and rivastigmine, in patients with mild-to-moderate Alzheimer's
disease (AD).
METHODS: We conducted a systematic review for published articles and included
randomised, double-blind, placebo-controlled trials and head-to-head randomised
trials evaluating the efficacy and safety of ChEIs in patients with AD. We
examined Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS-Cog),
Neuropsychiatric Inventory (NPI), Clinician's Interview-Based Impression of
Change plus caregiver's input (CIBIC+) and Clinical Global Impression of Change
(CGIC) as efficacy endpoints. Withdrawals due to adverse events and number of
patients experiencing nausea, vomiting, diarrhoea and dizziness were examined as
safety profiles. Network meta-analyses were sequentially performed for efficacy
and safety outcomes based on drug/dose treatment conditions.
RESULTS: Among the 21 trials included, network meta-analysis showed that all
treatments were significantly more efficacious than placebo in cognition measured
by ADAS-Cog. All treatments except galantamine were significantly more
efficacious than placebo in global change in CIBIC+ or CGIC. Across all
conditions, no significant efficacy was observed in neuropsychiatric symptoms
measured by NPI. Derived hierarchies in the efficacy of treatment conditions were
variables across efficacy and safety.
CONCLUSIONS: Our analysis is the first attempt to incorporate available direct
and indirect evidence. The results suggest that ChEIs should have significant
efficacy for cognition and global change assessment, but the efficacy on
neuropsychiatric symptoms is questionable in patients with mild-to-moderate AD.

Copyright © 2015 John Wiley & Sons, Ltd.

DOI: 10.1002/gps.4405
PMID: 26680338  [Indexed for MEDLINE]


130. J Clin Pharm Ther. 2016 Aug;41(4):383-91. doi: 10.1111/jcpt.12410.

Network meta-analysis of Chinese herb injections combined with FOLFOX
chemotherapy in the treatment of advanced colorectal cancer.

Ge L(1)(2)(3), Wang YF(4), Tian JH(2)(3), Mao L(5), Zhang J(6), Zhang JH(7), Shen
XP(8), Yang KH(2)(3).

Author information:
(1)The First Clinical Medical College, Lanzhou University, Lanzhou, China.
(2)Evidence-based Medicine Center, Lanzhou University, Lanzhou, China.
(3)Key Laboratory of Evidence-based Medicine and Knowledge Translation of Gansu
Province, Lanzhou, China.
(4)School of Basic Medical Sciences, Gansu University of Traditional Chinese
Medicine, Lanzhou, China.
(5)The Second Clinical Medical College, Lanzhou University, Lanzhou, China.
(6)School of Nursing, Gansu University of Traditional Chinese Medicine, Lanzhou,
China.
(7)Evidence-based Medicine Center, Tianjin University of Traditional Chinese
Medicine, Tianjin, China.
(8)Department of Epidemiology and Biostatistics, School of Public Health, Lanzhou
University, Lanzhou, China.

WHAT IS KNOWN AND OBJECTIVE: Research has indicated that some Chinese herb
injections (CHIs) might be beneficial in combination with chemotherapy, including
remedies that might be used as effective chemosensitizers and radiosensitizers,
or as palliative therapy. Here, we carried out a network meta-analysis to assess
the clinical efficacy and safety of CHIs combined with oxaliplatin,
5-fluorouracil and leucovorin (FOLFOX) for advanced colorectal cancer (CRC).
METHODS: PubMed, EMBASE.com, the Cochrane Central Register of Controlled Trials
(CENTRAL), Chinese Biomedical Literature Database (CBM), Wanfang Database and
Chinese Journal Full-text Database were searched from inception to 31 December
2014, to identify relevant randomized controlled trails (RCTs). The risk of bias
in included RCTs was evaluated according to the Cochrane Handbook version 5.1.0.
Standard pairwise meta-analysis and Bayesian network meta-analysis were performed
to compare the efficacy and safety of different CHIs combined with FOLFOX. Data
were analysed using STATA 12.0 and WinBUGS1.4 software.
RESULTS AND DISCUSSION: We identified 63 eligible studies (with 4837 patients in
total), involving 9 CHIs. Pairwise meta-analysis showed that compared with FOLFOX
alone, combinations with Aidi injection and compound matrine injection could
significantly improve the overall response rate and quality of life and reduce
the incidence of nausea and vomiting (III-IV), diarrhoea (III-IV),
thrombocytopenia (III-IV), leukopenia (III-IV) and peripheral neurotoxicity
(III-IV). According to results of indirect comparison, there were no
statistically significant differences for most of comparison groups. Aidi+FOLFOX,
shenqifuzheng+FOLFOX and compound matrine+FOLFOX had the greatest probability of
being the best treatment in clinical efficacy and safety, considering the small
sample size.
WHAT IS NEW AND CONCLUSIONS: Most of the included studies were of low quality,
and there was a scarcity of eligible trials and numbers of participants. Based on
currently limited evidence, aidi, shenqifuzheng and compound matrine were
superior to other CHIs in patients receiving FOLFOX chemotherapy for advanced
CRC. More studies are required to confirm the efficacy of CHIs in combination
with FOLFOX for advanced CRC.

© 2016 John Wiley & Sons Ltd.

DOI: 10.1111/jcpt.12410
PMID: 27338003  [Indexed for MEDLINE]


131. BMC Gastroenterol. 2016 Jul 26;16(1):80. doi: 10.1186/s12876-016-0491-7.

Pharmacological regimens for eradication of Helicobacter pylori: an overview of
systematic reviews and network meta-analysis.

Xin Y(1), Manson J(2), Govan L(3), Harbour R(2), Bennison J(4), Watson E(5), Wu
O(3).

Author information:
(1)Health Economics and Health Technology Assessment (HEHTA), Institute of Health
and Wellbeing, University of Glasgow, Glasgow, UK. yiqiao.xin@glasgow.ac.uk.
(2)Knowledge and Information, Healthcare Improvement Scotland, Glasgow, UK.
(3)Health Economics and Health Technology Assessment (HEHTA), Institute of Health
and Wellbeing, University of Glasgow, Glasgow, UK.
(4)Scottish Intercollegiate Guideline Network (SIGN), NHS Education for Scotland,
Royal College of General Practitioners (Scotland), Mill Lane Surgery, Edinburgh,
UK.
(5)Department of gastroenterology, Royal Infirmary of Edinburgh, NHS Lothian,
Edinburgh, UK.

BACKGROUND: Approximately half of the world's population is infected with
Helicobacter pylori (H.pylori), a bacterium shown to be linked with a series of
gastrointestinal diseases. A growing number of systematic reviews (SRs) have been
published comparing the effectiveness of different treatments for H.pylori
infection but have not reached a consistent conclusion. The objective of this
study is to provide an overview of SRs of pharmacological therapies for the
eradication of H.pylori.
METHODS: Major electronic databases were searched to identify relevant SRs
published between 2002 and February 2016. Studies were considered eligible if
they included RCTs comparing different pharmacological regimens for treating
patients diagnosed as H.pylori infected and pooled the eradication rates in a
meta-analysis. A modified version of the 'A Measurement Tool to Assess Systematic
Reviews' (AMSTAR) was used to assess the methodological quality. A Bayesian
random effects network meta-analysis (NMA) was conducted to compare the different
proton pump inhibitors (PPI) within triple therapy.
RESULTS: 30 SRs with pairwise meta-analysis were included. In triple therapy, the
NMA ranked the esomeprazole to be the most effective PPI, followed by
rabeprazole, while no difference was observed among the three old generations of
PPI for the eradication of H.pylori. When comparing triple and bismuth-based
therapy, the relative effectiveness appeared to be dependent on the choice of
antibiotics within the triple therapy; moxifloxacin or levofloxacin-based triple
therapy were both associated with greater effectiveness than bismuth-based
therapy as a second-line treatment, while bismuth-based therapy achieved similar
or greater eradication rate compared to clarithromycin-based therapy.
Inconsistent findings were reported regarding the use of
levofloxacin/moxifloxacin in the first-line treatment; this could be due to the
varied resistant rate to different antibiotics across regions and populations.
Critical appraisal showed a low-moderate level of overall methodological quality
of included studies.
CONCLUSIONS: Our analysis suggests that the new generation of PPIs and use of
moxifloxacin or levofloxacin within triple therapy as second-line treatment were
associated with greater effectiveness. Given the varied antibiotic resistant rate
across regions, the appropriateness of pooling results together in meta-analysis
should be carefully considered and the recommendation of the choice of
antibiotics should be localized.

DOI: 10.1186/s12876-016-0491-7
PMCID: PMC4962503
PMID: 27460211  [Indexed for MEDLINE]


132. Antimicrob Agents Chemother. 2016 Jul 22;60(8):4869-77. doi:
10.1128/AAC.00577-16. Print 2016 Aug.

Development and Evaluation of a Gentamicin Pharmacokinetic Model That Facilitates
Opportunistic Gentamicin Therapeutic Drug Monitoring in Neonates and Infants.

Germovsek E(1), Kent A(2), Metsvaht T(3), Lutsar I(3), Klein N(4), Turner MA(5),
Sharland M(2), Nielsen EI(6), Heath PT(2), Standing JF(4).

Author information:
(1)Inflammation, Infection and Rheumatology Section, Institute of Child Health,
University College London, London, United Kingdom eva.germovsek.11@ucl.ac.uk.
(2)Paediatric Infectious Diseases Research Group, Institute for Infection and
Immunity, St. George's, University of London, Cranmer Terrace, London, United
Kingdom.
(3)Department of Microbiology, University of Tartu, Tartu, Estonia.
(4)Inflammation, Infection and Rheumatology Section, Institute of Child Health,
University College London, London, United Kingdom.
(5)Department of Women's and Children's Health, Institute of Translational
Medicine, University of Liverpool, Liverpool, United Kingdom.
(6)Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.

Trough gentamicin therapeutic drug monitoring (TDM) is time-consuming, disruptive
to neonatal clinical care, and a patient safety issue. Bayesian models could
allow TDM to be performed opportunistically at the time of routine blood tests.
This study aimed to develop and prospectively evaluate a new gentamicin model and
a novel Bayesian computer tool (neoGent) for TDM use in neonatal intensive care.
We also evaluated model performance for predicting peak concentrations and the
area under the concentration-time curve from time 0 h to time t h (AUC0- t). A
pharmacokinetic meta-analysis was performed on pooled data from three studies
(1,325 concentrations from 205 patients). A 3-compartment model was used with the
following covariates: allometric weight scaling, postmenstrual and postnatal age,
and serum creatinine concentration. Final parameter estimates (standard errors)
were as follows: clearance, 6.2 (0.3) liters/h/70 kg of body weight; central
volume (V), 26.5 (0.6) liters/70 kg; intercompartmental disposition (Q), 2.2
(0.3) liters/h/70 kg; peripheral volume V2, 21.2 (1.5) liters/70 kg;
intercompartmental disposition (Q2), 0.3 (0.05) liters/h/70 kg; peripheral volume
V3, 148 (52.0) liters/70 kg. The model's ability to predict trough concentrations
from an opportunistic sample was evaluated in a prospective observational cohort
study that included data from 163 patients and 483 concentrations collected in
five hospitals. Unbiased trough predictions were obtained; the median (95%
confidence interval [CI]) prediction error was 0.0004 (-1.07, 0.84) mg/liter.
Results also showed that peaks and AUC0- t values could be predicted (from one
randomly selected sample) with little bias but relative imprecision, with median
(95% CI) prediction errors being 0.16 (-4.76, 5.01) mg/liter and 10.8 (-24.9,
62.2) mg · h/liter, respectively. neoGent was implemented in R/NONMEM and in the
freely available TDMx software.

Copyright © 2016, American Society for Microbiology. All Rights Reserved.

DOI: 10.1128/AAC.00577-16
PMCID: PMC4958175
PMID: 27270281  [Indexed for MEDLINE]


133. BMJ Open. 2016 Jul 8;6(7):e010919. doi: 10.1136/bmjopen-2015-010919.

Comparative efficacy and acceptability of first-generation and second-generation
antidepressants in the acute treatment of major depression: protocol for a
network meta-analysis.

Furukawa TA(1), Salanti G(2), Atkinson LZ(3), Leucht S(4), Ruhe HG(5), Turner
EH(6), Chaimani A(7), Ogawa Y(1), Takeshima N(1), Hayasaka Y(1), Imai H(1),
Shinohara K(1), Suganuma A(1), Watanabe N(1), Stockton S(3), Geddes JR(8),
Cipriani A(8).

Author information:
(1)Department of Health Promotion and Human Behavior, Kyoto University Graduate
School of Medicine/School of Public Health, Kyoto, Japan.
(2)Department of Clinical Research, Institute of Social and Preventive Medicine,
University of Bern, Bern, Switzerland Institute of Primary Health Care (BIHAM),
University of Bern, Switzerland Department of Hygiene and Epidemiology,
University of Ioannina, Ioannina, Greece.
(3)Department of Psychiatry, University of Oxford, Oxford, UK.
(4)Department of Psychiatry and Psychotherapy, TU- Munich, Munchen, Germany.
(5)Department of Psychiatry, Academic Medical Center, University of Amsterdam,
Amsterdam, The Netherlands University Center for Psychiatry, University of
Groningen, Groningen, The Netherlands.
(6)Behavioral Health and Neurosciences Division, VA Portland Health Care System,
Portland, Oregon, USA Departments of Psychiatry and Pharmacology, Oregon Health &
Science University, Portland, Oregon, USA.
(7)Department of Hygiene and Epidemiology, University of Ioannina, Ioannina,
Greece.
(8)Department of Psychiatry, University of Oxford, Oxford, UK Oxford Health NHS
Foundation Trust, Warneford Hospital, Oxford, UK.

INTRODUCTION: Many antidepressants are indicated for the treatment of major
depression. Two network meta-analyses have provided the most comprehensive
assessments to date, accounting for both direct and indirect comparisons;
however, these reported conflicting interpretation of results. Here, we present a
protocol for a systematic review and network meta-analysis aimed at updating the
evidence base and comparing all second-generation as well as selected
first-generation antidepressants in terms of efficacy and acceptability in the
acute treatment of major depression.
METHODS AND ANALYSIS: We will include all randomised controlled trials reported
as double-blind and comparing one active drug with another or with placebo in the
acute phase treatment of major depression in adults. We are interested in
comparing the following active agents: agomelatine, amitriptyline, bupropion,
citalopram, clomipramine, desvenlafaxine, duloxetine, escitalopram, fluoxetine,
fluvoxamine, levomilnacipran, milnacipran, mirtazapine, nefazodone, paroxetine,
reboxetine, sertraline, trazodone, venlafaxine, vilazodone and vortioxetine. The
main outcomes will be the proportion of patients who responded to or dropped out
of the allocated treatment. Published and unpublished studies will be sought
through relevant database searches, trial registries and websites; all reference
selection and data extraction will be conducted by at least two independent
reviewers. We will conduct a random effects network meta-analysis to synthesise
all evidence for each outcome and obtain a comprehensive ranking of all
treatments. To rank the various treatments for each outcome, we will use the
surface under the cumulative ranking curve and the mean ranks. We will employ
local as well as global methods to evaluate consistency. We will fit our model in
a Bayesian framework using OpenBUGS, and produce results and various checks in
Stata and R. We will also assess the quality of evidence contributing to network
estimates of the main outcomes with the GRADE framework.
ETHICS AND DISSEMINATION: This review does not require ethical approval.
PROSPERO REGISTRATION NUMBER: CRD42012002291.

Published by the BMJ Publishing Group Limited. For permission to use (where not
already granted under a licence) please go to
http://www.bmj.com/company/products-services/rights-and-licensing/

DOI: 10.1136/bmjopen-2015-010919
PMCID: PMC4947714
PMID: 27401359  [Indexed for MEDLINE]


134. Am J Orthod Dentofacial Orthop. 2016 Jul;150(1):13-32. doi:
10.1016/j.ajodo.2015.12.025.

Comparative effectiveness of pharmacologic and nonpharmacologic interventions for
orthodontic pain relief at peak pain intensity: A Bayesian network meta-analysis.

Sandhu SS(1), Cheema MS(2), Khehra HS(3).

Author information:
(1)Professor, Department of Orthodontics and Dentofacial Orthopedics, Genesis
Institute of Dental Sciences and Research, Ferozepur, Punjab, India. Electronic
address: drsatpalsandhu@yahoo.co.in.
(2)Private practice, Calgary, Alberta, Canada.
(3)Private practice, Jalandhar, Punjab, India.

INTRODUCTION: The objective of this network meta-analysis was to synthesize the
evidence of the comparative effectiveness for various interventions used for
orthodontic pain relief during peak pain intensity.
METHODS: MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials
databases were searched to December 31, 2014, to identify relevant studies.
Additional studies were found by hand searching of journals and reference lists.
Unpublished articles were also searched. Eligible studies were randomized
controlled trials evaluating the effectiveness of pharmacologic or
nonpharmacologic interventions for pain relief after placement of separators or
an initial aligning archwire. A covariate-adjusted arm-based 3-level hierarchical
Bayesian random-effects model was used for this network meta-analysis.
RESULTS: Twenty-four randomized controlled trials (2273 participants; 997 male,
1276 female; mean age, 18.2 years; SD, 4.4 years) were included in this network
meta-analysis. A total of 26 interventions were identified and classified into 6
classes based on their mechanism of action. Compared with placebo-class,
nonsteroidal anti-inflammatory drug analgesics and lasers were the most effective
intervention classes with a shared median rank of 2 (95% credible interval [CrI],
1-3), followed by "other" analgesics (median rank, 3; 95% CrI, 1-4), behavior
therapy (median rank, 4; 95% CrI, 3-6), and miscellaneous (median rank, 5; 95%
CrI 3-6). The most effective individual interventions in the nonsteroidal
anti-inflammatory drug analgesics and lasers classes were etoricoxib (median
rank, 1; 95% CrI, 1-3) and gallium-arsenide superpulsed lasers (median rank, 3;
95% CrI, 1-13), respectively. Assessment of transitivity and consistency
assumption showed no threat to the network meta-analysis estimates. There was no
evidence of significant publication bias. Heterogeneity was mild to moderate
(tau-square, 0.044; 95% CrI, 0.040-0.055).
CONCLUSIONS: The results show that analgesics and lasers are effective in the
management of orthodontic pain at its peak intensity. Further research is
required to improve the quality of evidence, especially for analgesic
interventions.

Copyright © 2016 American Association of Orthodontists. Published by Elsevier
Inc. All rights reserved.

DOI: 10.1016/j.ajodo.2015.12.025
PMID: 27364203  [Indexed for MEDLINE]


135. Int J Nurs Stud. 2016 Jul;59:156-62. doi: 10.1016/j.ijnurstu.2016.04.004. Epub
2016 Apr 25.

Skin antiseptics in venous puncture site disinfection for preventing blood
culture contamination: A Bayesian network meta-analysis of randomized controlled
trials.

Liu W(1), Duan Y(2), Cui W(1), Li L(1), Wang X(1), Dai H(1), You C(1), Chen M(3).

Author information:
(1)Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu
610041, China.
(2)Department of Orthopaedic Surgery, West China Hospital, Sichuan University,
Chengdu 610041, China.
(3)Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu
610041, China. Electronic address: chenmaojunNS@126.com.

OBJECTIVE: To compare the efficacy of several antiseptics in decreasing the blood
culture contamination rate.
DESIGN: Network meta-analysis.
DATA SOURCE: Electronic searches of PubMed and Embase were conducted up to
November 2015. Only randomized controlled trials or quasi-randomized controlled
trials were eligible. We applied no language restriction. A comprehensive review
of articles in the reference lists was also accomplished for possible relevant
studies.
REVIEW METHODS: Relevant studies evaluating efficacy of different antiseptics in
venous puncture site for decreasing the blood culture contamination rate were
included. The data were extracted from the included randomized controlled trials
by two authors independently. The risk of bias was evaluated using Detsky scale
by two authors independently. We used WinBUGS1.43 software and statistic model
described by Chaimani to perform this network meta-analysis. Then graphs of
statistical results of WinBUGS1.43 software were generated using 'networkplot',
'ifplot', 'netfunnel' and 'sucra' procedure by STATA13.0. Odds ratio and 95%
confidence intervals were assessed for dichotomous data. A probability of p less
than 0.05 was considered to be statistically significant. Compared with ordinary
meta-analyses, this network meta-analysis offered hierarchies for the efficacy of
different antiseptics in decreasing the blood culture contamination rate.
RESULTS: Seven randomized controlled trials involving 34,408 blood samples were
eligible for the meta-analysis. No significant difference was found in blood
culture contamination rate among different antiseptics. No significant difference
was found between non-alcoholic antiseptics and alcoholic antiseptics, alcoholic
chlorhexidine and povidone iodine, chlorhexidine and iodine compounds, povidone
iodine and iodine tincture in this aspect, respectively.
CONCLUSIONS: Different antiseptics may not affect the blood culture contamination
rate. Different intervals between the skin disinfection and the venous puncture,
the different settings (emergency room, medical wards, and intensive care units)
and the performance of the phlebotomy may affect the blood culture contamination
rate.

Copyright © 2016 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.ijnurstu.2016.04.004
PMID: 27222460  [Indexed for MEDLINE]


136. Medicine (Baltimore). 2016 Jul;95(30):e4071. doi: 10.1097/MD.0000000000004071.

Treatment efficacy of anti-hypertensive drugs in monotherapy or combination: ATOM
systematic review and meta-analysis of randomized clinical trials according to
PRISMA statement.

Paz MA(1), de-La-Sierra A, Sáez M, Barceló MA, Rodríguez JJ, Castro S, Lagarón C,
Garrido JM, Vera P, Coll-de-Tuero G.

Author information:
(1)aHospital de Santa Caterina, Girona bHospital Mutua Terrassa, University of
Barcelona-Terrassa (Barcelona) cResearch Group on Statistics, Econometrics and
Health (GRECS), University of Girona dCIBER of Epidemiology and Public Health
(CIBERESP) eDepartment of Medical Sciences, University of Girona fCAP Can Gibert
del Plà, Girona gResearch Unit, USR Girona, IdIAP Gol i Gorina, ICS, Spain.

BACKGROUND: The relative efficacy of antihypertensive drugs/combinations is not
well known. Identifying the most effective ones and the patients' characteristics
associated with best performance of the drugs will improve management of
hypertensive patients.
OBJECTIVE: To assess the blood pressure (BP) reduction attributed to
antihypertensive drugs and identify characteristics associated with BP decrease.
DATA SOURCES: MEDLINE, Cochrane Central Register of Controlled Trials from
inception through July 2012 and selected papers.
STUDY ELIGIBILITY CRITERIA: Double-blind, randomized clinical trials whose main
result was the reduction in BP by antihypertensive treatment, with study
population ≥50 or ≥25 if the study was a crossover, follow-up of at least 8
weeks, and available required data.
STUDY APPRAISAL AND SYNTHESIS METHODS: Study data were independently extracted by
multiple observers and introduced in an electronic database. Inconsistencies were
resolved by discussion and referral back to the original articles. Meta-analysis
was performed according to PRISMA statement and using a Bayesian framework.
MAIN OUTCOME(S) AND MEASURE(S): Mean decrease in systolic (SBP) and diastolic
blood pressure (DBP) achieved by each drug or combination.
RESULTS: Two hundred eight trials including 94,305 patients were identified. In
monotherapy, most drugs achieved 10 to 15 mm Hg SBP and 8 to 10 mm Hg DBP
decreases.Olmesartan/amlodipine, olmesartan/hydrochlorothiazide,
felodipine/metoprolol, and valsartan/hydrochlorothiazide were the combinations
leading to the greatest mean SBP reductions (>20 mm Hg). Female sex and body mass
index >25 kg/m were associated with more pronounced SBP and DBP reductions,
whereas Afro-American ethnicity was associated with BP reductions smaller than
the median. Results were adjusted by study duration, cardiovascular disease, and
diabetes mellitus. Still, the estimation was performed using the mean
administered doses, which do not exactly match those of the available drug
formats.
LIMITATIONS: Data corresponded to those obtained in each of the included trials;
the analysis of the combinations was limited to the most recent ones; estimations
were performed using the mean administered doses.
CONCLUSIONS AND IMPLICATIONS: Certain drug combinations achieve BP reductions
ranging from 20 to 25/10 to 15 mm Hg. Sex, ethnicity, and obesity are associated
with antihypertensive response. This information can contribute to better
selection of the antihypertensive drug, depending on the magnitude of
pretreatment BP elevation. Guidelines should be revised.

DOI: 10.1097/MD.0000000000004071
PMCID: PMC5265817
PMID: 27472680  [Indexed for MEDLINE]

Conflict of interest statement: The authors have no conflicts of interest to
disclose.


137. Beijing Da Xue Xue Bao Yi Xue Ban. 2016 Jun 18;48(3):454-9.

[Impact of glucagon-like peptide-1 receptor agonists on nasopharyngitis and upper
respiratory tract infection among patients with type 2 diabetes: a network
meta-analysis].

[Article in Chinese]

Li ZX(1), Wu SS(2), Yang ZR(3), Zhan SY(1), Sun F(1).

Author information:
(1)Department of Epidemiology and Biostatistics, Peking University School of
Public Health, Beijing 100191, China.
(2)National Clinical Research Center for Digestive Diseases, Beijing Friendship
Hospital, Capital Medical University, Beijing 100050, China.
(3)Primary Care Unit, University of Cambridge, Cambridge CB21TN, UK.

OBJECTIVE: To systematically review the effects of glucagon-like peptide-1
receptor agonists (GLP-1RAs) on two common respiratory system adverse events
(RSAE: nasopharyngitis and upper respiratory tract infection) among type 2
diabetes (T2DM).
METHODS: Medline, Embase, Clinical trials and Cochrane library were searched from
inception through May 2015 to identify randomized clinical trials(RCTs) assessed
safety of GLP-1RAs versus placebo or other anti-diabetic drugs in T2DM. Network
meta-analysis within a Bayesian framework was performed to calculate odds ratios
for the incidence of RSAE.
RESULTS: In the study, 50 RCTs were included, including 13 treatments: 7 GLP-1RAs
(exenatide, exenatide-long-release-agent, liraglutide, lixisenatide,
taspoglutide, albiglutide and dulaglutide), placebo and 5 traditional
anti-diabetic drugs(insulin, metformin, sulfonylureas, sitagliptin and
thiazolidinediones ketones). Compared with insulin, taspoglutide significantly
decreased the incidence of nasopharyngitis (OR=0.67, 95%CI: 0.46-0.96).
Significant lowering effects on upper respiratory tract infection were found when
taspoglutide versus placebo (OR=0.57, 95%CI: 0.34-0.99) and insulin (OR=0.39,
95%CI: 0.23-0.73). The result from the network meta-analysis based on Bayesian
theory could be used to rank all the treatments included, which showed that
taspoglutide ranked last with minimum risk on nasopharyngitis and upper
respiratory tract infection.
CONCLUSION: Taspoglutide was associated with significantly lowering effect on
RSAE.


PMID: 27318907  [Indexed for MEDLINE]


138. JAMA. 2016 Jun 14;315(22):2424-34. doi: 10.1001/jama.2016.7602.

Association of Pharmacological Treatments for Obesity With Weight Loss and
Adverse Events: A Systematic Review and Meta-analysis.

Khera R(1), Murad MH(2), Chandar AK(3), Dulai PS(4), Wang Z(5), Prokop LJ(6),
Loomba R(4), Camilleri M(7), Singh S(8).

Author information:
(1)Department of Internal Medicine, University of Iowa Carver College of
Medicine, Iowa City.
(2)Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery,
Mayo Clinic, Rochester, Minnesota3Division of Preventive Medicine, Mayo Clinic,
Rochester, Minnesota.
(3)Division of Gastroenterology and Liver Diseases, Case Western Reserve
University, Cleveland, Ohio.
(4)Division of Gastroenterology, University of California, San Diego, La Jolla.
(5)Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery,
Mayo Clinic, Rochester, Minnesota.
(6)Department of Library Services, Mayo Clinic, Rochester, Minnesota.
(7)Clinical Enteric Neuroscience Translational and Epidemiological Research
(CENTER), Mayo Clinic, Rochester, Minnesota.
(8)Division of Gastroenterology, University of California, San Diego, La
Jolla8Division of Biomedical Informatics, University of California, San Diego, La
Jolla.

Erratum in
    JAMA. 2016 Sep 6;316(9):995.

Comment in
    BMJ. 2016 Jun 14;353:i3330.

IMPORTANCE: Five medications have been approved for the management of obesity,
but data on comparative effectiveness are limited.
OBJECTIVE: To compare weight loss and adverse events among drug treatments for
obesity using a systematic review and network meta-analysis.
DATA SOURCES: MEDLINE, EMBASE, Web of Science, Scopus, and Cochrane Central from
inception to March 23, 2016; clinical trial registries.
STUDY SELECTION: Randomized clinical trials conducted among overweight and obese
adults treated with US Food and Drug Administration-approved long-term weight
loss agents (orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate,
or liraglutide) for at least 1 year compared with another active agent or
placebo.
DATA EXTRACTION AND SYNTHESIS: Two investigators identified studies and
independently abstracted data using a predefined protocol. A Bayesian network
meta-analysis was performed and relative ranking of agents was assessed using
surface under the cumulative ranking (SUCRA) probabilities. Quality of evidence
was assessed using GRADE criteria.
MAIN OUTCOMES AND MEASURES: Proportions of patients with at least 5% weight loss
and at least 10% weight loss, magnitude of decrease in weight, and
discontinuation of therapy because of adverse events at 1 year.
RESULTS: Twenty-eight randomized clinical trials with 29 018 patients (median
age, 46 years; 74% women; median baseline body weight, 100.5 kg; median baseline
body mass index, 36.1) were included. A median 23% of placebo participants had at
least 5% weight loss vs 75% of participants taking phentermine-topiramate (odds
ratio [OR], 9.22; 95% credible interval [CrI], 6.63-12.85; SUCRA, 0.95), 63% of
participants taking liraglutide (OR, 5.54; 95% CrI, 4.16-7.78; SUCRA, 0.83), 55%
taking naltrexone-bupropion (OR, 3.96; 95% CrI, 3.03-5.11; SUCRA, 0.60), 49%
taking lorcaserin (OR, 3.10; 95% CrI, 2.38-4.05; SUCRA, 0.39), and 44% taking
orlistat (OR, 2.70; 95% CrI, 2.34-3.09; SUCRA, 0.22). All active agents were
associated with significant excess weight loss compared with placebo at 1
year-phentermine-topiramate, 8.8 kg (95% CrI, -10.20 to -7.42 kg); liraglutide,
5.3 kg (95% CrI, -6.06 to -4.52 kg); naltrexone-bupropion, 5.0 kg (95% CrI, -5.94
to -3.96 kg); lorcaserin, 3.2 kg (95% CrI, -3.97 to -2.46 kg); and orlistat, 2.6
kg (95% CrI, -3.04 to -2.16 kg). Compared with placebo, liraglutide (OR, 2.95;
95% CrI, 2.11-4.23) and naltrexone-bupropion (OR, 2.64; 95% CrI, 2.10-3.35) were
associated with the highest odds of adverse event-related treatment
discontinuation. High attrition rates (30%-45% in all trials) were associated
with lower confidence in estimates.
CONCLUSIONS AND RELEVANCE: Among overweight or obese adults, orlistat,
lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide,
compared with placebo, were each associated with achieving at least 5% weight
loss at 52 weeks. Phentermine-topiramate and liraglutide were associated with the
highest odds of achieving at least 5% weight loss.

DOI: 10.1001/jama.2016.7602
PMCID: PMC5617638
PMID: 27299618  [Indexed for MEDLINE]


139. BMJ Open. 2016 Jun 7;6(6):e010142. doi: 10.1136/bmjopen-2015-010142.

Comparative efficacy of selective serotonin reuptake inhibitors (SSRI) in
treating major depressive disorder: a protocol for network meta-analysis of
randomised controlled trials.

Jia Y(1), Zhu H(1), Leung SW(2).

Author information:
(1)State Key Laboratory of Quality Research in Chinese Medicine, Institute of
Chinese Medical Sciences, University of Macau, Macao, China.
(2)State Key Laboratory of Quality Research in Chinese Medicine, Institute of
Chinese Medical Sciences, University of Macau, Macao, China School of
Informatics, University of Edinburgh, Edinburgh, UK.

INTRODUCTION: There have been inconsistent findings from randomised controlled
trials (RCTs) and systematic reviews on the efficacies of selective serotonin
reuptake inhibitors (SSRIs) as the first-line treatment of major depressive
disorder (MDD). Besides inconsistencies among randomised controlled trials
(RCTs), their risks of bias and evidence grading have seldom been evaluated in
meta-analysis. This study aims to compare the efficacy of SSRIs by conducting a
Bayesian network meta-analysis, which will be the most comprehensive evaluation
of evidence to resolve the inconsistency among previous studies.
METHODS AND ANALYSES: SSRIs including citalopram, escitalopram, fluoxetine,
fluvoxamine, paroxetine, sertraline and vilazodone have been selected. Systematic
database searching and screening will be conducted for the RCTs on drug treatment
of patients with MDD according to pre-specified search strategies and selection
criteria. PubMed, the Cochrane Library, EMBASE, ScienceDirect, the US Food and
Drug Administration Website, ClinicalTrial.gov and WHO Clinical Trials will be
searched. Outcome data including Hamilton Depression Rating Scale (HDRS),
Montgomery-Åsberg Depression Rating Scale (MADRS) and Clinical Global Impression
(CGI) from eligible RCTs will be extracted. The outcomes will be analysed as ORs
and mean differences under a random-effects model. A Bayesian network
meta-analysis will be conducted with WinBUGS software, to compare the efficacies
of SSRIs. Subgroup and sensitivity analysis will be performed to explain the
study heterogeneity and evaluate the robustness of the results. Meta-regression
analysis will be conducted to determine the possible factors affecting the
efficacy outcomes. The Cochrane risk of bias assessment tool will be used to
assess the RCT quality, and the Grading of Recommendation, Assessment,
Development and Evaluation will be used to assess the strength of evidence from
the meta-analysis.
ETHICS AND DISSEMINATION: No ethical approval is required because this study
includes neither confidential personal patient data nor interventions with
patients.
PROTOCOL REGISTRATION NUMBER: CRD42015024879.

Published by the BMJ Publishing Group Limited. For permission to use (where not
already granted under a licence) please go to
http://www.bmj.com/company/products-services/rights-and-licensing/

DOI: 10.1136/bmjopen-2015-010142
PMCID: PMC4908880
PMID: 27267106  [Indexed for MEDLINE]


140. PLoS One. 2016 Jun 6;11(6):e0155389. doi: 10.1371/journal.pone.0155389.
eCollection 2016.

Nivolumab versus Cabozantinib: Comparing Overall Survival in Metastatic Renal
Cell Carcinoma.

Wiecek W(1), Karcher H(1).

Author information:
(1)LASER Analytica, Halton House, 20-23 Holborn, London, EC1N 2JD, United
Kingdom.

Renal-cell carcinoma (RCC) affects over 330,000 new patients every year, of whom
1/3 present with metastatic RCC (mRCC) at diagnosis. Most mRCC patients treated
with a first-line agent relapse within 1 year and need second-line therapy. The
present study aims to compare overall survival (OS) between nivolumab and
cabozantinib from two recent pivotal studies comparing, respectively, each one of
the two emerging treatments against everolimus in patients who relapse following
first-line treatment. Comparison is traditionally carried out using the Bucher
method, which assumes proportional hazard. Since OS curves intersected in one of
the pivotal studies, models not assuming proportional hazards were also
considered to refine the comparison. Four Bayesian parametric survival network
meta-analysis models were implemented on overall survival (OS) data digitized
from the Kaplan-Meier curves reported in the studies. Three models allowing
hazard ratios (HR) to vary over time were assessed against a fixed-HR model. The
Bucher method favored cabozantinib, with a fixed HR for OS vs. nivolumab of 1.09
(95% confidence interval: [0.77, 1.54]). However, all models with time-varying HR
showed better fits than the fixed-HR model. The log-logistic model fitted the
data best, exhibiting a HR for OS initially favoring cabozantinib, the trend
inverting to favor nivolumab after month 5 (95% credible interval <1 from 10
months). The initial probability of cabozantinib conferring superior OS was 54%,
falling to 41.5% by month 24. Numerical differences in study-adjusted OS
estimates between the two treatments remained small. This study evidences that HR
for OS of nivolumab vs. cabozantinib varies over time, favoring cabozantinib in
the first months of treatment but nivolumab afterwards, a possible indication
that patients with poor prognosis benefit more from cabozantinib in terms of
survival, nivolumab benefiting patients with better prognosis. More evidence,
including real-world observational data, is needed to compare effectiveness
between cabozantinib and nivolumab.

DOI: 10.1371/journal.pone.0155389
PMCID: PMC4894561
PMID: 27271250  [Indexed for MEDLINE]


141. Aliment Pharmacol Ther. 2016 Jun;43(12):1262-75. doi: 10.1111/apt.13642. Epub
2016 Apr 28.

Systematic review with network meta-analysis: comparative effectiveness and
safety of strategies for preventing NSAID-associated gastrointestinal toxicity.

Yuan JQ(1)(2), Tsoi KK(1)(3), Yang M(4), Wang JY(5), Threapleton DE(1)(2), Yang
ZY(1)(2), Zou B(4), Mao C(1)(2), Tang JL(1)(2), Chan FK(3).

Author information:
(1)School of Public Health and Primary Care, Faculty of Medicine, The Chinese
University of Hong Kong, Hong Kong.
(2)Municipal Key Laboratory for Health Risk Analysis, Shenzhen Research Institute
of the Chinese University of Hong Kong, Shenzhen, China.
(3)Department of Medicine and Therapeutics, Faculty of Medicine, Institute of
Digestive Disease, The Chinese University of Hong Kong, Hong Kong.
(4)Department of Gastroenterology, Peking University Shenzhen Hospital, Shenzhen,
China.
(5)Department of Gastroenterology, Zhongshan Hospital, Fudan University,
Shanghai, China.

BACKGROUND: Many strategies are used to prevent nonsteroidal anti-inflammatory
drug (NSAID)-associated gastrointestinal toxicity, but the comparative
effectiveness remains unclear.
AIM: To evaluate the comparative effectiveness of clinical strategies for
preventing gastrointestinal toxicity induced by NSAIDs.
METHODS: MEDLINE, EMBASE and the Cochrane Library (from their inception to May
2015) were searched for randomised controlled trials comparing the risk of
gastrointestinal adverse events in patients taking nonselective NSAIDs, selective
cyclooxygenase(COX)-2 inhibitors or nonselective NSAIDs/COX-2 inhibitors plus
gastroprotective agents [proton pump inhibitors (PPIs), histamine-2 receptor
antagonists, misoprostol]. Both pairwise meta-analysis and Bayesian network
meta-analysis were performed.
RESULTS: Analyses were based on 82 trials including 125 053 participants. Network
meta-analysis demonstrated that selective COX-2 inhibitors + PPIs [Risk ratio
(RR), 95% Credible Interval (CrI): ulcer complications 0.07, 0.02-0.18],
selective COX-2 inhibitors (RR, 95% CrI: ulcer complications 0.25, 0.15- 0.38;
symptomatic ulcer 0.12, 0.04-0.30), nonselective NSAIDs + PPIs (RR, 95% CrI:
ulcer complications 0.28, 0.18-0.41; symptomatic ulcer 0.11, 0.04-0.23),
nonselective NSAIDs + misoprostol (RR, 95% CrI: ulcer complications 0.47,
0.24-0.81; symptomatic ulcer 0.41, 0.13-1.00) were associated with significantly
lower risk of clinical gastrointestinal events compared with nonselective NSAIDs.
For all effectiveness endpoints, selective COX-2 inhibitors + PPIs was associated
with the lowest absolute event probability and the highest rank, followed by
selective COX-2 inhibitors and thirdly by nonselective NSAIDs + PPIs.
CONCLUSION: The combination of selective COX-2 inhibitors plus PPIs provides the
best gastrointestinal protection, followed by selective COX-2 inhibitors, and
thirdly by nonselective NSAIDs plus PPIs.

© 2016 John Wiley & Sons Ltd.

DOI: 10.1111/apt.13642
PMID: 27121479  [Indexed for MEDLINE]


142. Ann Rheum Dis. 2016 Jun;75(6):1152-60. doi: 10.1136/annrheumdis-2015-207677. Epub
2015 Aug 6.

Comparative efficacy of non-steroidal anti-inflammatory drugs in ankylosing
spondylitis: a Bayesian network meta-analysis of clinical trials.

Wang R(1), Dasgupta A(1), Ward MM(1).

Author information:
(1)Intramural Research Program, National Institute of Arthritis and
Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda,
Maryland, USA.

OBJECTIVE: To compare the efficacy of 20 non-steroidal anti-inflammatory drugs
(NSAIDs) in the short-term treatment of ankylosing spondylitis (AS).
METHODS: We performed a systematic literature review of randomised controlled
trials of NSAIDs in patients with active AS. We included trials that reported
efficacy at 2-12 weeks. Efficacy outcomes were the change in pain score and
change in the duration of morning stiffness. We also examined the number of
adverse events. We used Bayesian network meta-analysis to compare effects
directly and indirectly between drugs.
RESULTS: We included 26 trials (66 treatment arms) of 20 NSAIDs with 3410
participants in the network meta-analysis. Fifty-eight per cent of trials had
fewer than 50 participants. All 20 NSAIDs reduced pain more than placebo
(standardised mean difference ranging from -0.65 to -2.2), with 15 NSAIDs
significantly better than placebo. Etoricoxib was superior to celecoxib,
ketoprofen and tenoxicam in pain reduction, but no other interdrug comparisons
were significant. There were no significant differences among NSAIDs in decreases
in the duration of morning stiffness or the likelihood of adverse events. Adverse
events were uncommon in these short-term studies. In 16 trials that used NSAIDs
at full doses, etoricoxib was superior to all but two other NSAIDs in pain
reduction.
CONCLUSIONS: Etoricoxib was more effective in reducing pain in AS than some other
NSAIDs, but there was otherwise insufficient evidence to conclude that any
particular NSAID was more effective in the treatment of AS. Comparisons were
limited by small studies.

Published by the BMJ Publishing Group Limited. For permission to use (where not
already granted under a licence) please go to
http://www.bmj.com/company/products-services/rights-and-licensing/

DOI: 10.1136/annrheumdis-2015-207677
PMID: 26248636  [Indexed for MEDLINE]


143. Arthritis Rheumatol. 2016 Jun;68(6):1432-41. doi: 10.1002/art.39594.

Risk of End-Stage Renal Disease in Patients With Lupus Nephritis, 1971-2015: A
Systematic Review and Bayesian Meta-Analysis.

Tektonidou MG(1), Dasgupta A(2), Ward MM(2).

Author information:
(1)University of Athens School of Medicine, Athens, Greece.
(2)National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH,
Bethesda, Maryland.

OBJECTIVE: End-stage renal disease (ESRD) is a major consequence of lupus
nephritis, but how this risk has changed over time is unknown. We conducted this
systematic review to examine changes in ESRD among adults with lupus nephritis
from 1971 to 2015 and to estimate risks of ESRD among contemporary patients.
METHODS: We searched PubMed, Embase, and the Cochrane Database of Systematic
Reviews for cohort studies and clinical trials on ESRD in adults with lupus
nephritis. We analyzed studies from developed and developing countries
separately. The outcome was probability of ESRD at 5, 10, and 15 years of lupus
nephritis.
RESULTS: We included 187 articles that reported on 18,309 patients. In developed
countries, the 5-year risk of ESRD decreased from 16% (95% confidence interval
[95% CI] 14-17%) in 1970-1979 to 11% (95% CI 10-12%) in the mid-1990s and then
plateaued. ESRD risks at 10 years and 15 years showed steeper declines in the
1970s and 1980s but also plateaued in 1993-1997, with a notable increase in the
late 2000s. The decrease in risk after 1980 coincided with increased use of
cyclophosphamide. The 15-year ESRD risk was higher in developing countries than
in developed countries. Patients with class IV lupus nephritis had the greatest
risk of ESRD, with a 15-year risk of 44% during the 2000s.
CONCLUSION: Risks of ESRD in lupus nephritis improved between the 1970s and the
mid-1990s and then plateaued, with an increase in the late 2000s. This pattern
suggests limitations in the effectiveness of, or access to, current treatments.

© 2016, American College of Rheumatology.

DOI: 10.1002/art.39594
PMCID: PMC5071782
PMID: 26815601  [Indexed for MEDLINE]


144. Clin Breast Cancer. 2016 Jun;16(3):188-95. doi: 10.1016/j.clbc.2016.02.007. Epub
2016 Feb 11.

Network Meta-Analysis Comparing Overall Survival for Fulvestrant 500 mg Versus
Alternative Therapies for Treatment of Postmenopausal, Estrogen Receptor-Positive
Advanced Breast Cancer Following Failure on Prior Endocrine Therapy.

Telford C(1), Jones N(2), Livings C(3), Batson S(3).

Author information:
(1)AstraZeneca Pharmaceuticals, Global Payer Evidence & Pricing, Gaithersburg,
MD. Electronic address: claire.telford@astrazeneca.com.
(2)AstraZeneca Pharmaceuticals, Global Payer Evidence & Pricing, Gaithersburg,
MD.
(3)DRG Abacus, Bicester, United Kingdom.

BACKGROUND: We conducted a review of randomized trials to compare the overall
survival (OS) with fulvestrant 500 mg versus alternative treatment for estrogen
receptor-positive advanced breast cancer following endocrine therapy failure.
MATERIALS AND METHODS: Hazard ratios (HRs) were obtained by modeling OS data with
the Weibull distribution. A fixed-effect Bayesian network meta-analysis was
conducted. The evidence network included anastrozole 1 mg, letrozole 2.5 mg,
fulvestrant 250 mg, exemestane 25 mg, megestrol acetate 40 mg, and everolimus 10
mg plus exemestane 25 mg as comparators. Post-antiestrogen and post-aromatase
inhibitor subgroup networks were analyzed.
RESULTS: In the overall analysis, the HRs suggested improved OS for fulvestrant
500 mg versus fulvestrant 250 mg and megestrol acetate 40 mg, and numerically
favorable differences with fulvestrant 500 mg versus other comparators. In the
antiestrogen subgroup, the HRs suggested improved OS for fulvestrant 500 mg
versus fulvestrant 250 mg and megestrol acetate 40 mg; numerical differences in
the HRs were seen versus anastrozole 1 mg and letrozole 2.5 mg. In the aromatase
inhibitor subgroup, the HRs for OS numerically favored fulvestrant 500 mg versus
fulvestrant 250 mg and exemestane 25 mg.
CONCLUSION: Acknowledging the limitations of the present network meta-analysis,
these findings suggest that fulvestrant 500 mg might provide improved OS versus
fulvestrant 250 mg and megestrol acetate 40 mg for treatment of estrogen
receptor-positive ABC following endocrine therapy failure. Although OS efficacy
versus everolimus 10 mg plus exemestane 25 mg (for overall evidence network),
anastrozole 1 mg, exemestane 25 mg, and letrozole 2.5 mg is numerically
favorable, additional studies are required to draw formal conclusions.

Copyright © 2016 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.clbc.2016.02.007
PMID: 26971303  [Indexed for MEDLINE]


145. Hu Li Za Zhi. 2016 Jun;63(3):73-82. doi: 10.6224/JN.63.3.73.

[The Effectiveness of Different Corticosteroid Injections in Patients With Carpal
Tunnel Syndrome: A Bayesian Network Meta-Analysis].

[Article in Chinese; Abstract available in Chinese from the publisher]

Chen PC(1), Chuang CH(2).

Author information:
(1)MD, Department of Rehabilitation, Kaohsiung Chang Gung Memorial Hospital,
Taiwan, ROC.
(2)MSN, RN, Head Nurse, Department of Rehabilitation, Kaohsiung Chang Gung
Memorial Hospital, and Adjunct Lecturer, Department of Nursing, Chang Gung
University of Science and Technology, Taiwan, ROC. chinhui@cgmh.org.tw.

BACKGROUND: Corticosteroid injection is one of the interventions used to
alleviate the symptoms of carpal tunnel syndrome. The consistency across domestic
and overseas studies of the results of corticosteroid injections in terms of
easing carpal tunnel syndrome has not previously been analyzed.
PURPOSE: This meta-analysis explored the symptom severity and functional status
of different corticosteroid injection strategies in treating patients with carpal
tunnel syndrome.
METHODS: A systematic review was performed, keywords including: carpal tunnel
syndrome, corticosteroid [Title/Abstract], placebo, disability, and pain
intensity were used to query electronic databases, including Cochrane Library,
CINAHL (Cumulative Index to Nursing and Allied Health Literature), ProQuest,
PubMed database. All of the articles that were indexed on these databases, met
the inclusion criteria, and were published prior to June 2015 were extracted for
analysis. A standardized critical appraisal tool from the "Cochrane Handbook
Systematic Reviews of Intervention" to assess the risk of bias tool was used to
assess methodological quality. WinBUGS software was used to conduct the
meta-analysis.
RESULTS: The 10 articles that were qualified and used in the present study
contained a total of 633 participants. Median symptom severity was -1.16 (95%CrI
[-1.95, .38]) on the symptom severity scale for ultrasound-guided in-plane
injection among patients with carpal tunnel syndrome. The surface under the
cumulative ranking curve (SUCRA) achieved 95%. The median MD was -.74 (95%CrI
[-2.0, .52]) on the functional status scale for ultrasound-guided in-plane
injection among patients with carpal tunnel syndrome. The (SUCRA) achieved 78%.
The results indicate that the three injection methods reduced the severity and
improved the functional status in comparison with the placebo, ultrasound-guided
in-plane corticosteroid injection.
CONCLUSIONS: Corticosteroid injections alleviate symptom severity and promote
functional status in patients with carpal tunnel syndrome. Ultrasound-guided
in-plane injections demonstrated greater effectiveness. The network meta-analysis
provides a reference for rehabilitation nursing.

Publisher:
不同類固醇注射介入腕隧道症候群病人之成效—貝氏網絡統合分析.類固醇注射是緩解腕隧道症候群之介入措施之一，綜觀國內外的研究，並沒有針對類固醇注射緩解腕隧道症候群成效
分析一致性的結果。.本統合分析在了解不同的局部注射類固醇策略，於改善腕隧道症候群病人嚴重程度和功能之成效。.採系統性回顧法，關鍵字為：腕隧道症候群（carpal
tunnel
syndrome）、類固醇（corticosteroid）[Title/Abstract]、安慰劑（placebo）、失能（disability）、疼痛強度（pa
in intensity），搜尋Cochrane Library、CINAHL（Cumulative Index to Nursing and Allied
Health Literature）、ProQuest、PubMed各資料庫，截至2015年6月符合納入準則進行文獻搜尋。研究品質以“Cochrane
Handbook for Systematic Reviews of Intervention” to assess the risk of bias
tool做評讀，使用WinBUGS統計軟體進行統合分析。.評讀後納入10篇品質良好的研究，共633位個案。接受超音波導引平行類固醇注射病人的嚴重程度量表（symp
tom severity scale）median MD為-1.16（95%CrI [-1.95, .38]），SUCRA（surface under the
cumulative ranking curve曲線下表面累計排名）達95%，病人的功能程度量表（functional status scale）median
MD為-.74（95%CrI [-2.0,
.52]，SUCRA達78%，三種注射法與安慰劑相比較，超音波導引平行類固醇注射法改善嚴重程度及功能程度成效最優。.類固醇注射有助於減輕腕隧道症候群病人的症狀嚴重
度及提升功能程度，其中超音波導引平行類固醇注射成效更高，本網絡統合分析可提供復健護理之參考。.

PMID: 27250961  [Indexed for MEDLINE]


146. J Dent Res. 2016 Jun;95(6):613-22. doi: 10.1177/0022034516631285. Epub 2016 Feb
24.

Directly Placed Restorative Materials: Review and Network Meta-analysis.

Schwendicke F(1), Göstemeyer G(2), Blunck U(2), Paris S(2), Hsu LY(3), Tu YK(3).

Author information:
(1)Department of Operative and Preventive Dentistry, Charité-Universitätsmedizin
Berlin, Berlin, Germany falk.schwendicke@charite.de.
(2)Department of Operative and Preventive Dentistry, Charité-Universitätsmedizin
Berlin, Berlin, Germany.
(3)Institute of Epidemiology and Preventive Medicine, College of Public Health,
National Taiwan University, Taipei, Taiwan.

For restoring cavitated dental lesions, whether carious or not, a large number of
material combinations are available. We aimed to systematically review and
synthesize data of comparative dental restorative trials. A systematic review was
performed. Randomized controlled trials published between 2005 and 2015 were
included that compared the survival of ≥2 restorative and/or adhesive materials
(i.e., no need for restorative reintervention). Pairwise and Bayesian network
meta-analyses were performed, with separate evaluations for cervical cavitated
lesions and load-bearing posterior cavitated lesions in permanent and primary
teeth. A total of 11,070 restorations (5,330 cervical, 5,740 load bearing) had
been placed in 3,633 patients in the included trials. Thirty-six trials
investigated restoration of cervical lesions (all in permanent teeth) and 36 of
load-bearing lesions (8 in primary and 28 in permanent teeth). Resin-modified
glass ionomer cements had the highest chance of survival in cervical cavitated
lesions; composites or compomers placed via 2-step self-etch and 3-step
etch-and-rinse adhesives were ranked next. Restorations placed with 2-step
etch-and-rinse or 1-step self-etch adhesives performed worst. For load-bearing
restorations, conventional composites had the highest probability of survival,
while siloranes were found least suitable. Ambiguity remains regarding which
adhesive strategy to use in load-bearing cavitated lesions. Most studies showed
high risk of bias, and several comparisons were prone for publication bias. If
prioritized for survival, resin-modified glass ionomer cements might be
recommended to restore cervical lesions. For load-bearing ones, conventional or
bulk fill composites seem most suitable. The available evidence is quantitatively
and qualitatively insufficient for further recommendations, especially with
regard to adhesive strategies in posterior load-bearing situations. Moreover,
different material classifications might yield different findings on the same
materials. Future trials should aim for sufficient power, longer follow-up times,
and high internal validity to prove or refute differences between certain
material combinations. An agreed material classification for future syntheses is
desirable.

© International & American Associations for Dental Research 2016.

DOI: 10.1177/0022034516631285
PMID: 26912220  [Indexed for MEDLINE]


147. J Pain Symptom Manage. 2016 Jun;51(6):1091-1102.e4. doi:
10.1016/j.jpainsymman.2015.12.336. Epub 2016 Mar 25.

Prevalence of Neuropathic Pain in Cancer Patients: Pooled Estimates From a
Systematic Review of Published Literature and Results From a Survey Conducted in
50 Italian Palliative Care Centers.

Roberto A(1), Deandrea S(2), Greco MT(3), Corli O(1), Negri E(4), Pizzuto M(5),
Ruggeri F(6).

Author information:
(1)Pain and Palliative Care Research Unit, IRCCS-Mario Negri Institute for
Pharmacological Research, Milan, Italy.
(2)Institute for Health and Consumer Protection, DG Joint Research Centre,
European Commission, Ispra, Italy.
(3)Pain and Palliative Care Research Unit, IRCCS-Mario Negri Institute for
Pharmacological Research, Milan, Italy; Unità di Statistica Medica e Biometria
"G. A. Maccacaro", Dipartimento di Scienze Cliniche e di Comunità, Università
degli Studi di Milano, Milan, Italy. Electronic address: mtgrc@yahoo.it.
(4)Department of Epidemiology, IRCCS-Mario Negri Institute for Pharmacological
Research, Milan, Italy.
(5)Palliative Care and Pain Therapy Unit, Istituti Clinici di Perfezionamento
Hospital, Milan, Italy.
(6)Consiglio Nazionale delle Ricerche, Istituto di Matematica Applicata e
Tecnologie Informatiche, Milan, Italy.

CONTEXT: Because of the increasing body of literature on neuropathic cancer pain
(NCP), an accurate estimate of its prevalence requires recurring updates.
OBJECTIVES: To provide this estimate using information from a systematic review
and a survey.
METHODS: Using MEDLINE, Embase, and a previous review, we searched for studies
published up to 2014 reporting data on NCP prevalence in adult cancer
populations. Pooled prevalence rates from observational prospective studies were
computed. The association between NCP prevalence and possible predictors was
investigated for oncology and palliative settings. Prevalence rates were
extracted from a questionnaire answered by 137 physicians working in 50 Italian
centers of palliative care. Estimates from studies conducted in palliative
settings and from the experts were analyzed separately and eventually pooled with
an informative Bayesian random-effect model.
RESULTS: Twenty-nine observational studies were identified. The overall pooled
prevalence was 31.2%, with high heterogeneity; similar figures were observed when
oncology and palliative settings were individually considered. A slightly higher
prevalence of NCP was detected for hospice/inpatients as compared to outpatients,
in both settings. The mean NCP prevalence reported by the survey experts was
44.2%; the pooled Bayesian estimate for the palliative setting corresponded to
43.0% (95% CI: 40.0-46.0). The subgroup with the lowest heterogeneity and where
the literature and experts' estimates were closest is hospice/inpatients, with a
pooled Bayesian prevalence rate of 34.9% (95% CI: 29.9-41.0).
CONCLUSION: The systematic review and the survey suggest that more than one in
three patients with cancer pain also experiences NCP.

Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published
by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.jpainsymman.2015.12.336
PMID: 27017920  [Indexed for MEDLINE]


148. JAMA Oncol. 2016 Jun 1;2(6):751-60. doi: 10.1001/jamaoncol.2015.6113.

Association of Pathologic Complete Response to Neoadjuvant Therapy in
HER2-Positive Breast Cancer With Long-Term Outcomes: A Meta-Analysis.

Broglio KR(1), Quintana M(1), Foster M(2), Olinger M(1), McGlothlin A(1), Berry
SM(1), Boileau JF(3), Brezden-Masley C(4), Chia S(5), Dent S(6), Gelmon K(5),
Paterson A(7), Rayson D(8), Berry DA(9).

Author information:
(1)Berry Consultants, LLC, Austin, Texas.
(2)Medical Sciences Library, Texas A&M University, College Station.
(3)Department of Surgery, McGill University, Montreal, Quebec, Canada.
(4)St Michael's Hospital, Toronto, Ontario, Canada.
(5)Department of Medical Oncology, BC Cancer Agency, Vancouver, British Columbia,
Canada.
(6)Division of Medical Oncology, Department of Medicine, University of Ottawa,
Ottawa, Ontario, Canada.
(7)Department of Oncology, Tom Baker Cancer Centre and University of Calgary,
Calgary, Alberta, Canada.
(8)Division of Medical Oncology, Queen Elizabeth II Health Sciences Center and
Dalhousie University, Halifax, Nova Scotia, Canada.
(9)Berry Consultants, LLC, Austin, Texas9Department of Biostatistics, University
of Texas MD Anderson Cancer Center, Houston.

IMPORTANCE: The expense and lengthy follow-up periods for randomized clinical
trials (RCTs) of adjuvant systemic therapy in breast cancer make them impractical
and even impossible to conduct. Randomized clinical trials of neoadjuvant
systemic therapy for breast cancer may help resolve this dilemma.
OBJECTIVE: To assess the utility of pathologic complete response (pCR) for
neoadjuvant drug development in human epidermal growth factor receptor 2 (HER2
[also referred to as ERBB2])-positive breast cancer.
DATA SOURCES: We searched MEDLINE (Ovid), Embase (Ovid), CENTRAL (Wiley), and
Northern Light Life Sciences Conference Abstracts (Ovid) in December 2014.
Searches combined terms for "breast cancer" and "neoadjuvant therapy," with no
limit on publication date.
STUDY SELECTION: Cohort studies and RCTs were selected that met following
criteria: stages I to III HER2-positive breast cancer, neoadjuvant therapy, and
reports of both pCR and an event-free survival (EFS)-type outcome. The initial
search identified 2614 publications, of which 38 studies met the selection
criteria.
DATA EXTRACTION AND SYNTHESIS: Two authors independently screened each study for
inclusion and extracted the data. Data were analyzed using Bayesian hierarchical
models.
MAIN OUTCOMES AND MEASURES: Event-free survival and overall survival (OS) hazard
ratios (HRs) for pCR vs non-pCR. For RCTs, main outcome measures were treatment
benefits in pCR and the corresponding treatment HRs for EFS and OS.
RESULTS: A total of 36 studies with EFS by pCR status representing 5768 patients
with HER2-positive breast cancer were included in the patient-level analysis.
Overall, the improvement in EFS for pCR vs non-pCR was substantial: HR, 0.37 (95%
probability interval [PI], 0.32-0.43). This association was greater for patients
with hormone receptor-negative disease (HR, 0.29 [95% PI, 0.24-0.36]) than
hormone receptor-positive disease (HR, 0.52 [95% PI, 0.40-0.66]). In RCTs, the R2
correlations between odds ratios for pCR and HRs were 0.63 for EFS and 0.29 for
OS. Based on absolute treatment improvements in pCR rate, predicted HRs for EFS
for RCTs were concordant with observed HRs.
CONCLUSIONS AND RELEVANCE: Pathologic complete response in HER2-positive breast
cancer is associated with substantially longer times to recurrence and death.
This relationship is maintained in RCTs. For any particular new therapy the
relationship between pCR and survival may differ. Quantifying the importance of
pCR is necessary for designing efficient clinical trials, which should adapt to
the relationship between pCR and survival for the therapy under investigation.

DOI: 10.1001/jamaoncol.2015.6113
PMID: 26914222  [Indexed for MEDLINE]


149. Z Rheumatol. 2016 Jun;75(5):508-16. doi: 10.1007/s00393-015-0023-9.

Relative efficacy and tolerability of etoricoxib, celecoxib, and naproxen in the
treatment of osteoarthritis : A Bayesian network meta-analysis of randomized
controlled trials based on patient withdrawal.

Song GG(1), Seo YH(1), Kim JH(1), Choi SJ(1), Ji JD(1), Lee YH(2).

Author information:
(1)Division of Rheumatology, Department of Internal Medicine, Korea University
Anam Hospital, Korea University College of Medicine, 73, Inchon-ro, Seongbuk-gu,
136-705, Seoul, Korea.
(2)Division of Rheumatology, Department of Internal Medicine, Korea University
Anam Hospital, Korea University College of Medicine, 73, Inchon-ro, Seongbuk-gu,
136-705, Seoul, Korea. lyhcgh@korea.ac.kr.

AIMS: This study aimed to assess the relative efficacy and tolerability of
etoricoxib, celecoxib, and naproxen at recommended dosages in patients with
osteoarthritis (OA).
METHODS: Randomized controlled trials (RCTs) examining the efficacy and
tolerability of etoricoxib 30-60 mg, celecoxib 200-400 mg, and naproxen 1000 mg,
based on the number of patient withdrawals among those with OA, were included in
this network meta-analysis. We performed a Bayesian random-effects network
meta-analysis to combine direct and indirect evidence from the RCTs.
RESULTS: Eight RCTs, including 5,942 patients, met the inclusion criteria. The
proportion of patient withdrawals due to lack of efficacy was significantly lower
in the etoricoxib 30-60 mg (OR 0.21, 95 % CrI 0.12-0.38), celecoxib 200-400 mg
(OR 0.29, 95 % CrI 0.18-0.47), and naproxen 1000 mg (OR 0.31, 95 % CrI 0.18-0.51)
groups than in the placebo group. The number of patient withdrawals due to lack
of efficacy tended to be lower in the etoricoxib 30-60 mg group than in the
naproxen 1000 mg and celecoxib 200-400 mg groups, although they did not reach
statistical significance (OR 0.68, 95 % CrI 0.36-1.33 and OR 0.70, 95 % CrI
0.38-1.37, respectively). Ranking probabilities based on the surface under the
cumulative ranking curve (SUCRA) indicated that etoricoxib 30-60 mg had the
highest probability of being the best treatment based on the number of
withdrawals due to lack of efficacy (SUCRA = 0.9168) followed by celecoxib
200-400 mg (SUCRA = 0.5659), naproxen 1000 mg (SUCRA = 0.5171), and placebo
(SUCRA = 0.000189). With respect to tolerability, the number of withdrawals due
to adverse events was not significantly different among etoricoxib, celecoxib,
naproxen, and placebo, although it tended to be lower with etoricoxib and
placebo.
CONCLUSIONS: Etoricoxib 30-60 mg, celecoxib 200-400 mg, and naproxen 1000 mg were
more efficacious than placebo. However, there was no significant difference in
efficacy and tolerability between the medications.

DOI: 10.1007/s00393-015-0023-9
PMID: 26768273  [Indexed for MEDLINE]


150. JACC Cardiovasc Interv. 2016 May 23;9(10):1036-46. doi:
10.1016/j.jcin.2016.02.013.

Optimal P2Y12 Inhibitor in Patients With ST-Segment Elevation Myocardial
Infarction Undergoing Primary Percutaneous Coronary Intervention: A Network
Meta-Analysis.

Rafique AM(1), Nayyar P(2), Wang TY(3), Mehran R(4), Baber U(5), Berger PB(6),
Tobis J(7), Currier J(8), Dave RH(7), Henry TD(9).

Author information:
(1)Department of Medicine/Cardiology, Cedars-Sinai Heart Institute, Los Angeles,
California; Department of Medicine/Cardiology, UCLA Medical Center, Los Angeles,
California.
(2)Department of Medicine/Cardiology, Cedars-Sinai Heart Institute, Los Angeles,
California.
(3)Duke Clinical Research Institute, Durham, North Carolina.
(4)Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai Hospital, New
York, New York.
(5)Department of Medicine/Cardiology, Mount Sinai Hospital, New York, New York.
(6)Northwell Health, New York, New York.
(7)Department of Medicine/Cardiology, UCLA Medical Center, Los Angeles,
California.
(8)Department of Medicine/Cardiology, UCLA Medical Center, Los Angeles,
California; Department of Medicine/Cardiology, VA Medical Center, Los Angeles,
California.
(9)Division of Cardiology, Cedars-Sinai Heart Institute, Los Angeles, California.
Electronic address: timothy.henry@cshs.org.

Comment in
    JACC Cardiovasc Interv. 2016 May 23;9(10):1047-50.

OBJECTIVES: The study sought to compare the clinical efficacy and safety of P2Y12
inhibitors in patients with ST-segment elevation myocardial infarction (STEMI)
undergoing primary percutaneous intervention (PPCI).
BACKGROUND: Limited data exist regarding the comparative efficacy and safety of
P2Y12 inhibitors in STEMI patients undergoing PPCI.
METHODS: Clinical trials enrolling STEMI patients were identified and relevant
data was extracted. Major adverse cardiovascular events (MACE) were defined as
the composite of all cause mortality, MI, and target vessel revascularization.
Network meta-analysis was performed using Bayesian methods.
RESULTS: A total of 37 studies with 88,402 STEMI patients and 5,077 MACE were
analyzed. Outcomes at 1 month (22 studies and 60,783 patients) suggest that
prasugrel was associated with: lower MACE than clopidogrel (standard dose odds
ratio [OR]: 0.59, 95% confidence interval [CI]: 0.50 to 0.69; high-dose OR: 0.60,
95% CI: 0.51 to 0.71; upstream OR: 0.79, 95% CI: 0.66 to 0.94), and ticagrelor
(standard dose OR: 0.69, 95% CI: 0.56 to 0.84; upstream OR: 0.72, 95% CI: 0.50 to
1.05); lower mortality and MI than clopidogrel and standard ticagrelor; lower
stroke risk than standard clopidogrel and standard or upstream ticagrelor; and
lower stent thrombosis than standard or upstream clopidogrel. At 1-year (10
studies, n = 40,333) prasugrel was associated with lower mortality and MACE than
other P2Y12 inhibitors. MACE was particularly lower with prasugrel in studies
where patients received bivalirudin, drug-eluting stents, and but not
glycoprotein IIb/IIIa inhibitor.
CONCLUSIONS: In STEMI patients undergoing PPCI, prasugrel and ticagrelor are more
efficacious than clopidogrel; in addition, prasugrel was superior to ticagrelor
particularly in conjunction with bivalirudin and drug-eluting stents.

Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier
Inc. All rights reserved.

DOI: 10.1016/j.jcin.2016.02.013
PMID: 27198684  [Indexed for MEDLINE]


151. RETRACTED ARTICLE

Lancet. 2016 May 21;387(10033):2093-2105. doi: 10.1016/S0140-6736(16)30002-2.
Epub 2016 Mar 18.

RETRACTED: Effectiveness of non-steroidal anti-inflammatory drugs for the
treatment of pain in knee and hip osteoarthritis: a network meta-analysis.

da Costa BR(1), Reichenbach S(2), Keller N(1), Nartey L(3), Wandel S(4), Jüni
P(5), Trelle S(6).

Author information:
(1)Institute of Primary Health Care (BIHAM), University of Bern, Bern,
Switzerland.
(2)Institute of Social and Preventive Medicine, University of Bern, Bern,
Switzerland; Department of Rheumatology, Immunology and Allergology, University
Hospital and University of Bern, Switzerland.
(3)CTU Bern, Department of Clinical Research, University of Bern, Bern,
Switzerland.
(4)Cogitars GmbH (in Liq), Wangen an der Aare, Switzerland.
(5)Institute of Primary Health Care (BIHAM), University of Bern, Bern,
Switzerland; Applied Health Research Centre, Li Ka Shing Knowledge Institute of
St Michael's Hospital, University of Toronto, Toronto, Canada; Department of
Medicine, University of Toronto, Toronto, Canada.
(6)Institute of Social and Preventive Medicine, University of Bern, Bern,
Switzerland; CTU Bern, Department of Clinical Research, University of Bern, Bern,
Switzerland. Electronic address: sven.trelle@ctu.unibe.ch.

Retraction in
    Lancet. 2017 Jul 8;390(10090):109.

Comment in
    Lancet. 2016 May 21;387(10033):2065-6.
    BMJ. 2016;352:i1609.

Corrected and republished in
    Lancet. 2017 Jul 8;390(10090):e21-e33.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are the backbone of
osteoarthritis pain management. We aimed to assess the effectiveness of different
preparations and doses of NSAIDs on osteoarthritis pain in a network
meta-analysis.
METHODS: For this network meta-analysis, we considered randomised trials
comparing any of the following interventions: NSAIDs, paracetamol, or placebo,
for the treatment of osteoarthritis pain. We searched the Cochrane Central
Register of Controlled Trials (CENTRAL) and the reference lists of relevant
articles for trials published between Jan 1, 1980, and Feb 24, 2015, with at
least 100 patients per group. The prespecified primary and secondary outcomes
were pain and physical function, and were extracted in duplicate for up to seven
timepoints after the start of treatment. We used an extension of multivariable
Bayesian random effects models for mixed multiple treatment comparisons with a
random effect at the level of trials. For the primary analysis, a random walk of
first order was used to account for multiple follow-up outcome data within a
trial. Preparations that used different total daily dose were considered
separately in the analysis. To assess a potential dose-response relation, we used
preparation-specific covariates assuming linearity on log relative dose.
FINDINGS: We identified 8973 manuscripts from our search, of which 74 randomised
trials with a total of 58,556 patients were included in this analysis. 23 nodes
concerning seven different NSAIDs or paracetamol with specific daily dose of
administration or placebo were considered. All preparations, irrespective of
dose, improved point estimates of pain symptoms when compared with placebo. For
six interventions (diclofenac 150 mg/day, etoricoxib 30 mg/day, 60 mg/day, and 90
mg/day, and rofecoxib 25 mg/day and 50 mg/day), the probability that the
difference to placebo is at or below a prespecified minimum clinically important
effect for pain reduction (effect size [ES] -0·37) was at least 95%. Among
maximally approved daily doses, diclofenac 150 mg/day (ES -0·57, 95% credibility
interval [CrI] -0·69 to -0·46) and etoricoxib 60 mg/day (ES -0·58, -0·73 to
-0·43) had the highest probability to be the best intervention, both with 100%
probability to reach the minimum clinically important difference. Treatment
effects increased as drug dose increased, but corresponding tests for a linear
dose effect were significant only for celecoxib (p=0·030), diclofenac (p=0·031),
and naproxen (p=0·026). We found no evidence that treatment effects varied over
the duration of treatment. Model fit was good, and between-trial heterogeneity
and inconsistency were low in all analyses. All trials were deemed to have a low
risk of bias for blinding of patients. Effect estimates did not change in
sensitivity analyses with two additional statistical models and accounting for
methodological quality criteria in meta-regression analysis.
INTERPRETATION: On the basis of the available data, we see no role for
single-agent paracetamol for the treatment of patients with osteoarthritis
irrespective of dose. We provide sound evidence that diclofenac 150 mg/day is the
most effective NSAID available at present, in terms of improving both pain and
function. Nevertheless, in view of the safety profile of these drugs, physicians
need to consider our results together with all known safety information when
selecting the preparation and dose for individual patients.
FUNDING: Swiss National Science Foundation (grant number 405340-104762) and Arco
Foundation, Switzerland.

Copyright © 2016 Elsevier Ltd. All rights reserved.

DOI: 10.1016/S0140-6736(16)30002-2
PMID: 26997557  [Indexed for MEDLINE]


152. Syst Rev. 2016 May 21;5:84. doi: 10.1186/s13643-016-0260-2.

The magnitude and mechanisms of the weekend effect in hospital admissions: A
protocol for a mixed methods review incorporating a systematic review and
framework synthesis.

Chen YF(1)(2), Boyal A(3), Sutton E(4), Armoiry X(5), Watson S(5)(6), Bion J(3),
Tarrant C(4); HiSLAC Collaborative.

Author information:
(1)Division of Health Sciences, Warwick Medical School, University of Warwick,
Coventry, CV4 7AL, UK. Y-F.Chen@warwick.ac.uk.
(2)Warwick Centre for Applied Health Research & Delivery, Division of Health
Sciences, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK.
Y-F.Chen@warwick.ac.uk.
(3)Queen Elizabeth Hospital Birmingham and University of Birmingham, Birmingham,
UK.
(4)Department of Health Sciences, University of Leicester, Leicester, UK.
(5)Division of Health Sciences, Warwick Medical School, University of Warwick,
Coventry, CV4 7AL, UK.
(6)Warwick Centre for Applied Health Research & Delivery, Division of Health
Sciences, Warwick Medical School, University of Warwick, Coventry, CV4 7AL, UK.

BACKGROUND: Growing literature has demonstrated that patients admitted to
hospital during weekends tend to have less favourable outcomes, including
increased mortality, compared with similar patients admitted during weekdays.
Major policy interventions such as the 7-day services programme in the UK NHS
have been initiated to reduce this weekend effect, although the mechanisms behind
the effect are unclear. Here, we propose a mixed methods review to systematically
examine the literature surrounding the magnitude and mechanisms of the weekend
effect.
METHODS: MEDLINE, CINAHL, HMIC, EMBASE, EthOS, CPCI and the Cochrane Library were
searched from Jan 2000 to April 2015 using terms related to 'weekends or
out-of-hours' and 'hospital admissions'. The 5404 retrieved records were screened
by the review team, and will feed into two component reviews: a systematic review
of the magnitude of the weekend effect and a framework synthesis of the
mechanisms of the weekend effect. A repeat search of MEDLINE will be conducted
mid-2016 to update both component reviews. The systematic review will include
quantitative studies of non-specific hospital admissions. The primary outcome is
the weekend effect on mortality, which will be estimated using a Bayesian random
effects meta-analysis. Weekend effects on adverse events, length of hospital stay
and patient experience will also be examined. The development of the framework
synthesis has been informed by the initial scoping of the literature and focus
group discussions. The synthesis will examine both quantitative and qualitative
studies that have compared the processes and quality of care between weekends and
weekdays, and explicate the underlying mechanisms of the weekend effect.
DISCUSSION: The weekend effect is a complex phenomenon that has major
implications for the organisation of health services. Its magnitude and
underlying mechanisms have been subject to heated debate. Published literature
reviews have adopted restricted scopes or methods and mainly focused on
quantitative evidence. This proposed review intends to provide a comprehensive
and in-depth synthesis of diverse evidence to inform future policy and research
aiming to address the weekend effect.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2016: CRD42016036487.

DOI: 10.1186/s13643-016-0260-2
PMCID: PMC4875695
PMID: 27209320  [Indexed for MEDLINE]


153. Cochrane Database Syst Rev. 2016 May 13;(5):CD012183. doi:
10.1002/14651858.CD012183.

Biologics or tofacitinib for rheumatoid arthritis in incomplete responders to
methotrexate or other traditional disease-modifying anti-rheumatic drugs: a
systematic review and network meta-analysis.

Singh JA(1), Hossain A, Tanjong Ghogomu E, Kotb A, Christensen R, Mudano AS,
Maxwell LJ, Shah NP, Tugwell P, Wells GA.

Author information:
(1)Department of Medicine, Birmingham VA Medical Center, Faculty Office Tower
805B, 510 20th Street South, Birmingham, AL, USA, 35294.

BACKGROUND: This is an update of the 2009 Cochrane overview and network
meta-analysis (NMA) of biologics for rheumatoid arthritis (RA).
OBJECTIVES: To assess the benefits and harms of nine biologics (abatacept,
adalimumab, anakinra, certolizumab pegol, etanercept, golimumab, infliximab,
rituximab, tocilizumab) and small molecule tofacitinib, versus comparator (MTX,
DMARD, placebo (PL), or a combination) in adults with rheumatoid arthritis who
have failed to respond to methotrexate (MTX) or other disease-modifying
anti-rheumatic drugs (DMARDs), i.e., MTX/DMARD incomplete responders
(MTX/DMARD-IR).
METHODS: We searched for randomized controlled trials (RCTs) in the Cochrane
Central Register of Controlled Trials (CENTRAL) (via The Cochrane Library Issue
6, June 2015), MEDLINE (via OVID 1946 to June 2015), and EMBASE (via OVID 1947 to
June 2015). Data extraction, risk of bias and GRADE assessments were done in
duplicate. We calculated both direct estimates using standard meta-analysis and
used Bayesian mixed treatment comparisons approach for NMA estimates to calculate
odds ratios (OR) and 95% credible intervals (CrI). We converted OR to risk ratios
(RR) which are reported in the abstract for the ease of interpretation.
MAIN RESULTS: This update included 73 new RCTs for a total of 90 RCTs; 79 RCTs
with 32,874 participants provided usable data. Few trials were at high risk of
bias for blinding of assessors/participants (13% to 21%), selective reporting
(4%) or major baseline imbalance (8%); a large number had unclear risk of bias
for random sequence generation (68%) or allocation concealment (74%).Based on
direct evidence of moderate quality (downgraded for inconsistency),
biologic+MTX/DMARD was associated with a statistically significant and clinically
meaningful improvement in ACR50 versus comparator (RR 2.71 (95% confidence
interval (CI) 2.36 to 3.10); absolute benefit 24% more patients (95% CI 19% to
29%), number needed to treat for an additional beneficial outcome (NNTB) = 5 (4
to 6). NMA estimates for ACR50 in tumor necrosis factor (TNF) biologic+MTX/DMARD
(RR 3.23 (95% credible interval (Crl) 2.75 to 3.79), non-TNF biologic+MTX/DMARD
(RR 2.99; 95% Crl 2.36 to 3.74), and anakinra + MTX/DMARD (RR 2.37 (95% Crl 1.00
to 4.70) were similar to the direct estimates.Based on direct evidence of
moderate quality (downgraded for inconsistency), biologic+MTX/DMARD was
associated with a clinically and statistically important improvement in function
measured by the Health Assessment Questionnaire (0 to 3 scale, higher = worse
function) with a mean difference (MD) based on direct evidence of -0.25 (95% CI
-0.28 to -0.22); absolute benefit of -8.3% (95% CI -9.3% to -7.3%), NNTB = 3 (95%
CI 2 to 4). NMA estimates for TNF biologic+MTX/DMARD (absolute benefit, -10.3%
(95% Crl -14% to -6.7%) and non-TNF biologic+MTX/DMARD (absolute benefit, -7.3%
(95% Crl -13.6% to -0.67%) were similar to respective direct estimates.Based on
direct evidence of moderate quality (downgraded for inconsistency),
biologic+MTX/DMARD was associated with clinically and statistically significantly
greater proportion of participants achieving remission in RA (defined by disease
activity score DAS < 1.6 or DAS28 < 2.6) versus comparator (RR 2.81 (95% CI, 2.23
to 3.53); absolute benefit 18% more patients (95% CI 12% to 25%), NNTB = 6 (4 to
9)). NMA estimates for TNF biologic+MTX/DMARD (absolute improvement 17% (95% Crl
11% to 23%)) and non-TNF biologic+MTX/DMARD (absolute improvement 19% (95% Crl
12% to 28%) were similar to respective direct estimates.Based on direct evidence
of moderate quality (downgraded for inconsistency), radiographic progression
(scale 0 to 448) was statistically significantly reduced in those on biologics +
MTX/DMARDs versus comparator, MD -2.61 (95% CI -4.08 to -1.14). The absolute
reduction was small, -0.58% (95% CI -0.91% to -0.25%) and we are unsure of the
clinical relevance of this reduction. NMA estimates of TNF biologic+MTX/DMARD
(absolute reduction -0.67% (95% Crl -1.4% to -0.12%) and non-TNF
biologic+MTX/DMARD (absolute reduction, -0.68% (95% Crl -2.36% to 0.92%)) were
similar to respective direct estimates.Based on direct evidence of moderate
quality (downgraded for imprecision), results for withdrawals due to adverse
events were inconclusive, with wide confidence intervals encompassing the null
effect and evidence of an important increase in withdrawals, RR 1.11 (95% CI 0.96
to 1.30). The NMA estimates of TNF biologic+MTX/DMARD (RR 1.24 (95% Crl 0.99 to
1.57)) and non-TNF biologic+MTX/DMARD (RR 1.20 (95% Crl 0.87 to 1.67)) were
similarly inconclusive and downgraded to low for both imprecision and
indirectness.Based on direct evidence of high quality, biologic+MTX/DMARD was
associated with clinically significantly increased risk (statistically borderline
significant) of serious adverse events on biologic+MTX/DMARD (Peto OR [can be
interpreted as RR due to low event rate] 1.12 (95% CI 0.99 to 1.27); absolute
risk 1% (0% to 2%), As well, the NMA estimate for TNF biologic+MTX/DMARD (Peto OR
1.20 (95% Crl 1.01 to 1.43)) showed moderate quality evidence of an increase in
the risk of serious adverse events. The other two NMA estimates were downgraded
to low quality due to imprecision and indirectness and had wide confidence
intervals resulting in uncertainty around the estimates: non-TNF biologics +
MTX/DMARD: 1.07 (95% Crl 0.89 to 1.29) and anakinra: RR 1.06 (95% Crl 0.65 to
1.75).Based on direct evidence of low quality (downgraded for serious
imprecision), results were inconclusive for cancer (Peto OR 1.07 (95% CI 0.68 to
1.68) for all biologic+MTX/DMARD combinations. The NMA estimates of TNF
biologic+MTX/DMARD (Peto OR 1.21 (95% Crl 0.63 to 2.38) and non-TNF
biologic+MTX/DMARD (Peto OR 0.99 (95% Crl 0.58 to 1.78)) were similarly
inconclusive and downgraded to low quality for both imprecision and
indirectness.Main results text shows the results for tofacitinib and differences
between medications.
AUTHORS' CONCLUSIONS: Based primarily on RCTs of 6 months' to 12 months'
duration, there is moderate quality evidence that the use of biologic+MTX/DMARD
in people with rheumatoid arthritis who have failed to respond to MTX or other
DMARDs results in clinically important improvement in function and higher ACR50
and remission rates, and increased risk of serious adverse events than the
comparator (MTX/DMARD/PL; high quality evidence). Radiographic progression is
slowed but its clinical relevance is uncertain. Results were inconclusive for
whether biologics + MTX/DMARDs are associated with an increased risk of cancer or
withdrawals due to adverse events.

DOI: 10.1002/14651858.CD012183
PMID: 27175934  [Indexed for MEDLINE]


154. BMC Public Health. 2016 May 12;16:396. doi: 10.1186/s12889-016-3083-0.

Effect of gargling with tea and ingredients of tea on the prevention of influenza
infection: a meta-analysis.

Ide K(1), Yamada H(2), Kawasaki Y(1).

Author information:
(1)Department of Drug Evaluation & Informatics, Graduate School of Pharmaceutical
Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526,
Japan.
(2)Department of Drug Evaluation & Informatics, Graduate School of Pharmaceutical
Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526,
Japan. hyamada@u-shizuoka-ken.ac.jp.

BACKGROUND: Influenza viruses can spread easily from person to person, and annual
influenza epidemics are serious public health issues worldwide.
Non-pharmaceutical public health interventions could potentially be effective for
combatting influenza epidemics, but combined interventions and/or interventions
with greater effectiveness are needed. Experimental studies have reported that
tea and its ingredients (especially catechins) have antiviral activities.
Although several clinical studies have investigated the use of tea or its
ingredients to prevent influenza infections, the effect of gargling these
substances has remained uncertain.
METHODS: We conducted a meta-analysis of randomized controlled studies and
prospective cohort studies to assess the effect of gargling with tea and its
ingredients on the prevention of influenza infection. The published literature
was searched using the Cochrane Library, PubMed/MEDLINE (1966 to September 2015),
Web of Science (1981 to September 2015), and Ichu-shi Web (1983 to September
2015). The extracted studies were read by two reviewers independently, and their
overall scientific quality was evaluated. Studies meeting our inclusion criteria
were pooled using the Mantel-Haenszel method in a fixed effects model and were
also analyzed in a random effects model. The qualities of the model fits were
assessed using the Akaike information criterion (AIC) and Bayesian information
criterion (BIC).
RESULTS: The literature search and review identified 5 studies that met the
inclusion criteria for the meta-analysis (total number of participants, 1890;
mean age range, 16-83 years). The participants who gargled with tea or its
ingredients showed a lower risk of influenza infection than did participants who
gargled with placebo/water or who did not gargle (fixed effects model,
Mantel-Haenszel method: relative risk [RR] = 0.70, 95 % confidence interval
[CI] = 0.54-0.89; random effects model: RR = 0.71, 95 % CI = 0.56-0.91). The
fixed effects model had a better quality of fit than the random effects model
(fixed effects model: AIC = 6.04, BIC = 5.65; random effects model: AIC = 8.74,
BIC = 7.52).
CONCLUSIONS: Gargling with tea and its ingredients may have a preventative effect
for influenza infection. However, additional large-scale studies in different
populations and a pooled analysis of these studies are needed to confirm the
effect.

DOI: 10.1186/s12889-016-3083-0
PMCID: PMC4866433
PMID: 27175786  [Indexed for MEDLINE]


155. PLoS One. 2016 May 9;11(5):e0155050. doi: 10.1371/journal.pone.0155050.
eCollection 2016.

Anti-Tumor Effects of Ketogenic Diets in Mice: A Meta-Analysis.

Klement RJ(1), Champ CE(2), Otto C(3), Kämmerer U(4).

Author information:
(1)Department of Radiotherapy and Radiation Oncology, Leopoldina Hospital
Schweinfurt, Schweinfurt, Germany.
(2)Department of Radiation Oncology, University of Pittsburgh Medical Center,
Pittsburgh, Pennsylvania, United States of America.
(3)Department of General, Visceral, Vascular and Pediatric Surgery, University
Hospital of Würzburg, Würzburg, Germany.
(4)Department of Obstetrics and Gynaecology, University Hospital of Würzburg,
Würzburg, Germany.

BACKGROUND: Currently ketogenic diets (KDs) are hyped as an anti-tumor
intervention aimed at exploiting the metabolic abnormalities of cancer cells.
However, while data in humans is sparse, translation of murine tumor models to
the clinic is further hampered by small sample sizes, heterogeneous settings and
mixed results concerning tumor growth retardation. The aim was therefore to
synthesize the evidence for a growth inhibiting effect of KDs when used as a
monotherapy in mice.
METHODS: We conducted a Bayesian random effects meta-analysis on all studies
assessing the survival (defined as the time to reach a pre-defined endpoint such
as tumor volume) of mice on an unrestricted KD compared to a high carbohydrate
standard diet (SD). For 12 studies meeting the inclusion criteria either a mean
survival time ratio (MR) or hazard ratio (HR) between the KD and SD groups could
be obtained. The posterior estimates for the MR and HR averaged over four priors
on the between-study heterogeneity τ2 were MR = 0.85 (95% highest posterior
density interval (HPDI) = [0.73, 0.97]) and HR = 0.55 (95% HPDI = [0.26, 0.87]),
indicating a significant overall benefit of the KD in terms of prolonged mean
survival times and reduced hazard rate. All studies that used a brain tumor model
also chose a late starting point for the KD (at least one day after tumor
initiation) which accounted for 26% of the heterogeneity. In this subgroup the KD
was less effective (MR = 0.89, 95% HPDI = [0.76, 1.04]).
CONCLUSIONS: There was an overall tumor growth delaying effect of unrestricted
KDs in mice. Future experiments should aim at differentiating the effects of KD
timing versus tumor location, since external evidence is currently consistent
with an influence of both of these factors.

DOI: 10.1371/journal.pone.0155050
PMCID: PMC4861343
PMID: 27159218  [Indexed for MEDLINE]


156. PLoS One. 2016 May 9;11(5):e0154206. doi: 10.1371/journal.pone.0154206.
eCollection 2016.

Efficacy and Acceptability of Glycemic Control of Glucagon-Like Peptide-1
Receptor Agonists among Type 2 Diabetes: A Systematic Review and Network
Meta-Analysis.

Li Z(1), Zhang Y(2), Quan X(1), Yang Z(1), Zeng X(3), Ji L(4), Sun F(1), Zhan
S(1).

Author information:
(1)Department of Epidemiology and Biostatistics, School of Public Health, Peking
University Health Science Center, Beijing, China.
(2)Department of Clinical Epidemiology and Biostatistics, McMaster University,
1280 Main Street West, Hamilton, ON, Canada.
(3)Center for Evidence-based and Translational Medicine, Zhongnan Hospital, Wuhan
University, Wuhan, China.
(4)Department of Endocrinology and Metabolism, People's Hospital, Peking
University, Beijing, China.

OBJECTIVE: To synthesize current evidence of the impact of Glucagon-like
peptide-1 receptor agonists (GLP-1 RAs) on hypoglycemia, treatment
discontinuation and glycemic level in patients with type 2 diabetes.
DESIGN: Systematic review and network meta-analysis.
DATA SOURCES: Literature search (Medline, Embase, the Cochrane library), website
of clinical trial, bibliographies of published systematic reviews.
ELIGIBILITY CRITERIA: Randomized controlled trials with available data comparing
GLP-1 RAs with placebo or traditional anti-diabetic drugs in patients with type 2
diabetes.
DATA SYNTHESIS: Traditional pairwise meta-analyses within DerSimonian-Laird
random effects model and network meta-analysis within a Bayesian framework were
performed to calculate odds ratios for the incidence of hypoglycemia, treatment
discontinuation, HbA1c<7.0% and HbA1c<6.5%. Ranking probabilities for all
treatments were estimated to obtain a treatment hierarchy using the surface under
the cumulative ranking curve (SUCRA) and mean ranks.
RESULTS: 78 trials with 13 treatments were included. Overall, all GLP-1 RAs
except for albiglutide increased the risk of hypoglycemia when compared to
placebo. Reduction in the incidence of hypoglycemia was found for all GLP-1 RAs
versus insulin (except for dulaglutide) and sulphonylureas. For the incidence of
treatment discontinuation, increase was found for exenatide, liraglutide,
lixisenatide and taspoglutide versus placebo, insulin and sitagliptin. For
glycemic level, decrease was found for all GLP-1 RAs versus placebo. Dulaglutide,
exenatide long-acting release (exe_lar), liraglutide and taspoglutide had
significant lowering effect when compared with sitagliptin (HbA1c<7.0%) and
insulin (HbA1c<6.5%). Finally, according to SUCRAs, placebo, thiazolidinediones
and albiglutide had the best decrease effect on hypoglycemia; sulphanylureas,
sitagliptin and insulin decrease the incidence of treatment discontinuation most;
exe_lar and dulaglutide had the highest impact on glycemic level among 13
treatments.
CONCLUSIONS: Among 13 treatments, GLP-1 RAs had a significant reduction with
glycemic level but a slight increase effect on hypoglycemia and treatment
discontinuation. While albiglutide had the best decrease effect on hypoglycemia
and treatment discontinuation among all GLP-1 RAs. However, further evidence is
necessary for more conclusive inferences on mechanisms underlying the rise in
hypoglycemia.

DOI: 10.1371/journal.pone.0154206
PMCID: PMC4861281
PMID: 27158818  [Indexed for MEDLINE]


157. Am J Kidney Dis. 2016 May;67(5):728-41. doi: 10.1053/j.ajkd.2015.10.011. Epub
2015 Nov 18.

Renin-Angiotensin System Inhibitors and Kidney and Cardiovascular Outcomes in
Patients With CKD: A Bayesian Network Meta-analysis of Randomized Clinical
Trials.

Xie X(1), Liu Y(1), Perkovic V(2), Li X(3), Ninomiya T(2), Hou W(1), Zhao N(1),
Liu L(1), Lv J(4), Zhang H(5), Wang H(1).

Author information:
(1)Renal Division, Peking University First Hospital; Peking University Institute
of Nephrology; Key Laboratory of Renal Disease, Ministry of Health of China; Key
Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking
University), Ministry of Education, Peking, China.
(2)The George Institute for Global Health, the University of Sydney, Sydney,
Australia.
(3)Department of Nephrology, Affiliated Hospital of Weifang Medical College,
Weifang, Shandong, China.
(4)Renal Division, Peking University First Hospital; Peking University Institute
of Nephrology; Key Laboratory of Renal Disease, Ministry of Health of China; Key
Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking
University), Ministry of Education, Peking, China; The George Institute for
Global Health, the University of Sydney, Sydney, Australia. Electronic address:
jichenglv75@gmail.com.
(5)Renal Division, Peking University First Hospital; Peking University Institute
of Nephrology; Key Laboratory of Renal Disease, Ministry of Health of China; Key
Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking
University), Ministry of Education, Peking, China. Electronic address:
hongzh@bjmu.edu.cn.

Comment in
    Am J Kidney Dis. 2016 May;67(5):713-5.

BACKGROUND: There is much uncertainty regarding the relative effects of
angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor
blockers (ARBs) in populations with chronic kidney disease (CKD).
STUDY DESIGN: Systematic review and Bayesian network meta-analysis.
SETTING & POPULATION: Patients with CKD treated with renin-angiotensin system
(RAS) inhibitors.
SELECTION CRITERIA FOR STUDIES: Randomized trials in patients with CKD treated
with RAS inhibitors.
PREDICTOR: ACE inhibitors and ARBs compared to each other and to placebo and
active controls.
OUTCOME: Primary outcome was kidney failure; secondary outcomes were major
cardiovascular events, all-cause death.
RESULTS: 119 randomized controlled trials (n = 64,768) were included. ACE
inhibitors and ARBs reduced the odds of kidney failure by 39% and 30% (ORs of
0.61 [95% credible interval, 0.47-0.79] and 0.70 [95% credible interval,
0.52-0.89]), respectively, compared to placebo, and by 35% and 25% (ORs of 0.65
[95% credible interval, 0.51-0.80] and 0.75 [95% credible interval, 0.54-0.97]),
respectively, compared with other active controls, whereas other active controls
did not show evidence of a significant effect on kidney failure. Both ACE
inhibitors and ARBs produced odds reductions for major cardiovascular events (ORs
of 0.82 [95% credible interval, 0.71-0.92] and 0.76 [95% credible interval,
0.62-0.89], respectively) versus placebo. Comparisons did not show significant
effects on risk for cardiovascular death. ACE inhibitors but not ARBs
significantly reduced the odds of all-cause death versus active controls (OR,
0.72; 95% credible interval, 0.53-0.92). Compared with ARBs, ACE inhibitors were
consistently associated with higher probabilities of reducing kidney failure,
cardiovascular death, or all-cause death.
LIMITATIONS: Trials with RAS inhibitor therapy were included; trials with direct
comparisons of other active controls with placebo were not included.
CONCLUSIONS: Use of ACE inhibitors or ARBs in people with CKD reduces the risk
for kidney failure and cardiovascular events. ACE inhibitors also reduced the
risk for all-cause mortality and were possibly superior to ARBs for kidney
failure, cardiovascular death, and all-cause mortality in patients with CKD,
suggesting that they could be the first choice for treatment in this population.

Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All
rights reserved.

DOI: 10.1053/j.ajkd.2015.10.011
PMID: 26597926  [Indexed for MEDLINE]


158. Environ Res. 2016 May;147:415-24. doi: 10.1016/j.envres.2016.03.003. Epub 2016
Mar 9.

Air pollution exposure, cause-specific deaths and hospitalizations in a highly
polluted Italian region.

Carugno M(1), Consonni D(2), Randi G(3), Catelan D(4), Grisotto L(5), Bertazzi
PA(6), Biggeri A(4), Baccini M(4).

Author information:
(1)Department of Clinical Sciences and Community Health, Università degli Studi
di Milano, Via San Barnaba, 8, 20122 Milan, Italy. Electronic address:
michele.carugno@unimi.it.
(2)Epidemiology Unit, Department of Preventive Medicine, Fondazione IRCCS Ca'
Granda-Ospedale Maggiore Policlinico, Via San Barnaba, 8, 20122 Milan, Italy.
(3)Department of Clinical Sciences and Community Health, Università degli Studi
di Milano, Via San Barnaba, 8, 20122 Milan, Italy.
(4)Department of Statistics, Informatics and Applications "G. Parenti,"
University of Florence, Viale Morgagni, 59, 50134 Florence, Italy; Biostatistics
Unit, Cancer Prevention and Research Institute (ISPO), Via Cosimo Il Vecchio, 2,
50139 Florence, Italy.
(5)Department of Statistics, Informatics and Applications "G. Parenti,"
University of Florence, Viale Morgagni, 59, 50134 Florence, Italy.
(6)Department of Clinical Sciences and Community Health, Università degli Studi
di Milano, Via San Barnaba, 8, 20122 Milan, Italy; Epidemiology Unit, Department
of Preventive Medicine, Fondazione IRCCS Ca' Granda-Ospedale Maggiore
Policlinico, Via San Barnaba, 8, 20122 Milan, Italy.

BACKGROUND: The Lombardy region in northern Italy ranks among the most air
polluted areas of Europe. Previous studies showed air pollution short-term
effects on all-cause mortality. We examine here the effects of particulate matter
with aerodynamic diameter ≤10µm (PM10) and nitrogen dioxide (NO2) exposure on
deaths and hospitalizations from specific causes, including cardiac,
cerebrovascular and respiratory diseases.
METHODS: We considered air pollution, mortality and hospitalization data for a
non-opportunistic sample of 18 highly polluted and most densely populated areas
of the region in the years 2003-2006. We obtained area-specific effect estimates
for PM10 and NO2 from a Poisson regression model on the daily number of total
deaths or cause-specific hospitalizations and then combined them in a Bayesian
random-effects meta-analysis. For cause-specific mortality, we applied a
case-crossover analysis. Age- and season-specific analyses were also performed.
Effect estimates were expressed as percent variation in mortality or
hospitalizations associated with a 10µg/m(3) increase in PM10 or NO2
concentration.
RESULTS: Natural mortality was positively associated with both pollutants (0.30%,
90% Credibility Interval [CrI]: -0.31; 0.78 for PM10; 0.70%, 90%CrI: 0.10; 1.27
for NO2). Cardiovascular deaths showed a higher percent variation in association
with NO2 (1.12%, 90% Confidence Interval [CI]: 0.14; 2.11), while the percent
variation for respiratory mortality was highest in association with PM10 (1.64%,
90%CI: 0.35; 2.93). The effect of both pollutants was more evident in the summer
season. Air pollution was also associated to hospitalizations, the highest
variations being 0.77% (90%CrI: 0.22; 1.43) for PM10 and respiratory diseases,
and 1.70% (90%CrI: 0.39; 2.84) for NO2 and cerebrovascular diseases. The effect
of PM10 on respiratory hospital admissions appeared to increase with age. For
both pollutants, effects on cerebrovascular hospitalizations were more evident in
subjects aged less than 75 years.
CONCLUSIONS: Our study provided a sound characterization of air pollution
exposure and its potential effects on human health in the most polluted, and also
most populated and productive, Italian region, further documenting the need for
effective public health policies.

Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.envres.2016.03.003
PMID: 26969808  [Indexed for MEDLINE]


159. Eur J Cardiothorac Surg. 2016 May;49(5):1428-40. doi: 10.1093/ejcts/ezv387. Epub
2015 Nov 3.

Safety and efficacy of miniaturized extracorporeal circulation when compared with
off-pump and conventional coronary artery bypass grafting: evidence synthesis
from a comprehensive Bayesian-framework network meta-analysis of 134 randomized
controlled trials involving 22 778 patients.

Kowalewski M(1), Pawliszak W(2), Raffa GM(3), Malvindi PG(4), Kowalkowska ME(5),
Zaborowska K(2), Kowalewski J(6), Tarelli G(7), Taggart DP(8), Anisimowicz L(2).

Author information:
(1)Department of Cardiac Surgery, Dr Antoni Jurasz Memorial University Hospital
in Bydgoszcz, Bydgoszcz, Poland Faculty of Health Sciences, Collegium Medicum,
Nicolaus Copernicus Univeristy in Toruń, Toruń, Poland
kowalewskimariusz@gazeta.pl.
(2)Department of Cardiac Surgery, Dr Antoni Jurasz Memorial University Hospital
in Bydgoszcz, Bydgoszcz, Poland.
(3)Department for the Treatment and Study of Cardiothoracic Diseases and
Cardiothoracic Transplantation, IRCCS-ISMETT (Istituto Mediterraneo per i
Trapianti e Terapie ad alta specializzazione), Palermo, Italy.
(4)University Hospital Southampton NHS Foundation Trust, Wessex Cardiothoracic
Centre, Southampton, UK.
(5)Department and Clinic of Obstetrics, Gynecology, and Oncological Gynecology,
Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland.
(6)Department of Lung Cancer and Thoracic Surgery, Collegium Medicum in
Bydgoszcz, Nicolaus Copernicus University, Toruń, Poland.
(7)Department of Cardiac Surgery, Humanitas Clinical and Research Center,
Rozzano, Milan, Italy.
(8)Department of Cardiac Surgery, John Radcliffe Hospital, Oxford, UK.

Comment in
    Eur J Cardiothorac Surg. 2016 Jul;50(1):189.

OBJECTIVES: Coronary artery bypass grafting (CABG) remains the standard of care
in patients with extensive coronary artery disease. Yet the use of
cardiopulmonary bypass (CPB) is believed to be a major determinant of
perioperative morbidity. Novel techniques are sought to tackle the shortcomings
of CPB, among them off-pump coronary artery bypass (OPCAB) and miniaturized
extracorporeal circulation (MECC) systems have been extensively tested in
randomized controlled trials (RCTs). To assess perioperative safety and efficacy
of MECC and OPCAB when compared with conventional extracorporeal circulation
(CECC).
METHODS: Published literature and major congress proceedings were screened for
RCTs evaluating the safety and efficacy of MECC, OPCAB and CECC. Selected
end-points such as 30-day all-cause mortality, myocardial infarction (MI),
cerebral stroke, postoperative atrial fibrillation (POAF) and renal dysfunction
were assessed in a Bayesian-framework network meta-analysis.
RESULTS: A total of 134 studies with 22 778 patients were included. When compared
with CECC, both OPCAB and MECC significantly reduced 30-day all-cause mortality
[odds ratios (95% credible intervals): 0.75 (0.51-0.99) and 0.46 (0.22-0.91)],
respectively. No differences in respect to MI were demonstrated with either
strategy. OPCAB, when compared with CECC, reduced the odds of cerebral stroke
[0.57 (0.34-0.80)]; 60% reduction was observed with MECC when compared with CECC
[0.40 (0.19-0.78)]. Both OPCAB and MECC reduced the odds of POAF [0.66
(0.48-0.90) and 0.62 (0.35-0.98), respectively] when compared with CECC. OPCAB
conferred over 30% reduction of renal dysfunction when compared with CECC [0.69
(0.46-0.92)]. MECC reduced these odds by more than 50% [0.47 (0.24-0.89)].
Ranking of treatments emerging from the probability analysis (highest to lowest
SUCRA values) was MECC followed by OPCAB and CECC.
CONCLUSIONS: MECC and OPCAB both improve perioperative outcomes following
coronary bypass surgery when compared with conventional CABG performed with
extracorporeal circulation. MECC may represent an attractive compromise between
OPCAB and CECC.

© The Author 2015. Published by Oxford University Press on behalf of the European
Association for Cardio-Thoracic Surgery. All rights reserved.

DOI: 10.1093/ejcts/ezv387
PMID: 26537755  [Indexed for MEDLINE]


160. Ir J Med Sci. 2016 May;185(2):503-11. doi: 10.1007/s11845-016-1447-1. Epub 2016
Mar 29.

Are beta-blockers effective for preventing post-coronary artery bypass grafting
atrial fibrillation? Direct and network meta-analyses.

Ji T(1), Feng C(2), Sun L(3), Ye X(4), Bai Y(2), Chen Q(2), Qin Y(2), Zhu J(5),
Zhao X(6).

Author information:
(1)Department of Geriatrics, Shanghai First People's Hospital Affiliated with
Shanghai Jiaotong University, Shanghai, China.
(2)Department of Cardiology, Changhai Hospital, Second Military Medical
University, Shanghai, China.
(3)Department of Nephrology, Shanghai Changzheng Hospital, Second Military
Medical University, Shanghai, China.
(4)Department of Health Statistics, Second Military Medical University, Shanghai,
China.
(5)Department of Cardiology, Changhai Hospital, Second Military Medical
University, Shanghai, China. zjq77324@126.com.
(6)Department of Cardiology, Changhai Hospital, Second Military Medical
University, Shanghai, China. 13601713431@163.com.

BACKGROUND: Atrial fibrillation is the most common arrhythmia in clinical
practice and is a major contributor to mortality. Recently, several studies have
reported different results for treatments aimed at reducing the risk of
postoperative AF.
AIMS: The aim of this study was to evaluate the efficacy of beta-blockers (BBs)
in preventing post-coronary artery bypass grafting (CABG) AF and to compare the
efficacies of different BB treatments using a network meta-analytical approach.
METHODS: The PubMed, EMBASE and Cochrane Library databases were searched (Jan
1995 to May 2014) to identify randomized controlled trials. Two independent
investigators separately extracted the data using a seven-point scoring system to
assess randomization, allocation concealment, blinding, withdrawals and dropouts.
A direct meta-analysis of these randomized controlled trials was conducted. Then,
six trials comparing different BB treatments for the prevention of postoperative
AF were added to perform a Bayesian network meta-analysis with mixed treatment
comparisons.
RESULTS: Treatment with BBs was associated with a significant reduction in the
postoperative incidence of AF compared with placebo/control [22.37 % compared
with 34.45 %, relative risk (RR) = 0.53, 95 % confidence interval (CI):
0.37-0.75, p < 0.00001].
CONCLUSIONS: The network meta-analysis revealed no significant differences among
eight types of BB treatments but did provide a ranking. BB treatments could
significantly reduce the occurrence of post-CABG AF. Insufficient evidence was
available to show that one BB treatment was more effective than the others were.
According to our network meta-analysis, bisoprolol and landiolol+bisoprolol are
better alternatives compared with the other treatments.

DOI: 10.1007/s11845-016-1447-1
PMID: 27083460  [Indexed for MEDLINE]


161. J Neurointerv Surg. 2016 May;8(5):507-11. doi: 10.1136/neurintsurg-2015-011668.
Epub 2015 Apr 28.

Recurrence, retreatment, and rebleed rates of coiled aneurysms with respect to
the Raymond-Roy scale: a meta-analysis.

Darflinger R(1), Thompson LA(2), Zhang Z(2), Chao K(1).

Author information:
(1)Department of Radiology, Kaiser Permanente Los Angeles Medical Center, Los
Angeles, California, USA.
(2)Division of Biostatistics, Center for Devices and Radiological Health, Food
and Drug Administration, Washington, District of Columbia, USA.

BACKGROUND AND PURPOSE: The Raymond-Roy grading scale is used for aneurysm
coiling with only limited data on its validity. The scale was developed based on
the extent of initial aneurysm occlusion from 1 to 3. However, the model
usefulness in evaluating recurrence, retreatment, and rebleeding is unknown. Our
goal was to perform a meta-analysis to evaluate the predictiveness of the Raymond
scale.
METHODS: We performed a systematic review of the English literature for aneurysm
coiling which reported the initial embolization results, based on the Raymond-Roy
grading scale, and the respective recurrence rates, retreatment rates, and
rebleed rates. This yielded data for 4587 aneurysms. We conducted a Bayesian
random effects meta-analysis to evaluate the outcomes with respect to the
reported initial embolization results.
RESULTS: We found the Raymond scale to be predictive of retreatment, with
statistically higher rates of retreatment with higher initial Raymond grade.
Furthermore, we found a higher probability of rebleeding for initial grades 2 or
3 versus grade 1, which approached significance. The rebleed rates were probably
affected by monitoring and treatment of recurrence. However, although there was a
trend towards higher recurrence rates with initial grade, this was not
statistically significant.
CONCLUSIONS: The modified Raymond-Roy scale appears to provide reasonable
predictive value for treated aneurysm, especially for the clinically more
important aspects of retreatment and rebleed rates.

Published by the BMJ Publishing Group Limited. For permission to use (where not
already granted under a licence) please go to
http://www.bmj.com/company/products-services/rights-and-licensing/

DOI: 10.1136/neurintsurg-2015-011668
PMID: 25921230  [Indexed for MEDLINE]


162. Liver Int. 2016 May;36(5):634-41. doi: 10.1111/liv.12959. Epub 2015 Oct 1.

Comparative efficacy of antiviral therapy in preventing vertical transmission of
hepatitis B: a network meta-analysis.

Njei B(1)(2), Gupta N(1), Ewelukwa O(3), Ditah I(4), Foma M(5), Lim JK(1).

Author information:
(1)Section of Digestive Diseases and Yale Liver Center, Yale University School of
Medicine, New Haven, CT, USA.
(2)Investigative Medicine Program, Yale Center of Clinical Investigation, New
Haven, CT, USA.
(3)Gastroenterology and Hepatology, University of Florida, Gainesville, FL, USA.
(4)Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
(5)Division of Clinical Pathology, University of Yaounde 1, Yaounde, Cameroon.

BACKGROUND & AIMS: Antiviral drugs are safe and effective in the third trimester
to prevent intrauterine transmission of hepatitis B virus, and are recommended
for hepatitis B virus (HBV) infected gravid mothers (between weeks 28 and 32)
with high viral load, followed by postnatal hepatitis B immunization in the
newborn. We estimated the comparative efficacy of antiviral drugs for prevention
of vertical transmission of HBV, through a network meta-analysis of clinical
trials.
METHODS: We conducted a comprehensive search of MEDLINE, EMBASE and published
proceedings from major liver meetings from January 1980 to November 2014. We
conducted pair-wise meta-analyses and Bayesian framework using Markov chain Monte
Carlo methods, combining direct and indirect evidence for any given pair of
treatments.
RESULTS: Seventeen clinical trials involving 2764 newborns of hepatitis B surface
antigen seropositive mothers were eligible for analysis. There were no clinical
trials involving tenofovir or entecavir. On pair-wise meta-analyses, telbivudine
(hazard ratio, HR 0.12, 95% confidence interval (CI) 0.04-0.37; I(2)  = 0%), and
Lamivudine (HR 0.40, 95% CI 0.24-0.65; I(2)  = 0%), were more effective than
placebo in reducing vertical transmission of HBV in high viremic hepatitis B e
antigen (HBeAg)-positive chronic Hepatitis B Chinese patients. Sensitivity
analyses limited to studies with HBeAg seropositive mothers revealed similar
results.
CONCLUSIONS: Based on a Bayesian network meta-analysis of clinical trials,
combining direct and indirect treatment comparisons, telbivudine appears to be
more effective than Lamivudine for preventing vertical transmission of HBV
infection. Trials assessing the efficacy of tenofovir or entecavir compared to
placebo or other antiviral drugs are lacking.

© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

DOI: 10.1111/liv.12959
PMCID: PMC4824664
PMID: 26352650  [Indexed for MEDLINE]


163. Nutrition. 2016 May;32(5):515-23. doi: 10.1016/j.nut.2015.10.023. Epub 2015 Dec
19.

Comparative efficacy of vitamin D status in reducing the risk of bladder cancer:
A systematic review and network meta-analysis.

Zhao Y(1), Chen C(2), Pan W(3), Gao M(4), He W(3), Mao R(1), Lin T(5), Huang
J(3).

Author information:
(1)Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen
University, Guangzhou, China.
(2)Department of Urology, Sun Yat-Sen Memorial Hospital, Guangzhou, China.
Electronic address: changhaochen526@gmail.com.
(3)Department of Urology, Sun Yat-Sen Memorial Hospital, Guangzhou, China.
(4)Department of Acupuncture, The People Hospital of Honghuagang District, Zunyi,
China.
(5)Department of Urology, Sun Yat-Sen Memorial Hospital, Guangzhou, China.
Electronic address: tianxinl@sina.com.

OBJECTIVES: The optimal concentration of individual vitamin D intake for
preventing bladder cancer has not, to our knowledge, been defined. To evaluate
the comparative efficacy of different serum 25-hydroxyvitamin D concentrations in
preventing bladder cancer, we conducted a systematic search of the literature
published up to April 2015.
METHODS: We applied a pairwise meta-analysis to estimate direct evidence from
intervention-control studies and a network meta-analysis within a Bayesian
framework to combine direct and indirect evidence. Moreover, a dose-response
curve was utilized to predict the optimal median serum 25-hydroxyvitamin D
concentration based on the odds ratio (OR) for each quintile concentration.
METHODS: Seven studies of a total of 90757 participants, including 2509 bladder
cancer patients, were included. Two prospective cohort studies with 57 591
participants and 494 bladder cancer patients, and five case-control studies with
33 166 participants and 2264 bladder cancer patients. From the network
meta-analysis, we observed that sufficient serum 25-hydroxyvitamin D
concentrations (>75 nmol/L) were superior to all other 25-hydroxyvitamin D
concentrations in decreasing the risk of bladder cancer: OR = 0.68 and 95%
credible interval (CrI) 0.52 to 0.87 compared with severely deficient
concentrations (<25 nmol/L); OR = 0.65 and 95% CrI 0.49 to 0.86 compared with
moderately deficient concentrations (25-37.5 nmol/L); OR = 0.61 and 95% CrI 0.47
to 0.80 compared with slightly deficient concentrations (37.5-50 nmol/L); and
OR = 0.65 and 95% CrI 0.48 to 0.85 compared with insufficient concentrations
(50-75 nmol/L). In addition, we noted a roughly inverse correlation between
bladder cancer risk and 25-hydroxyvitamin D concentrations (R(2) = 0.98,
P = 0.007).
CONCLUSIONS: Ensuring sufficient serum 25-hydroxyvitamin D concentrations might
play an important role in decreasing the risk of bladder cancer. The serum
25-hydroxyvitamin D concentration ≥74 nmol/L was associated with a 60% lower risk
of bladder cancer incidence.

Copyright © 2016 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.nut.2015.10.023
PMID: 26822497  [Indexed for MEDLINE]


164. Osteoporos Int. 2016 May;27(5):1709-18. doi: 10.1007/s00198-015-3455-9. Epub 2015
Dec 22.

Fracture risk in oral glucocorticoid users: a Bayesian meta-regression leveraging
control arms of osteoporosis clinical trials.

Amiche MA(1), Albaum JM(2), Tadrous M(2)(3), Pechlivanoglou P(2), Lévesque LE(4),
Adachi JD(5), Cadarette SM(2).

Author information:
(1)Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street,
Toronto, ON, M5S 3M2, Canada. amine.amiche@mail.utoronto.ca.
(2)Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street,
Toronto, ON, M5S 3M2, Canada.
(3)St. Michael's Hospital, Toronto, ON, Canada.
(4)Department of Public Health Sciences, Queens University, Kingston, ON, Canada.
(5)Department of Medicine, McMaster University, Hamilton, ON, Canada.

Little data exist on the frequency of fracture among oral glucocorticoid users.
We examined the effect of oral glucocorticoids on fracture incidence using data
from randomized controlled trials. Patients starting glucocorticoids had a higher
probability of fracture and decline in bone mineral density compared to chronic
glucocorticoid users.INTRODUCTION: Oral glucocorticoids (GCs) are the leading
cause of secondary osteoporosis. However, there have been few studies that
quantify the rate of fracture among GC users. We sought to provide a pooled
estimate of fracture risk from randomized controlled trials (RCTs) of GC-treated
patients.
METHODS: We updated a MEDLINE search published by the American College of
Rheumatology through to March 2015 and identified RCTs of osteoporosis therapies
that reported fracture and bone mineral density (BMD) among oral GC users. We
restricted the analysis to placebo or control arms. RCT arms were stratified by
GC exposure at enrolment to GC initiators (≤6 months) and chronic GC users
(>6 months). Bayesian meta-regression was used to estimate the annual probability
of vertebral fracture (primary), non-vertebral fracture and percentage change in
lumbar spine and femoral neck BMD.
RESULTS: The annual incidence of vertebral and non-vertebral fracture was 5.1 %
(95 % CrI = 2.8-8.2) and 2.5 % (95 % CrI = 1.2--4.2) among GC initiators, and
3.2 % (95 % CrI = 1.8-5.0) and 3.0 % (95 % CrI = 0.8-5.9) among chronic GC users.
Our meta-regression identified a non-significant effect of group-level variables
(mean age, mean BMD, mean GC daily dose, patients with previous vertebral
fractures, proportion of women and adjuvant used) on vertebral fracture rate.
CONCLUSION: Our study found higher vertebral fracture incidence among GC
initiators, yet a relative decline in fracture incidence with longer exposure.
Our findings suggest that fracture incidence among oral GC users may be more
common than previously estimated. Optimizing GC-induced osteoporosis management
during early exposure to GC is essential to prevent fractures.

DOI: 10.1007/s00198-015-3455-9
PMID: 26694595  [Indexed for MEDLINE]


165. Rheumatol Int. 2016 May;36(5):663-72. doi: 10.1007/s00296-016-3468-5. Epub 2016
Mar 21.

Comparative efficacy and tolerability of duloxetine, pregabalin, and milnacipran
for the treatment of fibromyalgia: a Bayesian network meta-analysis of randomized
controlled trials.

Lee YH(1), Song GG(2).

Author information:
(1)Division of Rheumatology, Department of Internal Medicine, Korea University
Anam Hospital, Korea University College of Medicine, 73, Inchon-ro, Seongbuk-gu,
Seoul, 02841, Korea. lyhcgh@korea.ac.kr.
(2)Division of Rheumatology, Department of Internal Medicine, Korea University
Anam Hospital, Korea University College of Medicine, 73, Inchon-ro, Seongbuk-gu,
Seoul, 02841, Korea.

The aim of this study was to assess the relative efficacy and tolerability of
duloxetine, pregabalin, and milnacipran at the recommended doses in patients with
fibromyalgia. Randomized controlled trials (RCTs) examining the efficacy and
safety of duloxetine 60 mg, pregabalin 300 mg, pregabalin 150 mg, milnacipran 200
mg, and milnacipran 100 mg compared to placebo in patients with fibromyalgia were
included in this Bayesian network meta-analysis. Nine RCTs including 5140
patients met the inclusion criteria. The proportion of patients with >30 %
improvement from baseline in pain was significantly higher in the duloxetine 60
mg, pregabalin 300 mg, milnacipran 100 mg, and milnacipran 200 mg groups than in
the placebo group [pairwise odds ratio (OR) 2.33, 95 % credible interval (CrI)
1.50-3.67; OR 1.68, 95 % CrI 1.25-2.28; OR 1.62, 95 % CrI 1.16-2.25; and OR 1.61;
95 % CrI 1.15-2.24, respectively]. Ranking probability based on the surface under
the cumulative ranking curve (SUCRA) indicated that duloxetine 60 mg had the
highest probability of being the best treatment for achieving the response level
(SUCRA = 0.9431), followed by pregabalin 300 mg (SUCRA = 0.6300), milnacipran 100
mg (SUCRA = 0.5680), milnacipran 200 mg (SUCRA = 0.5617), pregabalin 150 mg
(SUCRA = 0.2392), and placebo (SUCRA = 0.0580). The risk of withdrawal due to
adverse events was lower in the placebo group than in the pregabalin 300 mg,
duloxetine 60 mg, milnacipran 100 mg, and milnacipran 200 mg groups. However,
there was no significant difference in the efficacy and tolerability between the
medications at the recommended doses. Duloxetine 60 mg, pregabalin 300 mg,
milnacipran 100 mg, and milnacipran 200 mg were more efficacious than placebo.
However, there was no significant difference in the efficacy and tolerability
between the medications at the recommended doses.

DOI: 10.1007/s00296-016-3468-5
PMID: 27000046  [Indexed for MEDLINE]


166. BMJ. 2016 Apr 21;353:i1777. doi: 10.1136/bmj.i1777.

Methotrexate monotherapy and methotrexate combination therapy with traditional
and biologic disease modifying antirheumatic drugs for rheumatoid arthritis:
abridged Cochrane systematic review and network meta-analysis.

Hazlewood GS(1), Barnabe C(2), Tomlinson G(3), Marshall D(4), Devoe D(5),
Bombardier C(6).

Author information:
(1)Department of Medicine, University of Calgary, Calgary, AB, Canada, T2N4Z6
McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB,
Canada, T2N4Z6 Institute of Health, Policy, Management and Evaluation, University
of Toronto, Toronto, ON, Canada, M5T3M6 Department of Community Health Sciences,
University of Calgary, Calgary, AB, Canada, T2N4Z6.
(2)Department of Medicine, University of Calgary, Calgary, AB, Canada, T2N4Z6
McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB,
Canada, T2N4Z6 Department of Community Health Sciences, University of Calgary,
Calgary, AB, Canada, T2N4Z6.
(3)Department of Medicine and Institute of Health Policy, Management, and
Evaluation, University of Toronto, Toronto, ON, Canada, M5G2C4.
(4)McCaig Institute for Bone and Joint Health, University of Calgary, Calgary,
AB, Canada, T2N4Z6 Department of Community Health Sciences, University of
Calgary, Calgary, AB, Canada, T2N4Z6.
(5)Department of Community Health Sciences, University of Calgary, Calgary, AB,
Canada, T2N4Z6.
(6)Department of Medicine and Institute of Health Policy, Management, and
Evaluation, University of Toronto, Toronto, ON, Canada, M5G2C4 Toronto General
Research Institute, University Health Network, Toronto, ON, Canada, M6J3S3 Mount
Sinai Hospital, Division of Rheumatology, Toronto, ON, Canada, M5T3L9.

OBJECTIVE: To compare methotrexate based disease modifying antirheumatic drug
(DMARD) treatments for rheumatoid arthritis in patients naive to or with an
inadequate response to methotrexate.
DESIGN: Systematic review and Bayesian random effects network meta-analysis of
trials assessing methotrexate used alone or in combination with other
conventional synthetic DMARDs, biologic drugs, or tofacitinib in adult patients
with rheumatoid arthritis.
DATA SOURCES: Trials were identified from Medline, Embase, and Central databases
from inception to 19 January 2016; abstracts from two major rheumatology meetings
from 2009 to 2015; two trial registers; and hand searches of Cochrane reviews.
STUDY SELECTION CRITERIA: Randomized or quasi-randomized trials that compared
methotrexate with any other DMARD or combination of DMARDs and contributed to the
network of evidence between the treatments of interest.
MAIN OUTCOMES: American College of Rheumatology (ACR) 50 response (major clinical
improvement), radiographic progression, and withdrawals due to adverse events. A
comparison between two treatments was considered statistically significant if its
credible interval excluded the null effect, indicating >97.5% probability that
one treatment was superior.
RESULTS: 158 trials were included, with between 10 and 53 trials available for
each outcome. In methotrexate naive patients, several treatments were
statistically superior to oral methotrexate for ACR50 response: sulfasalazine and
hydroxychloroquine ("triple therapy"), several biologics (abatacept, adalimumab,
etanercept, infliximab, rituximab, tocilizumab), and tofacitinib. The estimated
probability of ACR50 response was similar between these treatments (range
56-67%), compared with 41% with methotrexate. Methotrexate combined with
adalimumab, etanercept, certolizumab, or infliximab was statistically superior to
oral methotrexate for inhibiting radiographic progression, but the estimated mean
change over one year with all treatments was less than the minimal clinically
important difference of 5 units on the Sharp-van der Heijde scale. Triple therapy
had statistically fewer withdrawals due to adverse events than methotrexate plus
infliximab. After an inadequate response to methotrexate, several treatments were
statistically superior to oral methotrexate for ACR50 response: triple therapy,
methotrexate plus hydroxychloroquine, methotrexate plus leflunomide, methotrexate
plus intramuscular gold, methotrexate plus most biologics, and methotrexate plus
tofacitinib. The probability of response was 61% with triple therapy and ranged
widely (27-70%) with other treatments. No treatment was statistically superior to
oral methotrexate for inhibiting radiographic progression. Methotrexate plus
abatacept had a statistically lower rate of withdrawals due to adverse events
than several treatments.
CONCLUSIONS: Triple therapy (methotrexate plus sulfasalazine plus
hydroxychloroquine) and most regimens combining biologic DMARDs with methotrexate
were effective in controlling disease activity, and all were generally well
tolerated in both methotrexate naive and methotrexate exposed patients.

Published by the BMJ Publishing Group Limited. For permission to use (where not
already granted under a licence) please go to
http://group.bmj.com/group/rights-licensing/permissions.


PMCID: PMC4849170
PMID: 27102806  [Indexed for MEDLINE]


167. Oncotarget. 2016 Apr 19;7(16):21753-62. doi: 10.18632/oncotarget.7832.

Systematic review with network meta-analysis: statins and risk of hepatocellular
carcinoma.

Zhou YY(1), Zhu GQ(2)(3), Wang Y(1), Zheng JN(2)(3), Ruan LY(2)(3), Cheng
Z(2)(3), Hu B(2)(3), Fu SW(1), Zheng MH(2)(4).

Author information:
(1)Department of Cardiology, Jinhua Municipal Hospital, Jinhua 321004, China.
(2)Department of Infection and Liver Diseases, Liver Research Center, The First
Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
(3)School of The First Clinical Medical Sciences, Wenzhou Medical University,
Wenzhou 325000, China.
(4)Institute of Hepatology, Wenzhou Medical University, Wenzhou 325000, China.

OBJECTIVES: Usage of statins is suggested to decrease the incidence of HCC. When
it comes to different statin subtypes, the chemopreventive action remains
controversial. We aim to compare the usage of different statins and reduction of
HCC risk.
METHODS: We searched PubMed, Embase.com and Cochrane Library database up to
August 10, 2015. Duplicated or overlapping reports were eliminated. We performed
a traditional pair-wise meta-analysis and a Bayesian network meta-analysis to
compare different treatments with a random-effects model.
RESULTS: We reviewed five observational studies enrolling a total of 87127
patients who received at least two different treatment strategies including
rosuvastatin, atorvastatin, simvastatin, pravastatin, fluvastatin, cerivastatin,
and lovastatin or observation alone. Direct comparisons showed that usage of
atorvastatin (OR 0.63, 95%CI 0.45-0.89) and fluvastatin (OR 0.58, 95%CI
0.40-0.85) could significantly cut the risk of liver cancer. The difference of
indirect comparisons between the included regimens is not statistically
significant. However, usage of all types of statins, such as fluvastatin (RR
0.55, 95%CI 0.26-1.11), atorvastatin (RR 0.59, 95%CI 0.30-1.16), simvastatin (RR
0.69, 95%CI 0.38-1.25), cerivastatin (RR 0.71, 95%CI 0.19-2.70), pravastatin (RR
0.72, 95%CI 0.37-1.45), lovastatin (RR 0.81, 95%CI 0.34-1.96) and rosuvastatin
(RR 0.92, 95%CI 0.44-1.80), appeared to be superior to observation alone.
Notably, fluvastatin was hierarchically the best when compared with the six other
statins.
CONCLUSIONS: Our analyses indicate the superiority of usage of statins in
reduction of liver cancer. Available evidence supports that fluvastatin is the
most effective strategy for reducing HCC risk compared with other statin
interventions.

DOI: 10.18632/oncotarget.7832
PMCID: PMC5008320
PMID: 26943041  [Indexed for MEDLINE]

Conflict of interest statement: The authors report no declarations of interest.


168. Cochrane Database Syst Rev. 2016 Apr 16;4:CD011383. doi:
10.1002/14651858.CD011383.pub2.

Interventions for necrotising pancreatitis.

Gurusamy KS(1), Belgaumkar AP, Haswell A, Pereira SP, Davidson BR.

Author information:
(1)Department of Surgery, Royal Free Campus, UCL Medical School, Royal Free
Hospital, Rowland Hill Street, London, UK, NW3 2PF.

BACKGROUND: Acute necrotising pancreatitis carries significant mortality,
morbidity, and resource use. There is considerable uncertainty as to how people
with necrotising pancreatitis should be treated.
OBJECTIVES: To assess the benefits and harms of different interventions in people
with acute necrotising pancreatitis.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials
(CENTRAL, 2015, Issue 4), MEDLINE, EMBASE, Science Citation Index Expanded, and
trials registers to April 2015 to identify randomised controlled trials (RCT). We
also searched the references of included trials to identify further trials.
SELECTION CRITERIA: We considered only RCTs performed in people with necrotising
pancreatitis, irrespective of aetiology, presence of infection, language,
blinding, or publication status for inclusion in the review.
DATA COLLECTION AND ANALYSIS: Two review authors independently identified trials
and extracted data. We calculated the odds ratio (OR) and mean difference with
95% confidence intervals (CI) using Review Manager 5 based on an available-case
analysis using fixed-effect and random-effects models. We planned a network
meta-analysis using Bayesian methods, but due to sparse data and uncertainty
about the transitivity assumption, performed only indirect comparisons and used
Frequentist methods.
MAIN RESULTS: We included eight RCTs with 311 participants in this review. After
exclusion of five participants, we included 306 participants in one or more
outcomes. Five trials (240 participants) investigated the three main treatments:
open necrosectomy (121 participants), minimally invasive step-up approach (80
participants), and peritoneal lavage (39 participants) and were included in the
network meta-analysis. Three trials (66 participants) investigated the variations
in the main treatments: early open necrosectomy (25 participants), delayed open
necrosectomy (11 participants), video-assisted minimally invasive step-up
approach (12 participants), endoscopic minimally invasive step-up approach (10
participants), minimally invasive step-up approach (planned surgery) (four
participants), and minimally invasive step-up approach (continued percutaneous
drainage) (four participants). The trials included infected or sterile
necrotising pancreatitis of varied aetiology.All the trials were at unclear or
high risk of bias and the overall quality of evidence was low or very low for all
the outcomes. Overall, short-term mortality was 30% and serious adverse events
rate was 139 serious adverse events per 100 participants. The differences in
short-term mortality and proportion of people with serious adverse events were
imprecise in all the comparisons. The number of serious adverse events and
adverse events were fewer in the minimally invasive step-up approach compared to
open necrosectomy (serious adverse events: rate ratio 0.41, 95% CI 0.25 to 0.68;
88 participants; 1 study; adverse events: rate ratio 0.41, 95% CI 0.25 to 0.68;
88 participants; 1 study). The proportion of people with organ failure and the
mean costs were lower in the minimally invasive step-up approach compared to open
necrosectomy (organ failure: OR 0.20, 95% CI 0.07 to 0.60; 88 participants; 1
study; mean difference in costs: USD -11,922; P value < 0.05; 88 participants; 1
studies). There were more adverse events with video-assisted minimally invasive
step-up approach group compared to endoscopic-assisted minimally invasive step-up
approach group (rate ratio 11.70, 95% CI 1.52 to 89.87; 22 participants; 1
study), but the number of interventions per participant was less with
video-assisted minimally invasive step-up approach group compared to endoscopic
minimally invasive step-up approach group (difference in medians: 2 procedures; P
value < 0.05; 20 participants; 1 study). The differences in any of the other
comparisons for number of serious adverse events, proportion of people with organ
failure, number of adverse events, length of hospital stay, and intensive therapy
unit stay were either imprecise or were not consistent. None of the trials
reported long-term mortality, infected pancreatic necrosis (trials that included
participants with sterile necrosis), health-related quality of life at any time
frame, proportion of people with adverse events, requirement for additional
invasive intervention, time to return to normal activity, and time to return to
work.
AUTHORS' CONCLUSIONS: Low to very low quality evidence suggested that the
minimally invasive step-up approach resulted in fewer adverse events, serious
adverse events, less organ failure, and lower costs compared to open
necrosectomy. Very low quality evidence suggested that the endoscopic minimally
invasive step-up approach resulted in fewer adverse events than the
video-assisted minimally invasive step-up approach but increased the number of
procedures required for treatment. There is currently no evidence to suggest that
early open necrosectomy is superior or inferior to peritoneal lavage or delayed
open necrosectomy. However, the CIs were wide and significant benefits or harms
of different treatments cannot be ruled out. The TENSION trial currently underway
in Netherlands is assessing the optimal way to perform the minimally invasive
step-up approach (endoscopic drainage followed by endoscopic necrosectomy if
necessary versus percutaneous drainage followed by video-assisted necrosectomy if
necessary) and is assessing important clinical outcomes of interest for this
review. Implications for further research on this topic will be determined after
the results of this RCT are available.

DOI: 10.1002/14651858.CD011383.pub2
PMID: 27083933  [Indexed for MEDLINE]


169. Eur J Endocrinol. 2016 Apr;174(4):465-72. doi: 10.1530/EJE-15-1119. Epub 2016 Jan
13.

The placebo effect in thyroid cancer: a meta-analysis.

Llavero-Valero M(1), Guillén-Grima F(2), Zafon C(1), Galofré JC(3).

Author information:
(1)Departments of Endocrinology and NutritionPreventive MedicineClínica
Universidad de Navarra, University of Navarra, Pío XII, 36, 31080, Pamplona,
SpainIdiSNANavarra's Health Research Institute, Pamplona, SpainDepartment of
Health SciencesPublic University of Navarra, Pamplona, SpainDepartment of
EndocrinologyHospital Vall d'Hebron, and Diabetes and Metabolism Research Unit,
Vall d'Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona and
CIBERDEM (ISCIII), Barcelona, Spain.
(2)Departments of Endocrinology and NutritionPreventive MedicineClínica
Universidad de Navarra, University of Navarra, Pío XII, 36, 31080, Pamplona,
SpainIdiSNANavarra's Health Research Institute, Pamplona, SpainDepartment of
Health SciencesPublic University of Navarra, Pamplona, SpainDepartment of
EndocrinologyHospital Vall d'Hebron, and Diabetes and Metabolism Research Unit,
Vall d'Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona and
CIBERDEM (ISCIII), Barcelona, Spain Departments of Endocrinology and
NutritionPreventive MedicineClínica Universidad de Navarra, University of
Navarra, Pío XII, 36, 31080, Pamplona, SpainIdiSNANavarra's Health Research
Institute, Pamplona, SpainDepartment of Health SciencesPublic University of
Navarra, Pamplona, SpainDepartment of EndocrinologyHospital Vall d'Hebron, and
Diabetes and Metabolism Research Unit, Vall d'Hebron Institut de Recerca (VHIR),
Universitat Autònoma de Barcelona and CIBERDEM (ISCIII), Barcelona, Spain
Departments of Endocrinology and NutritionPreventive MedicineClínica Universidad
de Navarra, University of Navarra, Pío XII, 36, 31080, Pamplona,
SpainIdiSNANavarra's Health Research Institute, Pamplona, SpainDepartment of
Health SciencesPublic University of Navarra, Pamplona, SpainDepartment of
EndocrinologyHospital Vall d'Hebron, and Diabetes and Metabolism Research Unit,
Vall d'Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona and
CIBERDEM (ISCIII), Barcelona, Spain.
(3)Departments of Endocrinology and NutritionPreventive MedicineClínica
Universidad de Navarra, University of Navarra, Pío XII, 36, 31080, Pamplona,
SpainIdiSNANavarra's Health Research Institute, Pamplona, SpainDepartment of
Health SciencesPublic University of Navarra, Pamplona, SpainDepartment of
EndocrinologyHospital Vall d'Hebron, and Diabetes and Metabolism Research Unit,
Vall d'Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona and
CIBERDEM (ISCIII), Barcelona, Spain Departments of Endocrinology and
NutritionPreventive MedicineClínica Universidad de Navarra, University of
Navarra, Pío XII, 36, 31080, Pamplona, SpainIdiSNANavarra's Health Research
Institute, Pamplona, SpainDepartment of Health SciencesPublic University of
Navarra, Pamplona, SpainDepartment of EndocrinologyHospital Vall d'Hebron, and
Diabetes and Metabolism Research Unit, Vall d'Hebron Institut de Recerca (VHIR),
Universitat Autònoma de Barcelona and CIBERDEM (ISCIII), Barcelona, Spain
jcgalofre@unav.es.

CONTEXT: The natural history of advanced thyroid malignancies is largely unknown.
The outcome of patients included in the placebo arm of clinical trials could be
reflective of their therapy-free evolution.
OBJECTIVE: To analyze the response rate, symptoms and adverse effects of locally
advanced or metastatic differentiated (DTC) and medullary thyroid cancer (MTC) in
patients treated with placebo in clinical trials.
DESIGN: PubMed (MEDLINE) and SCOPUS databases were searched through September
2015 to identify high-quality randomized controlled clinical trials. We included
studies that recruited patients with DTC or MTC with a placebo arm.
METHODS: We conducted a meta-analysis for each category of response rate,
adherence to treatment, and adverse events. An empirical Bayesian random-effect
model was used.
RESULTS: We identified five clinical trials. DTC and MTC were independently
analyzed. In the placebo arm, no complete response was observed; partial response
occurred in 1.6% (0.6-3) and 6.4% (3.4-10.3) of DTC and MTC respectively; stable
disease was described in 40.5% (34.6-46.9) and 53.9% (44.3-64.4) of DTC and MTC
respectively. DTC reached a disease control rate of 42.3% (36.2-48.9) and MTC of
60.2 (50.1-71.4). Treatment discontinuation rate was 3.5% (1.9-5.5) in DTC and
5.7% (3.0-9.4) in MTC. Rate of dose reduction was 7.3% (4.8-10.5) in DTC and 6.2%
(3.3-10.0) in MTC.
CONCLUSIONS: This meta-analysis provides extensive data on the response rate and
adverse effects of locally advanced or metastatic DTC and MTC in patients treated
with placebo. These results may be used for comparisons with results from
clinical trials without a placebo arm.

© 2016 European Society of Endocrinology.

DOI: 10.1530/EJE-15-1119
PMID: 26764417  [Indexed for MEDLINE]


170. Genet Epidemiol. 2016 Apr;40(3):188-201. doi: 10.1002/gepi.21953.

JAM: A Scalable Bayesian Framework for Joint Analysis of Marginal SNP Effects.

Newcombe PJ(1), Conti DV(2), Richardson S(1).

Author information:
(1)MRC Biostatistics Unit, Cambridge, United Kingdom.
(2)Division of Biostatistics, Department of Preventive Medicine, Zilkha
Neurogenetic Institute, University of Southern California, Los Angeles,
California, United States of America.

Recently, large scale genome-wide association study (GWAS) meta-analyses have
boosted the number of known signals for some traits into the tens and hundreds.
Typically, however, variants are only analysed one-at-a-time. This complicates
the ability of fine-mapping to identify a small set of SNPs for further
functional follow-up. We describe a new and scalable algorithm, joint analysis of
marginal summary statistics (JAM), for the re-analysis of published marginal
summary statistics under joint multi-SNP models. The correlation is accounted for
according to estimates from a reference dataset, and models and SNPs that best
explain the complete joint pattern of marginal effects are highlighted via an
integrated Bayesian penalized regression framework. We provide both enumerated
and Reversible Jump MCMC implementations of JAM and present some comparisons of
performance. In a series of realistic simulation studies, JAM demonstrated
identical performance to various alternatives designed for single region
settings. In multi-region settings, where the only multivariate alternative
involves stepwise selection, JAM offered greater power and specificity. We also
present an application to real published results from MAGIC (meta-analysis of
glucose and insulin related traits consortium) - a GWAS meta-analysis of more
than 15,000 people. We re-analysed several genomic regions that produced multiple
significant signals with glucose levels 2 hr after oral stimulation. Through
joint multivariate modelling, JAM was able to formally rule out many SNPs, and
for one gene, ADCY5, suggests that an additional SNP, which transpired to be more
biologically plausible, should be followed up with equal priority to the reported
index.

© 2016 The Authors Genetic Epidemiology Published by Wiley Periodicals, Inc.

DOI: 10.1002/gepi.21953
PMCID: PMC4817278
PMID: 27027514  [Indexed for MEDLINE]


171. Head Neck. 2016 Apr;38(4):628-34. doi: 10.1002/hed.23945. Epub 2015 Jun 26.

Analysis of sentinel node biopsy combined with other diagnostic tools in staging
cN0 head and neck cancer: A diagnostic meta-analysis.

Liao LJ(1)(2), Hsu WL(3), Wang CT(1)(2), Lo WC(2), Lai MS(1)(4).

Author information:
(1)Graduate Institute of Epidemiology and Preventive Medicine, College of Public
Health, National Taiwan University, Taipei, Taiwan.
(2)Department of Otolaryngology, Far Eastern Memorial Hospital, Taipei, Taiwan.
(3)Genomics Research Center, Academia Sinica, Taipei, Taiwan.
(4)Center of Comparative Effectiveness Research, National Center of Excellence
for Clinical Trial and Research, National Taiwan University Hospital, Taipei,
Taiwan.

BACKGROUND: The purpose of this was to find a staging strategy sensitive enough
to reduce the risk of occult metastases in cN0 head and neck cancer to below 15%
to 20%.
METHODS: A total of 73 articles were selected for analysis of the diagnostic
performance in staging cN0 head and neck cancer. Hypothetical estimation of
negative predictive value (NPV) was calculated based on the Bayesian theory.
RESULTS: The pooled estimates for sensitivity were 56.4% and 84.9% for
ultrasound-guided fine-needle aspiration (FNA) and sentinel node biopsy (SNB).
The pooled estimates for sensitivity were 47.0%, 56.6%, 48.3%, and 63.3% for CT,
MRI, positron emission tomography (PET), and ultrasound, respectively. The pooled
estimates for specificity were 88.9%, 82.5%, 86.2%, and 79.1% for CT, MRI, PET,
and ultrasound. In estimation, the CT or MRI with SNB strategies had NPV higher
than 85% even when the pretest metastatic rate was 60%.
CONCLUSION: The SNB procedure has the best performance. A combination of CT/MRI
and SNB for cN0 head and neck cancer is preferred.

© 2015 Wiley Periodicals, Inc.

DOI: 10.1002/hed.23945
PMID: 25524256  [Indexed for MEDLINE]


172. Medicine (Baltimore). 2016 Apr;95(15):e3302. doi: 10.1097/MD.0000000000003302.

Comparative Effectiveness of Blood Pressure-lowering Drugs in Patients who have
Already Suffered From Stroke: Traditional and Bayesian Network Meta-analysis of
Randomized Trials.

Wang WT(1), You LK, Chiang CE, Sung SH, Chuang SY, Cheng HM, Chen CH.

Author information:
(1)From the Division of Cardiology (W-TW, S-HS), Department of Internal Medicine,
Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medical Education
(L-KY, H-MC, C-HC), Taipei Veterans General Hospital, Taipei, Taiwan; Laboratory
of Evidence-based Health care, Department of Medical Education, Taipei Veterans
General Hospital, Taipei, Taiwan (L-KY, H-MC); Taipei Veterans General Hospital,
Taipei, Taiwan; General Clinical Research Center (C-EC), Taipei Veterans General
Hospital, Taipei, Taiwan; Institute of Public Health (S-HS, H-MC, C-HC) and
Community Medicine Research Center; Department of Medicine (S-HS, H-MC, C-HC),
National Yang-Ming University, Taipei, Taiwan; and Division of Preventive
Medicine and Health Service (S-YC), Research Institute of Population Health
Sciences, National Health Research Institutes, Miaoli, Taiwan.

Hypertension is the most important risk factor for stroke and stroke recurrence.
However, the preferred blood pressure (BP)-lowering drug class for patients who
have suffered from a stroke has yet to be determined. To investigate the relative
effects of BP-lowering therapies [angiotensin-converting enzyme inhibitor (ACEI),
angiotensin receptor blockers (ARB), β blockers, calcium channel blockers (CCBs),
diuretics, and combinations of these drugs] in patients with a prior stroke
history, we performed a systematic review and meta-analysis using both
traditional frequentist and Bayesian random-effects models and meta-regression of
randomized controlled trials (RCTs) on the outcomes of recurrent stroke, coronary
heart disease (CHD), and any major adverse cardiac and cerebrovascular events
(MACCE). Trials were identified from searches of published hypertension
guidelines, electronic databases, and previous systematic reviews. Fifteen RCTs
composed of 39,329 participants with previous stroke were identified. Compared
with the placebo, only ACEI along with diuretics significantly reduced recurrent
stroke events [odds ratio (OR) = 0.54, 95% credibility interval (95% CI)
0.33-0.90]. On the basis of the distribution of posterior probabilities, the
treatment ranking consistently identified ACEI along with diuretics as the
preferred BP-lowering strategy for the reduction of recurrent stroke and CHD (31%
and 35%, respectively). For preventing MACCE, diuretics appeared to be the
preferred agent for stroke survivors (34%). Moreover, the meta-regression
analysis failed to demonstrate a statistical significance between BP reduction
and all outcomes (P = 0.1618 for total stroke, 0.4933 for CHD, and 0.2411 for
MACCE). Evidence from RCTs supports the use of diuretics-based treatment,
especially when combined with ACEI, for the secondary prevention of recurrent
stroke and any vascular events in patients who have suffered from stroke.

DOI: 10.1097/MD.0000000000003302
PMCID: PMC4839815
PMID: 27082571  [Indexed for MEDLINE]


173. Medicine (Baltimore). 2016 Apr;95(15):e3185. doi: 10.1097/MD.0000000000003185.

Comparative Efficacy of Interventional Therapies for Early-stage Hepatocellular
Carcinoma: A PRISMA-compliant Systematic Review and Network Meta-analysis.

Lan T(1), Chang L, Rahmathullah MN, Wu L, Yuan YF.

Author information:
(1)From the Department of Hepatobiliary Surgery, Zhongnan Hospital of Wuhan
University, Wuhan, Hubei, China.

There are several interventional therapies that improve the prognosis and
increase the survival rate of early-stage hepatocellular carcinoma (early-stage
HCC), but it is uncertain about whether one is superior to others, and available
researches investigating the comparative effects of different treatments are
limited. The main objective of this Bayesian network meta-analysis was to compare
the efficacy of these different treatment strategies for early-stage HCC and rank
these interventions for practical consideration. We performed an electronic
search of PubMed, Embase, and Cochrane Library, and extracted data from
randomized controlled trials that compared different interventional therapies for
early-stage HCC. Direct comparison and network meta-analyses were conducted with
Aggregate Data Drug Information System software. Consistency models were created
to determine whether there was a significant difference between any 2 therapies,
and cumulative probability was used to rank different treatments. Twenty-one
randomized controlled trials involving 2691 patients were included. In our
network meta-analysis, the combination therapy of transcatheter arterial
chemoembolization (TACE) and radiofrequency ablation (RFA) was associated with
better 1-year survival rate, as compared with hepatic resection alone (P < 0.05,
odds ratio [OR] 0.25, 95% confidence interval [CI] 0.06-0.83), percutaneous
ethanol injection (PEI) alone (P < 0.05, OR 0.13, 95% CI 0.03-0.45), and RFA
alone (P < 0.05, OR 0.23, 95% CI 0.07-0.70). TACE + RFA had a higher 3-year
survival rate than PEI alone (P < 0.05, OR 0.32, 95% CI 0.15-0.72) and RFA alone
(P < 0.05, OR 0.45, 95% CI 0.24-0.87). And there was a statistical difference
between RFA + PEI and PEI alone (P < 0.05, OR 0.33, 95% CI 0.12-0.93) for 3-year
survival rate. The results of rank test and cumulative probability showed that
TACE + RFA ranked highest on the evaluation of 1-year, 3-year, and 5-year
survival rate. Based on Bayesian network meta-analysis combining direct and
indirect comparisons, the combination therapy of TACE and RFA seemed to be the
most effective strategy for early-stage HCC.

DOI: 10.1097/MD.0000000000003185
PMCID: PMC4839802
PMID: 27082558  [Indexed for MEDLINE]


174. Surgery. 2016 Apr;159(4):1157-69. doi: 10.1016/j.surg.2015.10.011. Epub 2015 Nov
19.

A network meta-analysis comparing perioperative outcomes of interventions aiming
to decrease ischemia reperfusion injury during elective liver resection.

Simillis C(1), Robertson FP(2), Afxentiou T(2), Davidson BR(2), Gurusamy KS(2).

Author information:
(1)Department of Surgery, Royal Free Campus, UCL Medical School, London, UK.
Electronic address: csimillis@gmail.com.
(2)Department of Surgery, Royal Free Campus, UCL Medical School, London, UK.

OBJECTIVE: This study sought to compare the perioperative outcomes of
interventions aiming to decrease ischemia-reperfusion (IR) injury during elective
liver resection.
METHOD: A comprehensive literature search was performed to identify randomized
controlled trials. A Bayesian network meta-analysis was performed using the
Markov chain Monte Carlo method in WinBUGS following the guidelines of the
National Institute for Health and Clinical Excellence Decision Support Unit. Odds
ratios for binary outcomes and mean differences for continuous outcomes were
calculated using a fixed effect model or a random effects model according to
model fit.
RESULTS: Forty-four trials with 2,457 patients having undergone liver resection
were included and were divided into 8 classes of interventions aimed at
decreasing IR injury and a control group, which was hepatectomy alone. There was
no difference between the different interventions in mortality, quantity of blood
transfusion, and durations of stay in an intensive therapy unit between any
pairwise comparisons. Patients treated with ischemic preconditioning,
cardiovascular modulators, and miscellaneous interventions had significantly
fewer serious adverse events compared with patients undergoing liver resection
alone. Ischemic preconditioning patients had significantly fewer transfusion
proportions and shorter operative time than patients treated with steroids.
Ischemic preconditioning had significantly less operative blood loss compared
with all other interventions, and a lesser duration of hospital stay than
hepatectomy alone. Sensitivity analysis showed that the drugs sevoflurane (a
volatile anesthetic), verapamil (a calcium channel blocker), and gabexate
mesilate (a thrombin inhibitor) produced fewer serious adverse events compared
with hepatectomy alone.
CONCLUSION: Ischemic preconditioning resulted in multiple beneficial clinical
endpoints and further RCTs seem to be needed to confirm its clinical benefits.

Copyright © 2016 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.surg.2015.10.011
PMID: 26606882  [Indexed for MEDLINE]


175. Ther Adv Respir Dis. 2016 Apr;10(2):89-104. doi: 10.1177/1753465815624612. Epub
2016 Jan 8.

Comparative efficacy of fixed-dose combinations of long-acting muscarinic
antagonists and long-acting β2-agonists: a systematic review and network
meta-analysis.

Schlueter M(1), Gonzalez-Rojas N(2), Baldwin M(2), Groenke L(2), Voss F(2),
Reason T(3).

Author information:
(1)IMS Health, 210 Pentonville Road, London N1 9JY, UK
mschlueter@uk.imshealth.com.
(2)Boehringer Ingelheim GmbH,  Ingelheim am Rhein, Germany.
(3)IMS Health, London, UK.

BACKGROUND: A number of long-acting muscarinic antagonist (LAMA)/long-acting
β2-agonist (LABA) fixed-dose combinations (FDCs) for treatment of
moderate-to-very severe chronic obstructive pulmonary disease (COPD) have
recently become available, but none have been directly compared in head-to-head
randomized controlled trials (RCTs). The purpose of this study was to assess the
relative clinical benefit of all currently available LAMA/LABA FDCs using a
Bayesian network meta-analysis (NMA).
METHODS: A systematic literature review identified RCTs investigating the
efficacy, safety and quality of life associated with licensed LAMA/LABA FDCs for
the treatment of moderate-to-very severe COPD. RCTs were screened for inclusion
in the NMA using prespecified eligibility criteria. Data were extracted for
outcomes of interest, including change in trough forced expiratory volume in 1
second (tFEV1) from baseline, St. George Respiratory Questionnaire (SGRQ)
percentage of responders, Transition Dyspnea Index (TDI) percentage of
responders, change in SGRQ score from baseline, change in TDI focal score from
baseline, moderate-to-severe exacerbations, all-cause discontinuation, and
discontinuation due to adverse events.
RESULTS: Following screening, a total of 27 trials from 26 publications with
30,361 subjects were eligible for inclusion in the NMA. Nonsignificant results
were seen in most analyses comparing efficacy, exacerbations and discontinuation
rates of included LAMA/LABA FDCs (i.e. aclidinium/formoterol 400/12 µg,
glycopyrronium/indacaterol 110/50 µg, tiotropium + olodaterol 5/5 µg,
umeclidinium/vilanterol 62.5/25 µg). Meta-regression controlling for
post-bronchodilator percentage of tFEV1 predicted at baseline as well as
meta-regression adjusting for concomitant use of inhaled corticosteroids at
baseline was performed to assess the magnitude of effect modification and
produced similar results as observed in the base case analysis.
CONCLUSION: All LAMA/LABA FDCs were found to have similar efficacy and safety.
Definitive assessment of the relative efficacy of different treatments can only
be performed through direct comparison in head-to-head RCTs. In the absence of
such data, this indirect comparison may be of value in clinical and health
economic decision-making.

© The Author(s), 2016.

DOI: 10.1177/1753465815624612
PMID: 26746383  [Indexed for MEDLINE]


176. Aliment Pharmacol Ther. 2016 Mar;43(6):663-73. doi: 10.1111/apt.13537. Epub 2016
Feb 1.

Systematic review with network meta-analysis: comparative effectiveness of
topical steroids vs. PPIs for the treatment of the spectrum of eosinophilic
oesophagitis.

Lipka S(1), Kumar A(2), Miladinovic B(2), Richter JE(3).

Author information:
(1)Division of Digestive Diseases and Nutrition, University of South Florida
Morsani College of Medicine, Tampa, FL, USA.
(2)Division of Evidence Based Medicine and Outcomes Research, Department of
Medicine, University of South Florida Morsani College of Medicine, Tampa, FL,
USA.
(3)Division of Digestive Diseases and Nutrition, Joy McCann Culverhouse Center
for Swallowing Disorders, University of South Florida Morsani College of
Medicine, Tampa, FL, USA.

BACKGROUND: Controversy surrounds the clinical and histological response to
topical steroids in patients with eosinophilic oesophagitis (EoE).
AIM: To perform a systematic review and network meta-analysis of randomised
controlled trials to assess the efficacy of topical steroids compared with
placebo or proton pump inhibitor (PPIs) for the management of eosinophilic
oesophagitis.
METHODS: Cochrane Central Register of Controlled Trials and MEDLINE from
inception to 1 July 2015 was searched. Data were extracted independently by two
authors. Methodological quality was assessed using the Cochrane risk of bias
tool. A network meta-analysis was performed using the Bayesian methods under
random-effects multiple treatment comparisons. Results were summarised as odds
ratio along with credibility intervals. We also calculated the ranking
probability for each treatment based on surface under the cumulative ranking
curve (SUCRA).
RESULTS: The overall methodological quality of included studies was low. SUCRA
ranking probability indicated that PPI had the highest probability of being the
best treatment for achieving histological remission and mean change in
eosinophils (0.81 and 0.85, respectively), followed by budesonide (0.74 and 0.63,
respectively) and fluticasone (0.5 and 0.5, respectively). None of the
comparisons indicated a statistically signicant difference.
CONCLUSIONS: The results from network meta-analysis show that there is no
statistically significant difference between PPI, budesonide and fluticasone for
the treatment of EoE as assessed by the histological and clinical response. The
evidence is limited by serious risk of bias and imprecision, which emphasises the
urgent need for large RCTs with adequate sample size and methodological rigour to
provide conclusive evidence.

© 2016 John Wiley & Sons Ltd.

DOI: 10.1111/apt.13537
PMID: 26834077  [Indexed for MEDLINE]


177. Am J Drug Alcohol Abuse. 2016 Mar;42(2):140-51. doi:
10.3109/00952990.2015.1136638. Epub 2016 Feb 23.

A meta-analysis of brief alcohol interventions for adolescents and young adults:
variability in effects across alcohol measures.

Tanner-Smith EE(1), Risser MD(2).

Author information:
(1)a Department of Human and Organizational Development , Peabody Research
Institute, Vanderbilt University , Nashville , TN , USA.
(2)b Lawrence Berkeley National Laboratory , Berkeley , CA , USA.

BACKGROUND: Brief alcohol interventions are one approach for reducing drinking
among youth, but may vary in effectiveness depending on the type of alcohol
assessments used to measure effects.
OBJECTIVES: To conduct a meta-analysis that examined the effectiveness of brief
alcohol interventions for adolescents and young adults, with particular emphasis
on exploring variability in effects across outcome measurement characteristics.
METHOD: Eligible studies were those using an experimental or quasi-experimental
design to examine the effects of a brief alcohol intervention on a
post-intervention alcohol use measure for youth aged 11-30. A comprehensive
literature review identified 190 unique samples that were included in the
meta-analysis. Taking a Bayesian approach, we used random-effects multilevel
models to estimate the average effect and model variability across outcome
measurement types.
RESULTS: Brief alcohol interventions led to significant reductions in
self-reported alcohol use among adolescents (g = 0.25, 95% credible interval [CrI
0.13, 0.37]) and young adults (g = 0.15, 95% CrI [0.12, 0.18]). These results
were consistent across outcomes with varying reference periods, but varied across
outcome construct type and assessment instruments. Among adolescents, effects
were larger when measured using the Timeline Followback; among young adults,
effects were smaller when measured using the Alcohol Use Disorders Identification
Test.
CONCLUSION: The strength of the beneficial effects of brief alcohol interventions
on youth's alcohol use may vary depending upon the outcome measure utilized.
Nevertheless, significant effects were observed across measures. Although effects
were modest in size, they were clinically significant and show promise for
interrupting problematic alcohol use trajectories among youth.

DOI: 10.3109/00952990.2015.1136638
PMCID: PMC4824184 [Available on 2017-03-01]
PMID: 26905387  [Indexed for MEDLINE]


178. Am J Sports Med. 2016 Mar;44(3):792-800. doi: 10.1177/0363546515580787. Epub 2015
Apr 29.

Effect of Leukocyte Concentration on the Efficacy of Platelet-Rich Plasma in the
Treatment of Knee Osteoarthritis.

Riboh JC(1), Saltzman BM(2), Yanke AB(2), Fortier L(3), Cole BJ(2).

Author information:
(1)Division of Sports Medicine, Rush University Medical Center, Chicago,
Illinois, USA jriboh@gmail.com.
(2)Division of Sports Medicine, Rush University Medical Center, Chicago,
Illinois, USA.
(3)Cornell School of Veterinary Medicine, Ithaca, New York, USA.

BACKGROUND: Leukocyte-poor platelet-rich plasma (LP-PRP) is hypothesized to be
more suitable for intra-articular injection than leukocyte-rich PRP (LR-PRP) in
the treatment of knee osteoarthritis.
PURPOSE: To compare clinical outcomes and rates of adverse reactions between
LP-PRP and LR-PRP for this application.
STUDY DESIGN: Meta-analysis.
METHODS: The MEDLINE, EMBASE, and Cochrane databases were reviewed. The primary
outcome was the incidence of local adverse reactions. Secondary outcomes were the
changes in International Knee Documentation Committee (IKDC) subjective score and
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score
between baseline and final follow-up measurements. A Bayesian network
meta-analysis was performed, with a post hoc meta-regression to correct for
baseline differences in WOMAC scores. Treatment rankings were based on surface
under the cumulative ranking (SUCRA) probabilities.
RESULTS: Included in the analysis were 6 randomized controlled trials (evidence
level 1) and 3 prospective comparative studies (evidence level 2) with a total of
1055 patients. Injection of LP-PRP resulted in significantly better WOMAC scores
than did injection of hyaluronic acid (mean difference, -21.14; 95% CI, -39.63 to
-2.65) or placebo (mean difference, -17.84; 95% CI, -34.95 to -0.73). No such
difference was observed with LR-PRP (mean difference, -14.28; 95% CI, -44.80 to
16.25). All treatment groups resulted in equivalent IKDC subjective scores. The
SUCRA analysis showed that LP-PRP was the highest ranked treatment for both
measures of clinical efficacy (WOMAC and IKDC). Finally, PRP injections resulted
in a higher incidence of adverse reactions than hyaluronic acid (odds ratio,
5.63; 95% CI, 1.38-22.90), but there was no difference between LR-PRP and LP-PRP
(odds ratio, 0.78; 95% CI, 0.05-11.93). These reactions were nearly always local
swelling and pain, with a single study reporting medical side effects including
syncope, dizziness, headache, gastritis, and tachycardia (17/1055 total
patients).
CONCLUSION: LP-PRP results in improved functional outcome scores compared with
hyaluronic acid and placebo when used for treatment of knee osteoarthritis.
LP-PRP and LR-PRP have similar safety profiles, although both induce more
transient reactions than does hyaluronic acid. Adverse reactions to PRP may not
be directly related to leukocyte concentration.

© 2015 The Author(s).

DOI: 10.1177/0363546515580787
PMID: 25925602  [Indexed for MEDLINE]


179. Chest. 2016 Mar;149(3):756-66. doi: 10.1016/j.chest.2015.11.013. Epub 2016 Jan
13.

Drug Treatment of Idiopathic Pulmonary Fibrosis: Systematic Review and Network
Meta-Analysis.

Canestaro WJ(1), Forrester SH(2), Raghu G(3), Ho L(3), Devine BE(4).

Author information:
(1)Pharmaceutical Outcomes Research and Policy Program, University of Washington
School of Pharmacy, Seattle, WA.
(2)GroupHealth Cooperative, Seattle, WA.
(3)Division of Pulmonary and Critical Care Medicine, Center for Interstitial Lung
Disease, University of Washington School of Medicine, Seattle, WA.
(4)Pharmaceutical Outcomes Research and Policy Program, University of Washington
School of Pharmacy, Seattle, WA. Electronic address: bdevine@uw.edu.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a form of chronic progressive
fibrosing interstitial lung disease of unknown origin. Recently, nintedanib and
pirfenidone demonstrated efficacy in slowing disease progression and were
approved by the US Food and Drug Administration. Although numerous treatments
have been evaluated in IPF, none have shown significant decreases in mortality.
The objective of this study was to identify all pharmacologic treatments
evaluated for IPF and analyze their efficacy via Bayesian network meta-analysis
and pairwise indirect treatment comparisons. This review did not evaluate the
effect of steroid therapy.
METHODS: We searched MEDLINE, Embase, and the Cochrane Library for studies
published on or before August 2014. Studies were required to contain a randomized
evaluation of nonsteroidal drug therapy for treatment of IPF and be published in
English. Key outcomes of interest for this analysis were pulmonary function as
measured by FVC as well as all-cause and respiratory-specific death. All outcomes
were analyzed via a Bayesian framework.
RESULTS: Our review identified 30 eligible studies that evaluated 16 unique
treatments. Under both the fixed-effect and random-effect models for
respiratory-specific mortality, no treatments performed better than placebo. For
all-cause mortality, pirfenidone and nintedanib had effects approaching
significance with credible intervals slightly crossing the null under a
fixed-effect model. Notably, for respiratory-specific mortality, all-cause
mortality, and decline in percent predicted FVC, nintedanib and pirfenidone were
virtually indistinguishable and no clear advantage was detected.
CONCLUSIONS: Although two treatments have been approved for IPF on the basis of
reduced decline in pulmonary function, neither one has a clear advantage on
mortality outcomes.

Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc.
All rights reserved.

DOI: 10.1016/j.chest.2015.11.013
PMID: 26836914  [Indexed for MEDLINE]


180. Clin Cancer Res. 2016 Mar 1;22(5):1086-94. doi: 10.1158/1078-0432.CCR-15-1208.
Epub 2015 Oct 26.

Pathological T0 Following Cisplatin-Based Neoadjuvant Chemotherapy for
Muscle-Invasive Bladder Cancer: A Network Meta-analysis.

Kim HS(1), Jeong CW(1), Kwak C(1), Kim HH(1), Ku JH(2).

Author information:
(1)Department of Urology, Seoul National University Hospital, Seoul, Korea.
(2)Department of Urology, Seoul National University Hospital, Seoul, Korea.
kuuro70@snu.ac.kr.

PURPOSE: To systematically assess and compare the relationship between various
neoadjuvant chemotherapy regimens and pCR in patients with muscle-invasive
bladder cancer.
EXPERIMENTAL DESIGN: We performed a literature search of PubMed, Embase, and the
Cochrane Library for all articles published before March 2015 and according to
the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA)
guidelines. There were 17 articles that met the study eligibility criteria and
were selected for the final analysis. A direct pair-wise meta-analysis was
performed for studies that compared the same regimen. Finally, a Bayesian network
meta-analysis was used to indirectly compare the regimens.
RESULTS: In a pair-wise meta-analysis, the
methotrexate/vinblastine/Adriamycin/cisplatin [MVAC; OR, 4.36; 95% confidence
interval (CI), 2.71-7.02] and gemcitabine/cisplatin (GC) regimens (OR, 4.92; 95%
CI, 2.93-8.24) were significantly associated with a better pCR than RC alone. In
a network meta-analysis, there was no significant difference in terms of pCR
achievement between the GC and MVAC regimens (OR, 1.14; 95% CI; 0.85-1.70).
However, in a subgroup network meta-analysis that only included prospective
randomized trials, the MVAC regimen was significantly correlated with a higher
rate of pCR (OR, 5.75; 95% CI, 1.96-24.18).
CONCLUSIONS: The results of this meta-analysis suggest that a GC regimen was
associated with a pCR rate that was similar to that of a MVAC regimen based on
retrospective data, but only the MVAC regimen was proven to achieve pCR in
prospective randomized trials. Additional prospective randomized trials comparing
both regimens will be necessary to establish the optimal neoadjuvant chemotherapy
regimen.

©2015 American Association for Cancer Research.

DOI: 10.1158/1078-0432.CCR-15-1208
PMID: 26503947  [Indexed for MEDLINE]


181. Diabet Med. 2016 Mar;33(3):280-9. doi: 10.1111/dme.12885. Epub 2015 Sep 8.

Effects of glucose-lowering and multifactorial interventions on cardiovascular
and mortality outcomes: a meta-analysis of randomized control trials.

Seidu S(1)(2), Achana FA(3), Gray LJ(1)(4), Davies MJ(1)(2), Khunti K(1)(2).

Author information:
(1)Leicester Diabetes Centre, Leicester General Hospital, Leicester, UK.
(2)Diabetes Research Centre, University of Leicester, Leicester, UK.
(3)Clinical Trials Unit, Warwick Medical School, University of Warwick, Coventry,
UK.
(4)Department of Health Sciences, University of Leicester, Leicester, UK.

INTRODUCTION: The effect of intensive glycaemic control alone or as part of a
multifactorial intervention on cardiovascular and mortality outcomes is not fully
understood. In addition, the interaction of duration of diabetes diagnosis on
cardiovascular and mortality outcomes is unclear.
AIM: To quantify the effect of intensive treatment (i.e. intensive glucose
lowering either alone or as part of a multifactorial intervention) on non-fatal
myocardial infarction (MI), non-fatal stroke, cardiovascular disease (CV)
mortality and all-cause mortality in patients with Type 2 diabetes. A secondary
objective was to investigate the association between the treatment effect and
trial-level characteristics such as average age, duration of Type 2 diabetes, the
percentage male and the baseline event rate.
METHODS: We searched MEDLINE, Embase and the Cochrane Central Register of
Controlled Trials without language restrictions from inception to 13 May 2015. We
included randomized controlled trials (RCTs) that evaluated intensive treatment
in adult patients with Type 2 diabetes. The review was registered on PROSPERO
(registration number 42014013860). We pooled rates across studies using random
effects meta-analysis and investigated study-level covariate associations using
Bayesian meta-regression.
RESULTS: A total of 19 RCTs were included: 16 examined non-fatal MI (n = 79 595),
14 non-fatal stroke (n = 78 568), 18 cardiovascular mortality (n = 83 938) and 18
all-cause mortality (n = 84 266). There was evidence to suggest that compared
with standard care, intensive treatment reduced the risk of non-fatal MI [risk
ratio (RR) 0.90, 95% confidence interval (CI) 0.83-0.96], but not non-fatal
stroke (RR 0.96, 95% CI 0.86-1.07), CV mortality (RR 1.00, 95% CI 0.90-1.11) or
all-cause mortality (RR 1.00, 95% CI 0.94-1.06). Compared with standard care,
multifactorial interventions alone reduced non-fatal stroke (RR 0.53, 95% CI
0.32-0.0.87) but not non-fatal MI (RR 0.66, 95% CI 0.38-1.03), CV mortality (RR
0.72, 95% CI 0.46-1.14) or all-cause mortality (RR 0.82, 95% CI 0.64-1.05). There
was no evidence to suggest that the effect of intensive treatment on
cardiovascular and mortality outcomes was associated with mean age, mean duration
of Type 2 diabetes and percentage of male patients across trials. There was
evidence to suggest that the effectiveness of intensive treatment to reduce
mortality outcomes increases as the baseline incidence of cardiovascular
mortality [ratio of hazard = 0.82, 95% credible interval (CrI) 0.65-0.99]
increased across trials, but not baseline incidence of non-fatal MI, non-fatal
stroke and all-cause mortality. Intensive glucose-lowering and multifactorial
interventions are predicted to have the desired beneficial effect of reducing CVD
mortality in populations where the incidence rate is greater than about 6.3 CVD
deaths per 1000 person-years or an average 10-year CVD risk of 6.3%.
CONCLUSIONS: Apart from non-fatal MIs, there was no evidence that intensive
glucose-lowering and multifactorial interventions reduced or increased the risk
of cardiovascular and mortality outcomes. Intensive glucose-lowering and
multifactorial interventions are likely to be beneficial in populations with a
higher baseline incidence of CV mortality, but there was no evidence of an
association with the mean duration of Type 2 diabetes. Multifactorial
interventions had a much greater impact on non-fatal MI and non-fatal strokes.
(PROSPERO registration no.: 42014013860).

© 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

DOI: 10.1111/dme.12885
PMID: 26282461  [Indexed for MEDLINE]


182. JAMA Psychiatry. 2016 Mar;73(3):199-210. doi: 10.1001/jamapsychiatry.2015.2955.

Efficacy, Acceptability, and Tolerability of Antipsychotics in
Treatment-Resistant Schizophrenia: A Network Meta-analysis.

Samara MT(1), Dold M(2), Gianatsi M(3), Nikolakopoulou A(3), Helfer B(1), Salanti
G(4), Leucht S(1).

Author information:
(1)Department of Psychiatry and Psychotherapy, Technische Universität München,
Munich, Germany.
(2)Department of Psychiatry and Psychotherapy, Medical University of Vienna,
Vienna, Austria.
(3)Department of Hygiene and Epidemiology, University of Ioannina School of
Medicine, Ioannina, Greece.
(4)Institute of Social and Preventive Medicine, University of Bern, Bern,
Switzerland5Berner Institut für Hausarztmedizin, University of Bern, Bern,
Switzerland6CTU Bern (Clinical Trials Unit), Department of Clinical Research,
University of Bern, Bern, Switz.

Comment in
    JAMA Psychiatry. 2016 Mar;73(3):187-8.

IMPORTANCE: In treatment-resistant schizophrenia, clozapine is considered the
standard treatment. However, clozapine use has restrictions owing to its many
adverse effects. Moreover, an increasing number of randomized clinical trials
(RCTs) of other antipsychotics have been published.
OBJECTIVE: To integrate all the randomized evidence from the available
antipsychotics used for treatment-resistant schizophrenia by performing a network
meta-analysis.
DATA SOURCES: MEDLINE, EMBASE, Biosis, PsycINFO, PubMed, Cochrane Central
Register of Controlled Trials, World Health Organization International Trial
Registry, and clinicaltrials.gov were searched up to June 30, 2014.
STUDY SELECTION: At least 2 independent reviewers selected published and
unpublished single- and double-blind RCTs in treatment-resistant schizophrenia
(any study-defined criterion) that compared any antipsychotic (at any dose and in
any form of administration) with another antipsychotic or placebo.
DATA EXTRACTION AND SYNTHESIS: At least 2 independent reviewers extracted all
data into standard forms and assessed the quality of all included trials with the
Cochrane Collaboration's risk-of-bias tool. Data were pooled using a
random-effects model in a Bayesian setting.
MAIN OUTCOMES AND MEASURES: The primary outcome was efficacy as measured by
overall change in symptoms of schizophrenia. Secondary outcomes included change
in positive and negative symptoms of schizophrenia, categorical response to
treatment, dropouts for any reason and for inefficacy of treatment, and important
adverse events.
RESULTS: Forty blinded RCTs with 5172 unique participants (71.5% men; mean [SD]
age, 38.8 [3.7] years) were included in the analysis. Few significant differences
were found in all outcomes. In the primary outcome (reported as standardized mean
difference; 95% credible interval), olanzapine was more effective than quetiapine
(-0.29; -0.56 to -0.02), haloperidol (-0. 29; -0.44 to -0.13), and sertindole
(-0.46; -0.80 to -0.06); clozapine was more effective than haloperidol (-0.22;
-0.38 to -0.07) and sertindole (-0.40; -0.74 to -0.04); and risperidone was more
effective than sertindole (-0.32; -0.63 to -0.01). A pattern of superiority for
olanzapine, clozapine, and risperidone was seen in other efficacy outcomes, but
results were not consistent and effect sizes were usually small. In addition,
relatively few RCTs were available for antipsychotics other than clozapine,
haloperidol, olanzapine, and risperidone. The most surprising finding was that
clozapine was not significantly better than most other drugs.
CONCLUSIONS AND RELEVANCE: Insufficient evidence exists on which antipsychotic is
more efficacious for patients with treatment-resistant schizophrenia, and blinded
RCTs-in contrast to unblinded, randomized effectiveness studies-provide little
evidence of the superiority of clozapine compared with other second-generation
antipsychotics. Future clozapine studies with high doses and patients with
extremely treatment-refractory schizophrenia might be most promising to change
the current evidence.

DOI: 10.1001/jamapsychiatry.2015.2955
PMID: 26842482  [Indexed for MEDLINE]


183. Medicine (Baltimore). 2016 Mar;95(11):e3060. doi: 10.1097/MD.0000000000003060.

Comparative Effectiveness of Biologic Therapy Regimens for Ankylosing
Spondylitis: A Systematic Review and a Network Meta-Analysis.

Chen C(1), Zhang X, Xiao L, Zhang X, Ma X.

Author information:
(1)From the Department of Spinal Surgery (CC, XLZ, XLM), Tianjin Hospital,
Tianjin; Air Force Centre of Aviation Medical Evaluation and Training (LX),
Hangzhou, Zhejiang; and Department of Orthopedics (XSZ), Chinese PLA General
Hospital, Beijing, China.

To establish the comparative effectiveness of all available biologic therapy
regimens for ankylosing spondylitis, we performed a systematic review and a
Bayesian network meta-analysis of randomized controlled trials. PubMed, Medline,
Embase, Cochrane library, and ClinicalTrials.gov were searched from the inception
of each database to June 2015. Systematic review and network meta-analysis was
reported according to the Preferred Reporting Items of Systematic Reviews and
Meta-Analyses Extension Statement for Reporting of Systematic Reviews
Incorporating Network Meta-analyses. The primary outcome was 20% improvement of
Assessments in SpondyloArthritis International Society Response Criteria (ASAS20)
at Week 12 or 14; secondary outcomes were ASAS40, ASAS5/6, ASAS partial remission
and 50% improvement in baseline Bath ankylosing spondylitis (AS) disease activity
index. We reported relative risks and 95% confidence intervals from direct
meta-analysis and 95% credible intervals from Bayesian network meta-analysis, and
ranked the treatment for outcomes. We also used Grading of Recommendations
Assessment, Development and Evaluation criteria to appraise quality of evidence.
Fourteen RCTs comprising 2672 active AS patients were included in the network
meta-analysis. Most biologic therapy regimens were more effective than placebo
regarding all the outcomes assessed, except for secukinumab and tocilizumab. No
differences between biologic therapies in the treatment of AS could be found,
except for the finding that infliximab 5 mg was superior to tocilizumab.
Infliximab 5 mg/kg had the highest probability of being ranked the best for
achieving ASAS20, whereas notably, secukinumab had the highest probability of
being ranked the second best. Our study suggests that no differences between
biologic therapies in the treatment of AS could be found except that infliximab 5
mg was superior to tocilizumab. Infliximab 5 mg/kg seems to be the better
biologic therapy regimen for AS. Secukinumab appears promising, though additional
data is warranted. Nevertheless, these interpretations should be accepted very
cautiously.

DOI: 10.1097/MD.0000000000003060
PMCID: PMC4839911
PMID: 26986130  [Indexed for MEDLINE]


184. Medicine (Baltimore). 2016 Mar;95(11):e3059. doi: 10.1097/MD.0000000000003059.

Treatments for the Fifth Metacarpal Neck Fractures: A Network Meta-analysis of
Randomized Controlled Trials.

Zong SL(1), Zhao G, Su LX, Liang WD, Li LG, Cheng G, Wang AJ, Cao XQ, Zheng QT,
Li LD, Kan SL.

Author information:
(1)From the Department of Orthopedics Institute, The Second Hospital of Tangshan
(S-LZ, GZ, L-XS, W-DL, L-GL, A-JW, X-QC, Q-TZ, L-DL); The Trauma Laboratory of
the North China University of Science and Technology, Tangshan, Hebei Province
(GC); and Department of Orthopedics Institute, Tianjin hospital, Tianjin Medical
University, Tianjin, People's Republic of China (S-LK).

The fifth metacarpal neck fractures (commonly termed boxer's fractures) are the
most common type of metacarpal fractures. Many types of treatments are available
in clinical practice, some of which have already been compared with other
treatments by various researchers. However, a comprehensive treatment comparison
is lacking. We estimated the comparative efficacy of different interventions for
total complications, through a network meta-analysis of randomized controlled
trials. We conducted a systematic search of the literature through October 2015.
The outcome measurements were the total complications. We used a Bayesian network
meta-analysis to combine direct and indirect evidence and to estimate the
relative effects of treatment. We identified 6 RCTs registering a total of 288
patients who were eligible for our network meta-analysis. The literature's
quality is relatively high. The median Structured Effectiveness for Quality
Evaluation of Study score for the included trials was 33.8. The overall
methodological quality was high. Of the 6 studies, all were 2-arm controlled
trials comparing active intervention. Among the 4 treatments--conservative
treatment (CT), antegrade intramedullary nailing (AIMN), transverse pinning (TP)
with K-wires, and plate fixation (PF)--CT had the best rankings (ie, lowest risk
of total complications), followed by PF, AIMN, and TP (ie, highest risk of total
complications). Furthermore, we also presented the results using surface under
the cumulative ranking curve. The surface under the cumulative ranking curve
probabilities were 94.1%, 52.9%, 37.3%, and 15.7% for CT, PF, AIMN, and TP,
respectively. In conclusion, current evidence suggested that conservative
treatment is the optimum treatment for the fifth metacarpal neck fractures
because of reduced total complication rates. Moreover, the TP with K-wires is the
worst option with highly total complication rates. PF and AIMN therapy should be
considered as the first-line choices. Larger and higher-quality randomized
controlled trials are required to confirm these conclusions and better inform
clinical decision-making.

DOI: 10.1097/MD.0000000000003059
PMCID: PMC4839910
PMID: 26986129  [Indexed for MEDLINE]


185. Menopause. 2016 Mar;23(3):294-303. doi: 10.1097/GME.0000000000000552.

Comparative efficacy and safety of estradiol transdermal preparations for the
treatment of vasomotor symptoms in postmenopausal women: an indirect comparison
meta-analysis.

Derzko C(1), Sergerie M, Siliman G, Alberton M, Thorlund K.

Author information:
(1)1Department of Obstetrics & Gynecology and Division of Endocrinology,
Department of Medicine, St Michael's Hospital, University of Toronto, Toronto,
Ontario 2Teva Canada Innovation, Montreal, Quebec 3Redwood Outcomes Inc,
Vancouver, British Columbia 4Department of Clinical Epidemiology & Biostatistics,
McMaster University, Hamilton, Ontario, Canada.

OBJECTIVE: Divigel and Estrogel are estradiol gels for the treatment of
postmenopausal women with moderate to severe vasomotor symptoms. They differ with
respect to several factors including estradiol concentration and surface
application, and cannot be compared solely on the basis of their estradiol dose.
No randomized clinical trials have compared them head to head, but both have been
compared with placebo. Therefore, the objective of this study was to conduct a
systematic review and network meta-analysis of the two estradiol gels.
METHODS: We performed a comprehensive systematic literature review. One
publication reporting on one Divigel trial, three publications reporting on two
Estrogel trials, and five publications reporting on other estradiol transdermal
preparations were identified. Efficacy outcomes were change from baseline in
daily hot flush frequency and change from baseline in daily hot flush severity.
Safety outcomes were frequency of treatment-related adverse events (AEs) and
frequency of treatment-emergent AEs leading to discontinuation. Bayesian indirect
treatment comparison meta-analysis of trial-level data was performed in
accordance with the International Society for Pharmacoeconomics and Outcomes
Research, Academy of Managed Care Pharmacy, National Pharmaceutical Council
(ISPOR-AMCP-NPC) Good Practice Questionnaire. All outcomes were compared with
respect to doses of the considered preparations.
RESULTS: For hot flush frequency, Divigel 0.25 mg was similar to Divigel 0.5 mg
and to Estrogel 0.75 mg, and was statistically significantly superior to Estrogel
1.5 mg. The largest effect was observed with Divigel 1.0 mg (mean difference of
3.91 hot flushes/wk vs placebo), and was statistically significantly superior to
all other interventions. The 1.5 mg Estrogel dose was associated with the
smallest estimate of efficacy. For hot flush severity, Divigel 0.25 mg was
similar to the efficacy of Divigel 0.5 mg, and for 0.25 mg and 0.5 mg of other
estradiol gels, but was statistically inferior to Divigel 1.0 mg, Estrogel
0.75 mg, Estrogel 1.5 mg, and the 1.0 and 1.5 mg doses of all other estradiol
gels. The estimated efficacy of Divigel 0.5 mg was similar to that of Estrogel
0.75 mg, Estrogel 1.5 mg, and the 0.25 and 0.5 mg doses of other transdermal
estradiol preparations. Risks of treatment-related AEs for Divigel 0.25 mg,
Divigel 0.5 mg, Estrogel 0.75 mg, and Estrogel 1.5 mg were similar and all were
of a slightly higher risk than placebo. Among these, Divigel 1.0 mg, Estrogel
1.5 mg, and other gels 0.5 mg were statistically significantly less safe than
placebo. However, for treatment-emergent AEs leading to discontinuation, none of
the gels were associated with statistically significantly higher relative risks
compared with placebo. In this study, statistically significant refers to the 95%
credible intervals used in the Bayesian Network Analysis.
CONCLUSIONS: Using network meta-analysis for indirect treatment comparison, we
have shown that the efficacy of Divigel 0.25 mg, as measured by reduced hot flush
frequency and severity, was similar to that of Divigel 0.5 mg and of Estrogel
0.75 and 1.5 mg. Overall, our analysis showed that Divigel 1.0 mg provided the
best efficacy profile, but that this treatment was also associated with a higher
risk of AEs. The network meta-analysis also showed that treatment with Estrogel
1.5 mg was associated with the smallest estimate of reduction in frequency of hot
flushes.

DOI: 10.1097/GME.0000000000000552
PMID: 26382309  [Indexed for MEDLINE]


186. Prog Cardiovasc Dis. 2016 Mar-Apr;58(5):483-94. doi: 10.1016/j.pcad.2015.12.001.
Epub 2015 Dec 7.

Risk of Myocardial Infarction in Patients with Long-Term Non-Vitamin K Antagonist
Oral Anticoagulant Treatment.

Tornyos A(1), Kehl D(2), D'Ascenzo F(3), Komócsi A(4).

Author information:
(1)Department of Interventional Cardiology, Heart Institute, University of Pécs.
(2)Department of Statistic and Econometrics, University of Pécs, Hungary.
(3)Division of Cardiology, Department of Internal Medicine, Citta della Salute e
della Scienza, Turin, Italy.
(4)Department of Interventional Cardiology, Heart Institute, University of Pécs.
Electronic address: andras.komocsi@pte.hu.

The relative cardiovascular (CV) safety of oral anticoagulants continues to be
debated, and in particular concerns for risk of myocardial infarction (MI) have
been raised. We analyzed the risk of MI in patients treated long term with oral
anticoagulants (vitamin K antagonists [VKA], direct thrombin inhibitors or
activated X factor antagonist) for atrial fibrillation, deep vein thrombosis or
pulmonary embolism using a network meta-analysis (NMA).METHODS: Randomized, phase
3 trials comparing novel anticoagulants to VKA were searched. Information on
study design and clinical outcomes was extracted. The primary end-point of the
analysis was the occurrence of MI or acute coronary syndrome. A Bayesian multiple
treatment analysis was performed using fixed-effect and random-effects modeling.
RESULTS: Twelve trials including 100,524 randomized patients were analyzed. The
odds for MI in NMA were worse with dabigatran when compared to VKA, rivaroxaban,
apixaban, and edoxaban (OR: 0.66 CI: 0.49-0.87; OR: 0.56 CI: 0.38-0.82, OR: 0.59
CI 0.40-0.88, and OR: 0.71 CI: 0.50-1.0, respectively).The posterior probability
of being the first best choice of treatment was 53.5% for rivaroxaban, 33.8% for
apixaban, 9.5% for ximelagatran, 2.0% for edoxaban, 1.2% for VKA, and 0.007% for
dabigatran.
CONCLUSIONS: There is a considerable heterogeneity regarding CV safety among oral
anticoagulants. Differences in risk of MI may influence the choice of treatment.
Multiple treatment NMA found 29%-44% higher odds of MI with dabigatran supporting
the concerns regarding its CV safety.

Copyright © 2015 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.pcad.2015.12.001
PMID: 26674596  [Indexed for MEDLINE]


187. PLoS One. 2016 Feb 26;11(2):e0149631. doi: 10.1371/journal.pone.0149631.
eCollection 2016.

Medical Therapies for Uterine Fibroids - A Systematic Review and Network
Meta-Analysis of Randomised Controlled Trials.

Gurusamy KS(1), Vaughan J(1), Fraser IS(2)(3), Best LM(1), Richards T(1).

Author information:
(1)University College London, Division of Surgery & Interventional Science, 9th
Floor, Royal Free Hospital, Pond Street, London, NW3 2QG, United Kingdom.
(2)Sydney Centre for Reproductive Health Research, Family Planning New South
Wales, Sydney, NSW 2131, Australia.
(3)University of Sydney, Sydney, NSW 2006, Australia.

BACKGROUND: Uterine fibroids are common, often symptomatic and a third of women
need repeated time off work. Consequently 25% to 50% of women with fibroids
receive surgical treatment, namely myomectomy or hysterectomy. Hysterectomy is
the definitive treatment as fibroids are hormone dependent and frequently
recurrent. Medical treatment aims to control symptoms in order to replace or
delay surgery. This may improve the outcome of surgery and prevent recurrence.
PURPOSE: To determine whether any medical treatment can be recommended in the
treatment of women with fibroids about to undergo surgery and in those for whom
surgery is not planned based on currently available evidence.
STUDY SELECTION: Two authors independently identified randomised controlled
trials (RCT) of all pharmacological treatments aimed at the treatment of fibroids
from a list of references obtained by formal search of MEDLINE, EMBASE, Cochrane
library, Science Citation Index, and ClinicalTrials.gov until December 2013.
DATA EXTRACTION: Two authors independently extracted data from identified
studies.
DATA SYNTHESIS: A Bayesian network meta-analysis was performed following the
National Institute for Health and Care Excellence-Decision Support Unit
guidelines. Odds ratios, rate ratios, or mean differences with 95% credible
intervals (CrI) were calculated.
RESULTS AND LIMITATIONS: A total of 75 RCT met the inclusion criteria, 47 of
which were included in the network meta-analysis. The overall quality of evidence
was very low. The network meta-analysis showed differing results for different
outcomes.
CONCLUSIONS: There is currently insufficient evidence to recommend any medical
treatment in the management of fibroids. Certain treatments have future promise
however further, well designed RCTs are needed.

DOI: 10.1371/journal.pone.0149631
PMCID: PMC4769153
PMID: 26919185  [Indexed for MEDLINE]


188. BMJ Open. 2016 Feb 24;6(2):e009417. doi: 10.1136/bmjopen-2015-009417.

SGLT-2 receptor inhibitors for treating patients with type 2 diabetes mellitus: a
systematic review and network meta-analysis.

Shyangdan DS(1), Uthman OA(2), Waugh N(3).

Author information:
(1)Warwick Medical School, Coventry, UK.
(2)Division of Health Sciences, Centre for Applied Health Research and Delivery
(WCAHRD), Warwick Medical School, Coventry, UK.
(3)Public Health Medicine and Health Technology Assessment Warwick Medical
School, Coventry, UK.

OBJECTIVE: Because of the lack of head-to-head trials, the aim was to indirectly
compare sodium glucose transporter-2 (SGLT-2) inhibitors in the treatment of type
2 diabetes.
DESIGN: Systematic review and network meta-analysis.
DATA SOURCES: MEDLINE and EMBASE were searched from January 2005 to January 2015.
ELIGIBILITY CRITERIA: Randomised controlled trials assessing the efficacy of
SGLT-2 inhibitors in patients with type 2 diabetes inadequately controlled with
diet and exercise alone or metformin monotherapy. Minimum duration 24 weeks.
Indirect comparison was undertaken using Bayesian methods.
RESULTS: In monotherapy, a greater proportion of patients achieved a glycated
haemoglobin (HbA1c) level of <7% on canagliflozin 300 mg than on canagliflozin
100 mg (risk ratio (RR) 0.72%, 95% credible intervals (CrI) 0.59% to 0.87%) and
dapagliflozin 10 mg (RR 0.63, 95% CrI 0.48 to 0.85) but there were no significant
differences compared with either dose of empagliflozin. In monotherapy,
canagliflozin 300 mg reduced HbA1c more than other SGLT-2 inhibitors (mean
difference ranged from 0.20% to 0.64%). There were no significant differences in
weight reduction. All the flozins reduced systolic blood pressure (SBP) more than
placebo, ranging from a reduction of 6 mm Hg with canagliflozin 300-2.6 mm Hg
with empagliflozin 10 mg. In dual therapy with metformin, all flozins were more
effective than placebo for achieving HbA1c <7%, and reducing HbA1c, weight and
SBP. The proportions achieving HbA1c level of <7% were mostly similar.
Canagliflozin 300 mg reduced HbA1c more than the other drugs but this just
reached statistical significance only against canagliflozin 100 mg (MD 0.15, CrI
0.04 to 0.26).
CONCLUSIONS: There were few differences among the SGLT-2 inhibitors, but in
monotherapy, the glucose-lowering effect of canagliflozin 300 mg is slightly
greater than most other SGLT-2 inhibitors.

Published by the BMJ Publishing Group Limited. For permission to use (where not
already granted under a licence) please go to
http://www.bmj.com/company/products-services/rights-and-licensing/

DOI: 10.1136/bmjopen-2015-009417
PMCID: PMC4769433
PMID: 26911584  [Indexed for MEDLINE]


189. BMJ Open. 2016 Feb 23;6(2):e009122. doi: 10.1136/bmjopen-2015-009122.

Comparative assessment of onabotulinumtoxinA and mirabegron for overactive
bladder: an indirect treatment comparison.

Freemantle N(1), Ginsberg DA(2), McCool R(3), Fleetwood K(4), Arber M(3), Khalaf
K(5), Loveman C(6), Ni Q(7), Glanville J(3).

Author information:
(1)Department of Primary Care and Population Health, University College London,
London, UK.
(2)USC Institute of Urology, Keck School of Medicine of USC, Los Angeles,
California, USA.
(3)York Health Economics Consortium, University of York, York, UK.
(4)Quantics, Edinburgh, UK.
(5)Allergan, Inc., Irvine, California, USA Xcenda, Palm Harbor, Florida, USA.
(6)Allergan Holdings Ltd, Marlow, UK.
(7)Allergan, Inc., Bridgewater, New Jersey, USA Celgene, Summit, New Jersey, USA.

CONTEXT: OnabotulinumtoxinA and mirabegron have recently gained marketing
authorisation to treat symptoms of overactive bladder (OAB).
OBJECTIVE: To evaluate the relative efficacy of mirabegron and onabotulinumtoxinA
in patients with idiopathic OAB.
DESIGN: Network meta-analysis.
DATA SOURCES: A search of 9 electronic databases, review documents, guidelines
and websites.
METHODS: Randomised trials comparing any licensed dose of onabotulinumtoxinA or
mirabegron with each other, anticholinergic drugs or placebo were eligible (19
randomised trials were identified). 1 reviewer extracted data from the studies
and a second reviewer checked the data. Candidate trials were assessed for
similarity and networks were developed for each outcome. Bayesian network
meta-analysis was conducted using both fixed-effects and random-effects models.
When there were differences in mean baseline values between mirabegron and
onabotulinumtoxinA trials they were adjusted for using network meta-regression
(NMR).
RESULTS: No studies directly comparing onabotulinumtoxinA to mirabegron were
identified. A network was created for each of the 7 outcomes, with 3-9 studies
included in each individual network. The trials included in the networks were
broadly similar. Patients in the onabotulinumtoxinA trials had more urinary
incontinence and urgency episodes at baseline than patients in the mirabegron
trials and these differences were adjusted for using NMR. Both onabotulinumtoxinA
and mirabegron were more efficacious than placebo at reducing the frequency of
urinary incontinence, urgency, urination and nocturia. OnabotulinumtoxinA was
more efficacious than mirabegron (50 and 25 mg) in completely resolving daily
episodes of urinary incontinence and urgency and in reducing the frequency of
urinary incontinence, urgency and urination. NMR supported the results of the
network meta-analysis.
CONCLUSIONS: In the absence of head-to-head trials comparing onabotulinumtoxinA
to mirabegron, this indirect comparison indicates that onabotulinumtoxinA may be
superior to mirabegron in improving symptoms of urinary incontinence, urgency and
urinary frequency in patients with idiopathic OAB.

Published by the BMJ Publishing Group Limited. For permission to use (where not
already granted under a licence) please go to
http://www.bmj.com/company/products-services/rights-and-licensing/

DOI: 10.1136/bmjopen-2015-009122
PMCID: PMC4769403
PMID: 26908514  [Indexed for MEDLINE]


190. PLoS One. 2016 Feb 18;11(2):e0149592. doi: 10.1371/journal.pone.0149592.
eCollection 2016.

Evaluation of a Rapid Point of Care Test for Detecting Acute and Established HIV
Infection, and Examining the Role of Study Quality on Diagnostic Accuracy: A
Bayesian Meta-Analysis.

Smallwood M(1), Vijh R(2), Nauche B(3), Lebouché B(4)(5), Joseph L(1)(2), Pant
Pai N(2)(6).

Author information:
(1)Department of Epidemiology, Biostatistics and Occupational Health, McGill
University, Montréal, Quebec, Canada.
(2)Division of Clinical Epidemiology, Department of Medicine, McGill University
Health Centre, Montreal, Quebec, Canada.
(3)Medical Library, Royal Victoria Hospital, McGill University Health Centre,
Montreal, Canada.
(4)Chronic Viral Illness Service, Research Institute of the McGill University
Health Centre, Montreal, Canada.
(5)Department of Family Medicine, McGill University, Montreal, Canada.
(6)Department of Medicine, McGill University, Montreal, Quebec, Canada.

INTRODUCTION: Fourth generation (Ag/Ab combination) point of care HIV tests like
the FDA-approved Determine HIV1/2 Ag/Ab Combo test offer the promise of timely
detection of acute HIV infection, relevant in the context of HIV control.
However, a synthesis of their performance has not yet been done. In this
meta-analysis we not only assessed device performance but also evaluated the role
of study quality on diagnostic accuracy.
METHODS: Two independent reviewers searched seven databases, including
conferences and bibliographies, and independently extracted data from 17 studies.
Study quality was assessed with QUADAS-2. Data on sensitivity and specificity
(overall, antigen, and antibody) were pooled using a Bayesian hierarchical random
effects meta-analysis model. Subgroups were analyzed by blood samples
(serum/plasma vs. whole blood) and study designs (case-control vs.
cross-sectional).
RESULTS: The overall specificity of the Determine Combo test was 99.1%, 95%
credible interval (CrI) [97.3-99.8]. The overall pooled sensitivity for the
device was at 88.5%, 95% [80.1-93.4]. When the components of the test were
analyzed separately, the pooled specificities were 99.7%, 95% CrI [96.8-100] and
99.6%, 95% CrI [99.0-99.8], for the antigen and antibody components,
respectively. Pooled sensitivity of the antibody component was 97.3%, 95% CrI
[60.7-99.9], and pooled sensitivity for the antigen component was found to be
12.3%, 95% (CrI) [1.1-44.2]. No significant differences were found between
subgroups by blood sample or study design. However, it was noted that many
studies restricted their study sample to p24 antigen or RNA positive specimens,
which may have led to underestimation of overall test performance. Detection
bias, selection (spectrum) bias, incorporation bias, and verification bias
impaired study quality.
CONCLUSIONS: Although the specificity of all test components was high, antigenic
sensitivity will merit from an improvement. Besides the accuracy of the device
itself, study quality, also impacts the performance of the test. These factors
must be kept in mind in future evaluations of an improved device, relevant for
global scale up and implementation.

DOI: 10.1371/journal.pone.0149592
PMCID: PMC4758636
PMID: 26891218  [Indexed for MEDLINE]


191. Int J Cardiol. 2016 Feb 15;205:89-96. doi: 10.1016/j.ijcard.2015.12.005. Epub
2015 Dec 17.

Efficacy and safety of antithrombotic regimens after coronary intervention in
patients on oral anticoagulation: Traditional and Bayesian meta-analysis of
clinical trials.

Liu J(1), Fan M(2), Zhao J(1), Zhao B(3), Zhang C(1), Liu C(1), Dong Y(4).

Author information:
(1)Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen
University, Guangzhou 510080, China.
(2)Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen
University, Guangzhou 510080, China.
(3)Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-sen
University, Guangzhou 510080, China.
(4)Department of Cardiology, The First Affiliated Hospital of Sun Yat-sen
University, Guangzhou 510080, China. Electronic address: dongxg@mail.sysu.edu.cn.

OBJECTIVE: To perform a systematic review and meta-analysis to assess the
efficacy and safety of diverse antithrombotic regimens in patients on long-term
anticoagulation after percutaneous coronary intervention (PCI).
METHODS: After searching electronic database (up to 27 June 2015), we included
trials comparing dual antiplatelet therapy (aspirin plus clopidogrel), oral
anticoagulant (OAC) plus clopidogrel, OAC plus aspirin, or triple therapy (OAC
with clopidogrel and aspirin). Efficacy outcomes were major adverse
cardiovascular event (MACE), ischemic stroke, myocardial infarction (MI), and
all-cause mortality; safety outcomes included major bleeding and any bleeding. We
conducted both traditional and Bayesian network meta-analysis, computing pooled
odds ratio (OR) with 95% confidence intervals (CI) to compare diverse
antithrombotic therapies simultaneously.
RESULTS: Eighteen trials were included in the quantitative analysis. OAC plus
clopidogrel and triple therapy were associated with a lower risk of MACE,
ischemic stroke, MI and all-cause mortality compared with dual antiplatelet or
OAC plus aspirin regimens. OAC plus clopidogrel was ranked the most efficacious
option without an increase in bleeding episodes. However, triple therapy improved
the efficacy outcomes at the expense of increasing hemorrhage. For the initial
short-term outcomes, OAC plus clopidogrel inconclusively reduced the risk of MACE
and had a significantly lower risk of any bleeding.
CONCLUSIONS: OAC plus clopidogrel may be the optimal antithrombotic therapy in
patients on oral anticoagulation undergoing PCI, which has equal or better
efficacy outcomes without increasing the rates of bleeding episodes. Moreover, we
found initial triple therapy to be unnecessary as it increased the risk of
bleeding.

Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

DOI: 10.1016/j.ijcard.2015.12.005
PMID: 26724753  [Indexed for MEDLINE]


192. Neurology. 2016 Feb 9;86(6):566-76. doi: 10.1212/WNL.0000000000002350. Epub 2016
Jan 13.

Accuracy of clinical diagnosis of Parkinson disease: A systematic review and
meta-analysis.

Rizzo G(1), Copetti M(1), Arcuti S(1), Martino D(1), Fontana A(1), Logroscino
G(2).

Author information:
(1)From the Department of Clinical Research in Neurology (G.R., S.A., G.L.),
University of Bari, Tricase; Department of Biomedical and Neuromotor Sciences
(G.R.), University of Bologna; Unit of Biostatistics (M.C., A.F.), IRCCS "Casa
Sollievo della Sofferenza," San Giovanni Rotondo, Italy; Department of Neurology
(D.M.), King's College NHS Foundation Trust; Department of Neurology (D.M.),
Queen Elizabeth Hospital, Lewisham and Greenwich NHS Trust, London, UK; and
Department of Basic Medical Science (G.L.), Neuroscience and Sense Organs,
University of Bari, Italy.
(2)From the Department of Clinical Research in Neurology (G.R., S.A., G.L.),
University of Bari, Tricase; Department of Biomedical and Neuromotor Sciences
(G.R.), University of Bologna; Unit of Biostatistics (M.C., A.F.), IRCCS "Casa
Sollievo della Sofferenza," San Giovanni Rotondo, Italy; Department of Neurology
(D.M.), King's College NHS Foundation Trust; Department of Neurology (D.M.),
Queen Elizabeth Hospital, Lewisham and Greenwich NHS Trust, London, UK; and
Department of Basic Medical Science (G.L.), Neuroscience and Sense Organs,
University of Bari, Italy. giancarlo.logroscino@uniba.it.

OBJECTIVE: To evaluate the diagnostic accuracy of clinical diagnosis of Parkinson
disease (PD) reported in the last 25 years by a systematic review and
meta-analysis.
METHODS: We searched for articles published between 1988 and August 2014. Studies
were included if reporting diagnostic parameters regarding clinical diagnosis of
PD or crude data. The selected studies were subclassified based on different
study setting, type of test diagnosis, and gold standard. Bayesian meta-analyses
of available data were performed.
RESULTS: We selected 20 studies, including 11 using pathologic examination as
gold standard. Considering only these 11 studies, the pooled diagnostic accuracy
was 80.6% (95% credible interval [CrI] 75.2%-85.3%). Accuracy was 73.8% (95% CrI
67.8%-79.6%) for clinical diagnosis performed mainly by nonexperts. Accuracy of
clinical diagnosis performed by movement disorders experts rose from 79.6% (95%
CrI 46%-95.1%) of initial assessment to 83.9% (95% CrI 69.7%-92.6%) of refined
diagnosis after follow-up. Using UK Parkinson's Disease Society Brain Bank
Research Center criteria, the pooled diagnostic accuracy was 82.7% (95% CrI
62.6%-93%).
CONCLUSION: The overall validity of clinical diagnosis of PD is not satisfying.
The accuracy did not significantly improve in the last 25 years, particularly in
the early stages of disease, where response to dopaminergic treatment is less
defined and hallmarks of alternative diagnoses such as atypical parkinsonism may
not have emerged. Misclassification rate should be considered to calculate the
sample size both in observational studies and randomized controlled trials.
Imaging and biomarkers are urgently needed to improve the accuracy of clinical
diagnosis in vivo.

© 2016 American Academy of Neurology.

DOI: 10.1212/WNL.0000000000002350
PMID: 26764028  [Indexed for MEDLINE]


193. Eur Heart J. 2016 Feb 7;37(6):536-45. doi: 10.1093/eurheartj/ehv563. Epub 2015
Nov 17.

The impact of proprotein convertase subtilisin-kexin type 9 serine protease
inhibitors on lipid levels and outcomes in patients with primary
hypercholesterolaemia: a network meta-analysis.

Lipinski MJ(1), Benedetto U(2), Escarcega RO(1), Biondi-Zoccai G(3), Lhermusier
T(1), Baker NC(1), Torguson R(1), Brewer HB Jr(1), Waksman R(4).

Author information:
(1)Medstar Cardiovascular Research Network, Medstar Heart and Vascular Institute,
Medstar Washington Hospital Center, 110 Irving Street, NW, Suite 4B-1,
Washington, DC 20010, USA.
(2)University of Bristol, School of Clinical Sciences, Bristol Royal Infirmary,
Bristol, UK.
(3)Department of Medico-Surgical Sciences and Biotechnologies, Sapienza
University of Rome, Latina, Italy.
(4)Medstar Cardiovascular Research Network, Medstar Heart and Vascular Institute,
Medstar Washington Hospital Center, 110 Irving Street, NW, Suite 4B-1,
Washington, DC 20010, USA ron.waksman@medstar.net.

Comment in
    Ann Intern Med. 2016 Mar 15;164(6):JC31.

AIMS: We performed a network meta-analysis of randomized controlled trials (RCTs)
in patients with primary hypercholesterolaemia to compare the impact of
proprotein convertase subtilisin-kexin type 9 serine protease (PCSK9) inhibitors
with placebo and ezetimibe on lipid levels and outcomes.
METHODS AND RESULTS: MEDLINE/PubMed, Cochrane CENTRAL, and ClinicalTrials.gov
were searched for RCTs assessing PCSK9 inhibitors vs. other therapies in patients
with primary hypercholesterolaemia. Network meta-analysis with both a frequentist
approach and a Bayesian framework was performed to directly and indirectly
compare PCSK9 inhibition on lipid levels with ezetimibe and placebo. Odds ratios
with 95% confidence intervals (OR [95% CIs]) were generated with random-effects
models to compare outcomes. Our meta-analysis included 17 RCTs with 13 083
patients that were randomized to PCSK9 inhibitors (n = 8250), placebo (n = 3957),
ezetimibe (n = 846), or PCSK9 inhibitors and ezetimibe (n = 30). The mean age was
59 ± 10, 52% were male, 34% had coronary artery disease, 51% had hypertension,
19% had diabetes mellitus, baseline LDL of 122 ± 36 mg/dL, total cholesterol of
199 ± 39 mg/dL, and HDL of 51 ± 14 mg/dL. inhibitors significantly reduced LDL
cholesterol by 57% relative to placebo (P < 0.001) and 36.1% relative to
ezetimibe (P < 0.001). Proprotein convertase subtilisin-kexin type 9 serine
protease inhibitors reduced the incidence of all-cause mortality [OR 0.43 (95% CI
0.22-0.82), P = 0.01] but was associated with an increased incidence of
neurocognitive adverse events [OR 2.34 (95% CI 1.11-4.93), I(2) = 4%, P = 0.02]
when compared with placebo.
CONCLUSION: Proprotein convertase subtilisin-kexin type 9 serine protease
inhibition significantly improved lipid profiles and reduced the incidence of
all-cause mortality compared with placebo but had a higher rate of neurocognitive
adverse events. Thus, PCSK9 inhibitor therapy may serve as an alternative for
patients with statin intolerance and for those who do not respond to other lipid
reduction therapy.

Published on behalf of the European Society of Cardiology. All rights reserved. ©
The Author 2015. For permissions please email: journals.permissions@oup.com.

DOI: 10.1093/eurheartj/ehv563
PMID: 26578202  [Indexed for MEDLINE]


194. PLoS Negl Trop Dis. 2016 Feb 5;10(2):e0004418. doi: 10.1371/journal.pntd.0004418.
eCollection 2016 Feb.

Albendazole and Corticosteroids for the Treatment of Solitary Cysticercus
Granuloma: A Network Meta-analysis.

Zhao BC(1)(2), Jiang HY(3)(4), Ma WY(5), Jin DD(2), Li HM(2), Lu H(2), Nakajima
H(6), Huang TY(1), Sun KY(1), Chen SL(1), Chen KB(2).

Author information:
(1)Department of Clinical Medicine, Zhongshan School of Medicine, Sun Yat-sen
University, Guangzhou, China.
(2)Department of Orthopedics, the Third Affiliated Hospital of Southern Medical
University, Guangzhou, China.
(3)Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen
University, Guangzhou, China.
(4)Key Laboratory for Tropical Disease Control, Sun Yat-sen University,
Guangzhou, China.
(5)Department of Anesthesiology, the Sun Yat-sen Memorial Hospital of Sun Yat-sen
University, Guangzhou, China.
(6)Department of Orthopedics and Rehabilitation Medicine, Fukui University of
Medical Sciences, Fukui, Japan.

BACKGROUND: Solitary cysticercus granuloma (SCG) is the commonest form of
neurocysticercosis in the Indian subcontinent and in travelers. Several different
treatment options exist for SCG. We conducted a Bayesian network meta-analysis of
randomized clinical trials (RCTs) to identify the best treatment option to
prevent seizure recurrence and promote lesion resolution for patients with SCG.
METHODS AND PRINCIPAL FINDINGS: PubMed, EMBASE and the Cochrane Library databases
(up to June 1, 2015) were searched for RCTs that compared any anthelmintics or
corticosteroids, alone or in combination, with placebo or head to head and
reported on seizure recurrence and lesion resolution in patients with SCG. A
total of 14 RCTs (1277 patients) were included in the quantitative analysis
focusing on four different treatment options. A Bayesian network model computing
odds ratios (OR) with 95% credible intervals (CrI) and probability of being best
(Pbest) was used to compare all interventions simultaneously. Albendazole and
corticosteroids combination therapy was the only regimen that significantly
decreased the risk of seizure recurrence compared with conservative treatment (OR
0.32, 95% CrI 0.10-0.93, Pbest 73.3%). Albendazole and corticosteroids alone or
in combination were all efficacious in hastening granuloma resolution, but the
combined therapy remained the best option based on probability analysis (OR 3.05,
95% CrI 1.24-7.95, Pbest 53.9%). The superiority of the combination therapy
changed little in RCTs with different follow-up durations and in sensitivity
analyses. The limitations of this study include high risk of bias and short
follow-up duration in most studies.
CONCLUSIONS: Dual therapy of albendazole and corticosteroids was the most
efficacious regimen that could prevent seizure recurrence and promote lesion
resolution in a follow-up period of around one year. It should be recommended for
the management of SCG until more high-quality evidence is available.

DOI: 10.1371/journal.pntd.0004418
PMCID: PMC4744042
PMID: 26849048  [Indexed for MEDLINE]


195. BMC Med. 2016 Feb 3;14:18. doi: 10.1186/s12916-016-0558-x.

Treatment of idiopathic pulmonary fibrosis: a network meta-analysis.

Rochwerg B(1)(2)(3), Neupane B(4), Zhang Y(5)(6), Garcia CC(7)(8)(9), Raghu
G(10), Richeldi L(11), Brozek J(12)(13), Beyene J(14), Schünemann H(15)(16)(17).

Author information:
(1)Department of Medicine, Division of Critical Care, McMaster University, 1200
Main St W, L8S 4L8, Hamilton, ON, Canada. rochwerg@mcmaster.ca.
(2)Department of Clinical Epidemiology & Biostatistics, McMaster University,
Hamilton, ON, Canada. rochwerg@mcmaster.ca.
(3)MacGRADE Centre, McMaster University, Hamilton, ON, Canada.
rochwerg@mcmaster.ca.
(4)Department of Clinical Epidemiology & Biostatistics, McMaster University,
Hamilton, ON, Canada. neupanbp@mcmaster.ca.
(5)Department of Clinical Epidemiology & Biostatistics, McMaster University,
Hamilton, ON, Canada. changran87@gmail.com.
(6)MacGRADE Centre, McMaster University, Hamilton, ON, Canada.
changran87@gmail.com.
(7)Department of Clinical Epidemiology & Biostatistics, McMaster University,
Hamilton, ON, Canada. cuelloca@mcmaster.ca.
(8)MacGRADE Centre, McMaster University, Hamilton, ON, Canada.
cuelloca@mcmaster.ca.
(9)Tecnologico de Monterrey, School of Medicine, Monterrey, Mexico.
cuelloca@mcmaster.ca.
(10)Department of Medicine (Division of Pulmonary and Critical Care Medicine),
University of Washington Seattle, Seattle, WA, USA. graghu@uw.edu.
(11)National Institute for Health Research Southampton Respiratory Biomedical
Research Unit and Clinical and Experimental Sciences, University of Southampton,
Southampton, UK. l.richeldi@soton.ac.uk.
(12)Department of Clinical Epidemiology & Biostatistics, McMaster University,
Hamilton, ON, Canada. brozekj@mcmaster.ca.
(13)MacGRADE Centre, McMaster University, Hamilton, ON, Canada.
brozekj@mcmaster.ca.
(14)Department of Clinical Epidemiology & Biostatistics, McMaster University,
Hamilton, ON, Canada. beyene@mcmaster.ca.
(15)Department of Medicine, Division of Critical Care, McMaster University, 1200
Main St W, L8S 4L8, Hamilton, ON, Canada. schuneh@mcmaster.ca.
(16)Department of Clinical Epidemiology & Biostatistics, McMaster University,
Hamilton, ON, Canada. schuneh@mcmaster.ca.
(17)MacGRADE Centre, McMaster University, Hamilton, ON, Canada.
schuneh@mcmaster.ca.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease
associated with high morbidity and mortality. Effective treatments for IPF are
limited. Several recent studies have investigated novel therapeutic agents for
IPF, but very few have addressed their comparative benefits and harms.
METHODS: We performed a Bayesian network meta-analysis (NMA) to assess the
effects of different treatments for IPF on mortality and serious adverse events
(SAEs). We searched MEDLINE and EMBASE for randomized controlled trials (RCTs) up
to August 2015. The Grading of Recommendations Assessment, Development and
Evaluation (GRADE) approach served to assess the certainty in the evidence of
direct and indirect estimates. We calculated the surface under the cumulative
ranking curve (SUCRA) for each treatment. We included parallel group RCTs,
including factorial designs, but excluded quasi-randomized and cross-over trials.
Studies were only included if they involved adult (≥18 years of age) patients
with IPF as defined by the 2011 criteria and examined one of the 10 interventions
of interest (ambrisentan, bosentan, imatinib, macitentan, N-acetylcysteine,
nintedanib, pirfenidone, sildenafil, prednisone/azathioprine/N-acetylcysteine
triple therapy, and vitamin K antagonist).
RESULTS: A total of 19 RCTs (5,694 patients) comparing 10 different interventions
with placebo and an average follow-up period of 1 year fulfilled the inclusion
criteria. SUCRA analysis suggests nintedanib, pirfenidone, and sildenafil are the
three treatments with the highest probability of reducing mortality in IPF.
Indirect comparison showed no significant difference in mortality between
pirfenidone and nintedanib (NMA OR, 1.05; 95% CrI, 0.45-2.78, moderate certainty
of evidence), pirenidone and sildenafil (NMA OR, 2.26; 95% CrI, 0.44-13.17, low
certainty of evidence), or nintedanib and sildenafil (NMA OR 2.40; 95% CrI,
0.47-14.66, low certainty of evidence). Sildenafil, pirfenidone, and nintedanib
were ranked second, fourth, and sixth out of 10 for SAEs.
CONCLUSION: In the absence of direct comparisons between treatment interventions,
this NMA suggests that treatment with nintedanib, pirfenidone, and sildenafil
extends survival in patients with IPF. The SAEs of these agents are similar to
the other interventions and include mostly dermatologic and gastrointestinal
manifestations. Head-to-head comparisons need to confirm these findings.

DOI: 10.1186/s12916-016-0558-x
PMCID: PMC4741055
PMID: 26843176  [Indexed for MEDLINE]


196. BJOG. 2016 Feb;123(3):346-54. doi: 10.1111/1471-0528.13456. Epub 2015 Nov 5.

A systematic review and network meta-analysis comparing the use of Foley
catheters, misoprostol, and dinoprostone for cervical ripening in the induction
of labour.

Chen W(1), Xue J(2), Peprah MK(3), Wen SW(4)(5), Walker M(4)(5), Gao Y(6), Tang
Y(7).

Author information:
(1)Department of Nephropathy, Xiangya Hospital, Central South University,
Changsha, Hunan, China.
(2)Department of Medical Records Information, Xiangya Hospital, Central South
University, Changsha, Hunan, China.
(3)Department of Epidemiology and Community Medicine, University of Ottawa,
Ottawa, ON, Canada.
(4)OMNI Research Group, Department of Obstetrics and Gynecology, University of
Ottawa, Ottawa, ON, Canada.
(5)Ottawa Hospital Research Institute Clinical Epidemiology Program, Ottawa, ON,
Canada.
(6)Department of Obstetrics and Gynaecology, Southern Medical University,
Guangzhou, Guangdong, China.
(7)Department of Urology, The Third Xiangya Hospital of Central South University,
Changsha, Hunan, China.

Comment in
    BJOG. 2016 Feb;123(3):355.
    BJOG. 2016 Nov;123(12 ):2048-2049.

BACKGROUND: Various methods are used for cervical ripening during the induction
of labour. It is still debatable which of these methods of treatment is optimal.
OBJECTIVE: To compare treatment techniques for cervical ripening in the induction
of labour.
SEARCH STRATEGY: Medline, Embase, and the Cochrane Collaboration databases were
searched using the keywords 'cervical ripening', 'labour induced', 'misoprostol',
'dinoprostone', and 'Foley catheter'.
SELECTION CRITERIA: Randomised controlled trials (RCTs) of cervical ripening
during the induction of labour, evaluating rates of failure to achieve vaginal
delivery within 24 hours, incidence of uterine hyperstimulation with fetal heart
rate (FHR) changes, and rates of caesarean section. Studies including women with
prelabour rupture of membranes were excluded.
DATA COLLECTION AND ANALYSIS: Outcome data were collected and analysed through
pairwise meta-analysis and network meta-analysis within a Bayesian framework.
MAIN RESULTS: A total of 96 RCTs (17,387 women) were included in the
meta-analysis. Vaginal misoprostol was the most effective cervical ripening
method to achieve vaginal delivery within 24 hours, but had the highest incidence
of uterine hyperstimulation with FHR changes. The use of a Foley catheter to
induce labour was associated with the lowest rate of uterine hyperstimulation
accompanied by FHR changes. The caesarean section rate was lowest using oral
misoprostol for the induction of labour.
AUTHOR'S CONCLUSIONS: No method of labour induction demonstrated overall
superiority when considering all three clinical outcomes. Decisions regarding the
choice of induction method will depend upon the relative preference for effecting
vaginal delivery within 24 hours, minimising the incidence of uterine
hyperstimulation with adverse FHR changes and avoiding caesarean section.
TWEETABLE ABSTRACT: Oral misoprostol for the induction of labour is safer than
vaginal misoprostol and has the lowest rate of caesarean section.

© 2015 Royal College of Obstetricians and Gynaecologists.

DOI: 10.1111/1471-0528.13456
PMID: 26538408  [Indexed for MEDLINE]


197. Clin Orthop Relat Res. 2016 Feb;474(2):495-516. doi: 10.1007/s11999-015-4619-9.
Epub 2015 Nov 16.

Is Local Infiltration Analgesia Superior to Peripheral Nerve Blockade for Pain
Management After THA: A Network Meta-analysis.

Jiménez-Almonte JH(1)(2), Wyles CC(3), Wyles SP(3), Norambuena-Morales GA(4),
Báez PJ(2), Murad MH(5), Sierra RJ(6).

Author information:
(1)Department of Orthopaedic Surgery, University of Kentucky, Lexington, KY, USA.
(2)Mayo Clinic Graduate School, Rochester, MN, USA.
(3)Mayo Clinic Medical School, Rochester, MN, USA.
(4)Department of Orthopedic Surgery, Mayo Clinic, 200 First St. SW, Rochester,
MN, 55905, USA.
(5)Division of Preventive Medicine, Mayo Clinic, Rochester, MN, USA.
(6)Department of Orthopedic Surgery, Mayo Clinic, 200 First St. SW, Rochester,
MN, 55905, USA. Sierra.Rafael@mayo.edu.

Comment in
    Clin Orthop Relat Res. 2016 Feb;474(2):517-9.

BACKGROUND: Local infiltration analgesia and peripheral nerve blocks are common
methods for pain management in patients after THA but direct head-to-head,
randomized controlled trials (RCTs) have not been performed. A network
meta-analysis allows indirect comparison of individual treatments relative to a
common comparator; in this case placebo (or no intervention), epidural analgesia,
and intrathecal morphine, yielding an estimate of comparative efficacy.
QUESTIONS/PURPOSES: We asked, when compared with a placebo, (1) does use of local
infiltration analgesia reduce patient pain scores and opioid consumption, (2)
does use of peripheral nerve blocks reduce patient pain scores and opioid
consumption, and (3) is local infiltration analgesia favored over peripheral
nerve blocks for postoperative pain management after THA?
METHODS: We searched six databases, from inception through June 30, 2014, to
identify RCTs comparing local infiltration analgesia or peripheral nerve block
use in patients after THA. A total of 35 RCTs at low risk of bias based on the
recommended Cochrane Collaboration risk assessment tool were included in the
network meta-analysis (2296 patients). Primary outcomes for this review were
patient pain scores at rest and cumulative opioid consumption, both assessed at
24 hours after THA. Because of substantial heterogeneity (variation of outcomes
between studies) across included trials, a random effect model for meta-analysis
was used to estimate the weighted mean difference (WMD) and 95% CI. The gray
literature was searched with the same inclusion criteria as published trials.
Only one unpublished trial (published abstract) fulfilled our criteria and was
included in this review. All other studies included in this systematic review
were full published articles. Bayesian network meta-analysis included all RCTs
that compared local infiltration analgesia or peripheral nerve blocks with
placebo (or no intervention), epidural analgesia, and intrathecal morphine.
RESULTS: Compared with placebo, local infiltration analgesia reduced patient pain
scores (WMD, -0.61; 95% CI, -0.97 to -0.24; p = 0.001) and opioid consumption
(WMD, -7.16 mg; 95% CI, -11.98 to -2.35; p = 0.004). Peripheral nerve blocks did
not result in lower pain scores or reduced opioid consumption compared with
placebo (WMD, -0.43; 95% CI, -0.99 to 0.12; p = 0.12 and WMD, -3.14 mg, 95% CI,
-11.30 to 5.02; p = 0.45). However, network meta-analysis comparing local
infiltration analgesia with peripheral nerve blocks through common comparators
showed no differences between postoperative pain scores (WMD, -0.36; 95% CI,
-1.06 to 0.31) and opioid consumption (WMD, -4.59 mg; 95% CI, -9.35 to 0.17),
although rank-order analysis found local infiltration analgesia to be ranked
first in more simulations than peripheral nerve blocks, suggesting that it may be
more effective.
CONCLUSIONS: Using the novel statistical network meta-analysis approach, we found
no differences between local infiltration analgesia and peripheral nerve blocks
in terms of analgesia or opioid consumption 24 hours after THA; there was a
suggestion of a slight advantage to peripheral nerve blocks based on rank-order
analysis, but the effect size in question is likely not large. Given the slight
difference between interventions, clinicians may choose to focus on other factors
such as cost and intervention-related complications when debating which analgesic
treatment to use after THA.
LEVEL OF EVIDENCE: Level I, therapeutic study.

DOI: 10.1007/s11999-015-4619-9
PMCID: PMC4709309
PMID: 26573322  [Indexed for MEDLINE]


198. Eur Radiol. 2016 Feb;26(2):451-8. doi: 10.1007/s00330-015-3831-z. Epub 2015 May
20.

Diagnostic accuracy and utility of coronary CT angiography with consideration of
unevaluable results: A systematic review and multivariate Bayesian random-effects
meta-analysis with intention to diagnose.

Menke J(1), Kowalski J(2).

Author information:
(1)Institute for Diagnostic and Interventional Radiology, University Medical
Center Goettingen, Robert-Koch-Strasse 40, 37075, Goettingen, Germany.
Menke-J@T-Online.de.
(2)Department of Cardiology, Dr. Lauterbach-Klinik, Heinrich-Mann-Strasse 5,
36448, Bad Liebenstein, Germany.

OBJECTIVES: To meta-analyze diagnostic accuracy, test yield and utility of
coronary computed tomography angiography (CCTA) in coronary artery disease (CAD)
by an intention-to-diagnose approach with inclusion of unevaluable results.
METHODS: Four databases were searched from 1/2005 to 3/2013 for prospective
studies that used 16-320-row or dual-source CTs and provided 3 × 2 patient-level
data of CCTA (positive, negative, or unevaluable) versus catheter angiography
(positive or negative) for diagnosing ≥50% coronary stenoses. A Bayesian
multivariate 3 × 2 random-effects meta-analysis considered unevaluable CCTAs.
RESULTS: Thirty studies (3422 patients) were included. Compared to 16-40 row CT,
test yield and accuracy of CCTA has significantly increased with ≥64-row CT
(P < 0.05). In ≥64-row CT, about 2.5% (95%-CI, 0.9-4.8%) of diseased patients and
7.5% (4.5-11.2%) of non-diseased patients had unevaluable CCTAs. A positive
likelihood ratio of 8.9 (6.1-13.5) indicated moderate suitability for identifying
CAD. A negative likelihood ratio of 0.022 (0.01-0.04) indicated excellent
suitability for excluding CAD. Unevaluable CCTAs had an equivocal likelihood
ratio of 0.42 (0.22-0.71). In the utility analysis, CCTA was useful at
intermediate pre-test probabilities (16-70%).
CONCLUSIONS: CCTA is useful at intermediate CAD pre-test probabilities. Positive
CCTAs require verification to confirm CAD, unevaluable CCTAs require alternative
diagnostics, and negative CCTAs exclude obstructive CAD with high certainty.
KEY POINTS: • This 3 × 2 Bayesian meta-analysis included unevaluable CCTAs with
intention-to-diagnose. • CCTA is currently useful at intermediate CAD pre-test
probabilities. • Unevaluable CCTAs should not, generally, be treated as if they
are positive. • Positive CCTAs require verification by other methods to confirm
CAD. • Negative CCTAs exclude CAD with high certainty.

DOI: 10.1007/s00330-015-3831-z
PMID: 25991489  [Indexed for MEDLINE]


199. Int J Epidemiol. 2016 Feb;45(1):186-205. doi: 10.1093/ije/dyv185. Epub 2015 Oct
7.

Systematic meta-analyses and field synopsis of genetic association studies in
colorectal adenomas.

Montazeri Z(1), Theodoratou E(2), Nyiraneza C(1), Timofeeva M(3), Chen W(2),
Svinti V(3), Sivakumaran S(2), Gresham G(1), Cubitt L(2), Carvajal-Carmona L(4),
Bertagnolli MM(5), Zauber AG(6), Tomlinson I(7), Farrington SM(3), Dunlop MG(3),
Campbell H(8), Little J(9).

Author information:
(1)School of Epidemiology, Public Health and Preventive Medicine, University of
Ottawa, Ottawa, Canada.
(2)Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK.
(3)Colon Cancer Genetics Group and Academic Coloproctology, Institute of Genetics
and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit
Western General Hospital, Edinburgh, UK.
(4)Biochemistry and Molecular Medicine, Genome and Biomedical Sciences Facility,
UC Davis School of Medicine, University of California Davis, Davis, CA, USA.
(5)Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA.
(6)Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer
Center, New York, NY, USA and.
(7)Wellcome Trust Centre for Human Genetics, Oxford, UK.
(8)Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK,
Colon Cancer Genetics Group and Academic Coloproctology, Institute of Genetics
and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit
Western General Hospital, Edinburgh, UK.
(9)School of Epidemiology, Public Health and Preventive Medicine, University of
Ottawa, Ottawa, Canada, jlittle@uottawa.ca.

BACKGROUND: Low penetrance genetic variants, primarily single nucleotide
polymorphisms, have substantial influence on colorectal cancer (CRC)
susceptibility. Most CRCs develop from colorectal adenomas (CRA). Here we report
the first comprehensive field synopsis that catalogues all genetic association
studies on CRA, with a parallel online database
[http://www.chs.med.ed.ac.uk/CRAgene/].
METHODS: We performed a systematic review, reviewing 9750 titles, and then
extracted data from 130 publications reporting on 181 polymorphisms in 74 genes.
We conducted meta-analyses to derive summary effect estimates for 37
polymorphisms in 26 genes. We applied the Venice criteria and Bayesian False
Discovery Probability (BFDP) to assess the levels of the credibility of
associations.
RESULTS: We considered the association with the rs6983267 variant at 8q24 as
'highly credible', reaching genome-wide statistical significance in at least one
meta-analysis model. We identified 'less credible' associations (higher
heterogeneity, lower statistical power, BFDP > 0.02) with a further four variants
of four independent genes: MTHFR c.677C>T p.A222V (rs1801133), TP53 c.215C>G
p.R72P (rs1042522), NQO1 c.559C>T p.P187S (rs1800566), and NAT1 alleles imputed
as fast acetylator genotypes. For the remaining 32 variants of 22 genes for which
positive associations with CRA risk have been previously reported, the
meta-analyses revealed no credible evidence to support these as true
associations.
CONCLUSIONS: The limited number of credible associations between low penetrance
genetic variants and CRA reflects the lower volume of evidence and associated
lack of statistical power to detect associations of the magnitude typically
observed for genetic variants and chronic diseases. The CRA gene database
provides context for CRA genetic association data and will help inform future
research directions.

© The Author 2015; all rights reserved. Published by Oxford University Press on
behalf of the International Epidemiological Association.

DOI: 10.1093/ije/dyv185
PMID: 26451011  [Indexed for MEDLINE]


200. Pediatrics. 2016 Feb;137(2):e20153896. doi: 10.1542/peds.2015-3896. Epub 2016 Jan
15.

Pharmacologic Interventions for Infantile Hemangioma: A Meta-analysis.

Chinnadurai S(1), Fonnesbeck C(2), Snyder KM(3), Sathe NA(4), Morad A(5), Likis
FE(6), McPheeters ML(4).

Author information:
(1)Departments of Otolaryngology, sivakumar.chinnadurai@vanderbilt.edu.
(2)Biostatistics.
(3)Division of Pediatric Hematology/Oncology, Helen DeVos Children's Hospital,
Grand Rapids, Michigan; and Division of Pediatric Hematology/Oncology, Monroe
Carell Jr Children's Hospital at Vanderbilt, Nashville, Tennessee.
(4)Health Policy, and Vanderbilt Evidence-Based Practice Center, Institute for
Medicine and Public Health, Vanderbilt University Medical Center, Nashville,
Tennessee;
(5)Pediatrics, and.
(6)Vanderbilt Evidence-Based Practice Center, Institute for Medicine and Public
Health, Vanderbilt University Medical Center, Nashville, Tennessee; Vanderbilt
University School of Nursing, Nashville, Tennessee.

CONTEXT: Infantile hemangiomas (IH) may be associated with significant functional
impact.
OBJECTIVE: The objective of this study was to meta-analyze studies of
pharmacologic interventions for children with IH.
DATA SOURCES: Data sources were Medline and other databases from 1982 to June
2015.
STUDY SELECTION: Two reviewers assessed studies using predetermined inclusion
criteria.
DATA EXTRACTION: One reviewer extracted data with review by a second.
RESULTS: We included 18 studies in a network meta-analysis assessing relative
expected rates of IH clearance associated with β-blockers and steroids. Oral
propranolol had the largest mean estimate of expected clearance (95%; 95%
Bayesian credible interval [BCI]: 88%-99%) relative to oral corticosteroids (43%,
95% BCI: 21%-66%) and control (6%, 95% BCI: 1%-11%). Strength of evidence (SOE)
was high for propranolol's effects on reducing lesion size compared with
observation/placebo. Corticosteroids demonstrated moderate effectiveness at
reducing size/volume (moderate SOE for improvement in IH). SOE was low for
effects of topical timolol versus placebo.
LIMITATIONS: Methodologic limitations of available evidence may compromise SOE.
Validity of meta-analytic estimates relies on the assumption of exchangeability
among studies, conditional on effects of the intervention. Results rely on
assumed lack of reporting bias.
CONCLUSIONS: Propranolol is effective at reducing IH size compared with placebo,
observation, and other treatments including steroids in most studies.
Corticosteroids demonstrate moderate effectiveness at reducing IH size/volume.
The meta-analysis estimates provide a relative ranking of anticipated rates of
lesion clearance among treatments. Families and clinicians making treatment
decisions should also factor in elements such as lesion size, location, number,
and type, and patient and family preferences.

Copyright © 2016 by the American Academy of Pediatrics.

DOI: 10.1542/peds.2015-3896
PMID: 26772662  [Indexed for MEDLINE]


201. Sci Rep. 2016 Jan 25;6:19847. doi: 10.1038/srep19847.

A Bayesian framework systematic review and meta-analysis of anesthetic agents
effectiveness/tolerability profile in electroconvulsive therapy for major
depression.

Fond G(1)(2), Bennabi D(3)(2), Haffen E(3)(2), Brunel L(1), Micoulaud-Franchi
JA(4), Loundou A(5), Lançon C(4)(5)(2), Llorca PM(2)(6), Auquier P(5)(7), Boyer
L(5)(7).

Author information:
(1)Université Paris Est-Créteil, Pôle de psychiatrie des hôpitaux universitaires
H Mondor DHU Pe-PSY, INSERM U955, Eq Psychiatrie translationelle, Fondation
FondaMental Fondation de coopération scientifique en santé mentale, Créteil,
France.
(2)Network of Expert centres, FondaMental Foundation, Créteil 94000, France.
(3)Department of Clinical Psychiatry, CIC-1431, University Hospital of Besançon,
EA Neurosciences 481, University of Franche-Comté, Besançon, France.
(4)Service d'explorations fonctionnelles du système nerveux, Clinique du sommeil,
CHU de Bordeaux, Place Amélie Raba-Léon, 33076 Bordeaux, France.
(5)Aix-Marseille University, EA 3279 Research Unit - Public Health: Chronic
diseases and quality of life, Marseille, France.
(6)University Hospital of Clermont-Ferrand, Clermont-Ferrand, France.
(7)Department of Epidemiology, Timone University Hospital, APHM, Marseille,
France.

The aim of this study was to assess the efficacy and tolerability/acceptability
of 6 anesthetic agents in ECT for depressive disorders. We systematically
reviewed 14 double-blind randomized controlled trials (610 participants).
Efficacy was measured by the mean scores on validated depression scales at 6 ECT
(or the nearest score if not available), number of responders at the end of
treatment and seizure duration. The acceptability was measured by the proportion
of patients who dropped out of the allocated treatment, and the tolerability by
the number of serious adverse events and post-treatment cognition assessment.
After excluding the trials responsible for heterogeneity, depression scores of
patients who were administered methohexital were found to be significantly more
improved than those who received propofol (p = 0.001). On the contrary, those who
were administered propofol had lower depression scores than those with thiopental
at the end of treatment (p = 0.002). Compared to propofol, methohexital was found
to be significantly associated with higher seizure duration (p = 0.018). No
difference was found for the acceptability profile (all p > 0.05). In summary,
ketamine and methohexital may be preferred to propofol or thiopental in regard of
effectiveness in depression scores and increased seizure duration. Further
studies are warranted to compare ketamine and methohexital.

DOI: 10.1038/srep19847
PMCID: PMC4726191
PMID: 26806849  [Indexed for MEDLINE]


202. Syst Rev. 2016 Jan 20;5:14. doi: 10.1186/s13643-016-0186-8.

The effectiveness and safety of treatments used for acute diarrhea and acute
gastroenteritis in children: protocol for a systematic review and network
meta-analysis.

Florez ID(1)(2), Al-Khalifah R(3)(4)(5), Sierra JM(6), Granados CM(7),
Yepes-Nuñez JJ(8)(9), Cuello-Garcia C(10)(11), Perez-Gaxiola G(12), Zea AM(13),
Hernandez GN(14), Veroniki AA(15), Guyatt GH(16)(17), Thabane L(18)(19).

Author information:
(1)Department of Clinical Epidemiology & Biostatistics, McMaster University,
Juravinski Site. G Wing, 2nd Floor; 711 Concession Street, Hamilton, ON, L8V 1
C3, Canada. ivan.florez@udea.edu.co.
(2)Department of Pediatrics, Universidad de Antioquia, Medellín, Colombia.
ivan.florez@udea.edu.co.
(3)Department of Clinical Epidemiology & Biostatistics, McMaster University,
Juravinski Site. G Wing, 2nd Floor; 711 Concession Street, Hamilton, ON, L8V 1
C3, Canada. reem_ah@yahoo.com.
(4)Department of Pediatrics, King Saud University, Riyadh, Saudi Arabia.
reem_ah@yahoo.com.
(5)Department of Pediatrics, Division of Endocrinology and Metabolism, McMaster
University, Hamilton, Canada. reem_ah@yahoo.com.
(6)Department of Pediatrics, Universidad de Antioquia, Medellín, Colombia.
javier.sierra@udea.edu.co.
(7)Department of Clinical Epidemiology & Biostatistics, Pontificia Universidad
Javeriana, Bogotá, Colombia. granado@javeriana.edu.co.
(8)Department of Clinical Epidemiology & Biostatistics, McMaster University,
Juravinski Site. G Wing, 2nd Floor; 711 Concession Street, Hamilton, ON, L8V 1
C3, Canada. juanjosey@gmail.com.
(9)Department of Pediatrics, Universidad de Antioquia, Medellín, Colombia.
juanjosey@gmail.com.
(10)Department of Clinical Epidemiology & Biostatistics, McMaster University,
Juravinski Site. G Wing, 2nd Floor; 711 Concession Street, Hamilton, ON, L8V 1
C3, Canada. cuelloca@mcmaster.ca.
(11)Hospital Pediatrico de Sinaloa, Culiacan, Mexico. cuelloca@mcmaster.ca.
(12)Hospital Pediatrico de Sinaloa, Culiacan, Mexico.
giordano@sinestetoscopio.com.
(13)School of Nutrition and Dietetics, Universidad de Antioquia, Medellín,
Colombia. adriana.zea.perdomo@gmail.com.
(14)Department of Pediatrics, Universidad de Antioquia, Medellín, Colombia.
gilma.hernandez@udea.edu.co.
(15)Knowledge Translation Program, Li Ka Shing Knowledge Institute, St. Michaels
Hospital, Toronto, Canada. VeronikiA@smh.ca.
(16)Department of Clinical Epidemiology & Biostatistics, McMaster University,
Juravinski Site. G Wing, 2nd Floor; 711 Concession Street, Hamilton, ON, L8V 1
C3, Canada. guyatt@mcmaster.ca.
(17)Department of Medicine, McMaster University, Hamilton, Canada.
guyatt@mcmaster.ca.
(18)Department of Clinical Epidemiology & Biostatistics, McMaster University,
Juravinski Site. G Wing, 2nd Floor; 711 Concession Street, Hamilton, ON, L8V 1
C3, Canada. thabanl@mcmaster.ca.
(19)Department of Pediatrics and Anesthesia, McMaster University, Hamilton, ON,
Canada. thabanl@mcmaster.ca.

BACKGROUND: Acute diarrhea and acute gastroenteritis (AD/AGE) are common among
children in low- and middle-income countries (LMIC) and high-income countries
(HIC). Supportive therapy including maintaining feeding, prevention of
dehydration, and use of oral rehydration solution (ORS), is the mainstay of
treatment in all children. Several additional treatments aiming to reduce the
episode duration have been compared to placebo, but the differences in
effectiveness among them are unknown.
METHODS AND ANALYSIS: We will conduct a systematic review of all randomized
controlled trials evaluating the use of zinc, vitamin A, probiotics, prebiotics,
synbiotics, racecadotril, smectite, and fermented and lactose-free milk/formula
for AD/AGE treatment in children. The primary outcomes are diarrhea duration and
mortality. Secondary outcomes are diarrhea lasting 3 or 7 days, stool frequency,
treatment failure, hospitalizations, and adverse events. We will search MEDLINE,
Ovid EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials
(CENTRAL), and LILACS through Ovid, as well as grey literature resources. Two
reviewers will independently screen titles and abstracts, review full texts,
extract information, and assess the risk of bias (ROB) and the confidence in the
estimate (with the grading of recommendations, assessment, development, and
evaluation [GRADE] approach). Results will be summarized narratively and
statistically. Subgroup analysis according to HIC vs. LMIC, age, nutrition
status, and ROB is planned. We will perform a Bayesian network meta-analysis to
combine the pooled direct and indirect treatment effect estimates for each
outcome, if adequate data is available.
DISCUSSION: This is the first systematic review and network meta-analysis that
aims to determine the relative effectiveness of pharmacological and nutritional
treatments for reducing the duration of AD/AGE in children. The results will help
to reduce the uncertainty of the effectiveness of the interventions, find
knowledge gaps, and/or encourage further research for other therapeutic options.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: CRD42015023778.

DOI: 10.1186/s13643-016-0186-8
PMCID: PMC4728803
PMID: 26818403  [Indexed for MEDLINE]


203. BMJ Open. 2016 Jan 13;6(1):e010251. doi: 10.1136/bmjopen-2015-010251.

Comparative safety and effectiveness of cognitive enhancers for Alzheimer's
dementia: protocol for a systematic review and individual patient data network
meta-analysis.

Veroniki AA(1), Straus SE(2), Ashoor HM(1), Hamid JS(3), Hemmelgarn BR(4),
Holroyd-Leduc J(4), Majumdar SR(5), McAuley G(6), Tricco AC(7).

Author information:
(1)Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario,
Canada.
(2)Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario,
Canada Department of Geriatric Medicine, University of Toronto, Toronto, Ontario,
Canada.
(3)Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario,
Canada Department of Clinical Epidemiology and Biostatistics, McMaster
University, Hamilton, Ontario, Canada.
(4)Departments of Medicine and Community Health Sciences, University of Calgary,
Calgary, Alberta, Canada.
(5)Department of General Internal Medicine, University of Alberta, Edmonton,
Alberta, Canada.
(6)Ontario Public Drug Programs, Ministry of Health and Long-Term Care, Toronto,
Ontario, Canada.
(7)Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario,
Canada Epidemiology Division, Dalla Lana School of Public Health, University of
Toronto, Toronto, Ontario, Canada.

INTRODUCTION: Alzheimer's dementia (AD) is the most common cause of dementia, and
several organisations, such as the National Institute for Health and Care
Excellence, suggest that management of patients with AD should be tailored to
their needs. To date, little research has been conducted on the treatment effect
in different subgroups of patients with AD. The aim of this study is to examine
the comparative effectiveness and safety of cognitive enhancers for different
patient characteristics.
METHODS AND ANALYSIS: We will update our previous literature search from January
2015 forward, using the same terms and electronic databases (eg, MEDLINE) from
our previous review. We will additionally search grey literature and scan the
reference lists of the included studies. Randomised clinical trials of any
duration conducted at any time comparing cognitive enhancers alone or in any
combination against other cognitive enhancers, or placebo in adults with AD will
be eligible. The outcomes of interest are cognition according to the Mini-Mental
State Examination, and overall serious adverse events. For each outcome and
treatment comparison, we will perform a Bayesian hierarchical random-effects
meta-analysis combining the individual patient data (IPD) from each eligible
study. If the identified treatment comparisons form a connected network diagram,
we will perform an IPD network meta-analysis (NMA) to estimate subgroup effects
for patients with different characteristics, such as AD severity and sex. We will
combine aggregated data from studies that we will not be able to obtain IPD, with
the IPD provided by the original authors, in a single model. We will use the
PRISMA-IPD and PRISMA-NMA statements to report our findings.
ETHICS AND DISSEMINATION: The findings of this study will be of interest to
stakeholders, including decision makers, guideline developers, clinicians,
methodologists and patients, and they will help to improve guidelines for the
management of patients with AD.
TRIAL REGISTRATION NUMBER: CRD42015023507.

Published by the BMJ Publishing Group Limited. For permission to use (where not
already granted under a licence) please go to
http://www.bmj.com/company/products-services/rights-and-licensing/

DOI: 10.1136/bmjopen-2015-010251
PMCID: PMC4735316
PMID: 26769792  [Indexed for MEDLINE]


204. PLoS One. 2016 Jan 6;11(1):e0146336. doi: 10.1371/journal.pone.0146336.
eCollection 2016.

Meta-Analysis of a Complex Network of Non-Pharmacological Interventions: The
Example of Femoral Neck Fracture.

Mosseri J(1)(2)(3), Trinquart L(1)(4)(5)(6)(7), Nizard R(2)(3), Ravaud
P(1)(4)(5)(6)(7).

Author information:
(1)INSERM U1153, Paris, France.
(2)Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Service de
Chirurgie orthopédique et traumatologique, Paris, France.
(3)Université Paris Diderot, Paris, France.
(4)Assistance Publique-Hôpitaux de Paris, Hôpital Hôtel-Dieu, Centre
d'épidémiologie clinique, Paris, France.
(5)French Cochrane Centre, Paris, France.
(6)Université Paris Descartes-Sorbonne Paris cité, Paris, France.
(7)Columbia University, Mailman School of Public Health, Department of
Epidemiology, New York, United States of America.

BACKGROUND: Surgical interventions raise specific methodological issues in
network meta-analysis (NMA). They are usually multi-component interventions
resulting in complex networks of randomized controlled trials (RCTs), with
multiple groups and sparse connections.
PURPOSE: To illustrate the applicability of the NMA in a complex network of
surgical interventions and to prioritize the available interventions according to
a clinically relevant outcome.
METHODS: We considered RCTs of treatments for femoral neck fracture in adults. We
searched CENTRAL, MEDLINE, EMBASE and ClinicalTrials.gov up to November 2015. Two
reviewers independently selected trials, extracted data and used the Cochrane
Collaboration's tool for assessing the risk of bias. A group of orthopedic
surgeons grouped similar but not identical interventions under the same node. We
synthesized the network using a Bayesian network meta-analysis model. We derived
posterior odds ratios (ORs) and 95% credible intervals (95% CrIs) for all
possible pairwise comparisons. The primary outcome was all-cause revision
surgery.
RESULTS: Data from 27 trials were combined, for 4,186 participants (72% women,
mean age 80 years, 95% displaced fractures). The median follow-up was 2 years.
With hemiarthroplasty (HA) and total hip arthroplasty (THA) as a comparison, risk
of surgical revision was significantly higher with the treatments unthreaded
cervical osteosynthesis (OR 8.0 [95% CrI 3.6-15.5] and 5.9 [2.4-12.0],
respectively), screw (9.4 [6.0-16.5] and 6.7 [3.9-13.6]) and plate (12.5
[5.8-23.8] and 7.8 [3.8-19.4]).
CONCLUSIONS: In older women with displaced femoral neck fractures, arthroplasty
(HA and THA) is the most effective treatment in terms of risk of revision
surgery.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO no. CRD42013004218.
LEVEL OF EVIDENCE: Network Meta-Analysis, Level 1.

DOI: 10.1371/journal.pone.0146336
PMCID: PMC4703382
PMID: 26735922  [Indexed for MEDLINE]


205. BMJ Open. 2016 Jan 5;6(1):e010264. doi: 10.1136/bmjopen-2015-010264.

Antimicrobial lock solutions for the prevention of catheter-related infection in
patients undergoing haemodialysis: study protocol for network meta-analysis of
randomised controlled trials.

Zhang J(1), Li RK(1), Chen KH(2), Ge L(3), Tian JH(3).

Author information:
(1)School of Nursing, Gansu University of Chinese Medicine, Lanzhou, China.
(2)Department of Nursing, Taipei Municipal Wanfang Hospital, Taipei Medical
University, Taipei, Taiwan Evidence-Based Knowledge Translation Center, Taipei
Municipal Wanfang Hospital, Taipei Medical University, Taipei, Taiwan School of
Nursing, Taipei Medical University, Taipei , Taiwan.
(3)Evidence-based Medicine Center of Lanzhou University, Lanzhou, China.

INTRODUCTION: Catheter-related infection (CRI) is a difficult clinical problem in
renal medicine, with blood stream infections occurring in up to 40% of patients
with haemodialysis (HD) catheters, conferring significant rates of morbidity and
mortality. Several approaches have been assessed as a means to prevent CRI.
Currently, an intervention that is the source of much discussion is the use of
antimicrobial lock solutions (ALS). A number of past conventional meta-analyses
have compared different ALS with heparin. However, there is no consensus
recommendation regarding which type of ALS is best. The purpose of our study is
to carry out a network meta-analysis comparing the efficacy of different ALS for
prevention of CRI in patients with HD and ranking these ALS for practical
consideration.
METHODS AND ANALYSIS: We will search six electronic databases, earlier relevant
meta-analyses and reference lists of included studies for randomised controlled
trials (RCTs) that compared ALS for preventing episodes of CRI in patients with
HD either head-to-head or against control interventions using non-ALS. Study
selection and data collection will be performed by two reviewers independently.
The Cochrane Risk of Bias Tool will be used to assess the quality of included
studies. The primary outcome of efficacy will be catheter-related bloodstream
infection (CRBSI). We will perform a Bayesian network meta-analysis to compare
the relative efficacy of different ALS by WinBUGS (V.1.4.3) and STATA (V.13.0).
The quality of evidence will be assessed by GRADE.
ETHICS AND DISSEMINATION: Ethical approval is not required given that this study
includes no confidential personal data and no data on interventions on patients.
The results of this study will be submitted to a peer-review journal for
publication.
TRIAL REGISTRATION NUMBER: CRD42015027010.

Published by the BMJ Publishing Group Limited. For permission to use (where not
already granted under a licence) please go to
http://www.bmj.com/company/products-services/rights-and-licensing/

DOI: 10.1136/bmjopen-2015-010264
PMCID: PMC4716163
PMID: 26733573  [Indexed for MEDLINE]


206. Aliment Pharmacol Ther. 2016 Jan;43(1):16-29. doi: 10.1111/apt.13446. Epub 2015
Oct 30.

Systematic review with meta-analysis: direct comparisons of biomarkers for the
diagnosis of fibrosis in chronic hepatitis C and B.

Houot M(1), Ngo Y(1), Munteanu M(1), Marque S(2), Poynard T(3)(4).

Author information:
(1)BioPredictive, Paris, France.
(2)Capionis, Paris, France.
(3)Hepatology Department, Assistance Publique-Hôpitaux de Paris, Hôpital
Pitié-Salpêtrière, Paris, France.
(4)INSERM & Université Pierre et Marie Curie - Univ Paris 06, UMR_S 938, Centre
de Recherche Saint-Antoine & Institute of Cardiometabolism and Nutrition (ICAN),
Paris, France.

Comment in
    Aliment Pharmacol Ther. 2017 Jan;45(1):190-191.

BACKGROUND: Blood tests and transient elastography (TE), proposed as alternatives
to biopsy for identifying advanced fibrosis (METAVIR-stage-F2 or greater) or
cirrhosis, have never been compared using an intention to diagnose approach, with
direct comparisons only, and Bayesian approach.
AIM: To permit more appropriate comparisons.
METHODS: From an overview of articles (2002-2014), we selected studies that
directly compared the diagnostic accuracy of FibroTest, aspartate
aminotransferase-platelet ratio index (APRI), FIB4 or TE, with biopsy as a
reference, in patients with chronic hepatitis C (CHC) or B (CHB). Investigators
abstracted and checked study details and quality by using pre-defined criteria.
Bayesian method in intention to diagnose was the primary outcome.
RESULTS: Of 1321 articles identified, 71 studies including 77 groups according to
aetiology (All-CB) were eligible: 37 Only-C, 28 Only-B and 12 Mixed-C-B. There
were 185 direct comparisons between the area under the ROC curves (AUROCs), 99
for the diagnosis of advanced fibrosis and 86 for cirrhosis. In All-CB, Bayesian
analyses revealed significant AUROCs differences in identifying advanced fibrosis
in favour of FibroTest vs. TE [credibility interval: 0.06(0.02-0.09)], FibroTest
vs. APRI [0.05 (0.03-0.07)] and for identifying cirrhosis TE vs. APRI [0.07
(0.02-0.13)] and FIB4 vs. APRI [0.04(0.02-0.05)]. No differences were observed
between TE and FibroTest, for identifying cirrhosis in All-CB, and in sub-groups
(Only-C, Only-B, Mixed-CB) for both cirrhosis and fibrosis.
CONCLUSIONS: In CHC and CHB, APRI had lower performances than FIB-4, TE and
FibroTest. TE had lower performance than FibroTest for identifying advanced
fibrosis in All-CB, without significant difference for identifying cirrhosis in
all groups.

© 2015 The Authors. Alimentary Pharmacology & Therapeutics published by John
Wiley & Sons Ltd.

DOI: 10.1111/apt.13446
PMCID: PMC4737301
PMID: 26516104  [Indexed for MEDLINE]


207. Am J Geriatr Psychiatry. 2016 Jan;24(1):31-41. doi: 10.1016/j.jagp.2015.05.010.
Epub 2015 May 21.

A Meta-Analysis of Executive Dysfunction and Antidepressant Treatment Response in
Late-Life Depression.

Pimontel MA(1), Rindskopf D(2), Rutherford BR(3), Brown PJ(3), Roose SP(3), Sneed
JR(4).

Author information:
(1)The Graduate Center, City University of New York, New York, NY; Queens
College, City University of New York, New York, NY.
(2)The Graduate Center, City University of New York, New York, NY.
(3)Columbia University and the New York State Psychiatric Institute, New York,
NY.
(4)The Graduate Center, City University of New York, New York, NY; Queens
College, City University of New York, New York, NY; Columbia University and the
New York State Psychiatric Institute, New York, NY. Electronic address:
joel.sneed@qc.cuny.edu.

OBJECTIVE: Depressed older adults with executive dysfunction (ED) may respond
poorly to antidepressant treatment. ED is a multifaceted construct and different
studies have measured different aspects of ED, making it unclear which aspects
predict poor response. Meta-analytic methods were used to determine whether ED
predicts poor antidepressant treatment response in late-life depression and to
determine which domains of executive functioning are responsible for this
relationship.
METHODS: A Medline search was conducted to identify regimented treatment trials
contrasting executive functioning between elderly responders and nonresponders;
only regimented treatment trials for depressed outpatients aged 50 and older were
included. Following the most recent PRISMA guidelines, 25 measures of executive
functioning were extracted from eight studies. Six domains were identified:
cognitive flexibility, planning and organization, response inhibition, selective
attention, verbal fluency, and the Dementia Rating Scale Initiation/Perseveration
composite score (DRS I/P). Hedge's g was calculated for each measure of executive
functioning. A three-level Bayesian hierarchical linear model (HLM) was used to
estimate effect sizes for each domain of executive functioning.
RESULTS: The effect of planning and organization was significantly different from
zero (Bayesian HLM estimate of domain effect size: 0.91; 95% CI: 0.32-1.58),
whereas cognitive flexibility, response inhibition, selective attention, verbal
fluency, and the DRS I/P composite score were not.
CONCLUSION: The domain of planning and organization is meaningfully associated
with poor antidepressant treatment response in late-life depression. These
findings suggest that therapies that focus on planning and organization may
provide effective augmentation strategies for antidepressant nonresponders with
late-life depression.

Copyright © 2016 American Association for Geriatric Psychiatry. Published by
Elsevier Inc. All rights reserved.

DOI: 10.1016/j.jagp.2015.05.010
PMCID: PMC4928373
PMID: 26282222  [Indexed for MEDLINE]


208. Am J Ther. 2016 Jan-Feb;23(1):e52-62. doi: 10.1097/MJT.0000000000000350.

Comparative Efficacy and Safety of Prasugrel, Ticagrelor, and Standard-Dose and
High-Dose Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention:
A Network Meta-analysis.

Singh S(1), Singh M, Grewal N, Khosla S.

Author information:
(1)1Department of Hospital Medicine, Ingalls Memorial Hospital, Harvey, IL;
2Department of Cardiovascular Medicine, Mount Sinai Medical Center, Chicago, IL;
3Department of Medicine, Chicago Medical School, North Chicago, IL; 4School of
Public Health, University of Illinois at Chicago, Chicago, IL; and 5Department of
Cardiovascular Medicine, Rosalind Franklin University of Medicine and Science,
North Chicago, IL.

Authors aimed to compare efficacy and safety of prasugrel, ticagrelor, and
standard-dose (SD) and high-dose (HD) clopidogrel in patients undergoing
percutaneous coronary intervention (PCI). PubMed, EMBASE, CENTRAL, and
clinicaltrials.gov were searched for studies comparing prasugrel, ticagrelor, SD
and HD clopidogrel in patients undergoing PCI. Frequentist and Bayesian network
meta-analyses were performed besides direct pairwise comparisons. Thirty trials,
comprising 34,563 person-year data, were included. Prasugrel emerged as a best
drug to prevent definite or probable stent thrombosis, followed by HD clopidogrel
and ticagrelor, with SD clopidogrel being the worst. Myocardial infarction was
least likely to be prevented by SD clopidogrel after PCI, and remaining 3 were
superior to it with little difference among them. SD clopidogrel was least
effective in preventing cardiovascular deaths after PCI. Prasugrel was most
effective in preventing cardiovascular deaths, although having only small
advantage over ticagrelor and HD clopidogrel. Ticagrelor reduced all-cause
mortality by a small margin compared with rest of treatments. SD clopidogrel,
followed by ticagrelor, resulted in significantly lower thrombolysis in
myocardial infarction major bleeding complications compared with prasugrel.
Analysis of any bleeding revealed similar trend. HD clopidogrel performed better
than prasugrel in terms of bleeding complications. In conclusion, Prasugrel is
likely most effective drug to prevent post-PCI ischemic events but at the expense
of higher bleeding. Ticagrelor followed by HD clopidogrel seems to strike the
right balance between efficacy and safety. HD clopidogrel can be considered as an
alternative to newer P2Y12 inhibitors.

DOI: 10.1097/MJT.0000000000000350
PMID: 26448337  [Indexed for MEDLINE]


209. Asian Pac J Cancer Prev. 2016;17(2):867-72.

Simultaneous Comparison of Efficacy and Adverse Events of Interventions for
Patients with Esophageal Cancer: Protocol for a Systematic Review and Bayesian
Network Meta-analysis.

Doosti-Irani A(1), Mansournia MA, Rahimi-Foroushani A, Cheraghi Z,
Holakouie-Naieni K.

Author information:
(1)Department of Epidemiology and Biostatistics, School of Public Health, Tehran
University of Medical Sciences, Tehran, Iran E-mail : holakoik@hotmail.com.

BACKGROUND: Esophageal cancer is one of the most serious malignancies. Due to the
aggressive nature of this cancer, the prognosis is poor. A network meta-analysis
with simultaneous comparison of multiple treatments can help determine better
treatment options that have higher effects on overall survival of patients with
lower adverse events. The aim of this review is to simultaneously compare
efficacy and adverse events of treatment interventions for esophageal cancer.
MATERIALS AND METHODS: In this review, only randomized control trials (RCT) will
be considered for network meta-analysis. All international electronic databases
including Medline, Web of Sciences, Scopus, Cochran's library, EMBASE and
Cancerlit will be searched to find randomized control trials which compared two
or more treatment interventions for esophageal cancer. A network plot will be
drawn for visual representation of all available treatment interventions.
Bayesian approach will be used to combine the direct and indirect evidence.
Treatment effects (e.g. hazard ratio for time to event outcomes, risk ratio for
binary outcomes, and rate ratio for count outcomes with 95% credible interval)
will be reported. Moreover, cumulative probability of the treatment ranks will be
reported using the surface under the cumulative ranking (SUCRA) graphs.
Consistency assumption will be assessed by the loop-specific and
design-by-treatment interaction approaches.
CONCLUSIONS: The results of this study may be helpful for the patients,
clinicians and health policy makers in selecting treatments that have the best
effect on survival and lowest adverse events.


PMID: 26925694  [Indexed for MEDLINE]


210. Br J Ophthalmol. 2016 Jan;100(1):78-85. doi: 10.1136/bjophthalmol-2014-306102.
Epub 2015 Jun 25.

Glaucoma in Asia: regional prevalence variations and future projections.

Chan EW(1), Li X(2), Tham YC(3), Liao J(3), Wong TY(4), Aung T(3), Cheng CY(4).

Author information:
(1)Department of Ophthalmology, National University of Singapore and National
University Health System, Singapore, Singapore.
(2)Department of Biostatistics, Mailman School of Public Health, Columbia
University, New York, USA Duke-NUS Graduate Medical School, Singapore, Singapore.
(3)Department of Ophthalmology, National University of Singapore and National
University Health System, Singapore, Singapore Singapore Eye Research Institute,
Singapore, Singapore.
(4)Department of Ophthalmology, National University of Singapore and National
University Health System, Singapore, Singapore Duke-NUS Graduate Medical School,
Singapore, Singapore Singapore Eye Research Institute, Singapore, Singapore.

PURPOSE: To evaluate glaucoma prevalence and disease burden across Asian
subregions from 2013 to 2040.
METHODS: We conducted a systematic review and meta-analysis of 23
population-based studies of 1318 primary open angle glaucoma (POAG) cases in
66,800 individuals and 691 primary angle closure glaucoma (PACG) cases in 72,767
individuals in Asia. Regions in Asia were defined based on United Nations' (UN)
classification of macro-geographic regions. PubMed, Medline and Web of Science
databases were searched for population-based glaucoma prevalence studies using
standardised criteria published to 31 December 2013. Pooled glaucoma prevalence
for individuals aged 40-80 years was calculated using hierarchical Bayesian
approaches. Prevalence differences by geographic subregion, subtype and
habitation were examined with random effects meta-regression models. Estimates of
individuals with glaucoma from 2013 to 2040 were based on the UN World Population
Prospects.
RESULTS: In 2013, pooled overall glaucoma prevalence was 3.54% (95% credible
interval (CrI) 1.83 to 6.28). POAG (2.34%, 95% CrI 0.96 to 4.55) predominated
over PACG (0.73%, 95% CrI 0.18 to 1.96). With age and gender adjustment, PACG
prevalence was higher in East than South East Asia (OR 5.55, 95% CrI 1.52 to
14.73), and POAG prevalence was higher in urban than rural populations (OR 2.11,
95% CrI 1.57 to 2.38). From 2013 to 2040, South Central Asia will record the
steepest increase in number of glaucoma individuals from 17.06 million to 32.90
million compared with other Asian subregions. In 2040, South-Central Asia is also
projected to overtake East Asia for highest overall glaucoma and POAG burden,
while PACG burden remains highest in East Asia.
CONCLUSIONS: Across the Asian subregions, there was greater glaucoma burden in
South-Central and East Asia. Sustainable public health strategies to combat
glaucoma in Asia are needed.

Published by the BMJ Publishing Group Limited. For permission to use (where not
already granted under a licence) please go to
http://www.bmj.com/company/products-services/rights-and-licensing/

DOI: 10.1136/bjophthalmol-2014-306102
PMID: 26112871  [Indexed for MEDLINE]


211. Cancer Treat Rev. 2016 Jan;42:73-81. doi: 10.1016/j.ctrv.2015.10.013. Epub 2015
Nov 10.

Surgical excision margins in primary cutaneous melanoma: A meta-analysis and
Bayesian probability evaluation.

Wheatley K(1), Wilson JS(1), Gaunt P(1), Marsden JR(2).

Author information:
(1)Cancer Research UK Clinical Trials Unit, Institute of Cancer & Genomic
Sciences, College of Medical and Dental Sciences, University of Birmingham,
Birmingham B15 2TT, United Kingdom.
(2)Skin Oncology Service, Queen Elizabeth Hospital Birmingham, Mindelsohn Way,
Edgbaston, Birmingham B15 2WB, United Kingdom.

Comment in
    Cancer Treat Rev. 2016 Apr;45:76.

BACKGROUND: Surgery is the only curative treatment for primary cutaneous
melanoma, therefore it is important to determine excision margins that minimise
risk of local recurrence, distant recurrence and death.
METHODS: MEDLINE, EMBASE and Cochrane CENTRAL were searched from 2009 to 2015.
Inclusion criteria were: population/setting - patients with primary melanoma;
comparison - narrow versus wide margins; outcomes - overall survival,
melanoma-specific survival, recurrence-free survival, and loco-regional
recurrence; design - randomized controlled trials (RCTs). Results were pooled
using meta-analysis and data explored using likelihood Bayesian probability
plots.
RESULTS: Six RCTs with 4233 patients were included. Narrow margins were defined
as 1 or 2 cm of clinically normal skin around the melanoma; wide margins as 3, 4
or 5 cm. Hazard ratios (HR) were as follows (HR>1 indicates wide margin better):
overall survival 1.09 (95% CI 0.98-1.22; p=0.1); melanoma-specific survival 1.17
(CI 1.03-1.34; p=0.02); recurrence-free survival 1.08 (CI 0.97-1.20; p=0.2);
loco-regional recurrence 1.10 (CI 0.96-1.26; p=0.2), with no evidence of
heterogeneity between trials for any end point or within subgroup analyses. There
was an 94% probability that overall survival was worse with a narrow margin and a
43% probability that it was more than 10% worse in proportional terms (i.e.
HR>1.1). Probabilities that narrow margins were worse were 99%, 92% and 92% for
melanoma-specific survival, recurrence-free survival and loco-regional recurrence
respectively.
CONCLUSIONS: Contrary to recommendations in several national guidelines that
narrow margins are safe, this systematic review and meta-analysis provides
evidence that a narrow margin may lead to a worse outcome than a wide margin.

Copyright © 2015 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.ctrv.2015.10.013
PMID: 26563920  [Indexed for MEDLINE]


212. CNS Drugs. 2016 Jan;30(1):27-39. doi: 10.1007/s40263-015-0308-1.

A Systematic Review and Network Meta-Analysis to Assess the Relative Efficacy of
Antipsychotics for the Treatment of Positive and Negative Symptoms in Early-Onset
Schizophrenia.

Harvey RC(1), James AC(2), Shields GE(3).

Author information:
(1)BresMed Health Solutions, North Church Business House, 84 Queen Street,
Sheffield, S1 2DW, UK. bharvey@bresmed.co.uk.
(2)Highfield Unit Oxford, Warneford Hospital, Oxford, UK.
(3)BresMed Health Solutions, North Church Business House, 84 Queen Street,
Sheffield, S1 2DW, UK.

INTRODUCTION: Early-onset schizophrenia (EOS) is a serious debilitating disorder
with considerable morbidity and a reduced life expectancy; therefore, early
diagnosis and effective treatments are particularly important. Negative symptoms
are more prominent in adolescents and children (compared with adults), and are
key predictors of worse functional and clinical outcomes in EOS. Therefore, this
study aimed to explore the relative efficacy of antipsychotics used in the
treatment of EOS, with a focus on studies reporting effectiveness using the
Positive and Negative Syndrome scale (PANSS), a scale that includes an overall
symptom measure, in addition to separate subscales for positive and, importantly,
negative symptoms.
METHODS: A systematic literature review was conducted using the MEDLINE and
Cochrane Central Register of Controlled Trials databases to identify trials
conducted in children and adolescents with schizophrenia, and symptom control was
reported using the PANSS. A Bayesian random-effects network meta-analysis was
performed, synthesising data for a number of outcomes, including mean change from
baseline in PANSS scores, treatment discontinuation and weight gain.
RESULTS: Eleven studies were included in the evidence synthesis, comprising 1714
patients across eight active interventions (aripiprazole, haloperidol, molindone,
olanzapine, paliperidone, quetiapine, risperidone and ziprasidone) and placebo.
All treatments showed a greater reduction in total PANSS scores vs placebo;
however, only three interventions (molindone, olanzapine and risperidone) were
associated with a statistically significant reduction in total PANSS scores at 6
weeks vs placebo. Haloperidol had the greatest reduction vs placebo; however,
this result was not statistically significant [mean difference, -15.6, 95%
credible interval (-35.4, 4.1)]. Haloperidol, olanzapine and risperidone showed a
statistically significant reduction in positive PANSS scores vs placebo; however,
whilst all interventions showed a trend of reduction in negative PANSS scores vs
placebo, no comparisons were statistically significant.
CONCLUSIONS: Many of the treatments are efficacious in controlling symptoms, and
all showed a trend of superiority vs placebo for total, positive and negative
PANSS scores, although only olanzapine and risperidone yielded statistically
significant results vs placebo for both total and positive PANSS scores. Varying
results for discontinuation and weight gain demonstrate a need to balance
efficacy with side-effect profiles.

DOI: 10.1007/s40263-015-0308-1
PMID: 26801655  [Indexed for MEDLINE]


213. Curr Med Res Opin. 2016;32(4):721-9. doi: 10.1185/03007995.2016.1140026. Epub
2016 Jan 25.

An indirect comparison and cost per responder analysis of adalimumab,
methotrexate and apremilast in the treatment of methotrexate-naïve patients with
psoriatic arthritis.

Betts KA(1), Griffith J(2), Friedman A(2), Zhou ZY(3), Signorovitch JE(4),
Ganguli A(2).

Author information:
(1)a Analysis Group, Inc. , Los Angeles , CA , USA ;
(2)b AbbVie Inc. , North Chicago , IL , USA ;
(3)c Analysis Group, Inc. , New York , NY , USA ;
(4)d Analysis Group, Inc. , Boston , MA , USA.

OBJECTIVE: Apremilast was recently approved for the treatment of active psoriatic
arthritis (PsA). However, no studies compare apremilast with methotrexate or
biologic therapies, so its relative comparative efficacy remains unknown. This
study compared the response rates and incremental costs per responder associated
with methotrexate, apremilast, and biologics for the treatment of active PsA.
METHODS: A systematic literature review was performed to identify phase 3
randomized controlled clinical trials of approved biologics, methotrexate, and
apremilast in the methotrexate-naïve PsA population. Using Bayesian methods, a
network meta-analysis was conducted to indirectly compare rates of achieving a
≥20% improvement in American College of Rheumatology component scores (ACR20).
The number needed to treat (NNT) and the incremental costs per ACR20 responder
(2014 US$) relative to placebo were estimated for each of the therapies.
RESULTS: Three trials (MIPA for methotrexate, PALACE-4 for apremilast, and ADEPT
for adalimumab) met all inclusion criteria. The NNTs relative to placebo were
2.63 for adalimumab, 6.69 for apremilast, and 8.31 for methotrexate. Among
methotrexate-naïve PsA patients, the 16 week incremental costs per ACR20
responder were $3622 for methotrexate, $26,316 for adalimumab, and $45,808 for
apremilast. The incremental costs per ACR20 responder were $222,488 for
apremilast vs. methotrexate.
CONCLUSION: Among methotrexate-naive PsA patients, adalimumab was found to have
the lowest NNT for one additional ACR20 response and methotrexate was found to
have the lowest incremental costs per ACR20 responder. There was no statistical
evidence of greater efficacy for apremilast vs. methotrexate. A head-to-head
trial between apremilast and methotrexate is recommended to confirm this finding.

DOI: 10.1185/03007995.2016.1140026
PMID: 26743448  [Indexed for MEDLINE]


214. Heart Lung Circ. 2016 Jan;25(1):46-52. doi: 10.1016/j.hlc.2015.05.020. Epub 2015
Jul 6.

Targeted Treatments for Pulmonary Arterial Hypertension: Interpreting Outcomes by
Network Meta-analysis.

Badiani B(1), Messori A(2).

Author information:
(1)HTA Unit, ESTAV Toscana Centro, Regional Health Service, 50100 Firenze, Italy.
(2)HTA Unit, ESTAV Toscana Centro, Regional Health Service, 50100 Firenze, Italy.
Electronic address: andrea.messori.it@gmail.com.

BACKGROUND: No meta-analysis for indirect comparisons has been conducted to study
the effectiveness of treatments for pulmonary arterial hypertension (PAH).
METHODS: Our search covered the literature up to December 2014. The following
five classes of agents indicated for PAH were evaluated: 1) oral endothelin
receptor antagonists (ERAs); 2) oral phosphodiesterase type 5 inhibitors
(PDE-5Is); 3) prostanoids administered by oral, intravenous, subcutaneous or
inhalatory route; 4) selective non-prostanoid prostacyclin receptor (IP receptor)
agonists (sPRAs); 5) soluble guanylate cyclase stimulators (sGCSs). Our
methodology was based on standard models of Bayesian network meta-analysis. The
end-point of our analysis was clinical worsening. Odds ratio was the outcome
measure along with 95% credible intervals.
RESULTS: Our search identified 17 randomised controlled trials (4,465 patients).
There were 15 head-to-head comparisons (five direct, 10 indirect). As expected,
nearly all values of odds ratio estimated for the direct comparisons versus
placebo favoured the treatment arm at levels of statistical significance. More
interestingly, none of the 10 head-to-head indirect comparisons between active
agents showed any statistically significant difference.
CONCLUSION: Our results indicate that these five classes of agents for PAH are
more effective than placebo and show no significant difference in effectiveness
from one another. In this context, choosing the treatment for an individual
patient is a quite difficult task.

Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic
Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ).
Published by Elsevier B.V. All rights reserved.

DOI: 10.1016/j.hlc.2015.05.020
PMID: 26233257  [Indexed for MEDLINE]


215. J Affect Disord. 2016 Jan 1;189:184-91. doi: 10.1016/j.jad.2015.09.022. Epub 2015
Sep 26.

Computerized cognitive training and functional recovery in major depressive
disorder: A meta-analysis.

Motter JN(1), Pimontel MA(1), Rindskopf D(2), Devanand DP(3), Doraiswamy PM(4),
Sneed JR(5).

Author information:
(1)The Graduate Center, City University of New York, USA; Queens College, City
University of New York, USA.
(2)The Graduate Center, City University of New York, USA.
(3)Columbia University and the New York State Psychiatric Institute, USA.
(4)Duke Medicine and Duke Institute for Brain Sciences, USA.
(5)Queens College, City University of New York, USA; Columbia University and the
New York State Psychiatric Institute, USA. Electronic address:
joel.sneed@qc.cuny.edu.

OBJECTIVE: Depression is common, frequently resistant to antidepressant
treatment, and associated with impairments in cognition and everyday functioning.
Computerized cognitive training (CCT) paradigms offer potential to improve
cognition, mood and everyday functioning, but their effectiveness is not well
established. The goal of this article was to conduct a systematic review and
meta-analysis to determine the efficacy of CCT in depressive disorders.
METHOD: A search was conducted to identify high quality randomized controlled CCT
trials per PRISMA guidelines using PsycINFO and MEDLINE with the keywords
"Cognitive training" or "Cognitive remediation" or "Cognitive rehabilitation" and
"Depression". 9 randomized trials for depressed adults met inclusion criteria.
Effect sizes (Hedge's g) were calculated for key outcome measures of mood symptom
severity, daily functioning, and cognition. A 3-level Bayesian hierarchical
linear model was used to estimate effect sizes for each domain and study.
Publication bias was assessed using Classic Fail Safe N's and homogeneity was
evaluated using Q and I(2) indexes.
RESULTS: Significant small-moderate effects for Symptom Severity (0.43) and Daily
Functioning (0.72), and moderate-large effects for Attention (0.67), Working
Memory (0.72), and Global Functioning (1.05) were found. No significant effects
were found for Executive Functioning or Verbal Memory. Moderator variable
analysis revealed decreased effect of CCT with age. Gender and concurrent
medication treatment did not affect the results.
LIMITATIONS: Small sample size, short duration, pseudo-specificity, and high
heterogeneity for Verbal Memory measures.
CONCLUSIONS: CCT is associated with improvement in depressive symptoms and
everyday functioning, though produces inconsistent effects on cognition.

Copyright © 2015 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.jad.2015.09.022
PMID: 26437233  [Indexed for MEDLINE]


216. J Clin Epidemiol. 2016 Jan;69:161-9. doi: 10.1016/j.jclinepi.2015.05.027. Epub
2015 Jun 5.

Publication bias and small-study effects magnified effectiveness of
antipsychotics but their relative ranking remained invariant.

Mavridis D(1), Efthimiou O(2), Leucht S(3), Salanti G(2).

Author information:
(1)Department of Primary Education, University of Ioannina, University Campus, PO
Box 1186, 45110 Ioannina, Greece; Department of Hygiene and Epidemiology,
University of Ioannina, PO Box 1186, 45110 Ioannina, Greece. Electronic address:
dmavridi@cc.uoi.gr.
(2)Department of Hygiene and Epidemiology, University of Ioannina, PO Box 1186,
45110 Ioannina, Greece.
(3)Department of Psychiatry and Psychotherapy, Technische Universität München,
Arcisstraβe 21, D-8033 Munich, Germany.

OBJECTIVES: Publication bias (PB) may seriously compromise inferences from
meta-analyses. The aim of this article was to assess the potential effect of
small-study effects and PB on the recently estimated relative effectiveness and
ranking of pharmacological treatments for schizophrenia.
STUDY DESIGN AND SETTING: We used a recently published network of 167 trials
involving 36,871 patients and comparing the effectiveness of 15 antipsychotics
and placebo. We used novel visual and statistical methods to explore if smaller
trials are associated with larger treatment effects and a selection model to
explore if the probability of trial publication is associated with the magnitude
of effect. We conducted a network meta-analysis of the published evidence as our
primary analysis and used a sensitivity analysis considering low, moderate, and
severe selection bias (that corresponds to the number of unpublished trials) with
an aim to evaluate robustness of point estimates and ranking. We explored whether
placebo-controlled and head-to-head trials are associated with different levels
of PB.
RESULTS: We found that small placebo-controlled trials exaggerated slightly the
efficacy of antipsychotics, and PB was not unlikely in the evidence based on
placebo-controlled trials; however, ranking of antipsychotics remained robust.
CONCLUSION: The total evidence comprises many head-to-head trials that do not
appear to be prone to small-study effects or PB, and indirect evidence appears to
"wash out" some of the biases in the placebo-controlled trials.

Copyright © 2016 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.jclinepi.2015.05.027
PMID: 26210055  [Indexed for MEDLINE]


217. Ophthalmology. 2016 Jan;123(1):129-40. doi: 10.1016/j.ophtha.2015.09.005. Epub
2015 Oct 31.

Comparative Effectiveness of First-Line Medications for Primary Open-Angle
Glaucoma: A Systematic Review and Network Meta-analysis.

Li T(1), Lindsley K(2), Rouse B(3), Hong H(4), Shi Q(3), Friedman DS(5), Wormald
R(6), Dickersin K(2).

Author information:
(1)Department of Epidemiology, Center for Clinical Trials and Evidence Synthesis,
Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. Electronic
address: tli19@jhu.edu.
(2)Department of Epidemiology, Center for Clinical Trials and Evidence Synthesis,
Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
(3)Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health,
Baltimore, Maryland.
(4)Department of Mental Health, Johns Hopkins Bloomberg School of Public Health,
Baltimore, Maryland.
(5)The Dana Center for Preventive Ophthalmology, Wilmer Eye Institute, Johns
Hopkins School of Medicine, Baltimore, Maryland.
(6)Cochrane Eyes and Vision Group, London School of Hygiene & Tropical Medicine,
London, United Kingdom.

TOPIC: Primary open-angle glaucoma (POAG) is a highly prevalent condition
worldwide and the most common cause of irreversible sight loss. The objective is
to assess the comparative effectiveness of first-line medical treatments in
patients with POAG or ocular hypertension through a systematic review and network
meta-analysis, and to provide relative rankings of these treatments.
CLINICAL RELEVANCE: Treatment for POAG currently relies completely on lowering
the intraocular pressure (IOP). Although topical drops, lasers, and surgeries can
be considered in the initial treatment of glaucoma, most patients elect to start
treatment with eye drops.
METHODS: We included randomized controlled trials (RCTs) that compared a single
active topical medication with no treatment/placebo or another single topical
medication. We searched CENTRAL, MEDLINE, EMBASE, and the Food and Drug
Administration's website. Two individuals independently assessed trial
eligibility, abstracted data, and assessed the risk of bias. We performed
Bayesian network meta-analyses.
RESULTS: We included 114 RCTs with data from 20 275 participants. The overall
risk of bias of the included trials is mixed. The mean reductions (95% credible
intervals) in IOP in millimeters of mercury at 3 months ordered from the most to
least effective drugs were as follows: bimatoprost 5.61 (4.94; 6.29), latanoprost
4.85 (4.24; 5.46), travoprost 4.83 (4.12; 5.54), levobunolol 4.51 (3.85; 5.24),
tafluprost 4.37 (2.94; 5.83), timolol 3.70 (3.16; 4.24), brimonidine 3.59 (2.89;
4.29), carteolol 3.44 (2.42; 4.46), levobetaxolol 2.56 (1.52; 3.62),
apraclonidine 2.52 (0.94; 4.11), dorzolamide 2.49 (1.85; 3.13), brinzolamide 2.42
(1.62; 3.23), betaxolol 2.24 (1.59; 2.88), and unoprostone 1.91 (1.15; 2.67).
CONCLUSIONS: All active first-line drugs are effective compared with placebo in
reducing IOP at 3 months. Bimatoprost, latanoprost, and travoprost are among the
most efficacious drugs, although the within-class differences were small and may
not be clinically meaningful. All factors, including adverse effects, patient
preferences, and cost, should be considered in selecting a drug for a given
patient.

Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc.
All rights reserved.

DOI: 10.1016/j.ophtha.2015.09.005
PMCID: PMC4695285
PMID: 26526633  [Indexed for MEDLINE]


218. Otolaryngol Head Neck Surg. 2016 Jan;154(1):9-23. doi: 10.1177/0194599815607841.
Epub 2015 Oct 1.

Sensitivity, Specificity, and Posttest Probability of Parotid Fine-Needle
Aspiration: A Systematic Review and Meta-analysis.

Liu CC(1), Jethwa AR(2), Khariwala SS(2), Johnson J(3), Shin JJ(4).

Author information:
(1)Division of Otolaryngology-Head and Neck Surgery, Department of Surgery,
University of Calgary, Calgary, Canada.
(2)Department of Otolaryngology-Head and Neck Surgery, University of Minnesota,
Minneapolis, Minnesota, USA.
(3)Department of Otolaryngology, University of Pittsburgh School of Medicine,
Pittsburgh, Pennsylvania, USA.
(4)Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts,
USA jennifer_shin@meei.harvard.edu.

OBJECTIVES: (1) To analyze the sensitivity and specificity of fine-needle
aspiration (FNA) in distinguishing benign from malignant parotid disease. (2) To
determine the anticipated posttest probability of malignancy and probability of
nondiagnostic and indeterminate cytology with parotid FNA.
DATA SOURCES: Independently corroborated computerized searches of PubMed, Embase,
and Cochrane Central Register were performed. These were supplemented with manual
searches and input from content experts.
REVIEW METHODS: Inclusion/exclusion criteria specified diagnosis of parotid mass,
intervention with both FNA and surgical excision, and enumeration of both
cytologic and surgical histopathologic results. The primary outcomes were
sensitivity, specificity, and posttest probability of malignancy. Heterogeneity
was evaluated with the I(2) statistic. Meta-analysis was performed via a 2-level
mixed logistic regression model. Bayesian nomograms were plotted via pooled
likelihood ratios.
RESULTS: The systematic review yielded 70 criterion-meeting studies, 63 of which
contained data that allowed for computation of numerical outcomes (n = 5647
patients; level 2a) and consideration of meta-analysis. Subgroup analyses were
performed in studies that were prospective, involved consecutive patients,
described the FNA technique utilized, and used ultrasound guidance. The I(2)
point estimate was >70% for all analyses, except within prospectively obtained
and ultrasound-guided results. Among the prospective subgroup, the pooled
analysis demonstrated a sensitivity of 0.882 (95% confidence interval [95% CI],
0.509-0.982) and a specificity of 0.995 (95% CI, 0.960-0.999). The probabilities
of nondiagnostic and indeterminate cytology were 0.053 (95% CI, 0.030-0.075) and
0.147 (95% CI, 0.106-0.188), respectively.
CONCLUSION: FNA has moderate sensitivity and high specificity in differentiating
malignant from benign parotid lesions. Considerable heterogeneity is present
among studies.

© American Academy of Otolaryngology-Head and Neck Surgery Foundation 2015.

DOI: 10.1177/0194599815607841
PMCID: PMC4896151
PMID: 26428476  [Indexed for MEDLINE]


219. World J Surg. 2016 Jan;40(1):89-99. doi: 10.1007/s00268-015-3252-9.

Mesh Location in Open Ventral Hernia Repair: A Systematic Review and Network
Meta-analysis.

Holihan JL(1), Nguyen DH(2), Nguyen MT(3), Mo J(4), Kao LS(5), Liang MK(6).

Author information:
(1)Department of General Surgery, University of Texas Health Science Center, 6431
Fannin St, Houston, TX, 77030, USA. Julie.L.Holihan@uth.tmc.edu.
(2)Department of General Surgery, University of Texas Health Science Center, 6431
Fannin St, Houston, TX, 77030, USA. Dhnguyen.06@gmail.com.
(3)Department of General Surgery, University of Texas Health Science Center, 6431
Fannin St, Houston, TX, 77030, USA. Mylan.thi.nguyen@gmail.com.
(4)Department of General Surgery, University of Texas Health Science Center, 6431
Fannin St, Houston, TX, 77030, USA. Mojiandi@gmail.com.
(5)Department of General Surgery, University of Texas Health Science Center, 6431
Fannin St, Houston, TX, 77030, USA. Lillian.S.Kao@uth.tmc.edu.
(6)Department of General Surgery, University of Texas Health Science Center, 6431
Fannin St, Houston, TX, 77030, USA. Mike.Liang@uth.tmc.edu.

There is no consensus on the ideal location for mesh placement in open ventral
hernia repair (OVHR). We aim to identify the mesh location associated with the
lowest rate of recurrence following OVHR using a systematic review and
meta-analysis. A search was performed for studies comparing at least two of four
locations for mesh placement during OVHR (onlay, inlay, sublay, and underlay).
Outcomes assessed were hernia recurrence and surgical site infection (SSI).
Pairwise meta-analysis was performed to compare all direct treatment of mesh
locations. A multiple treatment meta-analysis was performed to compare all mesh
locations in the Bayesian framework. Sensitivity analyses were planned for the
following: studies with a low risk of bias, incisional hernias, by hernia size,
and by mesh type (synthetic or biologic). Twenty-one studies were identified (n =
5,891). Sublay placement of mesh was associated with the lowest risk for
recurrence [OR 0.218 (95% CI 0.06-0.47)] and was the best of the four treatment
modalities assessed [Prob (best) = 94.2%]. Sublay was also associated with the
lowest risk for SSI [OR 0.449 (95% CI 0.12-1.16)] and was the best of the 4
treatment modalities assessed [Prob (best) = 77.3%]. When only assessing studies
at low risk of bias, of incisional hernias, and using synthetic mesh, the
probability that sublay had the lowest rate of recurrence and SSI was high.
Sublay mesh location has lower complication rates than other mesh locations.
While additional randomized controlled trials are needed to validate these
findings, this network meta-analysis suggests the probability of sublay being the
best location for mesh placement is high.

DOI: 10.1007/s00268-015-3252-9
PMID: 26423675  [Indexed for MEDLINE]


220. PLoS One. 2015 Dec 30;10(12):e0144856. doi: 10.1371/journal.pone.0144856.
eCollection 2015.

Comparison of the Novel Oral Anticoagulants Apixaban, Dabigatran, Edoxaban, and
Rivaroxaban in the Initial and Long-Term Treatment and Prevention of Venous
Thromboembolism: Systematic Review and Network Meta-Analysis.

Cohen AT(1), Hamilton M(2), Mitchell SA(3), Phatak H(2), Liu X(4), Bird A(5),
Tushabe D(6), Batson S(3).

Author information:
(1)Guy's and St Thomas' Hospitals, King's College, London, United Kingdom.
(2)BMS, Princeton, United States of America.
(3)Abacus International, Bicester, United Kingdom.
(4)Pfizer, New York, United States of America.
(5)Pfizer, Walton Oaks, United Kingdom.
(6)TUSH-D UK LTD, Birmingham, United Kingdom.

BACKGROUND: Anticoagulation with low molecular weight heparin and vitamin K
antagonists is the current standard of care (SOC) for venous thromboembolism
(VTE) treatment and prevention. Although novel oral anti-coagulants (NOACs) have
been compared with SOC in this indication, no head-to-head randomised controlled
trials (RCTs) have directly compared NOACs. A systematic review and network
meta-analysis (NMA) were conducted to compare the efficacy and safety of NOACs
for the initial and long-term treatment of VTE.
METHODS: Electronic databases (accessed July 2014) were systematically searched
to identify RCTs evaluating apixaban, dabigatran, edoxaban, and rivaroxaban
versus SOC. Eligible patients included adults with an objectively confirmed deep
vein thrombosis (DVT), pulmonary embolism (PE) or both. A fixed-effect Bayesian
NMA was conducted for outcomes of interest, and results were presented as
relative risks (RR) and 95% credible intervals (Crl).
RESULTS: Six Phase III RCTs met criteria for inclusion: apixaban (one RCT; n =
5,395); rivaroxaban (two RCTs; n = 3,423/4,832); dabigatran (two RCTs; n =
2,539/2,568); edoxaban (one RCT; n = 8,240). There were no statistically
significant differences between the NOACs with regard to the risk of 'VTE and
VTE-related death. Apixaban treatment was associated with the most favourable
safety profile of the NOACs, showing a statistically significantly reduced risk
of 'major or clinically relevant non-major (CRNM) bleed' compared with
rivaroxaban (0.47 [0.36, 0.61]), dabigatran (0.69 [0.51, 0.94]), and edoxaban
(0.54 [0.41, 0.69]). Dabigatran was also associated with a significantly lower
risk of 'major or CRNM bleed' compared with rivaroxaban (0.68 [0.53, 0.87]) and
edoxaban (0.77 [0.60, 0.99]).
CONCLUSIONS: Indirect comparisons showed statistically similar reductions in the
risk of 'VTE or VTE-related death for all NOACs. In contrast, reductions in
'major or CRNM bleed' for initial/long-term treatment were significantly better
with apixaban compared with all other NOACs, and with dabigatran compared with
rivaroxaban and edoxaban. Results from the current analysis indicate that the
NOACs offer clinical benefit over conventional therapy while highlighting
relative differences in their bleeding profile.

DOI: 10.1371/journal.pone.0144856
PMCID: PMC4696796
PMID: 26716830  [Indexed for MEDLINE]


221. Oncotarget. 2015 Dec 15;6(40):42515-29. doi: 10.18632/oncotarget.6452.

Antihypertensive treatments in adult autosomal dominant polycystic kidney
disease: network meta-analysis of the randomized controlled trials.

Xue C(1)(2), Zhou C(1), Dai B(1), Yu S(1), Xu C(1), Mao Z(1), Ye C(1), Chen D(1),
Zhao X(1), Wu J(1), Chen W(1)(3), Mei C(1).

Author information:
(1)Department of Nephrology, Shanghai Changzheng Hospital, Second Military
Medical University, Shanghai, China.
(2)Department of Nephrology, PLA 309 Hospital, Beijing, China.
(3)Department of Pharmacy, Shanghai Changzheng Hospital, Second Military Medical
University, Shanghai, China.

BACKGROUND: Blood pressure (BP) control is one of the most important treatments
of Autosomal dominant polycystic kidney disease (ADPKD). The comparative efficacy
of antihypertensive treatments in ADPKD patients is inconclusive.
METHODS: Network meta-analysis was used to evaluate randomized controlled trials
(RCT) which investigated antihypertensive treatments in ADPKD. PubMed, Embase,
Ovid, and Cochrane Collaboration were searched. The primary outcome was estimated
glomerular filtration rate (eGFR). Secondary outcomes were serum creatinine
(Scr), urinary albumin excretion (UAE), systolic BP (SBP), diastolic BP (DBP),
mean artery pressure (MAP) and left ventricular mass index (LVMI).
RESULTS: We included 10 RCTs with 1386 patients and six interventions:
angiotensin-converting enzyme inhibitors (ACEI), Angiotensin II receptor blocker
(ARB), combination of ACEI and ARB, calcium channel blockers (CCB), β-blockers
and dilazep. There was no difference of eGFR in all the treatments in both
network and direct comparisons. No significant differences of Scr, SBP, DBP, MAP,
and LVMI were found in network comparisons. However, ACEI signiﬁcantly reduced
SBP, DBP, MAP and LVMI when compared to CCB. Significantly increased UAE was
observed in CCB compared with ACEI or ARB. Bayesian probability analysis found
ARB ranked first in the surrogate measures of eGFR, UAE and SBP.
CONCLUSIONS: There is little evidence to detect differences of antihypertensive
treatments on kidney disease progression in ADPKD patients. More RCTs will be
needed in the future. Use of ARB may be an optimal choice in clinical practice.

DOI: 10.18632/oncotarget.6452
PMCID: PMC4767449
PMID: 26636542  [Indexed for MEDLINE]


222. Accid Anal Prev. 2015 Dec;85:207-18. doi: 10.1016/j.aap.2015.09.016.

Calibration of crash risk models on freeways with limited real-time traffic data
using Bayesian meta-analysis and Bayesian inference approach.

Xu C(1), Wang W(2), Liu P(3), Li Z(4).

Author information:
(1)Jiangsu Key Laboratory of Urban ITS, Southeast University, Si Pai Lou #2,
Nanjing 210096, China; Jiangsu Province Collaborative Innovation Center of Modern
Urban Traffic Technologies, Si Pai Lou #2, Nanjing 210096, China. Electronic
address: xuchengcheng@seu.edu.cn.
(2)Jiangsu Key Laboratory of Urban ITS, Southeast University, Si Pai Lou #2,
Nanjing 210096, China; Jiangsu Province Collaborative Innovation Center of Modern
Urban Traffic Technologies, Si Pai Lou #2, Nanjing 210096, China. Electronic
address: wangwei@seu.edu.cn.
(3)Jiangsu Key Laboratory of Urban ITS, Southeast University, Si Pai Lou #2,
Nanjing 210096, China; Jiangsu Province Collaborative Innovation Center of Modern
Urban Traffic Technologies, Si Pai Lou #2, Nanjing 210096, China. Electronic
address: pan_liu@hotmail.com.
(4)Jiangsu Key Laboratory of Urban ITS, Southeast University, Si Pai Lou #2,
Nanjing 210096, China; Jiangsu Province Collaborative Innovation Center of Modern
Urban Traffic Technologies, Si Pai Lou #2, Nanjing 210096, China. Electronic
address: lizhibin-2002@163.com.

This study aimed to develop a real-time crash risk model with limited data in
China by using Bayesian meta-analysis and Bayesian inference approach. A
systematic review was first conducted by using three different Bayesian
meta-analyses, including the fixed effect meta-analysis, the random effect
meta-analysis, and the meta-regression. The meta-analyses provided a numerical
summary of the effects of traffic variables on crash risks by quantitatively
synthesizing results from previous studies. The random effect meta-analysis and
the meta-regression produced a more conservative estimate for the effects of
traffic variables compared with the fixed effect meta-analysis. Then, the
meta-analyses results were used as informative priors for developing crash risk
models with limited data. Three different meta-analyses significantly affect
model fit and prediction accuracy. The model based on meta-regression can
increase the prediction accuracy by about 15% as compared to the model that was
directly developed with limited data. Finally, the Bayesian predictive densities
analysis was used to identify the outliers in the limited data. It can further
improve the prediction accuracy by 5.0%.

Copyright © 2015 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.aap.2015.09.016
PMID: 26468977  [Indexed for MEDLINE]


223. Ann Intern Med. 2015 Dec 1;163(11):848-60. doi: 10.7326/M15-1400. Epub 2015 Sep
29.

Behavioral Programs for Type 2 Diabetes Mellitus: A Systematic Review and Network
Meta-analysis.

Pillay J, Armstrong MJ, Butalia S, Donovan LE, Sigal RJ, Vandermeer B, Chordiya
P, Dhakal S, Hartling L, Nuspl M, Featherstone R, Dryden DM.

BACKGROUND: Behavioral programs may improve outcomes for individuals with type 2
diabetes mellitus, but there is a large diversity of behavioral interventions and
uncertainty about how to optimize the effectiveness of these programs.
PURPOSE: To identify factors moderating the effectiveness of behavioral programs
for adults with type 2 diabetes.
DATA SOURCES: 6 databases (1993 to January 2015), conference proceedings (2011 to
2014), and reference lists.
STUDY SELECTION: Duplicate screening and selection of 132 randomized, controlled
trials evaluating behavioral programs compared with usual care, active controls,
or other behavioral programs.
DATA EXTRACTION: One reviewer extracted and another verified data. Two reviewers
independently assessed risk of bias.
DATA SYNTHESIS: Behavioral programs were grouped on the basis of program content
and delivery methods. A Bayesian network meta-analysis showed that most lifestyle
and diabetes self-management education and support programs (usually offering ≥
11 contact hours) led to clinically important improvements in glycemic control (≥
0.4% reduction in hemoglobin A1c [HbA1c]), whereas most diabetes self-management
education programs without added support-especially those offering 10 or fewer
contact hours-provided little benefit. Programs with higher effect sizes were
more often delivered in person than via technology. Lifestyle programs led to the
greatest reductions in body mass index. Reductions in HbA1c seemed to be greater
for participants with a baseline HbA1c level of 7.0% or greater, adults younger
than 65 years, and minority persons (subgroups with ≥ 75% nonwhite participants).
LIMITATIONS: All trials had medium or high risk of bias. Subgroup analyses were
indirect, and therefore exploratory. Most outcomes were reported immediately
after the interventions.
CONCLUSION: Diabetes self-management education offering 10 or fewer hours of
contact with delivery personnel provided little benefit. Behavioral programs seem
to benefit persons with suboptimal or poor glycemic control more than those with
good control.
PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO
registration number: CRD42014010515).

DOI: 10.7326/M15-1400
PMID: 26414227  [Indexed for MEDLINE]


224. Br J Surg. 2015 Dec;102(13):1603-18. doi: 10.1002/bjs.9913. Epub 2015 Sep 30.

Systematic review and network meta-analysis comparing clinical outcomes and
effectiveness of surgical treatments for haemorrhoids.

Simillis C(1), Thoukididou SN(1), Slesser AA(1), Rasheed S(1), Tan E(1), Tekkis
PP(1).

Author information:
(1)Department of Colorectal Surgery, Royal Marsden Hospital, Fulham Road, London
SW3 6JJ, UK.

BACKGROUND: The aim was to compare the clinical outcomes and effectiveness of
surgical treatments for haemorrhoids.
METHODS: Randomized clinical trials were identified by means of a systematic
review. A Bayesian network meta-analysis was performed using the Markov chain
Monte Carlo method in WinBUGS.
RESULTS: Ninety-eight trials were included with 7827 participants and 11 surgical
treatments for grade III and IV haemorrhoids. Open, closed and radiofrequency
haemorrhoidectomies resulted in significantly more postoperative complications
than transanal haemorrhoidal dearterialization (THD), LigaSure™ and Harmonic®
haemorrhoidectomies. THD had significantly less postoperative bleeding than open
and stapled procedures, and resulted in significantly fewer emergency
reoperations than open, closed, stapled and LigaSure™ haemorrhoidectomies. Open
and closed haemorrhoidectomies resulted in more pain on postoperative day 1 than
stapled, THD, LigaSure™ and Harmonic® procedures. After stapled, LigaSure™ and
Harmonic® haemorrhoidectomies patients resumed normal daily activities earlier
than after open and closed procedures. THD provided the earliest time to first
bowel movement. The stapled and THD groups had significantly higher haemorrhoid
recurrence rates than the open, closed and LigaSure™ groups. Recurrence of
haemorrhoidal symptoms was more common after stapled haemorrhoidectomy than after
open and LigaSure™ operations. No significant difference was identified between
treatments for anal stenosis, incontinence and perianal skin tags.
CONCLUSION: Open and closed haemorrhoidectomies resulted in more postoperative
complications and slower recovery, but fewer haemorrhoid recurrences. THD and
stapled haemorrhoidectomies were associated with decreased postoperative pain and
faster recovery, but higher recurrence rates. The advantages and disadvantages of
each surgical treatment should be discussed with the patient before surgery to
allow an informed decision to be made.

© 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.

DOI: 10.1002/bjs.9913
PMID: 26420725  [Indexed for MEDLINE]


225. J Pain. 2015 Dec;16(12):1221-1232. doi: 10.1016/j.jpain.2015.07.009. Epub 2015
Sep 9.

Inhaled Cannabis for Chronic Neuropathic Pain: A Meta-analysis of Individual
Patient Data.

Andreae MH(1), Carter GM(2), Shaparin N(3), Suslov K(4), Ellis RJ(5), Ware MA(6),
Abrams DI(7), Prasad H(8), Wilsey B(8), Indyk D(4), Johnson M(9), Sacks HS(4).

Author information:
(1)Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New
York. Electronic address: mhandreae@gmail.com.
(2)Foundation for Integrative AIDS Research, Brooklyn, New York.
(3)Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New
York.
(4)Icahn School of Medicine at Mount Sinai, New York, New York.
(5)Department of Neurosciences, University of California, San Diego, California.
(6)Department of Anesthesia and Family Medicine, McGill University, Montréal,
Québec, Canada.
(7)AIDS Program, San Francisco General Hospital, University of California, San
Francisco, California.
(8)Department of Physical Medicine and Rehabilitation, VA Northern California and
University of California Davis Medical Center, Sacramento, California.
(9)Teachers College, Columbia University, New York, New York.

Chronic neuropathic pain, the most frequent condition affecting the peripheral
nervous system, remains underdiagnosed and difficult to treat. Inhaled cannabis
may alleviate chronic neuropathic pain. Our objective was to synthesize the
evidence on the use of inhaled cannabis for chronic neuropathic pain. We
performed a systematic review and a meta-analysis of individual patient data. We
registered our protocol with PROSPERO CRD42011001182. We searched in Cochrane
Central, PubMed, EMBASE, and AMED. We considered all randomized controlled trials
investigating chronic painful neuropathy and comparing inhaled cannabis with
placebo. We pooled treatment effects following a hierarchical random-effects
Bayesian responder model for the population-averaged subject-specific effect. Our
evidence synthesis of individual patient data from 178 participants with 405
observed responses in 5 randomized controlled trials following patients for days
to weeks provides evidence that inhaled cannabis results in short-term reductions
in chronic neuropathic pain for 1 in every 5 to 6 patients treated (number needed
to treat = 5.6 with a Bayesian 95% credible interval ranging between 3.4 and 14).
Our inferences were insensitive to model assumptions, priors, and parameter
choices. We caution that the small number of studies and participants, the short
follow-up, shortcomings in allocation concealment, and considerable attrition
limit the conclusions that can be drawn from the review. The Bayes factor is 332,
corresponding to a posterior probability of effect of 99.7%.PERSPECTIVE: This
novel Bayesian meta-analysis of individual patient data from 5 randomized trials
suggests that inhaled cannabis may provide short-term relief for 1 in 5 to 6
patients with neuropathic pain. Pragmatic trials are needed to evaluate the
long-term benefits and risks of this treatment.

Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights
reserved.

DOI: 10.1016/j.jpain.2015.07.009
PMCID: PMC4666747
PMID: 26362106  [Indexed for MEDLINE]


226. Lupus. 2015 Dec;24(14):1520-8. doi: 10.1177/0961203315595131. Epub 2015 Jul 9.

Relative efficacy and safety of tacrolimus, mycophenolate mofetil, and
cyclophosphamide as induction therapy for lupus nephritis: a Bayesian network
meta-analysis of randomized controlled trials.

Lee YH(1), Song GG(2).

Author information:
(1)Division of Rheumatology, Department of Internal Medicine, Korea University
College of Medicine, Seoul, Korea lyhcgh@korea.ac.kr.
(2)Division of Rheumatology, Department of Internal Medicine, Korea University
College of Medicine, Seoul, Korea.

AIMS: This study aimed to assess the relative efficacy and safety of tacrolimus,
mycophenolate mofetil (MMF) and cyclophosphamide (CYC) as induction therapy for
lupus nephritis.
METHODS: Randomized controlled trials (RCTs) examining the efficacy and safety of
tacrolimus, MMF and CYC for induction therapy in patients with lupus nephritis
were included. We performed a Bayesian random-effects network meta-analysis to
combine direct and indirect evidence from the RCTs.
RESULTS: Nine RCTs including 972 patients met the inclusion criteria and
pair-wise comparisons were performed, including 11 direct comparisons. Tacrolimus
showed a significantly higher overall response rate (complete remission plus
partial remission) than CYC (OR 2.35, 95% confidence interval (CI) 1.03-5.45),
and was more efficacious than MMF (OR 1.60, 95% CI 0.70-3.57). MMF was superior
to CYC in terms of overall response (OR 1.45, 95% CI 0.96-2.42). Ranking
probability based on the surface under the cumulative ranking curve (SUCRA)
indicated that tacrolimus had the highest probability of being the best treatment
for achieving the overall response (SUCRA = 0.9321), followed by MMF
(SUCRA = 0.5385) and CYC (SUCRA = 0.0294). In terms of safety, tacrolimus showed
the highest probability of decreasing the risk of serious infections
(SUCRA = 0.9253), followed by MMF (SUCRA = 0.4027) and CYC (SUCRA = 0.1720).
CONCLUSIONS: Tacrolimus was the most efficacious induction treatment for patients
with lupus nephritis, and had the highest probability of decreasing the risk of
serious infections. Higher remission rates combined with a more favorable safety
profile suggest that MMF is superior to CYC as induction treatment in these
patients.

© The Author(s) 2015.

DOI: 10.1177/0961203315595131
PMID: 26162684  [Indexed for MEDLINE]


227. Rheumatol Int. 2015 Dec;35(12):1965-74. doi: 10.1007/s00296-015-3291-4. Epub 2015
May 21.

Comparative efficacy and safety of tofacitinib, with or without methotrexate, in
patients with active rheumatoid arthritis: a Bayesian network meta-analysis of
randomized controlled trials.

Lee YH(1), Bae SC(2), Song GG(3).

Author information:
(1)Division of Rheumatology, Department of Internal Medicine, Korea University
Anam Hospital, Korea University College of Medicine, 126-1 ga, Anam-dong,
Seongbuk-gu, Seoul, 136-705, Korea. lyhcgh@korea.ac.kr.
(2)Division of Rheumatology, Department of Internal Medicine, The Hospital for
Rheumatic Diseases, Hanyang University Medical Center, Seoul, Korea.
(3)Division of Rheumatology, Department of Internal Medicine, Korea University
Anam Hospital, Korea University College of Medicine, 126-1 ga, Anam-dong,
Seongbuk-gu, Seoul, 136-705, Korea.

This study aimed to assess the relative efficacy and safety of tofacitinib 5 and
10 mg twice daily, or in combination with methotrexate (MTX), in patients with
active RA. Randomized controlled trials (RCTs) examining the efficacy and safety
of tofacitinib in patients with active RA were included in this network
meta-analysis. We performed a Bayesian network meta-analysis to combine the
direct and indirect evidence from the RCTs. Ten RCTs including 4867 patients met
the inclusion criteria. There were 21 pairwise comparisons including 11 direct
comparisons of seven interventions. The ACR20 response rate was significantly
higher in the tofacitinib 10 mg + MTX group than in the placebo and MTX groups
(OR 7.56, 95 % credible interval (CrI) 3.07-21.16; OR 3.67, 95 % CrI 2.60-5.71,
respectively). Ranking probabilities based on the surface under the cumulative
ranking curve (SUCRA) indicated that tofacitinib 10 mg + MTX had the highest
probability of being the best treatment for achieving the ACR20 response rate
(SUCRA = 0.9254), followed by tofacitinib 5 mg + MTX (SUCRA = 0.7156), adalimumab
40 mg + MTX (SUCRA = 0.6097), tofacitinib 10 mg (SUCRA = 0.5984), tofacitinib
5 mg (SUCRA = 0.4749), MTX (SUCRA = 0.1674), and placebo (SUCRA = 0.0086). In
contrast, the safety based on the number of withdrawals due to adverse events did
not differ significantly among the seven interventions. Tofacitinib, at dosages 5
and 10 mg twice daily, in combination with MTX, was the most efficacious
intervention for active RA and was not associated with a significant risk for
withdrawals due to adverse events.

DOI: 10.1007/s00296-015-3291-4
PMID: 25994093  [Indexed for MEDLINE]


228. Neurology. 2015 Nov 24;85(21):1859-68. doi: 10.1212/WNL.0000000000002142. Epub
2015 Oct 28.

Efficacy of nonvenous medications for acute convulsive seizures: A network
meta-analysis.

Arya R(1), Kothari H(2), Zhang Z(2), Han B(2), Horn PS(2), Glauser TA(2).

Author information:
(1)From the Comprehensive Epilepsy Center, Division of Neurology (R.A., P.S.H.,
T.A.G.), and the Division of Epidemiology and Biostatistics (P.S.H.), Cincinnati
Children's Hospital Medical Center, OH; the Department of Pediatrics (H.K.), The
Unterberg Children's Hospital at Monmouth Medical Center, Long Branch, NJ; the
Department of Mathematical Sciences (Z.Z.), University of Cincinnati, OH; and
Biogen (B.H.), Cambridge, MA. Ravindra.Arya@cchmc.org.
(2)From the Comprehensive Epilepsy Center, Division of Neurology (R.A., P.S.H.,
T.A.G.), and the Division of Epidemiology and Biostatistics (P.S.H.), Cincinnati
Children's Hospital Medical Center, OH; the Department of Pediatrics (H.K.), The
Unterberg Children's Hospital at Monmouth Medical Center, Long Branch, NJ; the
Department of Mathematical Sciences (Z.Z.), University of Cincinnati, OH; and
Biogen (B.H.), Cambridge, MA.

OBJECTIVE: This is a network meta-analysis of nonvenous drugs used in randomized
controlled trials (RCTs) for treatment of acute convulsive seizures and
convulsive status epilepticus.
METHODS: Literature was searched according to Preferred Reporting Items for
Systematic reviews and Meta-Analyses guidelines for RCTs examining treatment of
acute convulsive seizures or status epilepticus with at least one of the study
arms being a nonvenous medication. After demographic and outcome data extraction,
a Bayesian network meta-analysis was performed and efficacy results were
summarized using treatment effects and their credible intervals (CrI). We also
calculated the probability of each route-drug combination being the most
clinically effective for a given outcome, and provided their Bayesian
hierarchical ranking.
RESULTS: This meta-analysis of 16 studies found that intramuscular midazolam
(IM-MDZ) is superior to other nonvenous medications regarding time to seizure
termination after administration (2.145 minutes, 95% CrI 1.308-3.489), time to
seizure cessation after arrival in the hospital (3.841 minutes, 95% CrI
2.697-5.416), and time to initiate treatment (0.779 minutes, 95% CrI
0.495-1.221). Additionally, intranasal midazolam (IN-MDZ) was adjudged most
efficacious for seizure cessation within 10 minutes of administration (90.4% of
participants, 95% CrI 79.4%-96.9%), and persistent seizure cessation for ≥1 hour
(78.5% of participants, 95% CrI 59.5%-92.1%). Paucity of RCTs produced evidence
gaps resulting in small networks, routes/drugs included in some networks but not
others, and some trials not being connected to any network.
CONCLUSIONS: Despite the evidence gaps, IM-MDZ and IN-MDZ exhibit the best
efficacy data for the nonvenous treatment of acute convulsive seizures or status
epilepticus.

© 2015 American Academy of Neurology.

DOI: 10.1212/WNL.0000000000002142
PMCID: PMC4662705
PMID: 26511448  [Indexed for MEDLINE]


229. BMC Musculoskelet Disord. 2015 Nov 19;16:363. doi: 10.1186/s12891-015-0815-8.

A Bayesian network meta-analysis: Comparing the clinical effectiveness of local
corticosteroid injections using different treatment strategies for carpal tunnel
syndrome.

Chen PC(1), Chuang CH(2), Tu YK(3), Bai CH(4), Chen CF(5)(6)(7), Liaw M(8).

Author information:
(1)Department of Rehabilitation, Kaohsiung Chang Gung Memorial Hospital,
Kaohsiung, Taiwan. b9302081@cgmh.org.tw.
(2)Department of Nursing, Kaohsiung Chang Gung Memorial Hospital, No.123, Dapi
Road, Niaosong District, Kaohsiung, 83301, Taiwan. chinhui@cgmh.org.tw.
(3)Institute of Epidemiology and Preventive Medicine, College of Public Health,
National Taiwan University, Taipei, Taiwan. yukangtu@ntu.edu.tw.
(4)School of Public Health, Taipei Medical University, Taipei, Taiwan.
baich@tmu.edu.tw.
(5)School of Public Health, Taipei Medical University, Taipei, Taiwan.
clifchen@tmu.edu.tw.
(6)Division of Plastic Surgery, Department of Surgery, Wan Fang Hospital, Taipei
Medical University, Taipei, Taiwan. clifchen@tmu.edu.tw.
(7)Cochrane Taiwan, Taipei Medical University, Taipei, Taiwan.
clifchen@tmu.edu.tw.
(8)Department of Rehabilitation, Kaohsiung Chang Gung Memorial Hospital,
Kaohsiung, Taiwan. meiyunliaw@cgmh.org.tw.

Erratum in
    BMC Musculoskelet Disord. 2015;16(1):394.

BACKGROUND: Local corticosteroid injections are commonly used to improve the
short-term symptomatic severity and the functional status of the hands affected
by carpal tunnel syndrome. We conducted a systematic review and Bayesian
network-meta-analysis to compare the clinical effectiveness of local
corticosteroid injections using different injection approaches.
METHODS: Electronic literature in Cochrane Central Register of Controlled Trials
(CENTRAL), MEDLINE, EMBASE, Web of Science, and other sources were searched to
identify clinical studies comparing different injection approaches with each
other or placebo for carpal tunnel syndrome. Two review authors conducted
selection of studies, data extraction, and assessment of risk of bias
independently. Random-effects models were used to conduct the pairwise
meta-analysis and the Bayesian network meta-analysis.
RESULTS: Overall, 10 studies with 633 patients were included in the systematic
review. Among the injection approaches, local corticosteroid injections using the
ultrasound-guided in-plane injection (Ulnar-I) approach was the best treatment
strategy for clinical response (median OR versus placebo 128.30, 95% CrI 9.76 to
2299.00), change in symptom severity scale (median MD versus placebo -1.16, 95%
CrI -1.95 to -0.38) , and change in functional status scale (median MD versus
placebo -0.74, 95% CrI -2.00 to 0.52) at short-term follow-up period in the
network meta-analysis. Local corticosteroid injections using other injection
approaches were better than placebo for clinical response (for the PI approach,
median OR versus placebo 8.85, 95% CrI 3.00 to 33.15; for the DI approach, median
OR versus placebo 7.00, 95% CrI 0.53 to 118.80) , change in symptom severity
scale (for the Ulnar-O approach, median MD versus placebo -0.78, 95% CrI -1.43 to
-0.16; for the PI approach, median MD versus placebo -0.58, 95% CrI -0.95 to
-0.22), and change in functional status scale (for the Ulnar-O approach, median
MD versus placebo -0.63, 95% CrI -1.67 to 0.43; for the PI approach, median MD
versus placebo -0.46, 95% CrI -1.11 to 0.21) at short-term follow-up period. The
quality of studies is good.
CONCLUSIONS: According to our analyses, the ultrasound-guided in-plane injection
(Ulnar-I) approach was the most effective treatment among the injection
approaches for carpal tunnel syndrome.

DOI: 10.1186/s12891-015-0815-8
PMCID: PMC4653918
PMID: 26585378  [Indexed for MEDLINE]


230. BMJ Open. 2015 Nov 19;5(11):e009369. doi: 10.1136/bmjopen-2015-009369.

Mesh fixation methods in open inguinal hernia repair: a protocol for network
meta-analysis and trial sequential analysis of randomised controlled trials.

Ge L(1), Tian JH(2), Li L(3), Wang Q(4), Yang KH(2).

Author information:
(1)The First Clinical Medical College of Lanzhou University, Lanzhou, China
Evidence-based Medicine Center of Lanzhou University, Lanzhou, China Key
Laboratory of Evidence-based Medicine and Knowledge Translation of Gansu
Province, Lanzhou, China.
(2)Evidence-based Medicine Center of Lanzhou University, Lanzhou, China Key
Laboratory of Evidence-based Medicine and Knowledge Translation of Gansu
Province, Lanzhou, China.
(3)Department of Breast-Thyroid Surgery, The Second Xiangya Hospital of Central
South University, Changsha, China.
(4)Department of Gastrointestinal Surgery, Xijing Hospital of Digestive Diseases,
Xijing Hospital, Four Military Medical University, Xi'an, China.

INTRODUCTION: Randomised clinical trials (RCTs) have been used to compare and
evaluate different types of mesh fixation usually employed to repair open
inguinal hernia. However, there is no consensus among surgeons on the best type
of mesh fixation method to obtain optimal results. The choice often depends on
surgeons' personal preference. This study aims to compare different types of mesh
fixation methods to repair open inguinal hernias and their role in the incidences
of chronic groin pain, risk of hernia recurrence, complications, operative time,
length of hospital stay and postoperative pain, using Bayesian network
meta-analysis and trial sequential analysis of RCTs.
METHODS AND ANALYSIS: A systematic search will be performed using PubMed, EMBASE,
the Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Biomedical
Literature Database (CBM) and Chinese Journal Full-text Database, to include RCTs
of different mesh fixation methods (or fixation vs no fixation) during open
inguinal hernia repair. The risk of bias in included RCTs will be evaluated
according to the Cochrane Handbook V.5.1.0. Standard pairwise meta-analysis,
trial sequential analysis and Bayesian network meta-analysis will be performed to
compare the efficacy of different mesh fixation methods.
ETHICS AND DISSEMINATION: Ethical approval and patient consent are not required
since this study is a meta-analysis based on published studies. The results of
this network meta-analysis and trial sequential analysis will be submitted to a
peer-reviewed journal for publication.
PROTOCOL REGISTRATION NUMBER: PROSPERO CRD42015023758.

Published by the BMJ Publishing Group Limited. For permission to use (where not
already granted under a licence) please go to
http://www.bmj.com/company/products-services/rights-and-licensing/

DOI: 10.1136/bmjopen-2015-009369
PMCID: PMC4654284
PMID: 26586326  [Indexed for MEDLINE]


231. Int J Chron Obstruct Pulmon Dis. 2015 Nov 16;10:2495-517. doi:
10.2147/COPD.S92412. eCollection 2015.

Comparative efficacy of long-acting muscarinic antagonist monotherapies in COPD:
a systematic review and network meta-analysis.

Ismaila AS(1), Huisman EL(2), Punekar YS(3), Karabis A(2).

Author information:
(1)Value Evidence and Outcomes, GlaxoSmithKline, Research Triangle Park, NC, USA
; Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON,
Canada.
(2)Real World Strategy and Analytics, Mapi Group, Houten, the Netherlands.
(3)Value Evidence and Outcomes, GlaxoSmithKline, Uxbridge, UK.

BACKGROUND: Randomized, controlled trials comparing long-acting muscarinic
antagonist (LAMA) efficacy in COPD are limited. This network meta-analysis (NMA)
assessed the relative efficacy of tiotropium 18 µg once-daily (OD) and newer
agents (aclidinium 400 µg twice-daily, glycopyrronium 50 µg OD, and umeclidinium
62.5 µg OD).
METHODS: A systematic literature review identified randomized, controlled trials
of adult COPD patients receiving LAMAs. A NMA within a Bayesian framework
examined change from baseline in trough forced expiratory volume in 1 second
(FEV1), transitional dyspnea index focal score, St George's Respiratory
Questionnaire score, and rescue medication use.
RESULTS: Twenty-four studies (n=21,311) compared LAMAs with placebo/each other.
Aclidinium, glycopyrronium, tiotropium, and umeclidinium, respectively,
demonstrated favorable results versus placebo, for change from baseline (95%
credible interval) in 12-week trough FEV1 (primary endpoint: 101.40 mL
[77.06-125.60]; 117.20 mL [104.50-129.90]; 114.10 mL [103.10-125.20]; 136.70 mL
[104.20-169.20]); 24-week trough FEV1 (128.10 mL [84.10-172.00]; 135.80 mL
[123.10-148.30]; 106.40 mL [95.45-117.30]; 115.00 mL [74.51-155.30]); 24-week St
George's Respiratory Questionnaire score (-4.60 [-6.76 to -2.54]; -3.14 [-3.83 to
-2.45]; -2.43 [-2.92 to -1.93]; -4.69 [-7.05 to -2.31]); 24-week transitional
dyspnea index score (1.00 [0.41-1.59]; 1.01 [0.79-1.22]; 0.82 [0.62-1.02]; 1.00
[0.49-1.51]); and 24-week rescue medication use (data not available; -0.41
puffs/day [-0.62 to -0.20]; -0.52 puffs/day [-0.74 to -0.30]; -0.30 puffs/day
[-0.81 to 0.21]). For 12-week trough FEV1, differences in change from baseline
(95% credible interval) were -12.8 mL (-39.39 to 13.93), aclidinium versus
tiotropium; 3.08 mL (-7.58 to 13.69), glycopyrronium versus tiotropium; 22.58 mL
(-11.58 to 56.97), umeclidinium versus tiotropium; 15.90 mL (-11.60 to 43.15),
glycopyrronium versus aclidinium; 35.40 mL (-5.06 to 76.07), umeclidinium versus
aclidinium; and 19.50 mL (-15.30 to 54.38), umeclidinium versus glycopyrronium.
Limitations included inhaler-related factors and safety; longer-term outcomes
were not considered.
CONCLUSION: The new LAMAs studied had at least comparable efficacy to tiotropium,
the established class standard. Choice should depend on physician's and patient's
preference.

DOI: 10.2147/COPD.S92412
PMCID: PMC4655912
PMID: 26604738  [Indexed for MEDLINE]


232. BMJ. 2015 Nov 4;351:h5392. doi: 10.1136/bmj.h5392.

Treatment strategies for coronary in-stent restenosis: systematic review and
hierarchical Bayesian network meta-analysis of 24 randomised trials and 4880
patients.

Giacoppo D(1), Gargiulo G(1), Aruta P(1), Capranzano P(2), Tamburino C(2),
Capodanno D(3).

Author information:
(1)Department, Ferrarotto Hospital, Catania, Italy.
(2)Department, Ferrarotto Hospital, Catania, Italy Department of General Surgery
and Medical Surgical Specialties, Ferrarotto Hospital, University of Catania,
95124 Catania, Italy.
(3)Department, Ferrarotto Hospital, Catania, Italy Department of General Surgery
and Medical Surgical Specialties, Ferrarotto Hospital, University of Catania,
95124 Catania, Italy dcapodanno@gmail.com.

Erratum in
    BMJ. 2015;351:h6364.

Comment in
    Evid Based Med. 2016 Jun;21(3):90.

STUDY QUESTION: What is the most safe and effective interventional treatment for
coronary in-stent restenosis?
METHODS: In a hierarchical Bayesian network meta-analysis, PubMed, Embase,
Scopus, Cochrane Library, Web of Science, ScienceDirect, and major scientific
websites were screened up to 10 August 2015. Randomised controlled trials of
patients with any type of coronary in-stent restenosis (either of bare metal
stents or drug eluting stents; and either first or recurrent instances) were
included. Trials including multiple treatments at the same time in the same group
or comparing variants of the same intervention were excluded. Primary endpoints
were target lesion revascularisation and late lumen loss, both at six to 12
months. The main analysis was complemented by network subanalyses, standard
pairwise comparisons, and subgroup and sensitivity analyses.
STUDY ANSWER AND LIMITATIONS: Twenty four trials (4880 patients), including seven
interventional treatments, were identified. Compared with plain balloons, bare
metal stents, brachytherapy, rotational atherectomy, and cutting balloons, drug
coated balloons and drug eluting stents were associated with a reduced risk of
target lesion revascularisation and major adverse cardiac events, and with
reduced late lumen loss. Treatment ranking indicated that drug eluting stents had
the highest probability (61.4%) of being the most effective for target lesion
vascularisation; drug coated balloons were similarly indicated as the most
effective treatment for late lumen loss (probability 70.3%). The comparative
efficacy of drug coated balloons and drug eluting stents was similar for target
lesion revascularisation (summary odds ratio 1.10, 95% credible interval 0.59 to
2.01) and late lumen loss reduction (mean difference in minimum lumen diameter
0.04 mm, 95% credible interval -0.20 to 0.10). Risks of death, myocardial
infarction, and stent thrombosis were comparable across all treatments, but these
analyses were limited by a low number of events. Trials had heterogeneity
regarding investigation periods, baseline characteristics, and endpoint
reporting, with a lack of information at long term follow-up. Direct and indirect
evidence was also inconsistent for the comparison between drug eluting stents and
drug coated balloons.
WHAT THIS STUDY ADDS: Compared with other currently available interventional
treatments for coronary in-stent restenosis, drug coated balloons and drug
eluting stents are associated with superior clinical and angiographic outcomes,
with a similar comparative efficacy.
FUNDING, COMPETING INTERESTS, DATA SHARING: This study received no external
funding. The authors declare no competing interests. No additional data
available.

© Giacoppo et al 2015.


PMCID: PMC4632210
PMID: 26537292  [Indexed for MEDLINE]


233. Int J Chron Obstruct Pulmon Dis. 2015 Nov 3;10:2365-76. doi: 10.2147/COPD.S93191.
eCollection 2015.

The efficacy and safety of triple inhaled treatment in patients with chronic
obstructive pulmonary disease: a systematic review and meta-analysis using
Bayesian methods.

Kwak MS(1), Kim E(2), Jang EJ(3), Kim HJ(4), Lee CH(5).

Author information:
(1)Department of Internal Medicine, Healthcare Research Institute, Healthcare
System Gangnam Center, Seoul National University Hospital, Seoul, Republic of
Korea.
(2)Department of Statistics, Kyungpook National University, Daegu, Republic of
Korea.
(3)Department of Information Statistics, Andong National University, Andong,
Republic of Korea.
(4)Department of Preventive Medicine, College of Medicine, Korea University,
Seoul, Republic of Korea.
(5)Department of Internal Medicine, Division of Pulmonary and Critical Care
Medicine, Seoul National University College of Medicine, Seoul National
University Hospital, Seoul, Republic of Korea.

PURPOSE: Although tiotropium (TIO) and inhaled corticosteroid (ICS)/long-acting
β-agonists are frequently prescribed together, the efficacy of "triple therapy"
has not been scientifically demonstrated. We conducted a systematic review and
meta-analysis using Bayesian methods to compare triple therapy and TIO
monotherapy.
METHODS: We searched the MEDLINE, EMBASE, and Cochrane Library databases for
randomized controlled trials comparing the efficacy and safety of triple therapy
and TIO monotherapy in patients with chronic obstructive pulmonary disease
(COPD). We conducted a meta-analysis to compare the effectiveness and safety of
triple therapy and TIO monotherapy using Bayesian random effects models.
RESULTS: Seven trials were included, and the risk of bias in the majority of the
studies was acceptable. There were no statistically significant differences in
the incidence of death and acute exacerbation of disease in the triple therapy
and TIO monotherapy groups. Triple therapy improved the prebronchodilator forced
expiratory volume in 1 second (mean difference [MD], 63.68 mL; 95% credible
interval [CrI], 45.29-82.73), and patients receiving triple therapy showed more
improvement in St George Respiratory Questionnaire scores (MD, -3.11 points; 95%
CrI, -6.00 to -0.80) than patients receiving TIO monotherapy. However, both of
these differences were lower than the minimal clinically important difference
(MCID). No excessive adverse effects were reported in triple therapy group.
CONCLUSION: Triple therapy with TIO and ICSs/long-acting β-agonists was only
slightly more efficacious than TIO monotherapy in treating patients with COPD.
Further investigations into the efficacy of new inhaled drugs are needed.

DOI: 10.2147/COPD.S93191
PMCID: PMC4639518
PMID: 26604734  [Indexed for MEDLINE]


234. Circ Cardiovasc Interv. 2015 Nov;8(11):e002778. doi:
10.1161/CIRCINTERVENTIONS.115.002778.

Efficacy of various percutaneous interventions for in-stent restenosis:
comprehensive network meta-analysis of randomized controlled trials.

Sethi A(1), Malhotra G(2), Singh S(2), Singh PP(2), Khosla S(2).

Author information:
(1)From the Department of Cardiology, Chicago Medical School at Rosalind Franklin
University of Medicine, North Chicago, IL; and Division of Cardiology, Mount
Sinai Hospital Medical Center, Chicago, IL. drankursethi@gmail.com.
(2)From the Department of Cardiology, Chicago Medical School at Rosalind Franklin
University of Medicine, North Chicago, IL; and Division of Cardiology, Mount
Sinai Hospital Medical Center, Chicago, IL.

BACKGROUND: In-stent restenosis (ISR) remains a difficult problem in
interventional cardiology. The relative efficacy and safety of available
interventions is not clear. We aimed to perform a network meta-analysis using
both direct evidence and indirect evidence to compare all available
interventions.
METHODS AND RESULTS: We systematically searched electronic databases for
randomized trials comparing ≥2 treatments for ISR. A network meta-analysis was
performed using a Bayesian approach. Eleven treatments were compared in 31
studies with 8157 patient-years follow-up. Compared with balloon angioplasty,
everolimus-eluting stent (hazard ratio [95% credibility interval], 0.13
[0.048-0.35]), paclitaxel-eluting balloon (0.32 [0.20-0.49]), paclitaxel-eluting
cutting balloon (0.054 [0.0017-0.5]), paclitaxel-eluting stent (0.39
[0.24-0.62]), and sirolimus-eluting stent (0.32 [0.18-0.50]) are associated with
lower target vessel revascularization. Balloon angioplasty is not different from
cutting balloon (0.73 [0.31-1.5]), excimer laser (0.89 [0.29-2.7]), rotational
atherectomy (0.96 [0.53-1.7]), and vascular brachytherapy (0.60 [0.35-1.0]). In
drug-eluting stent ISR, balloon angioplasty was inferior to everolimus-eluting
stent (0.19 [0.049-0.76]), paclitaxel-eluting balloon (0.43 [0.18-0.80]),
paclitaxel-eluting stent (0.35 [0.13-0.76]), and sirolimus-eluting stent (0.36
[0.11-0.86]) for target vessel revascularization. There was no difference between
treatments in probable or definitive stent thrombosis. The results of binary
restenosis and target lesion revascularization were similar. Paclitaxel-eluting
cutting balloon, everolimus-eluting stent, and paclitaxel-eluting balloon have
the highest probability of being in the top 3 treatments based on low target
lesion revascularization, but there was no statistical significant difference
between them.
CONCLUSIONS: Balloon angioplasty is inferior to all drug-eluting treatments for
ISR, including drug-eluting stent ISR. Drug-eluting stent, particularly
everolimus-eluting stent, or paclitaxel-eluting cutting balloon and
paclitaxel-eluting balloon should be preferred for treating ISR.

© 2015 American Heart Association, Inc.

DOI: 10.1161/CIRCINTERVENTIONS.115.002778
PMID: 26546577  [Indexed for MEDLINE]


235. Curr Med Res Opin. 2015 Nov;31(11):2031-42. doi: 10.1185/03007995.2015.1084909.
Epub 2015 Sep 28.

Ranibizumab vs. aflibercept for wet age-related macular degeneration: network
meta-analysis to understand the value of reduced frequency dosing.

Szabo SM(1), Hedegaard M(2), Chan K(1), Thorlund K(1), Christensen R(3), Vorum
H(4), Jansen JP(5).

Author information:
(1)a a Redwood Outcomes , Vancouver , Canada.
(2)b b Novartis Healthcare , Copenhagen , Denmark.
(3)c c The Parker Institute, Department of Rheumatology, Copenhagen University
Hospital , Copenhagen , Denmark.
(4)d d Department of Ophthalmology , Aalborg University Hospital , Aalborg ,
Denmark.
(5)e e Redwood Outcomes , San Francisco , USA.

OBJECTIVE: Although a reduced aflibercept (2.0 mg) injection frequency relative
to the approved dosing posology is included in national treatment guidelines for
wet age-related macular degeneration (AMD), there is limited evidence of its
comparative efficacy. The objective was to compare the efficacy and safety of
reduced frequency dosing for aflibercept, relative to other approved and marketed
vascular endothelial growth factor inhibitors for wet AMD, over 12 months.
RESEARCH DESIGN AND METHODS: Based on a systematic literature review performed
according to a pre-specified protocol, a Bayesian network meta-analysis (NMA) was
conducted to indirectly compare posologies of aflibercept and ranibizumab (0.5
mg). The efficacy outcome, mean change from baseline in best-corrected visual
acuity (BCVA) on the ETDRS chart, was evaluated at 3 and 12 months; and safety
data at 12 months. Standard NMA models were used to analyze change at 3 months,
and fractional polynomial regression over 12 months. Safety data were analyzed
using binomial models with a logistic link function.
RESULTS: Five trials formed a complete evidence network. At 3 months, all
posologies of aflibercept and ranibizumab resulted in similar changes in BCVA.
Over 12 months, approved posologies of aflibercept and ranibizumab resulted in
similar changes from baseline, between 6.7 (95% credible interval [CrI], 5.5,
7.8) and 9.1 (8.1, 10.1) ETDRS letters; however, reduced frequency aflibercept
was associated with a smaller change (1.8 letters, [-25.9, 29.2]). There was a
trend towards a greater change in BCVA, with increasing frequency of dosing. All
posologies performed similarly with respect to safety, and CrIs were wide.
CONCLUSIONS: Approved posologies of ranibizumab and aflibercept are similarly
effective treatments for wet AMD. Reduced frequency aflibercept was associated
with the poorest visual outcomes, and sample sizes were small. Findings from
these analyses provide novel evidence of the comparative efficacy and safety of
aflibercept and ranibizumab for wet AMD.

DOI: 10.1185/03007995.2015.1084909
PMID: 26296050  [Indexed for MEDLINE]


236. Eur J Cancer. 2015 Nov;51(16):2330-44. doi: 10.1016/j.ejca.2015.07.007. Epub 2015
Sep 10.

Bayesian network meta-comparison of maintenance treatments for stage IIIb/IV
non-small-cell lung cancer (NSCLC) patients with good performance status not
progressing after first-line induction chemotherapy: results by performance
status, EGFR mutation, histology and response to previous induction.

Tan PS(1), Lopes G(2), Acharyya S(3), Bilger M(1), Haaland B(4).

Author information:
(1)Health Services and Systems Research, Duke-NUS Graduate Medical School,
Singapore.
(2)Hospital do Coração Cancer Center (HCor Onco), and Research Institute, Brazil;
Centro Paulista de Oncologia, Brazil; Oncoclinicas do Brasil, Brazil; Johns
Hopkins University, Baltimore, MD, USA.
(3)Centre for Quantitative Medicine, Office of Clinical Sciences, Duke-NUS
Graduate Medical School, Singapore.
(4)Centre for Quantitative Medicine, Office of Clinical Sciences, Duke-NUS
Graduate Medical School, Singapore; H. Milton Stewart School of Industrial and
Systems Engineering, Georgia Institute of Technology, USA. Electronic address:
ben.haaland@isye.gatech.edu.

BACKGROUND: Recent trials have suggested that maintenance treatments improve
outcomes for patients not progressing after first-line therapy for advanced
non-small-cell lung cancer (NSCLC). However, physicians have little guidance on
selecting which patients benefit the most and what drug or regimen is optimal.
Here, we report a systematic review and network meta-analysis of maintenance
treatments in subgroups determined by performance status (PS), epidermal growth
factor receptor (EGFR) mutation, histology and response to induction.
METHODS: PubMed and conference proceedings were reviewed and individual study
relative efficacy measures were meta-analysed in a Bayesian hierarchical model.
The primary outcome, overall survival (OS), was evaluated in terms of (i)
posterior surface under cumulative ranking curve (SUCRA), (ii) probability of
being best treatment, (iii) probability of outperforming no maintenance, and (iv)
posterior median hazard ratio (95% credible interval). Secondary outcomes were
progression-free survival (PFS) and adverse events.
FINDINGS: Twelve trials evaluating eight maintenance treatments in 3850 patients
were meta-analysed. Selected maintenance treatments showed clinically meaningful
benefits of ⩾20% reduction in hazards of death with ⩾90% probability of
outperforming no maintenance in terms of OS: (i) switch to or continue pemetrexed
(nonsquamous), continue gemcitabine, or switch to EGFR tyrosine kinase inhibitors
(TKIs) for PS 0 patients, (ii) switch to pemetrexed (nonsquamous) for PS 1
patients, (iii) switch to EGFR TKI for EGFR mutation positive patients, (iv)
switch to or continue pemetrexed or switch to EGFR TKI for nonsquamous patients,
(v) continue gemcitabine for squamous patients, (vi) switch to docetaxel or
continue gemcitabine for responders to induction, or (vii) switch to or continue
pemetrexed (nonsquamous) or switch to EGFR TKI for patients with stable disease
post-induction.
INTERPRETATION: Maintenance treatments show clinically meaningful survival
benefits in good performance status patients with advanced NSCLC not progressing
after first-line chemotherapy. Benefits are optimised by targeting specific
maintenance to individual patients guided by PS, EGFR mutation status, histology
and response to induction.

Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

DOI: 10.1016/j.ejca.2015.07.007
PMID: 26364517  [Indexed for MEDLINE]


237. Eur J Cancer. 2015 Nov;51(16):2314-20. doi: 10.1016/j.ejca.2015.07.031. Epub 2015
Sep 3.

Comparison of cardiac events associated with liposomal doxorubicin, epirubicin
and doxorubicin in breast cancer: a Bayesian network meta-analysis.

Yamaguchi N(1), Fujii T(2), Aoi S(3), Kozuch PS(4), Hortobagyi GN(5), Blum RH(1).

Author information:
(1)Department of Medicine, Division of Hematology/Oncology, Mount Sinai Beth
Israel, 16th Street and 1st Avenue, New York, NY 10003, USA.
(2)Department of Breast Medical Oncology, Division of Cancer Medicine, The
University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX
77030, USA; School of Public Health, The University of Texas Health Science
Center at Houston, 1200 Herman-Pressler Street, Houston, TX 77030, USA.
(3)Department of Medicine, Mount Sinai Beth Israel, 16th Street and 1st Avenue,
New York, NY 10003, USA.
(4)Department of Medicine, Division of Hematology/Oncology, Mount Sinai Beth
Israel, 16th Street and 1st Avenue, New York, NY 10003, USA. Electronic address:
pkozuch@chpnet.org.
(5)Department of Breast Medical Oncology, Division of Cancer Medicine, The
University of Texas MD Anderson Cancer Center, 1155 Pressler, Suite CPB5.3466,
Houston, TX 77030, USA.

BACKGROUND: Anthracyclines play a broad and important role in the care of
patients with either operable or metastatic breast cancer. However cardiotoxicity
narrows the therapeutic index of this drug class leading to potentially
clinically meaningful treatment delays or discontinuations. We conducted a
Bayesian network meta-analysis, a validated statistical methodology, allowing
direct and indirect comparison of cardiotoxicity of different anthracycline and
non-anthracycline regimens.
METHODS: We conducted a systematic review of prospective randomised controlled
trials through MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials
and Google Scholar comparing non-anthracycline based regimens (NON), doxorubicin
(DOX), epirubicin (EPI) and liposomal doxorubicin (LD). We included studies
published up to 1st January 2014 in both adjuvant and metastatic contexts.
Notably, HER2/neu-targeted regimens were excluded. We assessed the studies'
eligibility criteria and data collection with consensus of two independent
authors. Our primary outcome measure was cardiac events grade 3 or greater (CE3)
in accordance with Common Terminology Criteria for Adverse Events (CTCAE) Version
4.0. A Bayesian pairwise and network meta-analysis was conducted to estimate
pooled Odds Ratio (OR).
FINDINGS: Nineteen randomised controlled trials met eligibility criteria and were
included in this analysis. We found a trend showing that LD is less cardiotoxic
than DOX with an OR of 0.60 (95% confidence interval (CI) 0.34-1.07) There was no
difference between Epi and LD with an OR of 0.95 (95%CI 0.39-2.33). DOX is more
cardiotoxic than Non with an OR of 1.57 (95%CI 0.90-2.72).
INTERPRETATION: DOX has higher CE3 rates than NON does. LD statistically trended
to lower cardiac event rates than DOX. Non-statistical significance among EPI, LD
and DOX with regard to cardiac toxicity indicates that avoidance of CE3 should
not motivate selection of a particular anthracycline in otherwise healthy women
in whom total lifetime anthracycline exposure will likely be limited. Overall low
incidence of CE3 with any type of anthracycline indicates that we can safely use
any anthracycline if cumulative dose limits are not exceeded. While CE3 does not
limit our choice of anthracycline LD appears to be the least cardiotoxic.
FUNDING: Takeo Fujii is supported by the grant named Young Investigator Award for
Study Abroad in Clinical Epidemiology from St. Luke's Life Science Institution.

Copyright © 2015 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.ejca.2015.07.031
PMID: 26343314  [Indexed for MEDLINE]


238. Hepatology. 2015 Nov;62(5):1417-32. doi: 10.1002/hep.27999. Epub 2015 Oct 1.

Comparative effectiveness of pharmacological interventions for nonalcoholic
steatohepatitis: A systematic review and network meta-analysis.

Singh S(1)(2), Khera R(3), Allen AM(1), Murad MH(4), Loomba R(2)(5)(6).

Author information:
(1)Division of Gastroenterology and Hepatology, Department of Internal Medicine,
Mayo Clinic, Rochester, MN.
(2)Division of Gastroenterology, Department of Medicine, University of
California, San Diego, CA.
(3)Department of Internal Medicine, University of Iowa Hospitals and Clinics,
Iowa City, IA.
(4)Knowledge Synthesis Unit, Robert D. and Patricia E. Kern Center for the
Science of Health Care Delivery, Mayo Clinic, Rochester, MN.
(5)NAFLD Translational Research Unit, La Jolla, CA.
(6)Division of Epidemiology, Department of Family and Preventive Medicine,
University of California, San Diego, CA.

We performed a Bayesian network meta-analysis combining direct and indirect
treatment comparisons to assess the comparative effectiveness of pharmacological
agents for the treatment of nonalcoholic steatohepatitis (NASH). Through
systematic literature review, we identified nine randomized, controlled trials
(RCTs) including 964 patients with biopsy-proven NASH, comparing vitamin E,
thiazolidinediones (TZDs), pentoxifylline, or obeticholic acid to one another or
placebo. The primary outcome was improvement in fibrosis stage; secondary
outcomes were improvement in ballooning degeneration, lobular inflammation, and
steatosis. We reported relative risks (RRs) and 95% confidence intervals (CIs)
from direct meta-analysis and 95% credible intervals (CrIs) from Bayesian network
meta-analysis, and used Grading of Recommendations Assessment, Development and
Evaluation (GRADE) criteria to appraise quality of evidence. Moderate-quality
evidence supports the use of pentoxifylline (RR, 0.26; 95% CrI: 0.05-1.00) and
obeticholic acid (RR, 0.81; 95% CI: 0.70-0.95) over placebo in improving
fibrosis. High-quality evidence supports the effect of vitamin E, TZDs, and
obeticholic acid over placebo in improving ballooning degeneration. All four
interventions seemed to have at least moderate-quality evidence over placebo to
improve steatosis. Moderate-quality evidence supports that TZDs, pentoxifylline,
and obeticholic acid decrease lobular inflammation. All the head-to-head
comparisons were supported by very-low-quality evidence except for superiority of
TZDs over vitamin E on improving steatosis and lobular inflammation, which had
moderate-quality evidence.CONCLUSIONS: Based on direct and network meta-analysis,
pentoxifylline and obeticholic acid improve fibrosis, and vitamin E, TZDs, and
obeticholic acid improve ballooning degeneration in patients with NASH. Future
comparative trials of combination therapies targeting distinct histological
features are warranted.

© 2015 by the American Association for the Study of Liver Diseases.

DOI: 10.1002/hep.27999
PMID: 26189925  [Indexed for MEDLINE]


239. Int J Surg. 2015 Nov;23(Pt A):128-36. doi: 10.1016/j.ijsu.2015.09.064. Epub 2015
Oct 24.

A Cochrane systematic review and network meta-analysis comparing treatment
strategies aiming to decrease blood loss during liver resection.

Simillis C(1), Li T(2), Vaughan J(3), Becker LA(4), Davidson BR(3), Gurusamy
KS(3).

Author information:
(1)Department of Surgery, Royal Free Campus, UCL Medical School, London, UK.
Electronic address: csimillis@gmail.com.
(2)Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health,
Baltimore, MD, USA.
(3)Department of Surgery, Royal Free Campus, UCL Medical School, London, UK.
(4)Department of Family Medicine, SUNY Upstate Medical University, Syracuse, NY,
USA.

INTRODUCTION: Intraoperative haemorrhage remains one of the major risks during
liver resection, and perioperative blood loss and blood transfusion are important
factors affecting perioperative morbidity and mortality. The aim of this study is
to compare treatment strategies aiming to decrease blood loss during hepatectomy.
METHODS: A systematic review of the literature was performed to identify
randomised controlled trials reporting on the method of vascular occlusion,
parenchymal transection, and management of the cut surface during liver
resection. A Bayesian network meta-analysis was performed using WinBUGS.
RESULTS: Seven trials reporting on 496 participants randomised to seven treatment
strategies were analysed. Continuous vascular occlusion resulted in lower blood
loss compared to no vascular occlusion when parenchymal transection was performed
with clamp-crush and no fibrin sealant was used for the cut surface. People
undergoing liver resection by continuous vascular occlusion had decreased amounts
of blood transfused than people with intermittent vascular occlusion when
parenchymal transection was performed with clamp-crush and no fibrin sealant.
There was no significant difference in proportion of people transfused,
mortality, or hospital stay between the different strategies. There were
significantly more serious adverse events when surgery was performed using
radiofrequency dissecting sealer compared with standard clamp-crush method in the
absence of vascular occlusion and fibrin sealant.
CONCLUSIONS: Continuous vascular occlusion during hepatectomy results in
decreased blood loss and decreased blood transfusion requirements. Further
studies are needed to compare treatment strategies aiming to decrease blood loss,
defined by their method of vascular occlusion, parenchymal transection, and
management of the cut surface.

Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All
rights reserved.

DOI: 10.1016/j.ijsu.2015.09.064
PMID: 26432546  [Indexed for MEDLINE]


240. J Dent. 2015 Nov;43(11):1298-307. doi: 10.1016/j.jdent.2015.07.001. Epub 2015 Jul
6.

Antibacterial effects of cavity lining: a systematic review and network
meta-analysis.

Schwendicke F(1), Tu YK(2), Hsu LY(2), Göstemeyer G(3).

Author information:
(1)Department of Operative and Preventive Dentistry, Charité-Universitätsmedizin
Berlin, Aßmannshauser Str. 4-6, 14197 Berlin, Germany. Electronic address:
falk.schwendicke@charite.de.
(2)Institute of Epidemiology & Preventive Medicine, College of Public Health,
National Taiwan University, Taipei, Taiwan.
(3)Department of Operative and Preventive Dentistry, Charité-Universitätsmedizin
Berlin, Aßmannshauser Str. 4-6, 14197 Berlin, Germany.

OBJECTIVES: Cavity liners are frequently used prior placing a restoration, with
one main aim being to reduce the number of remaining bacteria. We systematically
appraised studies comparing antibacterial effects of different liners against
each other or no liner.
DATA STUDIES: reporting the number of sterile cavities before/after lining or
sealing, or the reduction in bacterial numbers (colony-forming-units) in two or
more treatment groups were included. Treatments were categorized as: no/placebo
liner, calcium hydroxide, mineral trioxide aggregate, antibiotic/disinfectant,
calcium phosphates, zinc oxide eugenol, black copper cement, and glass ionomer
cement liners. Pairwise and network meta-analyses were performed.
STUDY SELECTION: From 113 identified studies, 14 (500 treated lesions) were
included. Risk of bias was high or unclear. Based on 11 studies, network
meta-analysis found mineral trioxide lining to yield the greatest probability of
achieving sterile cavities after a lining/sealing period (73%), followed by
antibiotic/disinfectant (8%) and zinc oxide eugenol (7%). Only six studies
assessed bacterial reduction after lining/sealing, and zinc oxide eugenol was
found to have the highest probability of achieving a bacterial reduction. In both
analyses, not providing any lining was found to have low antibacterial effects.
CONCLUSION: Within the limitations of this review and the included studies,
certain liners seem more suitable to achieve sterile cavities or reduce bacterial
numbers than others. Given the paucity of data and the unclear impact of
remaining bacteria on clinical outcomes, further recommendations for specific
cavity treatments prior a restoration are not possible.
CLINICAL SIGNIFICANCE: There is insufficient evidence to generally recommend
cavity lining or the use of any specific liner based on their antibacterial
effects. Dentists might continue to use liners, but should be aware that such use
is not strongly supported by clinical studies.

Copyright © 2015 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.jdent.2015.07.001
PMID: 26159385  [Indexed for MEDLINE]


241. J Interv Card Electrophysiol. 2015 Nov;44(2):105-11. doi:
10.1007/s10840-015-0053-x. Epub 2015 Sep 5.

Bleeding risks with novel oral anticoagulants during catheter ablation of atrial
fibrillation: a systematic review and network meta-analysis.

Lu D(1), Zhang Q(1), Liu Q(1), Wang K(1), Wang S(1), Shan Q(2).

Author information:
(1)Department of Cardiology, The First Affiliated Hospital of Nanjing Medical
University, 300# Guangzhou road, Nanjing, 210029, Jiangsu Province, China.
(2)Department of Cardiology, The First Affiliated Hospital of Nanjing Medical
University, 300# Guangzhou road, Nanjing, 210029, Jiangsu Province, China.
qjshan@njmu.edu.cn.

BACKGROUND: Comprehensive comparisons of safety (measured by bleeding risk)
between multiple novel oral anticoagulants (NOACs and warfarin) in the
peri-procedural period of catheter ablation (CA) for atrial fibrillation (AF) are
rare.
METHODS AND RESULTS: MEDLINE, EMBASE, and COCHRANE LIBRARY were searched up to
February 2015 by two reviewers independently. Predefined inclusion criteria
identified 24 studies which were included in the analysis. Data were extracted by
two researchers, and a network meta-analysis was conducted in R with R2WinBugS
package, within Bayesian framework. Pooled odds ratios (OR) and 95% confidence
intervals (CI) were summarized to evaluate the bleeding risks of three novel
anticoagulants (dabigatran, rivaroxaban, apixaban) in AF patients undergoing
catheter ablation (CA). With respect to total bleeding risk, no significant
difference was observed between dabigatran, rivaroxaban, apixaban, and vitamin K
antagonists (VKAs) by mixed-treatment comparison. The similar results were seen
in the direct comparison. While dabigatran was associated with a lower rate of
minor bleeding in comparison to VKAs (OR = 0.67 with 95%CI 0.49-0.93).
CONCLUSIONS: Risks of bleeding with dabigatran, rivaroxaban, apixaban, and VKAs
were similar in peri-procedural period of CA for AF.

DOI: 10.1007/s10840-015-0053-x
PMID: 26342485  [Indexed for MEDLINE]


242. Medicine (Baltimore). 2015 Nov;94(45):e1732. doi: 10.1097/MD.0000000000001732.

Antithrombotic Treatment for Recurrent Miscarriage: Bayesian Network
Meta-Analysis and Systematic Review.

Zhang T(1), Ye X, Zhu T, Xiao X, Liu Y, Wei X, Liu Y, Wu C, Guan R, Li X, Guo X,
Hu H, He J.

Author information:
(1)From the Department of Health Statistics, Second Military Medical University
(TYZ, XFY, TTZ, XX CW, XJG, JH); School of Medicine, Shanghai Jiao Tong
University (YZL, XW); Department of Obstetrics and Gynecology (RG); Department of
Radiology (XL); Department of Hematology, Changhai Hospital, Second Military
Medical University, Shanghai, China (HLH) College of Art & Science, University of
San Francisco (YL).

Combined use of heparin and aspirin is frequently prescribed for treatment of
recurrent miscarriage (RM) in patients with antiphospholipid syndrome (APS), or
in those without apparent cause of RM other than thrombophilia; however, this
strategy is largely based on expert opinion and has not been well studied. The
option for the use of different antithrombotic therapies to improve live birth
remains unclear. In this network meta-analysis, we incorporated direct and
indirect evidence to evaluate effects of different antithrombotic treatments on
prevention of pregnancy losses.We searched PubMed and Embase for randomized
clinical trials comparing effects of at least 2 antithrombotic treatments on live
birth in RM patients published from 1965 through the early of May 2015. Potential
risk bias of eligible trials was evaluated according to the Cochrane
Collaboration guidelines. Bayesian network meta-analysis was used to estimate
relative effects on live birth.A total of 19 trials involving 2391 RM patients
with or without thrombophilia and 543 with APS were included. No beneficial
effect of antithrombotic treatment was observed either in RM patients with or
without thrombophilia or in patients with APS; however, for patients with or
without thrombophilia, low molecular weight heparin therapy had the greatest
probability (61.48%) of being the best option in terms of live birth; for
patients with APS, unfractionated heparin plus aspirin was the superior treatment
for RM with the highest possibility (75.15%) of being top 2 places for reducing
pregnancy losses. Aspirin was inferior in both groups.Our results do not support
the use of combined low molecular weight heparin and aspirin for RM treatment,
and suggested aspirin may have negative effects for lowering the risk of
pregnancy loss.

DOI: 10.1097/MD.0000000000001732
PMCID: PMC4912243
PMID: 26559249  [Indexed for MEDLINE]


243. Radiat Prot Dosimetry. 2015 Nov;167(1-3):306-10. doi: 10.1093/rpd/ncv268. Epub
2015 May 8.

Pooled Bayesian meta-analysis of two Polish studies on radiation-induced cancers.

Fornalski KW(1).

Author information:
(1)PGE EJ 1 Sp. z o.o., ul. Mysia 2, Warszawa 00-496, Poland
krzysztof.fornalski@gmail.com.

The robust Bayesian regression method was applied to perform meta-analysis of two
independent studies on influence of low ionising radiation doses on the
occurrence of fatal cancers. The re-analysed data come from occupational exposure
analysis of nuclear workers in Świerk (Poland) and from ecological study of
cancer risk from natural background radiation in Poland. Such two different types
of data were analysed, and three popular models were tested: constant, linear and
quadratic dose-response dependencies. The Bayesian model selection algorithm was
used for all models. The Bayesian statistics clearly indicates that the popular
linear no-threshold (LNT) assumption is not valid for presented cancer risks in
the range of low doses of ionising radiation. The subject of LNT hypothesis use
in radiation risk prediction and assessment is also discussed.

© The Author 2015. Published by Oxford University Press. All rights reserved. For
Permissions, please email: journals.permissions@oup.com.

DOI: 10.1093/rpd/ncv268
PMID: 25956788  [Indexed for MEDLINE]


244. PLoS One. 2015 Oct 20;10(10):e0139817. doi: 10.1371/journal.pone.0139817.
eCollection 2015.

Dietary Intervention for Overweight and Obese Adults: Comparison of
Low-Carbohydrate and Low-Fat Diets. A Meta-Analysis.

Sackner-Bernstein J(1), Kanter D(2), Kaul S(3).

Author information:
(1)ExVivos, LLC, Hastings-on-Hudson, NY, United States of America.
(2)Georgetown University Law Center, Washington, DC, United States of America.
(3)Cedars-Sinai Medical Center, Los Angeles, CA, United States of America.

BACKGROUND: Reduced calorie, low fat diet is currently recommended diet for
overweight and obese adults. Prior data suggest that low carbohydrate diets may
also be a viable option for those who are overweight and obese.
PURPOSE: Compare the effects of low carbohydrate versus low fats diet on weight
and atherosclerotic cardiovascular disease risk in overweight and obese patients.
DATA SOURCES: Systematic literature review via PubMed (1966-2014).
STUDY SELECTION: Randomized controlled trials with ≥8 weeks follow up, comparing
low carbohydrate (≤120gm carbohydrates/day) and low fat diet (≤30% energy from
fat/day).
DATA EXTRACTION: Data were extracted and prepared for analysis using double data
entry. Prior to identification of candidate publications, the outcomes of change
in weight and metabolic factors were selected as defined by Cochrane
Collaboration. Assessment of the effects of diets on predicted risk of
atherosclerotic cardiovascular disease risk was added during the data collection
phase.
DATA SYNTHESIS: 1797 patients were included from 17 trials with <1 year follow up
in 12. Compared with low fat diet, low carbohydrate was associated with
significantly greater reduction in weight (Δ = -2.0 kg, 95% CI: -3.1, -0.9) and
significantly lower predicted risk of atherosclerotic cardiovascular disease
events (p<0.03). Frequentist and Bayesian results were concordant. The
probability of greater weight loss associated with low carbohydrate was >99%
while the reduction in predicted risk favoring low carbohydrate was >98%.
LIMITATIONS: Lack of patient-level data and heterogeneity in dropout rates and
outcomes reported.
CONCLUSIONS: This trial-level meta-analysis of randomized controlled trials
comparing LoCHO diets with LoFAT diets in strictly adherent populations
demonstrates that each diet was associated with significant weight loss and
reduction in predicted risk of ASCVD events. However, LoCHO diet was associated
with modest but significantly greater improvements in weight loss and predicted
ASCVD risk in studies from 8 weeks to 24 months in duration. These results
suggest that future evaluations of dietary guidelines should consider low
carbohydrate diets as effective and safe intervention for weight management in
the overweight and obese, although long-term effects require further
investigation.

DOI: 10.1371/journal.pone.0139817
PMCID: PMC4618935
PMID: 26485706  [Indexed for MEDLINE]


245. PLoS One. 2015 Oct 16;10(10):e0140187. doi: 10.1371/journal.pone.0140187.
eCollection 2015.

A Systematic Review and Network Meta-Analysis of Biologic Agents in the First
Line Setting for Advanced Colorectal Cancer.

Kumachev A(1), Yan M(1), Berry S(2), Ko YJ(2), Martinez MC(3), Shah K(4), Chan
KK(5).

Author information:
(1)Faculty of Medicine, University of Toronto, Toronto Canada.
(2)Faculty of Medicine, University of Toronto, Toronto Canada; Sunnybrook Odette
Cancer Centre, University of Toronto, Toronto, Canada.
(3)Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Canada.
(4)Faculty of Medicine, Queens University, Kingston, Canada.
(5)Faculty of Medicine, University of Toronto, Toronto Canada; Sunnybrook Odette
Cancer Centre, University of Toronto, Toronto, Canada; Division of Biostatistics,
Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.

BACKGROUND: Epithelial growth factor receptor inhibitors (EGFRis) and bevacizumab
(BEV) are used in combination with chemotherapy for the treatment of metastatic
colorectal cancer (mCRC). However, few randomized controlled trials (RCTs) have
directly compared their relative efficacy on progression-free survival (PFS) and
overall survival (OS).
METHODS: We conducted a systematic review of first-line RCTs comparing (1) EGFRis
vs. BEV, with chemotherapy in both arms (2) EGFRis + chemotherapy vs.
chemotherapy alone, or (3) BEV + chemotherapy vs. chemotherapy alone, using
Cochrane methodology. Data on and PFS and OS were extracted using the Parmar
method. Pairwise meta-analyses and Bayesian network meta-analyses (NMA) were
conducted to estimate the direct, indirect and combined PFS and OS hazard ratios
(HRs) comparing EGFRis to BEV.
RESULTS: Seventeen RCTs contained extractable data for quantitative analysis.
Combining direct and indirect data using an NMA did not show a statistical
difference between EGFRis versus BEV (PFS HR = 1.11 (95% CR: 0.92-1.36) and OS HR
= 0.91 (95% CR: 0.75-1.09)). Direct meta-analysis (3 RCTs), indirect (14 RCTs)
and combined (17 RCTs) NMA of PFS HRs were concordant and did not show a
difference between EGFRis and BEV. Meta-analysis of OS using direct evidence,
largely influenced by one trial, showed an improvement with EGFRis therapy (HR =
0.79 (95% CR: 0.65-0.98)), while indirect and combined NMA of OS did not show a
difference between EGFRis and BEV Successive inclusions of trials over time in
the combined NMA did not show superiority of EGFRis over BEV.
CONCLUSIONS: Our findings did not support OS or PFS benefits of EGFRis over BEV
in first-line mCRC.

DOI: 10.1371/journal.pone.0140187
PMCID: PMC4608731
PMID: 26474403  [Indexed for MEDLINE]


246. BMJ Open. 2015 Oct 6;5(10):e008572. doi: 10.1136/bmjopen-2015-008572.

Comparative efficacy and acceptability of psychotherapies for acute anxiety
disorders in children and adolescents: study protocol for a network
meta-analysis.

Zhang Y(1), Zhou X(1), James AC(2), Qin B(1), Whittington CJ(3), Cuijpers P(4),
Del Giovane C(5), Liu Y(1), Cohen D(6), Weisz JR(7), Xie P(1).

Author information:
(1)Department of Neurology, The First Affiliated Hospital of Chongqing Medical
University, Chongqing, China.
(2)Department of Psychiatry, University of Oxford, Oxford, UK Highfield Family
and Adolescent Unit, Warneford Hospital, Oxford, UK.
(3)Research Department of Clinical, Educational & Health Psychology, Centre for
Outcomes Research and Effectiveness, University College London, London, UK.
(4)Department of Clinical Psychology, VU University Amsterdam, Amsterdam, The
Netherlands.
(5)Department of Diagnostic, Clinical and Public Health Medicine, University of
Modena and Reggio Emilia, Modena, Italy.
(6)Department of Child and Adolescent Psychiatry, Institut des Systèmes
Intelligents et de Robotiques, UPMC Univ Paris 06, UMR 7222, Sorbonne
Universités, AP-HP, Hôpital Pitié-Salpétrière, Paris, France.
(7)Department of Psychology, Harvard University, Cambridge, Massachusetts, USA.

INTRODUCTION: Anxiety disorders are associated with significant public health
burden in young individuals. Cognitive-behavioural therapy (CBT) is the most
commonly used psychotherapy for anxiety disorders in children and adolescents,
but previous reviews were hindered by a limited number of trials with direct
comparisons between different psychotherapies and their deliveries. Consequently,
the main aim of this research was to investigate the comparative efficacy and
acceptability of various types and deliveries of psychotherapies for anxiety
disorders in children and adolescents.
METHODS AND ANALYSIS: We will systematically search PubMed, EMBASE, Cochrane, Web
of Science, PsycINFO, CINAHL, ProQuest Dissertations and LiLACS for randomised
controlled trials, regardless of whether participants received blinding or not,
published from 1 January 1966 to 30 January 2015 (updated to 1 July 2015), that
compared any psychotherapy with either a control condition or an active
comparator with different types and/or different delivery formats for the acute
treatment of anxiety disorders in children and adolescents. Data extraction, risk
of bias and quality assessments will be independently extracted by two reviewers.
The primary outcome for efficacy will be mean overall change scores in anxiety
symptoms (self-rated or assessor-rated) from baseline to post-treatment between
two groups. The acceptability of treatment will be measured as the proportion of
patients who discontinued treatment during the acute phase of treatment. We will
assess efficacy, based on the standardised mean difference (SMD), and
acceptability, based on the OR, using a random-effects network meta-analysis
within a Bayesian framework. Subgroup and sensitivity analyses will be conducted
to assess the robustness of the findings.
ETHICS AND DISSEMINATION: No ethical issues are foreseen. The results will be
published in a peer-reviewed journal and will be disseminated electronically and
in print. The meta-analysis may be updated to inform and guide management of
anxiety in children and adolescents.
TRIAL REGISTRATION NUMBER: PROSPERO CRD42015016283.

Published by the BMJ Publishing Group Limited. For permission to use (where not
already granted under a licence) please go to
http://group.bmj.com/group/rights-licensing/permissions.

DOI: 10.1136/bmjopen-2015-008572
PMCID: PMC4606384
PMID: 26443658  [Indexed for MEDLINE]


247. Catheter Cardiovasc Interv. 2015 Oct;86 Suppl 1:S15-22. doi: 10.1002/ccd.26025.
Epub 2015 May 22.

Outcomes after multivessel or culprit-Vessel intervention for ST-elevation
myocardial infarction in patients with multivessel coronary disease: a Bayesian
cross-design meta-analysis.

Bittl JA(1), Tamis-Holland JE(2), Lang CD(3), He Y(4).

Author information:
(1)Munroe Regional Medical Center, Ocala, Florida.
(2)Mount Sinai Saint Luke's Hospital and the Icahn School of Medicine, New York,
New York.
(3)Alpert School of Medicine, Brown University, Providence, Rhode Island.
(4)Office of Research and Methodology, National Center for Health Statistics,
Centers for Disease Control and Prevention, Hyattsville, Maryland.

INTRODUCTION: During primary percutaneous coronary intervention (PCI), patients
with ST-elevation myocardial infarction (STEMI) and multivessel coronary disease
can undergo either multivessel intervention (MVI) or culprit-vessel intervention
(CVI) only.
BACKGROUND: Randomized controlled trials (RCTs) support the use of MVI, but
cohort studies support the use of CVI.
METHODS: We developed Bayesian models that incorporated parameters for study type
and study outcome after MVI or CVI.
RESULTS: A total of 18 studies (4 RCTs, 3 matched cohort studies, and 11
unmatched observational studies) enrolled 48,398 patients with STEMI and
multivessel CAD and reported outcomes after MVI or CVI-only at the time of
primary PCI. Using a Bayesian hierarchical model, we found that the point
estimates replicated previously reported trends, but the wide Bayesian credible
intervals (BCI) excluded any plausible mortality difference between MVI versus
CVI in all three study types: RCTs (odds ratio [OR] 0.60, 95% BCI 0.31-1.20),
matched cohort studies (OR 1.37, 95% BCI 0.86-2.24), or unmatched cohort studies
(OR 1.16, 95% BCI 0.70-1.89). Both the global summary (OR 1.10, 95% BCI
0.74-1.51) and a sensitivity analysis that weighted the RCTs 1-5 times as much as
observational studies revealed no credible advantage of one PCI strategy over the
other (OR 1.05, 95% BCI 0.64-1.48).
CONCLUSIONS: Bayesian approaches contextualize the comparison of different
strategies by study type and suggest that neither MVI nor CVI emerges as a
preferred strategy in an analysis that accounts mortality differences.

© 2015 Wiley Periodicals, Inc.

DOI: 10.1002/ccd.26025
PMID: 26011638  [Indexed for MEDLINE]


248. Gastroenterology. 2015 Oct;149(4):958-70.e12. doi: 10.1053/j.gastro.2015.06.006.
Epub 2015 Jun 16.

Comparative Effectiveness of Pharmacological Interventions for Severe Alcoholic
Hepatitis: A Systematic Review and Network Meta-analysis.

Singh S(1), Murad MH(2), Chandar AK(3), Bongiorno CM(4), Singal AK(5), Atkinson
SR(6), Thursz MR(6), Loomba R(7), Shah VH(8).

Author information:
(1)Division of Gastroenterology, University of California San Diego, La Jolla,
California. Electronic address: sis040@ucsd.edu.
(2)Knowledge and Evaluation Research Unit, Robert D. and Patricia E. Kern Center
for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota.
(3)Division of Gastroenterology and Liver Diseases, Case Western Reserve
University, Cleveland, Ohio.
(4)Department of Library Services, Mayo Clinic-St. Mary's Hospital Library,
Rochester, Minnesota.
(5)Division of Gastroenterology and Hepatology, University of Alabama,
Birmingham, Alabama.
(6)Division of Hepatology, Imperial College, London, United Kingdom.
(7)Division of Gastroenterology, Department of Medicine, and Division of
Epidemiology, Department of Family and Preventive Medicine, University of
California, San Diego, California.
(8)Division of Gastroenterology and Hepatology, Department of Internal Medicine,
Mayo Clinic, Rochester, Minnesota.

Comment in
    Gastroenterology. 2015 Oct;149(4):857-9.

BACKGROUND & AIMS: Severe alcoholic hepatitis (AH) has high mortality. We
assessed the comparative effectiveness of pharmacological interventions for
severe AH, through a network meta-analysis combining direct and indirect
treatment comparisons.
METHODS: We conducted a systematic literature review, through February 2015, for
randomized controlled trials of adults with severe AH (discriminant function ≥32
and/or hepatic encephalopathy) that compared the efficacy of active pharmacologic
interventions (corticosteroids, pentoxifylline, and N-acetylcysteine [NAC], alone
or in combination) with each other or placebo, in reducing short-term mortality
(primary outcome) and medium-term mortality, acute kidney injury, and/or
infections (secondary outcomes). We performed direct and Bayesian network
meta-analysis for all treatments, and used Grading of Recommendations Assessment,
Development and Evaluation criteria to appraise quality of evidence.
RESULTS: We included 22 randomized controlled trials (2621 patients) comparing 5
different interventions. In a direct meta-analysis, only corticosteroids
decreased risk of short-term mortality. In a network meta-analysis, moderate
quality evidence supported the use of corticosteroids alone (relative risk [RR],
0.54; 95% credible interval [CrI], 0.39-0.73) or in combination with
pentoxifylline (RR, 0.53; 95% CrI, 0.36-0.78) or NAC (RR, 0.15; 95% CI,
0.05-0.39), to reduce short-term mortality; low quality evidence showed that
pentoxifylline also decreased short-term mortality (RR, 0.70; 95% CrI,
0.50-0.97). The addition of NAC, but not pentoxifylline, to corticosteroids may
be superior to corticosteroids alone for reducing short-term mortality. No
treatment was effective in reducing medium-term mortality. Imprecise estimates
and the small number of direct trials lowered the confidence in several
comparisons.
CONCLUSIONS: In patients with severe AH, pentoxifylline and corticosteroids
(alone and in combination with pentoxifylline or NAC) can reduce short-term
mortality. No treatment decreases risk of medium-term mortality.

Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

DOI: 10.1053/j.gastro.2015.06.006
PMID: 26091937  [Indexed for MEDLINE]


249. Medicine (Baltimore). 2015 Oct;94(40):e1592. doi: 10.1097/MD.0000000000001592.

Network Meta-Analysis Comparing Relatively Selective COX-2 Inhibitors Versus
Coxibs for the Prevention of NSAID-Induced Gastrointestinal Injury.

Yang M(1), Wang HT, Zhao M, Meng WB, Ou JQ, He JH, Zou B, Lei PG.

Author information:
(1)From the Department of Gastroenterology, Songgang People's Hospital, Shenzhen,
Guangdong, China (MY, J-QO, MZ, J-HH, P-GL); Department of Gastroenterology,
Peking University Shenzhen Hospital, Shenzhen, Guangdong, China (MY, BZ);
Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military
Medical University, Xi'an, China (H-TW); and Special Minimally Invasive Surgery,
The First Hospital of Lanzhou University, Hepatopancreatobiliary Surgery
Institute of Gansu, Cancer Center of Clinical Medical College, Lanzhou
University, Lanzhou, Gansu Province, China (W-BM).

Currently 2 difference classes of cyclooxygenase (COX)-2 inhibitors, coxibs and
relatively selective COX-2 inhibitors, are available for patients requiring
nonsteroidal anti-inflammatory drug (NSAID) therapy; their gastroprotective
effect is hardly directly compared. The aim of this study was to compare the
gastroprotective effect of relatively selective COX-2 inhibitors with coxibs.
MEDLINE, EMBASE, and the Cochrane Library (from their inception to March 2015)
were searched for potential eligible studies. We included randomized controlled
trials comparing coxibs (celecoxib, etoricoxib, parecoxib, and lumiracoxib),
relatively selective COX-2 inhibitors (nabumetone, meloxicam, and etodolac), and
nonselective NSAIDs with a study duration ≥ 4 weeks. Comparative effectiveness
and safety data were pooled by Bayesian network meta-analysis. The primary
outcomes were ulcer complications and symptomatic ulcer. Summary effect-size was
calculated as risk ratio (RR), together with the 95% confidence interval (CI).
This study included 36 trials with a total of 112,351 participants. Network
meta-analyses indicated no significant difference between relatively selective
COX-2 inhibitors and coxibs regarding ulcer complications (RR, 1.38; 95% CI,
0.47-3.27), symptomatic ulcer (RR, 1.02; 95% CI, 0.09-3.92), and endoscopic ulcer
(RR, 1.18; 95% CI, 0.37-2.96). Network meta-analyses adjusting potential
influential factors (age, sex, previous ulcer disease, and follow-up time), and
sensitivity analyses did not reveal any major change to the main results. Network
meta-analyses suggested that relatively selective COX-2 inhibitors and coxibs
were associated with comparable incidences of total adverse events (AEs) (RR,
1.09; 95% CI, 0.93-1.31), gastrointestinal AEs (RR, 1.04; 95% CI, 0.87-1.25),
total withdrawals (RR, 1.00; 95% CI, 0.74-1.33), and gastrointestinal AE-related
withdrawals (RR, 1.02; 95% CI, 0.57-1.74). Relatively selective COX-2 inhibitors
appear to be associated with similar gastroprotective effect and tolerability as
coxibs. Owing to the indirectness of the comparisons, future research is required
to confirm the study conclusion.

DOI: 10.1097/MD.0000000000001592
PMCID: PMC4616749
PMID: 26448006  [Indexed for MEDLINE]


250. Oncotarget. 2015 Sep 29;6(29):28502-12. doi: 10.18632/oncotarget.4375.

Therapeutic efficacy of combined BRAF and MEK inhibition in metastatic melanoma:
a comprehensive network meta-analysis of randomized controlled trials.

Mai R(1), Zhou S(2), Zhong W(3), Rong S(2), Cong Z(2), Li Y(2), Xie Q(2), Chen
H(2), Li X(2), Liu S(2), Cheng Y(4), Huang Y(4), Zhou Y(4), Zhang G(2)(4).

Author information:
(1)Department of Laboratory Medicine, The First Affiliated Hospital of Shantou
University Medical College, Shantou, Guangdong, China.
(2)Department of Pathology, Shantou University Medical College, Shantou,
Guangdong, China.
(3)Department of Pathology, The First Affiliated Hospital, College of Medicine,
Zhejiang University, Hangzhou, Zhejiang, China.
(4)Department of Dermatology and Skin Science, University of British Columbia,
Vancouver, British Columbia, Canada.

BACKGROUND: Several recent randomized clinical trials have preliminarily
demonstrated that initial targeted therapy with combined BRAF and MEK inhibition
is more effective in metastatic melanoma (MM) than single agent. To guide
therapeutic decisions, we did a comprehensive network meta-analysis to identify
evidence to robustly support whether combined BRAF and MEK inhibition is the best
initial targeted therapeutic strategy for patients with MM.
METHODS: The databases of PubMed and trial registries were researched for
randomized clinical trials of targeted therapy. Data of outcome were extracted on
progression-free survival (PFS), objective response rate (ORR), and overall
survival (OS). Network meta-analysis using a Bayesian statistical model was
performed to evaluate relative hazard ratio (HR) for PFS and OS, odds ratio (OR)
for ORR.
RESULTS: Finally, 16 eligible trials comprising 5976 participants were included
in this meta-analysis. PFS were significantly prolonged in patients who received
combined BRAF-MEK inhibition compared with those who received BRAF inhibition
(HR: 0.58, 95%CI: 0.51-0.67, P < 0.0001) or MEK inhibition alone (HR: 0.29,
95%CI: 0.22-0.37, P < 0.0001). Combined BRAF-MEK inhibition also improved the OS
over BRAF inhibition (HR: 0.67, 95%CI: 0.56-0.81, P < 0.0001) or MEK inhibition
alone (HR: 0.48, 95%CI: 0.36-0.65, P < 0.0001). The ORR was superior in combined
BRAF and MEK inhibition comparing with BRAF inhibition (OR: 2.00, 95%CI:
1.66-2.44, P < 0.0001) or MEK inhibition alone (OR: 20.66, 95%CI: 12.22-35.47, P
< 0.0001).
CONCLUSIONS: This study indicates that concurrent inhibition of BRAF and MEK
improved the most effective therapeutic modality as compared as single BRAF or
MEK inhibition for patients with MM.

DOI: 10.18632/oncotarget.4375
PMCID: PMC4695075
PMID: 26143635  [Indexed for MEDLINE]


251. BMJ Open. 2015 Sep 9;5(9):e007768. doi: 10.1136/bmjopen-2015-007768.

Comparative efficacy and tolerability of first-generation and newer-generation
antidepressant medications for depressive disorders in children and adolescents:
study protocol for a systematic review and network meta-analysis.

Zhou X(1), Qin B(1), Whittington C(2), Cohen D(3), Liu Y(1), Del Giovane C(4),
Michael KD(5), Zhang Y(1), Xie P(1).

Author information:
(1)Department of Neurology, The First Affiliated Hospital of Chongqing Medical
University, Chongqing, China.
(2)Research Department of Clinical, Educational and Health Psychology, University
College London, London, UK.
(3)Department of Child and Adolescent Psychiatry, AP-HP, Hôpital
Pitié-Salpétrière, Institut des Systèmes Intelligents et de Robotiques (ISIR),
Centre National pour la Recherche Scientifique, Université Pierre et Marie Curie,
Paris, France.
(4)Department of Diagnostic, Clinical, and Public Health Medicine, University of
Modena and Reggio, Emilia, Modena, Italy.
(5)Department of Psychology, Appalachian State University, Boone, North Carolina,
USA.

INTRODUCTION: Depressive disorders are among the most common psychiatric
disorders in children and adolescents, and have adverse effects on their
psychosocial functioning. Questions concerning the efficacy and safety of
antidepressant medications in the treatment of depression in children and
adolescents, led us to integrate the direct and indirect evidence using network
meta-analysis to create hierarchies of these drugs.
METHODS AND ANALYSIS: Seven databases with PubMed, EMBASE, the Cochrane Library,
Web of Science, CINAHL, LiLACS and PsycINFO will be searched from 1966 to
December 2013 (updated to May, 2015). There are no restrictions on language or
type of publication. Randomised clinical trials assessing first-generation and
newer-generation antidepressant medications against active comparator or placebo
as acute treatment for depressive disorders in children and adolescents (under
18 years of age) will be included. The primary outcome for efficacy will be mean
improvement in depressive symptoms, as measured by the mean change score of a
depression rating scale from baseline to post-treatment. The tolerability of
treatment will be defined as side effect discontinuation, as defined by the
proportion of patients who discontinued treatment due to adverse events during
the trial. We will also assess the secondary outcome for efficacy (response
rate), acceptability (all-cause discontinuation) and suicide-related outcomes. We
will perform the Bayesian network meta-analyses for all relative outcome
measures. Subgroup analyses and sensitivity analyses will be conducted to assess
the robustness of the findings.
DISSEMINATION: The network meta-analysis will provide useful information on
antidepressant treatment for child and adolescent depression. The results will be
disseminated through peer-reviewed publication or conference presentations.
TRIAL REGISTRATION NUMBER: PROSPERO CRD42015016023.

Published by the BMJ Publishing Group Limited. For permission to use (where not
already granted under a licence) please go to
http://group.bmj.com/group/rights-licensing/permissions.

DOI: 10.1136/bmjopen-2015-007768
PMCID: PMC4567669
PMID: 26353868  [Indexed for MEDLINE]


252. Int J Chron Obstruct Pulmon Dis. 2015 Sep 9;10:1863-81. doi: 10.2147/COPD.S87082.
eCollection 2015.

Comparative efficacy of combination bronchodilator therapies in COPD: a network
meta-analysis.

Huisman EL(1), Cockle SM(2), Ismaila AS(3), Karabis A(1), Punekar YS(2).

Author information:
(1)Mapi Group, Real World Strategy and Analytics and Strategic Market Access,
Houten, the Netherlands.
(2)Value Evidence and Outcomes, GlaxoSmithKline, Uxbridge, UK.
(3)Value Evidence and Outcomes, GlaxoSmithKline R&D, Research Triangle Park, NC,
USA ; Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON,
Canada.

BACKGROUND: Several new fixed-dose combination bronchodilators have been recently
launched, and assessing their efficacy relative to each other, and with open dual
combinations is desirable. This network meta-analysis (NMA) assessed the efficacy
of umeclidinium and vilanterol (UMEC/VI) with that of available dual
bronchodilators in single/separate inhalers.
METHODS: A systematic literature review identified randomized controlled trials
of ≥10 weeks among chronic obstructive pulmonary disease patients (≥40 years),
assessing the efficacy of combination bronchodilators in single or separate
inhalers. Comparative assessment was conducted on change from baseline in trough
forced expiratory volume in 1 second (FEV1), St George's Respiratory
Questionnaire (SGRQ) total scores, transitional dyspnea index (TDI) focal scores,
and rescue medication use at 12 weeks and 24 weeks using an NMA within a Bayesian
framework.
RESULTS: A systematic literature review identified 77 articles of 26 trials
comparing UMEC/VI, indacaterol/glycopyrronium (QVA149), formoterol plus
tiotropium (TIO) 18 μg, salmeterol plus TIO, or indacaterol plus TIO, with TIO
and placebo as common comparators at 12 weeks and approximately 24 weeks. The NMA
showed that at 24 weeks, efficacy of UMEC/VI was not significantly different
compared with QVA149 on trough FEV1 (14.1 mL [95% credible interval: -14.2,
42.3]), SGRQ total score (0.18 [-1.28, 1.63]), TDI focal score (-0.30 [-0.73,
0.13]), and rescue medication use (0.02 [-0.27, 0.32]); compared with salmeterol
plus TIO on trough FEV1 (67.4 mL [-25.3, 159.4]), SGRQ total score (-0.11 [-1.84,
1.61]), and TDI focal score (0.58 [-0.33, 1.50]); and compared with formoterol
plus TIO 18 μg on SGRQ total score (-0.68 [-1.77, 0.39]). Results at week 12 were
consistent with week 24 outcomes. Due to lack of availability of evidence, no
comparison was made with formoterol plus TIO on FEV1 or TDI at 24 weeks.
CONCLUSION: UMEC/VI has comparable efficacy to other dual-bronchodilator
combinations on available efficacy endpoints.

DOI: 10.2147/COPD.S87082
PMCID: PMC4573199
PMID: 26392761  [Indexed for MEDLINE]


253. BMJ Open. 2015 Sep 8;5(9):e007473. doi: 10.1136/bmjopen-2014-007473.

Lung protective ventilation in patients undergoing major surgery: a systematic
review incorporating a Bayesian approach.

Zhang Z(1), Hu X(2), Zhang X(1), Zhu X(1), Chen L(3), Zhu L(1), Hu C(4), Du B(2);
China Critical Care Clinical Trials Group (CCCCTG).

Author information:
(1)Department of Critical Care Medicine, Jinhua Municipal Central Hospital,
Jinhua Hospital of Zhejiang University, Jinhua, Zhejiang, People's Republic of
China.
(2)Department of Medical ICU, Peking Union Medical College Hospital, Beijing,
People's Republic of China.
(3)Department of Emergency, Jinhua Municipal Central Hospital, Jinhua Hospital of
Zhejiang University, Jinhua, Zhejiang, People's Republic of China.
(4)Department of Critical Care Medicine, Zhejiang Hospital, Hangzhou, Zhejiang,
People's Republic of China.

OBJECTIVE: Protective ventilation (PV) has been validated in patients with acute
respiratory distress syndrome. However, the effect of PV in patients undergoing
major surgery is controversial. The study aimed to explore the beneficial effect
of PV on patients undergoing a major operation by systematic review and
meta-analysis.
SETTING: Various levels of medical centres.
PARTICIPANTS: Patients undergoing general anaesthesia.
INTERVENTIONS: PV with low tidal volume.
PRIMARY AND SECONDARY OUTCOME MEASURES: Study end points included acute lung
injury (ALI), pneumonia, atelectasis, mortality, length of stay (LOS) in
intensive care unit (ICU) and hospital.
METHODS: Databases including PubMed, Scopus, EBSCO and EMBASE were searched from
inception to May 2015. Search strategies consisted of terms related to PV and
anaesthesia. We reported OR for binary outcomes including ALI, mortality,
pneumonia, atelectasis and other adverse outcomes. Weighted mean difference was
reported for continuous outcomes such as LOS in the ICU and hospital, pH value,
partial pressure of carbon dioxide, oxygenation and duration of mechanical
ventilation (MV).
MAIN RESULTS: A total of 22 citations were included in the systematic review and
meta-analysis. PV had protective effect against the development of ALI as
compared with the control group, with an OR of 0.41 (95% CI 0.19 to 0.87). PV
tended to be beneficial with regard to the development of pneumonia (OR 0.46, 95%
CI 0.16 to 1.28) and atelectasis (OR 0.68, 95% CI 0.46 to 1.01), but statistical
significance was not reached. Other adverse outcomes such as new onset arrhythmia
were significantly reduced with the use of PV (OR 0.47, 95% CI 0.48 to 0.93).
CONCLUSIONS: The study demonstrates that PV can reduce the risk of ALI in
patients undergoing major surgery. However, there is insufficient evidence that
such a beneficial effect can be translated to more clinically relevant outcomes
such as mortality or duration of MV.
TRIAL REGISTRATION NUMBER: The study was registered in PROSPERO
(http://www.crd.york.ac.uk/PROSPERO/) under registration number CRD42013006416.

Published by the BMJ Publishing Group Limited. For permission to use (where not
already granted under a licence) please go to
http://group.bmj.com/group/rights-licensing/permissions.

DOI: 10.1136/bmjopen-2014-007473
PMCID: PMC4563268
PMID: 26351181  [Indexed for MEDLINE]


254. Diabetes Res Clin Pract. 2015 Sep;109(3):521-32. doi:
10.1016/j.diabres.2015.05.017. Epub 2015 May 14.

Metformin for the treatment of gestational diabetes: An updated meta-analysis.

Kitwitee P(1), Limwattananon S(1), Limwattananon C(1), Waleekachonlert O(2),
Ratanachotpanich T(2), Phimphilai M(3), Nguyen TV(4), Pongchaiyakul C(5).

Author information:
(1)Social and Administrative Pharmacy Program, Faculty of Pharmaceutical
Sciences, Khon Kaen University, Thailand.
(2)Clinical Pharmacy Research Unit, Faculty of Pharmacy, Mahasarakham Univeristy,
Thailand.
(3)Division of Endocrinology and Metabolism, Department of Medicine, Faculty of
Medicine, Chiang Mai University, Thailand.
(4)Bone and Mineral Research Program, Garvan Institute of Medical Research,
Sydney, Australia.
(5)Division of Endocrinology and Metabolism, Department of Medicine, Faculty of
Medicine, Khon Kaen University, Thailand. Electronic address: pchatl@kku.ac.th.

OBJECTIVE: To assess the efficacy of metformin and insulin in the treatment of
pregnant women with gestational diabetes mellitus (GDM).
METHODS: A meta-analysis was conducted by including randomized controlled trials
comparing metformin and insulin in GDM. An electronic search was conducted to
identify relevant studies. Data were synthesized by a random effects
meta-analysis model. A Bayesian analysis was also performed to account for
uncertainties in the treatment efficacy.
RESULTS: Eight clinical trials involving 1712 individuals were included in the
final analysis. The pooled estimates of metformin-insulin differences were very
small and statistically non-significant in fasting plasma glucose, postprandial
plasma glucose and HbA1c, measured at 36-37 weeks of gestation. Notably, 14-46%
of those receiving metformin required additional insulin. Compared with the
insulin group, metformin treatment was associated with a lower incidence of
neonatal hypoglycemia (relative risk, RR 0.74; 95% CI 0.58-0.93; P=0.01) and of
neonatal intensive care admission (RR 0.76; 95% CI 0.59-0.97; P=0.03). Bayesian
analysis revealed that the efficacy of metformin was consistently higher than
insulin with a probability of over 98% on these two neonatal complications. Other
outcomes were not significantly different between the two treatment groups.
CONCLUSION: In women with gestational diabetes, metformin use and insulin therapy
have comparable glycemic control profile, but metformin use was associated with
lower risk of neonatal hypoglycemia.

Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

DOI: 10.1016/j.diabres.2015.05.017
PMID: 26117686  [Indexed for MEDLINE]


255. J Environ Radioact. 2015 Sep;147:63-75. doi: 10.1016/j.jenvrad.2015.05.007. Epub
2015 May 30.

Foliar interception of radionuclides in dry conditions: a meta-analysis using a
Bayesian modeling approach.

Sy MM(1), Ancelet S(2), Henner P(3), Hurtevent P(3), Simon-Cornu M(4).

Author information:
(1)Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Laboratoire de
Modélisation pour l'Expertise Environnementale (LM2E), Cadarache, Bâtiment 159,
St Paul-lez-Durance, 13115, France. Electronic address: moustapha.sy@irsn.fr.
(2)Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PRP-HOM, SRBE,
Laboratoire d'Epidémiologie (LEPID) Fontenay-aux-Roses, 92262, France.
(3)Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Laboratoire de
Biogéochimie, Biodisponibilité et Transferts des radionucléides (L2BT),
Cadarache, Bâtiment 183, St Paul-lez-Durance, 13115, France.
(4)Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Laboratoire de
Modélisation pour l'Expertise Environnementale (LM2E), Cadarache, Bâtiment 159,
St Paul-lez-Durance, 13115, France.

Uncertainty on the parameters that describe the transfer of radioactive materials
into the (terrestrial) environment may be characterized thanks to datasets such
as those compiled within International Atomic Energy Agency (IAEA) documents.
Nevertheless, the information included in these documents is too poor to derive a
relevant and informative uncertainty distribution regarding dry interception of
radionuclides by the pasture grass and the leaves of vegetables. In this paper,
145 sets of dry interception measurements by the aboveground biomass of specific
plants were collected from published scientific papers. A Bayesian meta-analysis
was performed to derive the posterior probability distributions of the parameters
that reflect their uncertainty given the collected data. Four competing models
were compared in terms of both fitting performances and predictive abilities to
reproduce plausible dry interception data. The asymptotic interception factor,
applicable whatever the species and radionuclide to the highest aboveground
biomass values (e.g. mature leafy vegetables), was estimated with the best model,
to be 0.87 with a 95% credible interval (0.85, 0.89).

Copyright © 2015 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.jenvrad.2015.05.007
PMID: 26043277  [Indexed for MEDLINE]


256. Medicine (Baltimore). 2015 Sep;94(36):e1451. doi: 10.1097/MD.0000000000001451.

The Efficacy and Safety of Chemotherapy in Patients With Nonsmall Cell Lung
Cancer and Interstitial Lung Disease: A PRISMA-Compliant Bayesian Meta-Analysis
and Systematic Review.

Chen YJ(1), Chen LX, Han MX, Zhang TS, Zhou ZR, Zhong DS.

Author information:
(1)From the Department of Oncology, General Hospital of Tianjin Medical
University, Tianjin, P.R. China (YJC, DSZ); Department of Orthopedics, Tianjin
Medical University General Hospital, Heping District, P.R. China (LXC);
Department of Respiration, General Hospital of Tianjin Medical University,
Tianjin, P.R. China (MXH); Internal Medicine of Traditional Chinese Medicine
Department, Jing'an District Central Hospital of Shanghai, Shanghai, P.R. China
(TSZ); and Department of Radiation Oncology, Fudan University Shanghai Cancer
Center, Shanghai, P.R. China (ZRZ).

Chemotherapy plays a critical and venturous role against the co-morbidity of
nonsmall cell lung cancer and interstitial lung disease (NSCLC-ILD).We performed
a Bayesian meta-analysis and systematic review to evaluate the safety and
efficacy of the chemotherapy in NSCLC-ILD patients.EMBASE, PubMed, the Cochrane
Central Register of Controlled Trials, and clinicaltrials.gov (up to January
2015).We included all study designs except case reports, all studies with
NSCLC-ILD patients and all the possible chemotherapy regimens.Quality was
assessed by a components approach. We derived summary estimates using Bayesian
method through WinBUGS (version 1.4.3, MRC Biostatistics Unit, Cambridge,
UK).Seven studies involving 251 patients with NSCLC-ILD were included in the
meta-analysis. The treatment response (complete remission, 0; [partial remission,
39.1%; 95% credible interval [CrI], 32.6-45.7]; [stable disease, 36%; 95% CrI,
29.6-42.2]; [PD, 15.4%; 95% CrI, 11.3-19.8]; [nonevaluable, 6.4%; 95% CrI,
2.7-10.1]; [overall response rate, 41.3%; 95% CrI, 35.3-47.4]; [disease control
rate, 77.7%; 95% CrI, 72.2-82.7]) were comparable to that of patients with NSCLC
alone; the survival outcomes (median overall survival, median progression-free
survival, and 1-year survival rate) were slightly worse, especially the lower
1-year survival rate. Platinum-based doublets as first-line chemotherapy may be
related to higher incidence of acute exacerbation-ILD in first line chemotherapy
(AE, 8.47%; 95% CrI, 5.04-12.6).The data selection bias and small patient number
make the meta-analysis of treatment response and conclusions generated from these
data inaccurate.The present meta-analysis suggests that chemotherapy might be an
effective therapy for patients with NSCLC-ILD, but it might be associated with
higher incidence of acute exacerbation.

DOI: 10.1097/MD.0000000000001451
PMCID: PMC4616626
PMID: 26356699  [Indexed for MEDLINE]


257. Menopause. 2015 Sep;22(9):1021-5. doi: 10.1097/GME.0000000000000466.

Indirect comparison of teriparatide, denosumab, and oral bisphosphonates for the
prevention of vertebral and nonvertebral fractures in postmenopausal women with
osteoporosis.

Zhang L(1), Pang Y, Shi Y, Xu M, Xu X, Zhang J, Ji L, Zhao D.

Author information:
(1)Department of Rheumatology and Immunology, Changhai Hospital, Second Military
Medical University, Shanghai, China.

OBJECTIVE: This study aims to compare the efficacy of teriparatide, denosumab,
and oral bisphosphonates for reducing fracture risk in postmenopausal women with
osteoporosis.
METHODS: We searched the literature, via PubMed, Medline, Embase, and the
Cochrane Library, to screen citations from January 1996 to October 2014 for
inclusion in this study. A mixed-treatment comparison meta-analysis within a
Bayesian framework was performed by WinBUGS version 1.4.3 software. The
proportions of women with vertebral fractures and women with nonvertebral
fractures were analyzed.
RESULTS: Our meta-analysis results indicated that all of the therapies-except
etidronate-achieved a statistically significant reduction of fractures compared
with placebo. Teriparatide and denosumab were more effective than alendronate and
risedronate for reducing vertebral fracture (teriparatide vs alendronate: odds
ratio [OR], 1.76; 95% CI, 1.03-2.98; teriparatide vs risedronate: OR, 1.92; 95%
CI, 1.13-3.19; denosumab vs alendronate: OR, 1.67; 95% CI, 1.06-2.67; denosumab
vs risedronate: OR, 1.84; 95% CI, 1.16-2.92). Teriparatide, denosumab,
alendronate, and risedronate also reduced the risk of nonvertebral fracture
compared with placebo. Results of subgroup analysis showed that denosumab (OR,
0.6; 95% CI, 0.37-0.98), alendronate (OR, 0.61; 95% CI, 0.39-0.96), and
risedronate (OR, 0.63; 95% CI, 0.46-0.86) can reduce the risk of hip fracture and
that risedronate (OR, 0.59; 95% CI, 0.4-0.88) can also reduce the risk of
upper-arm fracture.
CONCLUSIONS: Teriparatide, denosumab, alendronate, and risedronate are effective
in reducing the risk of vertebral and nonvertebral fractures in postmenopausal
women with osteoporosis. Furthermore, denosumab, alendronate, and risedronate can
reduce the risk of hip fracture, and risedronate can also reduce the risk of
upper-arm fracture.

DOI: 10.1097/GME.0000000000000466
PMID: 25944523  [Indexed for MEDLINE]


258. Mol Ecol. 2015 Sep;24(18):4586-604. doi: 10.1111/mec.13345. Epub 2015 Sep 10.

Evolutionary processes driving spatial patterns of intraspecific genetic
diversity in river ecosystems.

Paz-Vinas I(1)(2)(3), Loot G(2)(4), Stevens VM(4), Blanchet S(1)(4).

Author information:
(1)Centre National de la Recherche Scientifique (CNRS), École Nationale de
Formation Agronomique (ENFA), UMR 5174 EDB (Laboratoire Évolution & Diversité
Biologique), Université Paul Sabatier, 118 route de Narbonne, 31062, Toulouse
Cedex 4, France.
(2)UPS, UMR 5174 (EDB), Université de Toulouse, 118 route de Narbonne, 31062,
Toulouse Cedex 4, France.
(3)UMR 7263 - IMBE, Équipe EGE, Centre Saint-Charles, Aix-Marseille Université,
CNRS, IRD, Université d'Avignon et des Pays de Vaucluse, Case 36, 3 place Victor
Hugo, 13331, Marseille Cedex 3, France.
(4)Station d'Écologie Expérimentale du CNRS à Moulis, USR 2936, Centre National
de la Recherche Scientifique (CNRS), 2 route du CNRS, 09200, Moulis, France.

Describing, understanding and predicting the spatial distribution of genetic
diversity is a central issue in biological sciences. In river landscapes, it is
generally predicted that neutral genetic diversity should increase downstream,
but there have been few attempts to test and validate this assumption across
taxonomic groups. Moreover, it is still unclear what are the evolutionary
processes that may generate this apparent spatial pattern of diversity. Here, we
quantitatively synthesized published results from diverse taxa living in river
ecosystems, and we performed a meta-analysis to show that a downstream increase
in intraspecific genetic diversity (DIGD) actually constitutes a general spatial
pattern of biodiversity that is repeatable across taxa. We further demonstrated
that DIGD was stronger for strictly waterborne dispersing than for overland
dispersing species. However, for a restricted data set focusing on fishes, there
was no evidence that DIGD was related to particular species traits. We then
searched for general processes underlying DIGD by simulating genetic data in
dendritic-like river systems. Simulations revealed that the three processes we
considered (downstream-biased dispersal, increase in habitat availability
downstream and upstream-directed colonization) might generate DIGD. Using random
forest models, we identified from simulations a set of highly informative summary
statistics allowing discriminating among the processes causing DIGD. Finally,
combining these discriminant statistics and approximate Bayesian computations on
a set of twelve empirical case studies, we hypothesized that DIGD were most
likely due to the interaction of two of these three processes and that contrary
to expectation, they were not solely caused by downstream-biased dispersal.

© 2015 John Wiley & Sons Ltd.

DOI: 10.1111/mec.13345
PMID: 26284462  [Indexed for MEDLINE]


259. Obesity (Silver Spring). 2015 Sep;23(9):1800-10. doi: 10.1002/oby.21180.

Meta-analysis of the relationship between breaks in sedentary behavior and
cardiometabolic health.

Chastin SF(1), Egerton T(2), Leask C(1), Stamatakis E(3)(4)(5).

Author information:
(1)Glasgow Caledonian University, School of Health and Life Science, Institute of
Applied Health Research, Glasgow, UK.
(2)Department of Neuroscience, Norwegian University of Science and Technology,
Trondheim, Norway.
(3)Charles Perkins Centre, University of Sydney, Sydney, Australia.
(4)Exercise Health and Performance Faculty Research Group, Faculty of Health
Sciences, University of Sydney, Sydney, Australia.
(5)Department of Epidemiology and Public Health, Physical Activity Research Group
(UCL-PARG), University College London, London, UK.

Comment in
    Obesity (Silver Spring). 2015 Sep;23(9):1739.

OBJECTIVE: The concept of "breaks" in sedentary behavior has emerged as a
potential modifier of detrimental effects on adiposity caused by sedentary
behavior. The existing research investigating the relationship between breaks in
sedentary behavior with adiposity and cardiometabolic health in adults was
systematically reviewed and quantitatively synthesized by this study.
METHODS: Observational and experimental studies that examined the relationships
between the frequency of interruptions of sedentary behavior and markers of
adiposity and cardiometabolic health in adults were identified by a systematic
search of the literature. A meta-analysis was conducted by using the inverse
variance method for experimental trials and a Bayesian posterior probability of
existence of an association between breaks with adiposity and cardiometabolic
markers for observational studies.
RESULTS: It was revealed by the pooled results from nine experimental studies
that breaks in sedentary periods of at least light intensity may have a positive
effect on glycemia but not on lipidemia for adults. It is unclear whether this
effect is independent of total sitting time. However, the 10 identified
observational studies showed an association with breaks, which was independent of
total sedentary time, but only for obesity metrics.
CONCLUSIONS: The theory that interrupting bouts of sedentary behavior with
light-intensity activity might help control adiposity and postprandial glycemia
was supported by the evidence. Further investigations with better methods of
measuring sedentary behavior patterns and improved study designs are necessary to
confirm this preliminary evidence.

© 2015 The Obesity Society.

DOI: 10.1002/oby.21180
PMID: 26308477  [Indexed for MEDLINE]


260. PLoS One. 2015 Sep 1;10(9):e0135702. doi: 10.1371/journal.pone.0135702.
eCollection 2015.

Systematic Review and Meta-Analysis of Response Rates and Diagnostic Yield of
Screening for Type 2 Diabetes and Those at High Risk of Diabetes.

Khunti K(1), Mani H(1), Achana F(2), Cooper N(3), Gray LJ(3), Davies MJ(1).

Author information:
(1)Diabetes Research Centre, University of Leicester, Leicester General Hospital,
Leicester, United Kingdom.
(2)Department of Health Sciences, University of Leicester, University Road,
Leicester United Kingdom; Clinical Trials Unit, Medical School, University of
Warwick, Coventry, United Kingdom.
(3)Department of Health Sciences, University of Leicester, University Road,
Leicester United Kingdom.

BACKGROUND: Screening for type 2 diabetes (T2DM) and individuals at risk of
diabetes has been advocated, yet information on the response rate and diagnostic
yield of different screening strategies are lacking.
METHODS: Studies (from 1998 to March/2015) were identified through Medline,
Embase and the Cochrane library and included if they used oral glucose tolerance
test (OGTT) and WHO-1998 diagnostic criteria for screening in a community
setting. Studies were one-step strategy if participants were invited directly for
OGTT and two, three/four step if participants were screened at one or more levels
prior to invitation to OGTT. The response rate and diagnostic yield were pooled
using Bayesian random-effect meta-analyses.
FINDINGS: 47 studies (422754 participants); 29 one-step, 11 two-step and seven
three/four-step were identified. Pooled response rate (95% Credible Interval) for
invitation to OGTT was 65.5% (53.7, 75.6), 63.1% (44.0, 76.8), and 85.4% (76.4,
93.3) in one, two and three/four-step studies respectively. T2DM yield was 6.6%
(5.3, 7.8), 13.1% (4.3, 30.9) and 27.9% (8.6, 66.3) for one, two and
three/four-step strategies respectively. The number needed to invite to the OGTT
to detect one case of T2DM was 15, 7.6 and 3.6 in one, two, and three/four-step
strategies. In two step strategies, there was no difference between the response
or yield rates whether the first step was blood test or risk-score. There was
evidence of substantial heterogeneity in rates across study populations but this
was not explained by the method of invitation, study location (rural versus
urban) and developmental index of the country in which the study was performed.
CONCLUSIONS: Irrespective of the invitation method, developmental status of the
countries and or rural/urban location, using a multi-step strategy increases the
initial response rate to the invitation to screening for diabetes and reduces the
number needed to have the final diagnostic test (OGTT in this study) for a
definite diagnosis.

DOI: 10.1371/journal.pone.0135702
PMCID: PMC4556656
PMID: 26325182  [Indexed for MEDLINE]


261. Syst Rev. 2015 Aug 27;4:114. doi: 10.1186/s13643-015-0099-y.

Comparison of physical interventions, behavioral interventions, natural health
products, and pharmacologics to manage hot flashes in patients with breast or
prostate cancer: protocol for a systematic review incorporating network
meta-analyses.

Hutton B(1)(2), Yazdi F(3), Bordeleau L(4), Morgan S(5), Cameron C(6), Kanji
S(7), Fergusson D(8)(9), Tricco A(10), Straus S(11), Skidmore B(12), Hersi M(13),
Pratt M(14), Mazzarello S(15), Brouwers M(16), Moher D(17)(18), Clemons M(19).

Author information:
(1)Ottawa Hospital Research Institute, Ottawa, Canada. bhutton@Ohri.ca.
(2)University of Ottawa School of Epidemiology, Public Health and Preventive
Medicine, Ottawa, Canada. bhutton@Ohri.ca.
(3)Ottawa Hospital Research Institute, Ottawa, Canada. fayazdi@Ohri.ca.
(4)Department of Oncology, McMaster University, Hamilton, Ontario, Canada.
bordeleaul@hhsc.ca.
(5)Division of Radiation Oncology, Department of Radiology, University of Ottawa,
Ottawa, Canada. smorgan@toh.on.ca.
(6)Cornerstone Research Group, Toronto, Canada. cgcamero@gmail.com.
(7)Ottawa Hospital Research Institute, Ottawa, Canada.
skanji@ottawahospital.on.ca.
(8)Ottawa Hospital Research Institute, Ottawa, Canada. dafergusson@Ohri.ca.
(9)University of Ottawa School of Epidemiology, Public Health and Preventive
Medicine, Ottawa, Canada. dafergusson@Ohri.ca.
(10)Li Ka Shing Knowledge Institute, St Mike's Hospital, Toronto, Canada.
triccoa@smh.ca.
(11)Li Ka Shing Knowledge Institute, St Mike's Hospital, Toronto, Canada.
sharon.straus@utoronto.ca.
(12)Ottawa Hospital Research Institute, Ottawa, Canada. bskidmore@rogers.com.
(13)Ottawa Hospital Research Institute, Ottawa, Canada. mhersi@ohri.ca.
(14)Ottawa Hospital Research Institute, Ottawa, Canada. Mipratt@ohri.ca.
(15)Department of Medicine, Division of Medical Oncology, The Ottawa Hospital,
Ottawa, Canada. smazarello@toh.on.ca.
(16)Department of Oncology, McMaster University, Hamilton, Ontario, Canada.
mbrouwer@mcmaster.ca.
(17)Ottawa Hospital Research Institute, Ottawa, Canada. dmoher@ohri.ca.
(18)University of Ottawa School of Epidemiology, Public Health and Preventive
Medicine, Ottawa, Canada. dmoher@ohri.ca.
(19)Department of Medicine, Division of Medical Oncology, The Ottawa Hospital,
Ottawa, Canada. mclemons@toh.on.ca.

BACKGROUND: Breast and prostate cancers are the most commonly diagnosed
non-dermatologic malignancies in Canada. Agents including endocrine therapies
(e.g., aromatase inhibitors, gonadotrophin-releasing hormone analogs,
anti-androgens, tamoxifen) and chemotherapy have improved survival for both
conditions. As endocrine manipulation is a mainstay of treatment, it is not
surprising that hot flashes are a common and troublesome adverse effect. Hot
flashes can cause chills, night sweats, anxiety, and insomnia, lessening
patients' quality of life. These symptoms impact treatment adherence, worsening
prognosis. While short-term estrogen replacement therapy is frequently used to
manage hot flashes in healthy menopausal women, its use is contraindicated in
breast cancer. Similarly, testosterone replacement therapy is contraindicated in
prostate cancer. It is therefore not surprising that non-hormonal pharmacological
treatments (anti-depressants, anti-epilectics, anti-hypertensives),
physical/behavioral treatments (e.g., acupuncture, yoga/exercise, relaxation
techniques, cognitive behavioral therapy), and natural health products (e.g.,
black cohosh, flax, vitamin E, ginseng) have been studied for control of hot
flashes. There is a need to identify which interventions minimize the frequency
and severity of hot flashes and their impact on quality of life. This systematic
review and network meta-analysis of randomized studies will synthesize available
evidence addressing this knowledge gap.
METHODS/DESIGN: An electronic search of Medline, Embase, AMED, PsycINFO, and the
Cochrane Register of Controlled Trials has been designed by an information
specialist and peer reviewed by a second information specialist. Study selection
and data collection will be performed by two reviewers independently. Risk of
bias assessments will be completed using the Cochrane Risk of Bias Scale.
Outcomes of interest will include validated measures of hot flash severity, hot
flash frequency, quality of life, and harms. Bayesian network meta-analyses will
be performed where judged appropriate based on review of clinical and
methodologic features of included studies.
DISCUSSION: Our review will include a broad range of interventions that patients
with breast and prostate cancer have attempted to use to manage hot flashes. Our
work will establish the extent of evidence underlying these interventions and
will employ an inclusive approach to analysis to inform comparisons between them.
Our findings will be shared with Cancer Care Ontario for consideration in the
development of guidance related to supportive care in these patients.
SYSTEMATIC REVIEW REGISTRATION:
PROSPERO: CRD42015024286.

DOI: 10.1186/s13643-015-0099-y
PMCID: PMC4549873
PMID: 26307105  [Indexed for MEDLINE]


262. PLoS One. 2015 Aug 14;10(8):e0135692. doi: 10.1371/journal.pone.0135692.
eCollection 2015.

Comparative Efficacy and Safety of Different Antiplatelet Agents for Prevention
of Major Cardiovascular Events and Leg Amputations in Patients with Peripheral
Arterial Disease: A Systematic Review and Network Meta-Analysis.

Katsanos K(1), Spiliopoulos S(2), Saha P(3), Diamantopoulos A(4), Karunanithy
N(4), Krokidis M(5), Modarai B(3), Karnabatidis D(2).

Author information:
(1)Department of Interventional Radiology, Guy's and St. Thomas' Hospitals, NHS
Foundation Trust, King's Health Partners, London, United Kingdom; Department of
Interventional Radiology, Patras University Hospital, School of Medicine, Rion,
Greece.
(2)Department of Interventional Radiology, Patras University Hospital, School of
Medicine, Rion, Greece.
(3)Academic Department of Surgery, Cardiovascular Division, Kings College London,
BHF Centre of Research Excellence & NIHR Biomedical Research Centre at King's
Health Partners, St. Thomas' Hospital, London, United Kingdom.
(4)Department of Interventional Radiology, Guy's and St. Thomas' Hospitals, NHS
Foundation Trust, King's Health Partners, London, United Kingdom.
(5)Department of Interventional Radiology, Addenbrooke's Hospital, Cambridge
University Hospitals NHS Foundation Trust, Cambridge, United Kingdom.

There is a lack of consensus regarding which type of antiplatelet agent should be
used in patients with peripheral arterial disease (PAD) and little is known on
the advantages and disadvantages of dual antiplatelet therapy. We conducted a
systematic review and network meta-analysis of available randomized controlled
trials (RCT) comparing different antiplatelet drugs (Aspirin, Ticlopidine,
Clopidogrel, Ticagrelor, Cilostazol, Picotamide and Vorapaxar as monotherapies or
in combination with aspirin) in PAD patients (PROSPERO public database;
CRD42014010299).We collated evidence from previous relevant meta-analyses and
searched online databases. Primary efficacy endpoints were: (1) the composite
rate of major adverse cardiovascular events (MACE; including vascular deaths,
non-fatal myocardial infarction and non-fatal stroke), and (2) the rate of major
leg amputations. The primary safety endpoint was the rate of severe bleeding
events. Bayesian models were employed for multiple treatment comparisons and
risk-stratified hierarchies of comparative efficacy were produced to aid medical
decision making. Number-Needed-to-Treat (NNT) and Number-Needed-to-Harm (NNH) are
reported in case of significant results. We analyzed 49 RCTs comprising 34,518
patients with 88,358 person-years of follow-up with placebo as reference
treatment. Aspirin, Cilostazol, Vorapaxar and Picotamide were ineffective in
reducing MACE. A significant MACE reduction was noted with Ticagrelor plus
aspirin (RR: 0.67; 95%CrI: 0.46-0.96, NNT = 66), Clopidogrel (RR: 0.72; 95%CrI:
0.58-0.91, NNT = 80), Ticlopidine (RR: 0.75; 95%CrI: 0.58-0.96, NNT = 87), and
Clopidogrel plus aspirin (RR: 0.78; 95%CrI: 0.61-0.99, NNT = 98). Dual
antiplatelet therapy with Clopidogrel plus aspirin significantly reduced major
amputations following leg revascularization (RR: 0.68; 95%CrI: 0.46-0.99 compared
to aspirin, NNT = 94). The risk of severe bleeding was significantly higher with
Ticlopidine (RR: 5.03; 95%CrI: 1.23-39.6, NNH = 25), Vorapaxar (RR: 1.80; 95%CrI:
1.22-2.69, NNH = 130), and Clopidogrel plus aspirin (RR: 1.48; 95%CrI: 1.05-2.10,
NNH = 215). Clopidogrel monotherapy showed the most favourable benefit-harm
profile (79% cumulative rank probability best and 77% cumulative rank probability
safest). In conclusion, Clopidogrel should be the indicated antiplatelet agent in
PAD patients. Dual antiplatelet therapy with aspirin and Clopidogrel can reduce
the rate of major leg amputations following revascularization, but carries a
slightly higher risk of severe bleeding.

DOI: 10.1371/journal.pone.0135692
PMCID: PMC4537264
PMID: 26274912  [Indexed for MEDLINE]


263. BMC Public Health. 2015 Aug 11;15:768. doi: 10.1186/s12889-015-2082-x.

Associations between neighbourhood walkability and daily steps in adults: a
systematic review and meta-analysis.

Hajna S(1), Ross NA(2)(3), Brazeau AS(4), Bélisle P(5), Joseph L(6)(7), Dasgupta
K(8)(9).

Author information:
(1)Department of Epidemiology, Biostatistics and Occupational Health, McGill
University, 1020 Pine Avenue West, Montréal, QC, Canada.
samantha.hajna@mail.mcgill.ca.
(2)Department of Epidemiology, Biostatistics and Occupational Health, McGill
University, 1020 Pine Avenue West, Montréal, QC, Canada. nancy.ross@mcgill.ca.
(3)Department of Geography, McGill University, 805 Sherbrooke Street West,
Montréal, QC, Canada. nancy.ross@mcgill.ca.
(4)Department of Medicine, Division of Clinical Epidemiology, McGill University
Health Centre, 687 Pine Avenue West, Montréal, QC, Canada.
anne-sophie.brazeau@mcgill.ca.
(5)Department of Medicine, Division of Clinical Epidemiology, McGill University
Health Centre, 687 Pine Avenue West, Montréal, QC, Canada.
patrick.belisle@clinepi.mcgill.ca.
(6)Department of Epidemiology, Biostatistics and Occupational Health, McGill
University, 1020 Pine Avenue West, Montréal, QC, Canada.
lawrence.joseph@mcgill.ca.
(7)Department of Medicine, Division of Clinical Epidemiology, McGill University
Health Centre, 687 Pine Avenue West, Montréal, QC, Canada.
lawrence.joseph@mcgill.ca.
(8)Department of Epidemiology, Biostatistics and Occupational Health, McGill
University, 1020 Pine Avenue West, Montréal, QC, Canada.
kaberi.dasgupta@mcgill.ca.
(9)Department of Medicine, Division of Clinical Epidemiology, McGill University
Health Centre, 687 Pine Avenue West, Montréal, QC, Canada.
kaberi.dasgupta@mcgill.ca.

BACKGROUND: Higher street connectivity, land use mix and residential density
(collectively referred to as neighbourhood walkability) have been linked to
higher levels of walking. The objective of our study was to summarize the current
body of knowledge on the association between neighbourhood walkability and
biosensor-assessed daily steps in adults.
METHODS: We conducted a systematic search of PubMed, SCOPUS, and Embase (Ovid)
for articles published prior to May 2014 on the association between walkability
(based on Geographic Information Systems-derived street connectivity, land use
mix, and/or residential density) and daily steps (pedometer or
accelerometer-assessed) in adults. The mean differences in daily steps between
adults living in high versus low walkable neighbourhoods were pooled across
studies using a Bayesian hierarchical model.
RESULTS: The search strategy yielded 8,744 unique abstracts. Thirty of these
underwent full article review of which six met the inclusion criteria. Four of
these studies were conducted in Europe and two were conducted in Asia. A
meta-analysis of four of these six studies indicates that participants living in
high compared to low walkable neighbourhoods accumulate 766 more steps per day
(95 % credible interval 250, 1271). This accounts for approximately 8 % of
recommended daily steps.
CONCLUSIONS: The results of European and Asian studies support the hypothesis
that higher neighbourhood walkability is associated with higher levels of
biosensor-assessed walking in adults. More studies on this association are needed
in North America.

DOI: 10.1186/s12889-015-2082-x
PMCID: PMC4532296
PMID: 26260474  [Indexed for MEDLINE]


264. PLoS One. 2015 Aug 6;10(8):e0134525. doi: 10.1371/journal.pone.0134525.
eCollection 2015.

Inter-Ethnic/Racial Facial Variations: A Systematic Review and Bayesian
Meta-Analysis of Photogrammetric Studies.

Wen YF(1), Wong HM(1), Lin R(2), Yin G(2), McGrath C(3).

Author information:
(1)Paediatric Dentistry & Orthodontics, Faculty of Dentistry, The University of
Hong Kong, Hong Kong SAR, China.
(2)Department of Statistics & Actuarial Science, Faculty of Science, The
University of Hong Kong, Hong Kong SAR, China.
(3)Periodontology & Public Health, Faculty of Dentistry, The University of Hong
Kong, Hong Kong SAR, China.

BACKGROUND: Numerous facial photogrammetric studies have been published around
the world. We aimed to critically review these studies so as to establish
population norms for various angular and linear facial measurements; and to
determine inter-ethnic/racial facial variations.
METHODS AND FINDINGS: A comprehensive and systematic search of PubMed, ISI Web of
Science, Embase, and Scopus was conducted to identify facial photogrammetric
studies published before December, 2014. Subjects of eligible studies were either
Africans, Asians or Caucasians. A Bayesian hierarchical random effects model was
developed to estimate posterior means and 95% credible intervals (CrI) for each
measurement by ethnicity/race. Linear contrasts were constructed to explore
inter-ethnic/racial facial variations. We identified 38 eligible studies
reporting 11 angular and 18 linear facial measurements. Risk of bias of the
studies ranged from 0.06 to 0.66. At the significance level of 0.05, African
males were found to have smaller nasofrontal angle (posterior mean difference:
8.1°, 95% CrI: 2.2°-13.5°) compared to Caucasian males and larger nasofacial
angle (7.4°, 0.1°-13.2°) compared to Asian males. Nasolabial angle was more
obtuse in Caucasian females than in African (17.4°, 0.2°-35.3°) and Asian (9.1°,
0.4°-17.3°) females. Additional inter-ethnic/racial variations were revealed when
the level of statistical significance was set at 0.10.
CONCLUSIONS: A comprehensive database for angular and linear facial measurements
was established from existing studies using the statistical model and
inter-ethnic/racial variations of facial features were observed. The results have
implications for clinical practice and highlight the need and value for high
quality photogrammetric studies.

DOI: 10.1371/journal.pone.0134525
PMCID: PMC4527668
PMID: 26247212  [Indexed for MEDLINE]


265. Arch Orthop Trauma Surg. 2015 Aug;135(8):1183-92. doi: 10.1007/s00402-015-2258-y.
Epub 2015 Jun 17.

Adverse effects associated with the direct anterior approach for total hip
arthroplasty: a Bayesian meta-analysis.

De Geest T(1), Fennema P, Lenaerts G, De Loore G.

Author information:
(1)Orthopedics AZ Damiaan, Gouwelozestraat 100, 8400, Ostend, Belgium,
tdegeest@azdamiaan.be.

INTRODUCTION: The direct anterior approach (DAA) is an increasingly popular
technique for performing total hip arthroplasty (THA). This muscle-sparing
approach may yield functional benefits. However, DAA has been associated with an
increased risk incidence (RI) of intra- and postoperative complications.
MATERIALS AND METHODS: A systematic review of the published literature was
conducted to document the cumulative RI of intra- and postoperative
complications, as well as the presence of a learning curve in subjects undergoing
THA with a DAA. Study selection and data extraction were carried out
independently in duplicate. A Bayesian zero-inflated random-effect model was used
to calculate pooled estimates for the different endpoints.
RESULTS: Thirty-eight studies (6485 patients) were analysed. RIs of 0.8 % [95 %
confidence interval (CI): 0.4-1.6 %] and 0.5 % (95 % CI: 0.3-0.9 %) were found
for intra-operative trochanter and femoral fractures, respectively, and of 0.9 %
(95 CI: 0.3-2.6 %) for postoperative transient lateral cutaneous femoral nerve
(LCFN) impairment. A clear RI for early revisions (2.1 %; 95 % CI: 1.4-2.8 %) and
other surgical re-interventions (1.3 %; 95 % CI: 0.7-1.9 %) was present, but
these values do not differ from reported RIs for THA overall. The RI for
dislocation was low (0.6 %; 95 % CI: 0.4-0.9 %) compared with the reported
literature.
CONCLUSIONS: DAA is a technically demanding procedure, with outcomes possibly
indicative of surgeon learning curve. A risk for intra-operative fractures and
LCFN is evident, although the risk for other adverse effects is comparable to
those with other approaches.

DOI: 10.1007/s00402-015-2258-y
PMID: 26081800  [Indexed for MEDLINE]


266. Br J Haematol. 2015 Aug;170(4):504-14. doi: 10.1111/bjh.13463. Epub 2015 Apr 24.

Front-line, dose-escalated immunochemotherapy is associated with a significant
progression-free survival advantage in patients with double-hit lymphomas: a
systematic review and meta-analysis.

Howlett C(1)(2), Snedecor SJ(3), Landsburg DJ(4), Svoboda J(4), Chong EA(4),
Schuster SJ(4), Nasta SD(4), Feldman T(5), Rago A(4), Walsh KM(4), Weber S(4),
Goy A(5), Mato A(6).

Author information:
(1)Department of Pharmacy and Clinical Services, John Theurer Cancer Center at
Hackensack University Medical Center, Hackensack, NJ, USA.
(2)Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey,
Piscataway, NJ, USA.
(3)Pharmerit International, Bethesda, MD, USA.
(4)Lymphoma Program, Abramson Cancer Center, University of Pennsylvania,
Philadelphia, PA, USA.
(5)John Theurer Cancer Center at Hackensack University Medical Center,
Hackensack, NJ, USA.
(6)Center for Chronic Lymphocytic Leukemia and Lymphoma Program, Abramson Cancer
Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia,
PA, USA.

'Double-hit lymphomas' (DHL), defined by concurrent MYC and BCL2 (or,
alternatively, BCL6) rearrangements, have a very poor outcome compared to
standard-risk, diffuse large B-cell lymphomas (DLBCL). Consequently,
dose-intensive (DI) therapies and/or consolidation with high-dose therapy and
transplant have been explored in DHL, although benefit has been debated. This
meta-analysis compared survival outcomes in DHL patients receiving dose-escalated
regimens [DI: R-Hyper-CVAD (rituximab, cyclophosphamide, vincristine,
doxorubicin, dexamethasone) or R-CODOX-M/IVAC (rituximab, cyclophosphamide,
doxorubicin, vincristine, methotrexate/ifosfamide, etoposide, high dose
cytarabine); or intermediate-dose: R-EPOCH (rituximab, etoposide, doxorubicin,
cyclophosphamide, vincristine, prednisone)] versus standard-dose regimens
(R-CHOP; rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) in
the first-line setting. Data were synthesized to estimate hazard ratios of
dose-escalated treatments versus R-CHOP using a Weibull proportional hazards
model within a Bayesian meta-analysis framework. Eleven studies examining 394
patients were included. Patients were treated with either front-line R-CHOP
(n = 180), R-EPOCH (n = 91), or R-Hyper-CVAD/rituximab, methotrexate, cytarabine
(R-M/C), R-CODOX-M/R-IVAC (DI) (n = 123). Our meta-analysis revealed that median
progression-free survival (n = 350) for the R-CHOP, R-EPOCH and DI groups was
12·1, 22·2, and 18·9 months, respectively. First-line treatment with R-EPOCH
significantly reduced the risk of a progression compared with R-CHOP (relative
risk reduction of 34%; P = 0·032); however, overall survival (n = 374) was not
significantly different across treatment approaches. A subset of patients might
benefit from intensive induction with/without transplant. Further investigation
into the role of transplant and novel therapy combinations is necessary.

© 2015 John Wiley & Sons Ltd.

DOI: 10.1111/bjh.13463
PMID: 25907897  [Indexed for MEDLINE]


267. Eur J Cancer. 2015 Aug;51(12):1570-9. doi: 10.1016/j.ejca.2015.04.027. Epub 2015
Jun 1.

Chemoradiotherapy regimens for locoregionally advanced nasopharyngeal carcinoma:
A Bayesian network meta-analysis.

Yan M(1), Kumachev A(1), Siu LL(2), Chan KK(3).

Author information:
(1)Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto,
Ontario M5S 1A8, Canada.
(2)Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto,
Ontario M5S 1A8, Canada; Division of Medical Oncology, Princess Margaret Cancer
Centre, 610 University Ave, Toronto, Ontario M5G 2M9, Canada.
(3)Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto,
Ontario M5S 1A8, Canada; Division of Medical Oncology, Sunnybrook Health Sciences
Centre, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada. Electronic
address: kelvin.chan@sunnybrook.ca.

Comment in
    Eur J Cancer. 2016 Mar;56:183-5.
    Eur J Cancer. 2016 Mar;56:186-7.

BACKGROUND: Concurrent chemoradiotherapy followed by adjuvant chemotherapy
(CRT-A) is often the regimen of choice in locoregionally advanced nasopharyngeal
carcinoma (NPC). Many alternative regimens have been reported in the literature,
however, it is unknown how effective these regimens are compared to each other
due to the lack of direct comparisons. Our objective was to perform a network
meta-analysis (NMA) to determine the relative survival benefits of these
treatments for locoregionally advanced NPC.
METHODS: We performed a systematic review following the Cochrane methodology,
using MEDLINE, EMBASE and CENTRAL to identify all randomised controlled trials
(RCTs) that compared different chemoradiotherapy regimens for locoregionally
advanced NPC. Overall survival (OS) was the primary outcome of interest, and
hazard ratios (HRs) were extracted using the Parmar method. Bayesian NMAs with
random effects were conducted using WinBUGS.
RESULTS: Twenty-five RCTs (5576 patients) were included in this review. All
together, these trials compared seven different regimens: radiotherapy (RT),
concurrent chemoradiotherapy (CRT), neoadjuvant followed by CRT (N-CRT), CRT-A,
RT-A, N-RT and N-RT-A. All regimens that contained CRT performed significantly
better than RT. CRT-A did not improve survival compared to CRT alone (0.98; 95%
credible regions: 0.71-1.34). For N-CRT versus CRT, the HR was 1.03 (0.69-1.47).
When CRT-A was compared against N-CRT, the resulting HR was 0.96 (0.64-1.48).
CONCLUSIONS: Adjuvant chemotherapy does not appear to improve survival following
CRT. The efficacies of CRT, CRT-A and N-CRT all appeared to be similar. Further
studies are warranted to determine the value of additional chemotherapy phases in
specific patient subgroups.

Copyright © 2015 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.ejca.2015.04.027
PMID: 26044925  [Indexed for MEDLINE]


268. Eur J Cardiothorac Surg. 2015 Aug;48(2):201-11. doi: 10.1093/ejcts/ezu408. Epub
2014 Nov 12.

Comparing energy sources for surgical ablation of atrial fibrillation: a Bayesian
network meta-analysis of randomized, controlled trials.

Phan K(1), Xie A(2), Kumar N(3), Wong S(4), Medi C(5), La Meir M(6), Yan TD(7).

Author information:
(1)The Collaborative Research (CORE) Group, Macquarie University, Sydney,
Australia Westmead Hospital, Sydney Medical School, University of Sydney, Sydney,
Australia.
(2)The Collaborative Research (CORE) Group, Macquarie University, Sydney,
Australia.
(3)Department of Cardiothoracic Surgery and Cardiology, Academic Hospital
Maastricht and Cardiovascular Research Institute Maastricht, Maastricht,
Netherlands.
(4)Gosford District Hospital, Gosford, Australia.
(5)Department of Cardiology and Cardiothoracic Surgery, Royal Prince Alfred
Hospital, Sydney, Australia.
(6)Department of Cardiothoracic Surgery and Cardiology, Academic Hospital
Maastricht and Cardiovascular Research Institute Maastricht, Maastricht,
Netherlands University Hospital Brussels, Brussels, Belgium.
(7)The Collaborative Research (CORE) Group, Macquarie University, Sydney,
Australia Department of Cardiology and Cardiothoracic Surgery, Royal Prince
Alfred Hospital, Sydney, Australia tristanyan@annalscts.com.

Simplified maze procedures involving radiofrequency, cryoenergy and microwave
energy sources have been increasingly utilized for surgical treatment of atrial
fibrillation as an alternative to the traditional cut-and-sew approach. In the
absence of direct comparisons, a Bayesian network meta-analysis is another
alternative to assess the relative effect of different treatments, using indirect
evidence. A Bayesian meta-analysis of indirect evidence was performed using 16
published randomized trials identified from 6 databases. Rank probability
analysis was used to rank each intervention in terms of their probability of
having the best outcome. Sinus rhythm prevalence beyond the 12-month follow-up
was similar between the cut-and-sew, microwave and radiofrequency approaches,
which were all ranked better than cryoablation (respectively, 39, 36, and 25 vs
1%). The cut-and-sew maze was ranked worst in terms of mortality outcomes
compared with microwave, radiofrequency and cryoenergy (2 vs 19, 34, and 24%,
respectively). The cut-and-sew maze procedure was associated with significantly
lower stroke rates compared with microwave ablation [odds ratio <0.01; 95%
confidence interval 0.00, 0.82], and ranked the best in terms of pacemaker
requirements compared with microwave, radiofrequency and cryoenergy (81 vs 14,
and 1, <0.01% respectively). Bayesian rank probability analysis shows that the
cut-and-sew approach is associated with the best outcomes in terms of sinus
rhythm prevalence and stroke outcomes, and remains the gold standard approach for
AF treatment. Given the limitations of indirect comparison analysis, these
results should be viewed with caution and not over-interpreted.

© The Author 2014. Published by Oxford University Press on behalf of the European
Association for Cardio-Thoracic Surgery. All rights reserved.

DOI: 10.1093/ejcts/ezu408
PMID: 25391388  [Indexed for MEDLINE]


269. Eur J Gastroenterol Hepatol. 2015 Aug;27(8):983-4. doi:
10.1097/MEG.0000000000000389.

Bayesian network meta-analysis to evaluate interferon-free treatments in naive
patients with genotype 1 hepatitis C virus infection.

Trippoli S(1), Fadda V, Maratea D, Messori A.

Author information:
(1)HTA Unit, ESTAV Toscana Centro, Regional Health Service, Firenze, Italy.

DOI: 10.1097/MEG.0000000000000389
PMID: 26114910  [Indexed for MEDLINE]


270. Eur J Gastroenterol Hepatol. 2015 Aug;27(8):882-94. doi:
10.1097/MEG.0000000000000376.

Comparative effectiveness of antiviral treatment for hepatitis B: a systematic
review and Bayesian network meta-analysis.

Govan L(1), Wu O, Xin Y, Hutchinson SJ, Hawkins N.

Author information:
(1)aHealth Economics and Health Technology Assessment, Institute of Health and
Wellbeing, University of Glasgow bSchool of Health & Life Sciences, Glasgow
Caledonian University, Glasgow cOxford Outcomes, Oxford, UK.

OBJECTIVE: A wide variety of competing drugs are available to patients for the
treatment of chronic hepatitis B. We update a recent meta-analysis to include
additional trial evidence with the aim of determining which treatment is the most
effective.
METHODS: Twelve monotherapy or combination therapy were evaluated in
treatment-naive individuals with hepatitis B e antigen (HBeAg) positive or
negative patients. Databases were searched for randomized controlled trials in
the first year of therapy. Bayesian random effects network meta-analysis was used
to calculate the pairwise odds ratios, 95% credible intervals and ranking of six
surrogate outcomes.
RESULTS: In total, 22 studies were identified (7508 patients): 12 studies
analysed HBeAg-positive patients, six analysed HBeAg-negative patients, and four
evaluated both. Tenofovir was most effective at increasing efficacy in
HBeAg-positive patients, ranking first for three outcomes and increased odds of
undetectable levels of hepatitis B virus (HBV) DNA compared with seven other
therapies (such as lamivudine: odds ratio 33.0; 95% credible interval 7.0-292.7).
For HBeAg-negative patients, the large network (seven therapies) ranked entecavir
alone or in combination with tenofovir highly for reduction in HBV DNA and
histologic improvement. In the smaller network (three therapies), tenofovir
ranked first for undetectable HBV DNA and histologic improvement. No data existed
to directly or indirectly compare these treatments.
CONCLUSION: For HBeAg-positive patients tenofovir is the most effective at
increasing efficacy, whereas for HBeAg-negative patients, either tenofovir or
entecavir is most effective. Further research should focus on strengthening the
network connections, in particular comparing tenofovir and entecavir in
HBeAg-negative patients.

DOI: 10.1097/MEG.0000000000000376
PMID: 25919772  [Indexed for MEDLINE]


271. Food Microbiol. 2015 Aug;49:33-40. doi: 10.1016/j.fm.2015.01.001. Epub 2015 Feb
11.

Management of Listeria monocytogenes in fermented sausages using the Food Safety
Objective concept underpinned by stochastic modeling and meta-analysis.

Mataragas M(1), Alessandria V(2), Rantsiou K(2), Cocolin L(2).

Author information:
(1)Università di Torino, Dipartimento di Scienze Agrarie, Forestali e Alimentari,
Via Leonardo da Vinci 44, Grugliasco, 10095 Turin, Italy; Agriculture University
of Athens, Department of Food Science and Technology, Laboratory of Food Quality
Control and Hygiene, Iera Odos 75, 11855, Athens, Greece. Electronic address:
mmat@aua.gr.
(2)Università di Torino, Dipartimento di Scienze Agrarie, Forestali e Alimentari,
Via Leonardo da Vinci 44, Grugliasco, 10095 Turin, Italy.

In the present work, a demonstration is made on how the risk from the presence of
Listeria monocytogenes in fermented sausages can be managed using the concept of
Food Safety Objective (FSO) aided by stochastic modeling (Bayesian analysis and
Monte Carlo simulation) and meta-analysis. For this purpose, the ICMSF equation
was used, which combines the initial level (H0) of the hazard and its subsequent
reduction (ΣR) and/or increase (ΣI) along the production chain. Each element of
the equation was described by a distribution to investigate the effect not only
of the level of the hazard, but also the effect of the accompanying variability.
The distribution of each element was determined by Bayesian modeling (H0) and
meta-analysis (ΣR and ΣI). The output was a normal distribution N(-5.36, 2.56)
(log cfu/g) from which the percentage of the non-conforming products, i.e. the
fraction above the FSO of 2 log cfu/g, was estimated at 0.202%. Different control
measures were examined such as lowering initial L. monocytogenes level and
inclusion of an additional killing step along the process resulting in reduction
of the non-conforming products from 0.195% to 0.003% based on the mean and/or
square-root change of the normal distribution, and 0.001%, respectively.

Copyright © 2015 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.fm.2015.01.001
PMID: 25846913  [Indexed for MEDLINE]


272. J Clin Epidemiol. 2015 Aug;68(8):860-9. doi: 10.1016/j.jclinepi.2015.03.017. Epub
2015 Apr 2.

Small studies are more heterogeneous than large ones: a meta-meta-analysis.

IntHout J(1), Ioannidis JP(2), Borm GF(3), Goeman JJ(3).

Author information:
(1)Radboud Institute for Health Sciences (RIHS), Radboud University Medical
Center, Mailbox 133, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands. Electronic
address: joanna.inthout@radboudumc.nl.
(2)Stanford Prevention Research Center, Department of Medicine, Stanford
University School of Humanities and Sciences, 1265 Welch Road, Stanford, CA
94305, USA; Department of Health Research and Policy, Stanford University School
of Medicine, 150 Governor's Lane, Stanford, CA 94305, USA; Department of
Statistics, Stanford University School of Humanities and Sciences, 390 Serra
Mall, Stanford, CA 94305, USA; Meta-Research Innovation Center at Stanford
(METRICS), Stanford University, 1265 Welch Road, Stanford, CA 94305, USA.
(3)Radboud Institute for Health Sciences (RIHS), Radboud University Medical
Center, Mailbox 133, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands.

OBJECTIVES: Between-study heterogeneity plays an important role in random-effects
models for meta-analysis. Most clinical trials are small, and small trials are
often associated with larger effect sizes. We empirically evaluated whether there
is also a relationship between trial size and heterogeneity (τ).
STUDY DESIGN AND SETTING: We selected the first meta-analysis per intervention
review of the Cochrane Database of Systematic Reviews Issues 2009-2013 with a
dichotomous (n = 2,009) or continuous (n = 1,254) outcome. The association
between estimated τ and trial size was evaluated across meta-analyses using
regression and within meta-analyses using a Bayesian approach. Small trials were
predefined as those having standard errors (SEs) over 0.2 standardized effects.
RESULTS: Most meta-analyses were based on few (median 4) trials. Within the same
meta-analysis, the small study τS(2) was larger than the large-study τL(2)
[average ratio 2.11; 95% credible interval (1.05, 3.87) for dichotomous and 3.11
(2.00, 4.78) for continuous meta-analyses]. The imprecision of τS was larger than
of τL: median SE 0.39 vs. 0.20 for dichotomous and 0.22 vs. 0.13 for continuous
small-study and large-study meta-analyses.
CONCLUSION: Heterogeneity between small studies is larger than between larger
studies. The large imprecision with which τ is estimated in a typical
small-studies' meta-analysis is another reason for concern, and sensitivity
analyses are recommended.

Copyright © 2015 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.jclinepi.2015.03.017
PMID: 25959635  [Indexed for MEDLINE]


273. Lancet Infect Dis. 2015 Aug;15(8):927-40. doi: 10.1016/S1473-3099(15)00066-3.
Epub 2015 May 21.

Spatial distribution of schistosomiasis and treatment needs in sub-Saharan
Africa: a systematic review and geostatistical analysis.

Lai YS(1), Biedermann P(1), Ekpo UF(2), Garba A(3), Mathieu E(4), Midzi N(5),
Mwinzi P(6), N'Goran EK(7), Raso G(1), Assaré RK(8), Sacko M(9), Schur N(1),
Talla I(10), Tchuenté LA(11), Touré S(12), Winkler MS(1), Utzinger J(1),
Vounatsou P(13).

Author information:
(1)Department of Epidemiology and Public Health, Swiss Tropical and Public Health
Institute, and University of Basel, Basel, Switzerland.
(2)Department of Biological Sciences, Federal University of Agriculture,
Abeokuta, Nigeria.
(3)Réseau International Schistosomose, Environnement, Amenagement et Lutte,
Niamey, Niger.
(4)National Center of Infectious Diseases, Centers for Disease Control and
Prevention, Atlanta, GA, USA.
(5)National Institute of Health Research, Harare, Zimbabwe.
(6)Centre for Global Health Research, Kenya Medical Research Institute, Kisumu,
Kenya.
(7)Unité de Formation et de Recherche Biosciences, Université Félix
Houphouët-Boigny, Abidjan, Côte d'Ivoire; Centre Suisse de Recherches
Scientifiques en Côte d'Ivoire, Abidjan, Côte d'Ivoire.
(8)Department of Epidemiology and Public Health, Swiss Tropical and Public Health
Institute, and University of Basel, Basel, Switzerland; Centre Suisse de
Recherches Scientifiques en Côte d'Ivoire, Abidjan, Côte d'Ivoire.
(9)Institut National de Recherche en Santé Publique, Bamako, Mali.
(10)Direction de la Lutte Contre la Maladie, Ministère de la Santé, Dakar,
Senegal.
(11)Laboratory of Parasitology and Ecology, University of Yaoundé, and Center for
Schistosomiasis and Parasitology, Yaoundé, Cameroon.
(12)Programme National de Lutte Contre la Schistosomiase, Ministère de la Santé,
Ouagadougou, Burkina Faso.
(13)Department of Epidemiology and Public Health, Swiss Tropical and Public
Health Institute, and University of Basel, Basel, Switzerland. Electronic
address: penelope.vounatsou@unibas.ch.

Erratum in
    Lancet Infect Dis. 2015 Jul;15(7):761.

Comment in
    Lancet Infect Dis. 2015 Aug;15(8):869-70.

BACKGROUND: Schistosomiasis affects more than 200 million individuals, mostly in
sub-Saharan Africa, but empirical estimates of the disease burden in this region
are unavailable. We used geostatistical modelling to produce high-resolution risk
estimates of infection with Schistosoma spp and of the number of doses of
praziquantel treatment needed to prevent morbidity at different administrative
levels in 44 countries.
METHODS: We did a systematic review to identify surveys including schistosomiasis
prevalence data in sub-Saharan Africa via PubMed, ISI Web of Science, and African
Journals Online, from inception to May 2, 2014, with no restriction of language,
survey date, or study design. We used Bayesian geostatistical meta-analysis and
rigorous variable selection to predict infection risk over a grid of 1 155 818
pixels at 5 × 5 km, on the basis of environmental and socioeconomic predictors
and to calculate the number of doses of praziquantel needed for prevention of
morbidity.
FINDINGS: The literature search identified Schistosoma haematobium and
Schistosoma mansoni surveys done in, respectively, 9318 and 9140 unique
locations. Infection risk decreased from 2000 onwards, yet estimates suggest that
163 million (95% Bayesian credible interval [CrI] 155 million to 172 million;
18·5%, 17·6-19·5) of the sub-Saharan African population was infected in 2012.
Mozambique had the highest prevalence of schistosomiasis in school-aged children
(52·8%, 95% CrI 48·7-57·8). Low-risk countries (prevalence among school-aged
children lower than 10%) included Burundi, Equatorial Guinea, Eritrea, and
Rwanda. The numbers of doses of praziquantel needed per year were estimated to be
123 million (95% CrI 121 million to 125 million) for school-aged children and 247
million (239 million to 256 million) for the entire population.
INTERPRETATION: Our results will inform policy makers about the number of
treatments needed at different levels and will guide the spatial targeting of
schistosomiasis control interventions.
FUNDING: European Research Council, China Scholarship Council, UBS Optimus
Foundation, and Swiss National Science Foundation.

Copyright © 2015 Elsevier Ltd. All rights reserved.

DOI: 10.1016/S1473-3099(15)00066-3
PMID: 26004859  [Indexed for MEDLINE]


274. PLoS One. 2015 Jul 31;10(7):e0134264. doi: 10.1371/journal.pone.0134264.
eCollection 2015.

Additive Effect on Survival of Anaesthetic Cardiac Protection and Remote Ischemic
Preconditioning in Cardiac Surgery: A Bayesian Network Meta-Analysis of
Randomized Trials.

Zangrillo A(1), Musu M(2), Greco T(3), Di Prima AL(4), Matteazzi A(4), Testa
V(4), Nardelli P(4), Febres D(4), Monaco F(4), Calabrò MG(4), Ma J(5), Finco
G(2), Landoni G(1).

Author information:
(1)Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific
Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.
(2)Department of Medical Sciences "M. Aresu", Cagliari University, Cagliari,
Italy.
(3)Vita-Salute San Raffaele University, Milan, Italy.
(4)Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific
Institute, Milan, Italy.
(5)Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical
University, Beijing, China.

INTRODUCTION: Cardioprotective properties of volatile agents and of remote
ischemic preconditioning have survival effects in patients undergoing cardiac
surgery. We performed a Bayesian network meta-analysis to confirm the beneficial
effects of these strategies on survival in cardiac surgery, to evaluate which is
the best strategy and if these strategies have additive or competitive effects.
METHODS: Pertinent studies were independently searched in BioMedCentral,
MEDLINE/PubMed, Embase, and the Cochrane Central Register (updated November
2013). A Bayesian network meta-analysis was performed. Four groups of patients
were compared: total intravenous anesthesia (with or without remote ischemic
preconditioning) and an anesthesia plan including volatile agents (with or
without remote ischemic preconditioning). Mortality was the main investigated
outcome.
RESULTS: We identified 55 randomized trials published between 1991 and 2013 and
including 6,921 patients undergoing cardiac surgery. The use of volatile agents
(posterior mean of odds ratio = 0.50, 95% CrI 0.28-0.91) and the combination of
volatile agents with remote preconditioning (posterior mean of odds ratio = 0.15,
95% CrI 0.04-0.55) were associated with a reduction in mortality when compared to
total intravenous anesthesia. Posterior distribution of the probability of each
treatment to be the best one, showed that the association of volatile anesthetic
and remote ischemic preconditioning is the best treatment to improve short- and
long-term survival after cardiac surgery, suggesting an additive effect of these
two strategies.
CONCLUSIONS: In patients undergoing cardiac surgery, the use of volatile
anesthetics and the combination of volatile agents with remote preconditioning
reduce mortality when compared to TIVA and have additive effects. It is necessary
to confirm these results with large, multicenter, randomized, double-blinded
trials comparing these different strategies in cardiac and non-cardiac surgery,
to establish which volatile agent is more protective than the others and how to
best apply remote ischemic preconditioning.

DOI: 10.1371/journal.pone.0134264
PMCID: PMC4521933
PMID: 26231003  [Indexed for MEDLINE]


275. PLoS One. 2015 Jul 22;10(7):e0132505. doi: 10.1371/journal.pone.0132505.
eCollection 2015.

Projection of Diabetes Population Size and Associated Economic Burden through
2030 in Iran: Evidence from Micro-Simulation Markov Model and Bayesian
Meta-Analysis.

Javanbakht M(1), Mashayekhi A(2), Baradaran HR(2), Haghdoost A(3), Afshin A(4).

Author information:
(1)Health Economics Research Unit, Institute of Applied Health Sciences,
University of Aberdeen, Aberdeen, United Kingdom.
(2)Endocrine Research Center, Institute of Endocrinology & Metabolism, Iran
University of Medical Sciences, Tehran, Iran.
(3)Kerman University of Medical Sciences, Kerman, Iran.
(4)Friedman School of Nutrition Science and Policy, Tufts University, Boston,
United States of America.

BACKGROUND: The aim of this study was to estimate the economic burden of diabetes
mellitus (DM) in Iran from 2009 to 2030.
METHODS: A Markov micro-simulation (MM) model was developed to predict the DM
population size and associated economic burden. Age- and sex-specific prevalence
and incidence of diagnosed and undiagnosed DM were derived from national health
surveys. A systematic review was performed to identify the cost of diabetes in
Iran and the mean annual direct and indirect costs of patients with DM were
estimated using a random-effect Bayesian meta-analysis. Face, internal, cross and
predictive validity of the MM model were assessed by consulting an expert group,
performing sensitivity analysis (SA) and comparing model results with published
literature and national survey reports. Sensitivity analysis was also performed
to explore the effect of uncertainty in the model.
RESULTS: We estimated 3.78 million cases of DM (2.74 million diagnosed and 1.04
million undiagnosed) in Iran in 2009. This number is expected to rise to 9.24
million cases (6.73 million diagnosed and 2.50 million undiagnosed) by 2030. The
mean annual direct and indirect costs of patients with DM in 2009 were US$ 556
(posterior standard deviation, 221) and US$ 689 (619), respectively. Total
estimated annual cost of DM was $3.64 (2009 US$) billion (including US$1.71
billion direct and US$1.93 billion indirect costs) in 2009 and is predicted to
increase to $9.0 (in 2009 US$) billion (including US$4.2 billion direct and
US$4.8 billion indirect costs) by 2030.
CONCLUSIONS: The economic burden of DM in Iran is predicted to increase markedly
in the coming decades. Identification and implementation of effective strategies
to prevent and manage DM should be considered as a public health priority.

DOI: 10.1371/journal.pone.0132505
PMCID: PMC4511591
PMID: 26200913  [Indexed for MEDLINE]


276. Lancet. 2015 Jul 18;386(9990):258-65. doi: 10.1016/S0140-6736(14)61704-9. Epub
2015 May 11.

Risk of serious infection in biological treatment of patients with rheumatoid
arthritis: a systematic review and meta-analysis.

Singh JA(1), Cameron C(2), Noorbaloochi S(3), Cullis T(4), Tucker M(4),
Christensen R(5), Ghogomu ET(6), Coyle D(6), Clifford T(6), Tugwell P(6), Wells
GA(2).

Author information:
(1)Birmingham Veterans Affairs Medical Center, Birmingham, AL, USA; Division of
Clinical Immunology and Rheumatology, University of Alabama at Birmingham,
Birmingham, AL, USA; Department of Orthopedic Surgery, Mayo Clinic College of
Medicine, Rochester, MN, USA. Electronic address: jasvinder.md@gmail.com.
(2)School of Epidemiology, Public Health and Preventive Medicine, University of
Ottawa, ON, Canada; University of Ottawa Heart Institute, Ottawa, ON, Canada.
(3)American University, Washington, DC, USA.
(4)Division of Clinical Immunology and Rheumatology, University of Alabama at
Birmingham, Birmingham, AL, USA.
(5)Musculoskeletal Statistics Unit, The Parker Institute, Department of
Rheumatology, Copenhagen University Hospitals, Bispebjerg and Frederiksberg,
Denmark.
(6)School of Epidemiology, Public Health and Preventive Medicine, University of
Ottawa, ON, Canada.

Comment in
    Lancet. 2015 Jul 18;386(9990):224-5.
    Ann Intern Med. 2015 Oct 20;163(8):JC5.
    Internist (Berl). 2016 Mar;57(3):298-300.

BACKGROUND: Serious infections are a major concern for patients considering
treatments for rheumatoid arthritis. Evidence is inconsistent as to whether
biological drugs are associated with an increased risk of serious infection
compared with traditional disease-modifying antirheumatic drugs (DMARDs). We did
a systematic review and meta-analysis of serious infections in patients treated
with biological drugs compared with those treated with traditional DMARDs.
METHODS: We did a systematic literature search with Medline, Embase, Cochrane
Central Register of Controlled Trials, and ClinicalTrials.gov from their
inception to Feb 11, 2014. Search terms included "biologics", "rheumatoid
arthritis" and their synonyms. Trials were eligible for inclusion if they
included any of the approved biological drugs and reported serious infections. We
assessed the risk of bias with the Cochrane Risk of Bias Tool. We did a Bayesian
network meta-analysis of published trials using a binomial likelihood model to
assess the risk of serious infections in patients with rheumatoid arthritis who
were treated with biological drugs, compared with those treated with traditional
DMARDs. The odds ratio (OR) of serious infection was the primary measure of
treatment effect and calculated 95% credible intervals using Markov Chain Monte
Carlo methods.
FINDINGS: The systematic review identified 106 trials that reported serious
infections and included patients with rheumatoid arthritis who received
biological drugs. Compared with traditional DMARDs, standard-dose biological
drugs (OR 1.31, 95% credible interval [CrI] 1.09-1.58) and high-dose biological
drugs (1.90, 1.50-2.39) were associated with an increased risk of serious
infections, although low-dose biological drugs (0.93, 0.65-1.33) were not. The
risk was lower in patients who were methotrexate naive compared with traditional
DMARD-experienced or anti-tumour necrosis factor biological drug-experienced
patients. The absolute increase in the number of serious infections per 1000
patients treated each year ranged from six for standard-dose biological drugs to
55 for combination biological therapy, compared with traditional DMARDs.
INTERPRETATION: Standard-dose and high-dose biological drugs (with or without
traditional DMARDs) are associated with an increase in serious infections in
rheumatoid arthritis compared with traditional DMARDs, although low-dose
biological drugs are not. Clinicians should discuss the balance between benefit
and harm with the individual patient before starting biological treatment for
rheumatoid arthritis.
FUNDING: Rheumatology Division at the University of Alabama at Birmingham.

Copyright © 2015 Elsevier Ltd. All rights reserved.

DOI: 10.1016/S0140-6736(14)61704-9
PMCID: PMC4580232
PMID: 25975452  [Indexed for MEDLINE]


277. Am J Ophthalmol. 2015 Jul;160(1):85-93.e3. doi: 10.1016/j.ajo.2015.04.003. Epub
2015 Apr 6.

Incidence of Late-Stage Age-Related Macular Degeneration in American Whites:
Systematic Review and Meta-analysis.

Rudnicka AR(1), Kapetanakis VV(2), Jarrar Z(2), Wathern AK(2), Wormald R(3),
Fletcher AE(4), Cook DG(2), Owen CG(2).

Author information:
(1)Population Health Research Institute, St George's, University of London,
London, United Kingdom. Electronic address: arudnick@sgul.ac.uk.
(2)Population Health Research Institute, St George's, University of London,
London, United Kingdom.
(3)London School of Hygiene & Tropical Medicine, London, United Kingdom; NIHR
Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital, London,
United Kingdom.
(4)London School of Hygiene & Tropical Medicine, London, United Kingdom.

PURPOSE: To estimate incidence of age-related macular degeneration (AMD) by
subtype in American whites aged ≥50 years.
DESIGN: Systematic review and meta-analysis.
METHODS:
SETTING: Prospective cohort studies of AMD incidence in populations of white
European ancestry published in MEDLINE, EMBASE, and Web of Science.
STUDY POPULATION: Fourteen publications in 10 populations that examined AMD
incident cases were identified.
OBSERVATION PROCEDURE: Data on age-sex-specific incidence of late AMD, geographic
atrophy (GA) and neovascular AMD (NVAMD), year of recruitment, AMD grading
method, and continent were extracted.
MAIN OUTCOME MEASURE(S): Annual incidence of late AMD, GA, and NVAMD by age-sex
in American whites aged ≥50 years from a Bayesian meta-analysis of incidence
studies was compared with incidence extrapolated from published prevalence
estimates.
RESULTS: Incidence rates from the review agreed with those derived from
prevalence, but the latter were based on more data, especially at older ages and
by AMD subtypes. Annual incidence (estimated from prevalence) of late AMD in
American whites was 3.5 per 1000 aged ≥50 years (95% credible interval 2.5, 4.7
per 1000), equivalent to 293 000 new cases in American whites per year (95%
credible interval 207 000, 400 000). Incidence rates approximately quadrupled per
decade in age. Annual incidence GA rates were 1.9 per 1000 aged ≥50 years, NVAMD
rates were 1.8 per 1000. Late AMD incidence was 38% higher in women vs men (95%
credible interval 6%, 82%).
CONCLUSIONS: Estimating AMD incidence from prevalence allows better
characterization at older ages and by AMD subtype where longitudinal data from
incidence studies are limited.

Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.ajo.2015.04.003
PMID: 25857680  [Indexed for MEDLINE]


278. Dis Colon Rectum. 2015 Jul;58(7):698-707. doi: 10.1097/DCR.0000000000000375.

Oral Mechanical Bowel Preparation for Colorectal Surgery: Systematic Review and
Meta-Analysis.

Dahabreh IJ(1), Steele DW, Shah N, Trikalinos TA.

Author information:
(1)1 Center for Evidence-Based Medicine, School of Public Health, Brown
University, Providence, Rhode Island 2 Department of Health Services, Policy, and
Practice, School of Public Health, Brown University, Providence, Rhode Island 3
Departments of Emergency Medicine and Pediatrics, Alpert Medical School, Brown
University, Providence, Rhode Island 4 Department of Surgery, Alpert Medical
School, Brown University, Providence, Rhode Island.

Comment in
    Dis Colon Rectum. 2016 Aug;59(8):e421.

BACKGROUND: Oral mechanical bowel preparation is often used before elective
colorectal surgery to reduce postoperative complications.
OBJECTIVE: The purpose of this study was to synthesize the evidence on the
comparative effectiveness and safety of oral mechanical bowel preparation versus
no preparation or enema.
DATA SOURCES: We searched MEDLINE, the Cochrane Central Register of Controlled
Trials, Embase, and CINAHL without any language restrictions (last search on
September 6, 2013). We also searched the US Food and Drug Administration Web site
and ClinicalTrials.gov and supplemented our searches by asking technical experts
and perusing reference lists.
STUDY SELECTION: We included English-language, full-text reports of randomized
clinical trials and nonrandomized comparative studies of patients undergoing
elective colon or rectal surgery. For adverse events we also included
single-group cohort studies of at least 200 participants.
INTERVENTIONS: Interventions included oral mechanical bowel preparation, oral
mechanical bowel preparation plus enema, enema only, and no oral mechanical bowel
preparation or enema.
MAIN OUTCOME MEASURES: Anastomotic leakage, all-cause mortality, wound infection,
peritonitis/intra-abdominal abscess, reoperation, surgical site infection,
quality of life, length of stay, and adverse events were measured. We synthesized
results across studies qualitatively and with Bayesian random-effects
meta-analyses.
RESULTS: A total of 18 randomized clinical trials, 7 nonrandomized comparative
studies, and 6 single-group cohorts were included. In meta-analyses of randomized
clinical trials, the credibility intervals of the summary OR included the null
value of 1.0 for comparisons of oral mechanical bowel preparation and either no
oral preparation or enema for overall mortality, anastomotic leakage, wound
infection, peritonitis, surgical site infection, and reoperation. These results
were robust to extensive sensitivity analyses. Evidence on adverse events was
sparse.
LIMITATIONS: The study was limited by weaknesses in the underlying evidence, such
as incomplete reporting of relevant information, exclusion of non-English and
relevant unpublished studies, and possible missed indexing of nonrandomized
studies.
CONCLUSIONS: Our results could not exclude modest beneficial or harmful effects
of oral mechanical bowel preparation compared with no preparation or enema.

DOI: 10.1097/DCR.0000000000000375
PMID: 26200685  [Indexed for MEDLINE]


279. Headache. 2015 Jul-Aug;55 Suppl 4:221-35. doi: 10.1111/head.12601. Epub 2015 Jul
14.

Triptans in the Acute Treatment of Migraine: A Systematic Review and Network
Meta-Analysis.

Cameron C(1)(2), Kelly S(2), Hsieh SC(2), Murphy M(2), Chen L(2), Kotb A(2),
Peterson J(2), Coyle D(1), Skidmore B(2), Gomes T(3), Clifford T(1)(4), Wells
G(1)(2).

Author information:
(1)School of Epidemiology, Public Health and Preventive Medicine, University of
Ottawa, Ottawa, Canada.
(2)University of Ottawa Heart Institute, Ottawa, Canada.
(3)Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael's
Hospital, Toronto, Canada.
(4)CADTH, Ottawa, Canada.

BACKGROUND: Although triptans are widely used in the acute management of
migraine, there is uncertainty around the comparative efficacy of triptans among
each other and vs non-triptan migraine treatments. We conducted systematic
reviews and network meta-analyses to compare the relative efficacy of triptans
(alone or in combination with other drugs) for acute treatment of migraines
compared with other triptan agents, non-steroidal anti-inflammatory drugs
(NSAIDs), acetylsalicylic acid (ASA), acetaminophen, ergots, opioids, or
anti-emetics.
METHODS: The Cochrane Library, MEDLINE, and EMBASE were searched for randomized
controlled trials that compared triptans (alone or in combination with other
drugs) with placebo-controlled or active migraine treatments. Study selection,
data extraction, and quality assessment were completed independently by multiple
reviewers. Outcome data were combined and analyzed using a Bayesian network
meta-analysis. For each outcome, odds ratios, relative risks, and absolute
probability of response were calculated.
RESULTS: A total of 133 randomized controlled trials met the inclusion criteria.
Standard dose triptans relieved headaches within 2 hours in 42 to 76% of
patients, and 2-hour sustained freedom from pain was achieved for 18 to 50% of
patients. Standard dose triptans provided sustained headache relief at 24 hours
in 29 to 50% of patients, and sustained freedom from pain in 18 to 33% of
patients. Use of rescue medications ranged from 20 to 34%. For 2-hour headache
relief, standard dose triptan achieved better outcomes (42 to 76% response) than
ergots (38%); equal or better outcomes than NSAIDs, ASA, and acetaminophen (46 to
52%); and equal or slightly worse outcomes than combination therapy (62 to 80%).
Among individual triptans, sumatriptan subcutaneous injection, rizatriptan ODT,
zolmitriptan ODT, and eletriptan tablets were associated with the most favorable
outcomes.
INTERPRETATION/CONCLUSIONS: Triptans are effective for migraine relief. Standard
dose triptans are associated with better outcomes than ergots, and most triptans
are associated with equal or better outcomes compared with NSAIDs, ASA, and
acetaminophen. Use of triptans in combination with ASA or acetaminophen, or using
alternative modes of administration such as injectables, may be associated with
slightly better outcomes than standard dose triptan tablets.

© 2015 American Headache Society.

DOI: 10.1111/head.12601
PMID: 26178694  [Indexed for MEDLINE]


280. J Clin Periodontol. 2015 Jul;42(7):647-57. doi: 10.1111/jcpe.12427.

Systemic antibiotics in the treatment of aggressive periodontitis. A systematic
review and a Bayesian Network meta-analysis.

Rabelo CC(1), Feres M(2), Gonçalves C(2), Figueiredo LC(2), Faveri M(2), Tu
YK(3), Chambrone L(4)(5).

Author information:
(1)Division of Periodontics, Federal University of Juiz de Fora (UFJF),
Governador Valadares, MG, Brazil.
(2)Dental Research Division, Department of Periodontology, Guarulhos University,
Guarulhos, SP, Brazil.
(3)Institute of Epidemiology & Preventive Medicine, College of Public Health,
National Taiwan University, Taipei, Taiwan.
(4)Department of Periodontics, College of Dentistry, The University of Iowa, Iowa
City, IA, USA.
(5)Unit of Basic Oral Investigation (UIBO), School of Dentistry, El Bosque
University, Bogota, Colombia.

Comment in
    Evid Based Dent. 2016 Dec;17 (4):100.

AIM: The aim of this study was to assess the effect of systemic antibiotic
therapy on the treatment of aggressive periodontitis (AgP).
METHODS: This study was conducted and reported in accordance with the PRISMA
statement. The MEDLINE, EMBASE and CENTRAL databases were searched up to June
2014 for randomized clinical trials comparing the treatment of subjects with AgP
with either scaling and root planing (SRP) alone or associated with systemic
antibiotics. Bayesian network meta-analysis was prepared using the Bayesian
random-effects hierarchical models and the outcomes reported at 6-month
post-treatment.
RESULTS: Out of 350 papers identified, 14 studies were eligible. Greater gain in
clinical attachment (CA) (mean difference [MD]: 1.08 mm; p < 0.0001) and
reduction in probing depth (PD) (MD: 1.05 mm; p < 0.00001) were observed for SRP
+ metronidazole (Mtz), and for SRP + Mtz + amoxicillin (Amx) (MD: 0.45 mm, MD:
0.53 mm, respectively; p < 0.00001) than SRP alone/placebo. Bayesian network
meta-analysis showed additional benefits in CA gain and PD reduction when SRP was
associated with systemic antibiotics.
CONCLUSIONS: SRP plus systemic antibiotics led to an additional clinical effect
compared with SRP alone in the treatment of AgP. Of the antibiotic protocols
available for inclusion into the Bayesian network meta-analysis, Mtz and Mtz/Amx
provided to the most beneficial outcomes.

© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

DOI: 10.1111/jcpe.12427
PMID: 26087839  [Indexed for MEDLINE]


281. Medicine (Baltimore). 2015 Jul;94(29):e1225. doi: 10.1097/MD.0000000000001225.

Immunonutrition Support for Patients Undergoing Surgery for Gastrointestinal
Malignancy: Preoperative, Postoperative, or Perioperative? A Bayesian Network
Meta-Analysis of Randomized Controlled Trials.

Song GM(1), Tian X, Zhang L, Ou YX, Yi LJ, Shuai T, Zhou JG, Zeng Z, Yang HL.

Author information:
(1)Form the Department of Nursing (G-MS), Tianjin Hospital, Tianjin; Graduate
College (XT, LZ, Y-XO, L-JY, TS, ZZ), Tianjin University of Traditional Chinese
Medicine, Tianjin; Department of Oncology (J-GZ), Affiliated Hospital of Zunyi
Medical University, Zunyi; and Acupuncture & Moxibustion Department (H-LY), First
Teaching Hospital affiliated Tianjin University of Traditional Chinese Medicine,
Tianjin, China.

Enteral immunonutrition (EIN) has been established to be as a significantly
important modality to prevent the postoperative infectious and noninfectious
complications, enhance the immunity of host, and eventually improve the prognosis
of gastrointestinal (GI) cancer patients undergoing surgery. However, different
support routes, which are the optimum option, remain unclear. To evaluate the
effects of different EIN support regimes for patients who underwent selective
surgery for resectable GI malignancy, a Bayesian network meta-analysis (NMA) of
randomized controlled trials (RCTs) was conducted. A search of PubMed, EMBASE,
and the Cochrane Central Register of Controlled Trials (CENTRAL) was
electronically searched until the end of December 2014. Moreover, we manually
checked reference lists of eligible trials and review and retrieval unpublished
literature. RCTs which investigated the comparative effects of EIN versus
standard enteral nutrition (EN) or different EIN regimes were included if the
clinical outcomes information can be extracted from it. A total of 27 RCTs were
incorporated into this study. Pair-wise meta-analyses suggested that preoperative
(relative risk [RR], 0.58; 95% confidence interval [CI], 0.43-0.78),
postoperative (RR, 0.63; 95% CI, 0.52-0.76), and perioperative EIN methods (RR,
0.46; 95% CI, 0.34-0.62) reduced incidence of postoperative infectious
complications compared with standard EN. Moreover, perioperative EIN (RR, 0.65;
95% CI, 0.44-0.95) reduced the incidence of postoperative noninfectious
complications, and the postoperative (mean difference [MD], -2.38; 95% CI, -3.4
to -1.31) and perioperative EIN (MD, -2.64; 95% CI, -3.28 to -1.99) also
shortened the length of postoperative hospitalization compared with standard EN.
NMA found that EIN support effectively improved the clinical outcomes of patients
who underwent selective surgery for GI cancer compared with standard EN. Our
results suggest EIN support is promising alternative for operation management in
comparison with standard EN, and perioperative EIN regime is the optimum option
for managing clinical status of patients who underwent selective surgery for GI
cancer.

DOI: 10.1097/MD.0000000000001225
PMCID: PMC4602990
PMID: 26200648  [Indexed for MEDLINE]


282. Medicine (Baltimore). 2015 Jul;94(28):e1089. doi: 10.1097/MD.0000000000001089.

A Systematic Review and Meta-Analysis of Medical Students' Perspectives on the
Engagement in Research.

Naing C(1), Wai VN, Durham J, Whittaker MA, Win NN, Aung K, Mak JW.

Author information:
(1)From the Institute for Research, Development and Innovation (IRDI) (CN, JWM),
International Medical University (IMU), Kuala Lumpur, Malaysia; School of
Medicine (VNW, KA), International Medical University (IMU), Kuala Lumpur,
Malaysia; School of Public Health (JD, MAW), University of Queensland, Brisbane,
Australia; and School of Health Sciences (NNW), International Medical University
(IMU), Kuala Lumpur, Malaysia.

Engaging students in active learning lies at the center of effective higher
education. In medical schools, students' engagement in learning and research has
come under increasing attention. The objective of this study was to synthesize
evidence on medical students' perspectives on the engagement in research. We
performed a systematic review and meta-analysis. Relevant studies were searched
in electronic databases. The methodological quality of the included studies was
assessed. Overall, 14 observational studies (with 17 data sets) were included. In
general, many studies did not use the same questionnaires and the outcome
measurements were not consistently reported; these presented some difficulties in
pooling the results. Whenever data permitted, we performed pooled analysis for
the 4 education outcomes. A Bayesian meta-analytical approach was supplemented as
a measure of uncertainty. A pooled analysis showed that 74% (95% confidence
interval [CI]: 1.57%-11.07%; I2: 95.2%) of those students who engaged in research
(while at the medical school) had positive attitudes toward their research
experiences, whereas 49.5% (95% CI: 36.4%-62.7%; I2: 93.4%) had positive
attitudes toward the study of medical sciences, 62.3% (95% CI: 46.7%-77.9%; I2:
96.3%) had self-reported changes in their practices, and 64% (95% CI:
30.8%-96.6%; I2: 98.5%) could have published their work. There was substantial
heterogeneity among studies. We acknowledged the caveats and the merit of the
current review. Findings showed that engagement in research resulted in favorable
reactions toward research and academic learning. Future well-designed studies
using standardized research tools on how to engage students in research are
recommended.

DOI: 10.1097/MD.0000000000001089
PMCID: PMC4617066
PMID: 26181541  [Indexed for MEDLINE]


283. Thromb Haemost. 2015 Jul;114(1):56-64. doi: 10.1160/TH14-10-0882. Epub 2015 May
28.

Evaluation of safety and effectiveness of factor VIII treatment in haemophilia A
patients with low titre inhibitors or a personal history of inhibitor. Patient
Data Meta-analysis of rAFH-PFM Post-Authorization Safety Studies.

Romanov V, Marcucci M, Cheng J, Thabane L, Iorio A(1).

Author information:
(1)Alfonso Iorio, MD, PhD, FRCP(C), HIRUCRL-140, Clinical Epidemiology and
Biostatistics, McMaster University, Hamilton, ON, Canada, Tel.: +1 905 525 9140
ext 22421, E-mail: iorioa@mcmaster.ca.

There is no prospective evidence on inhibitor recurrence among haemophilia A
patients with low titre inhibitors or history of inhibitors, and whether or how
therapeutic choices affect the risk of recurrence. The aims of this study were to
synthesise safety data in patients with moderate-severe haemophilia A and with
low titre inhibitors or inhibitor history enrolled in the rAHF PFM (ADVATE) -
Post-Authorization Safety Studies (ADVATE-PASS) international programme. The
study was conducted in clinics participating to the ADVATE PASS programme. The
patient population consisted of patients entering the studies with low titre (≤ 5
BU) inhibitors or a positive personal history of inhibitors. Patients on Immune
Tolerance Induction at study entry were excluded. Primary outcome was new or
recurrent inhibitor titre > 5 BU. Secondary outcomes were any increase of
inhibitor titre not reaching 5 BU; any unexplained change in treatment regimen.
Primary analysis was done by two-stage random effects meta-analysis. Secondary
analysis was done by a hierarchical Bayesian random effects logistic model. A
total of 219 patients from seven studies were included. Of these 214 (97.7 %)
patients had been previously treated for more than 50 exposure days. Two hundred
ten patients had positive history for inhibitors, nine a baseline measurable
titre. No patient presented a primary outcome event (95 % confidence interval
[CI] 0-1.6 %). Six patients with previous history developed a low titre
recurrence (overall rate 2.2, 95 %CI 0-4.8 %). When any increase of inhibitor
titre or any treatment change was accounted for, overall 3.7 % (95 % CI
0 %-8.0 %) of patients experienced the outcome. In conclusion, the observed rate
of events does not support the definition of this population as at high risk for
inhibitor development.

DOI: 10.1160/TH14-10-0882
PMID: 26017627  [Indexed for MEDLINE]


284. BMC Infect Dis. 2015 Jun 30;15:249. doi: 10.1186/s12879-015-0961-5.

The effect of sexually transmitted co-infections on HIV viral load amongst
individuals on antiretroviral therapy: a systematic review and meta-analysis.

Champredon D(1), Bellan SE(2), Delva W(3)(4), Hunt S(5), Shi CF(5), Smieja M(5),
Dushoff J(5).

Author information:
(1)McMaster University, Hamilton, ON, Canada, Austin, TX, USA.
david.champredon@gmail.com.
(2)Center for Computational Biology and Bioinformatics, The University of Texas
at Austin, Austin, TX, USA.
(3)The South African DST/NRF Centre of Excellence in Epidemiological Modelling
and Analysis (SACEMA), University of Stellenbosch, Stellenbosch, South Africa.
(4)International Centre for Reproductive Health (ICRH), Ghent University, Ghent,
Belgium.
(5)McMaster University, Hamilton, ON, Canada, Austin, TX, USA.

BACKGROUND: Antiretroviral therapy (ART) markedly reduces HIV transmission, and
testing and treatment programs have been advocated as a method for decreasing
transmission at the population level. Little is known, however, about the extent
to which sexually transmitted infections (STIs), which increase the HIV
infectiousness of untreated individuals, may decrease the effectiveness of
treatment as prevention.
METHODS: We searched major bibliographic databases to August 12(th), 2014 and
identified studies reporting differences in HIV transmission rate or in viral
load between individuals on ART who either were or were not co-infected with
another STI. We used hierarchical Bayesian models to estimate viral load
differences between individuals with and without STI co-infections.
RESULTS: The search strategy retrieved 1630 unique citations of which 14 studies
(reporting on 4607 HIV viral load measurements from 2835 unique individuals) met
the inclusion criteria. We did not find any suitable studies that estimated
transmission rates directly in both groups. Our meta-analysis of HIV viral load
measurements among treated individuals did not find a statistically significant
effect of STI co-infection; viral loads were, on average, 0.11 log10 (95% CI
-0.62 to 0.83) higher among co-infected versus non-co-infected individuals.
CONCLUSIONS: Direct evidence about the effects of STI co-infection on
transmission from individuals on ART is very limited. Available data suggests
that the average effect of STI co-infection on HIV viral load in individuals on
ART is less than 1 log10 difference, and thus unlikely to decrease the
effectiveness of treatment as prevention. However, there is not enough data to
rule out the possibility that particular STIs pose a larger threat.

DOI: 10.1186/s12879-015-0961-5
PMCID: PMC4486691
PMID: 26123030  [Indexed for MEDLINE]


285. Lancet. 2015 Jun 13;385(9985):2371-82. doi: 10.1016/S0140-6736(15)60263-X. Epub
2015 Mar 14.

Mortality in patients treated with extended duration dual antiplatelet therapy
after drug-eluting stent implantation: a pairwise and Bayesian network
meta-analysis of randomised trials.

Palmerini T(1), Benedetto U(2), Bacchi-Reggiani L(1), Della Riva D(1),
Biondi-Zoccai G(3), Feres F(4), Abizaid A(4), Hong MK(5), Kim BK(5), Jang Y(5),
Kim HS(6), Park KW(6), Genereux P(7), Bhatt DL(8), Orlandi C(1), De Servi S(9),
Petrou M(2), Rapezzi C(1), Stone GW(10).

Author information:
(1)Dipartimento Cardio-Toraco-Vascolare, University of Bologna, Italy.
(2)Oxford Heart Center, Oxford University, Oxford, UK.
(3)Department of Medico-Surgical Sciences and Biotechnologies, Sapienza
University of Rome, Latina, Italy.
(4)Istituto Dante Pazzanese de Cardiologia, Sao Paulo, Brazil.
(5)Severance Cardiovascular Hospital and Science Institute, Yonsei University
College of Medicine, Seoul, Korea.
(6)Department of Internal Medicine, Seoul National University Hospital, Seoul,
Korea.
(7)Columbia University Medical Center/New York-Presbyterian Hospital and the
Cardiovascular Research Foundation, New York, NY, USA; Hôpital du Sacré-Coeur de
Montréal, Montréal, Québec, Canada.
(8)Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical
School, Boston, MA, USA.
(9)Policlinico S Matteo, Pavia, Italy.
(10)Columbia University Medical Center/New York-Presbyterian Hospital and the
Cardiovascular Research Foundation, New York, NY, USA. Electronic address:
gs2184@columbia.edu.

Comment in
    Lancet. 2015 Jun 13;385(9985):2332-3.
    Lancet. 2015 Oct 17;386(10003):1533-4.
    Lancet. 2015 Oct 17;386(10003):1534-5.
    Ann Intern Med. 2015 Jul 21;163(2):JC2, JC3.
    Lancet. 2015 Oct 17;386(10003):1535.

BACKGROUND: Despite recent studies, the optimum duration of dual antiplatelet
therapy (DAPT) after coronary drug-eluting stent placement remains uncertain. We
performed a meta-analysis with several analytical approaches to investigate
mortality and other clinical outcomes with different DAPT strategies.
METHODS: We searched Medline, Embase, Cochrane databases, and proceedings of
international meetings on Nov 20, 2014, for randomised controlled trials
comparing different DAPT durations after drug-eluting stent implantation. We
extracted study design, inclusion and exclusion criteria, sample characteristics,
and clinical outcomes. DAPT duration was categorised in each study as shorter
versus longer, and as 6 months or shorter versus 1 year versus longer than 1
year. Analyses were done by both frequentist and Bayesian approaches.
FINDINGS: We identified ten trials published between Dec 16, 2011, and Nov 16,
2014, including 31,666 randomly assigned patients. By frequentist pairwise
meta-analysis, shorter DAPT was associated with significantly lower all-cause
mortality compared with longer DAPT (HR 0·82, 95% CI 0·69-0·98; p=0·02; number
needed to treat [NNT]=325), with no significant heterogeneity apparent across
trials. The reduced mortality with shorter compared with longer DAPT was
attributable to lower non-cardiac mortality (0·67, 0·51-0·89; p=0·006; NNT=347),
with similar cardiac mortality (0·93, 0·73-1·17; p=0.52). Shorter DAPT was also
associated with a lower risk of major bleeding, but a higher risk of myocardial
infarction and stent thrombosis. We noted similar results in a Bayesian framework
with non-informative priors. By network meta-analysis, patients treated with
6-month or shorter DAPT and 1-year DAPT had higher risk of myocardial infarction
and stent thrombosis but lower risk of mortality compared with patients treated
with DAPT for longer than 1 year. Patients treated with DAPT for 6 months or
shorter had similar rates of mortality, myocardial infarction, and stent
thrombosis, but lower rates of major bleeding than did patients treated with
1-year DAPT.
INTERPRETATION: Although treatment with DAPT beyond 1 year after drug-eluting
stent implantation reduces myocardial infarction and stent thrombosis, it is
associated with increased mortality because of an increased risk of
non-cardiovascular mortality not offset by a reduction in cardiac mortality.
FUNDING: None.

Copyright © 2015 Elsevier Ltd. All rights reserved.

DOI: 10.1016/S0140-6736(15)60263-X
PMID: 25777667  [Indexed for MEDLINE]


286. Genet Sel Evol. 2015 Jun 12;47:47. doi: 10.1186/s12711-015-0126-4.

Genome-wide association study for calving performance using high-density
genotypes in dairy and beef cattle.

Purfield DC(1)(2), Bradley DG(3), Evans RD(4), Kearney FJ(5), Berry DP(6).

Author information:
(1)Smurfit Institute of Genetics, University of Dublin, Trinity College, Dublin
2, Ireland. Deirdre.purfield@teagasc.ie.
(2)Animal & Grassland Research and Innovation Center, Teagasc, Moorepark, Fermoy,
Co. Cork, Ireland. Deirdre.purfield@teagasc.ie.
(3)Smurfit Institute of Genetics, University of Dublin, Trinity College, Dublin
2, Ireland. dbradley@tcd.ie.
(4)Irish Cattle Breeding Federation, Bandon, Co. Cork, Ireland. revans@icbf.com.
(5)Irish Cattle Breeding Federation, Bandon, Co. Cork, Ireland.
fkearney@icbf.com.
(6)Animal & Grassland Research and Innovation Center, Teagasc, Moorepark, Fermoy,
Co. Cork, Ireland. Donagh.Berry@teagasc.ie.

BACKGROUND: Calving difficulty and perinatal mortality are prevalent in
modern-day cattle production systems. It is well-established that there is a
genetic component to both traits, yet little is known about their underlying
genomic architecture, particularly in beef breeds. Therefore, we performed a
genome-wide association study using high-density genotypes to elucidate the
genomic architecture of these traits and to identify regions of the bovine genome
associated with them.
RESULTS: Genomic regions associated with calving difficulty (direct and maternal)
and perinatal mortality were detected using two statistical approaches: (1)
single-SNP (single nucleotide polymorphism) regression and (2) a Bayesian
approach. Data included high-density genotypes on 770 Holstein-Friesian, 927
Charolais and 963 Limousin bulls. Several novel or previously identified genomic
regions were detected but associations differed by breed. For example, two
genomic associations, one each on chromosomes 18 and 2 explained 2.49 % and 3.13
% of the genetic variance in direct calving difficulty in the Holstein-Friesian
and Charolais populations, respectively. Imputed Holstein-Friesian sequence data
was used to refine the genomic regions responsible for significant associations.
Several candidate genes on chromosome 18 were identified and four highly
significant missense variants were detected within three of these genes
(SIGLEC12, CTU1, and ZNF615). Nevertheless, only CTU1 contained a missense
variant with a putative impact on direct calving difficulty based on SIFT (0.06)
and Polyphen (0.95) scores. Using imputed sequence data, we refined a genomic
region on chromosome 4 associated with maternal calving difficulty in the
Holstein-Friesian population and found the strongest association with an intronic
variant in the PCLO gene. A meta-analysis was performed across the three breeds
for each calving performance trait to identify common variants associated with
these traits in the three breeds. Our results suggest that a portion of the
genetic variation in calving performance is common to all three breeds.
CONCLUSION: The genomic architecture of calving performance is complex and mainly
influenced by many polymorphisms of small effect. We identified several
associations of moderate effect size but the majority were breed-specific,
indicating that breed-specific alleles exist for calving performance or that the
linkage phase between genotyped allele and causal mutation varies between breeds.

DOI: 10.1186/s12711-015-0126-4
PMCID: PMC4464877
PMID: 26065883  [Indexed for MEDLINE]


287. BMJ Open. 2015 Jun 5;5(6):e007527. doi: 10.1136/bmjopen-2014-007527.

Comparative efficacy and safety of approved treatments for macular oedema
secondary to branch retinal vein occlusion: a network meta-analysis.

Regnier SA(1), Larsen M(2), Bezlyak V(1), Allen F(3).

Author information:
(1)Novartis Pharma AG, Basel, Switzerland.
(2)Department of Ophthalmology, Glostrup Hospital, University of Copenhagen,
Glostrup, Denmark.
(3)Novartis Pharmaceuticals UK Ltd., Frimley, Camberley, Surrey, UK.

OBJECTIVE: To compare the efficacy and safety of approved treatments for macular
oedema secondary to branch retinal vein occlusion (BRVO).
DESIGN: Randomised controlled trials (RCTs) evaluating the efficacy and safety of
approved treatments for macular oedema secondary to BRVO were identified from an
updated systematic review.
SETTING: A Bayesian network meta-analysis of RCTs of treatments for macular
oedema secondary to BRVO.
INTERVENTIONS: Ranibizumab 0.5 mg pro re nata, aflibercept 2 mg monthly (2q4),
dexamethasone 0.7 mg implant, laser photocoagulation, ranibizumab+laser, or sham
intervention. Bevacizumab and triamcinolone were excluded.
OUTCOME MEASURES: Efficacy outcomes were mean change in best corrected visual
acuity (Early Treatment Diabetic Retinopathy Study scale) and the percentage of
patients gaining ≥ 15 letters. Safety outcome was the percentage of patients with
increased intraocular pressure (IOP)/ocular hypertension (OH).
RESULTS: 8 RCTs were identified for inclusion with 1743 adult patients. The
probability of being the most efficacious treatment at month 6 or 12 based on
letters gained was 54% for ranibizumab monotherapy, 30% for aflibercept, 16% for
ranibizumab plus laser (adjunctive or prompt), and 0% for dexamethasone implant,
laser or sham. The probability of being the most efficacious treatment for
patients gaining ≥ 15 letters was 39% for aflibercept, 35% for ranibizumab
monotherapy, 24% for ranibizumab plus laser, 2% for dexamethasone implant, and
less than 1% for laser or sham. There was no statistical difference between
ranibizumab monotherapy and aflibercept for letters gained (+1.4 letters for
ranibizumab vs aflibercept with 95% credible interval (CrI) of -5.2 to +8.5
letters) or the OR for gaining ≥ 15 letters: 1.06 (95% CrI 0.16 to 8.94)).
Dexamethasone implant was associated with significantly higher IOP/OH than
antivascular endothelial growth factor agents (OR 13.1 (95% CrI 1.7 to 116.9)).
CONCLUSIONS: There was no statistically significant difference between
ranibizumab and aflibercept.

Published by the BMJ Publishing Group Limited. For permission to use (where not
already granted under a licence) please go to
http://group.bmj.com/group/rights-licensing/permissions.

DOI: 10.1136/bmjopen-2014-007527
PMCID: PMC4458587
PMID: 26048209  [Indexed for MEDLINE]


288. Aliment Pharmacol Ther. 2015 Jun;41(11):1055-65. doi: 10.1111/apt.13190. Epub
2015 Apr 13.

Systematic review with network meta-analysis: comparative efficacy and safety of
budesonide and mesalazine (mesalamine) for Crohn's disease.

Moja L(1), Danese S, Fiorino G, Del Giovane C, Bonovas S.

Author information:
(1)Department of Biomedical Sciences for Health, University of Milan, Milan,
Italy; Unit of Clinical Epidemiology, IRCCS Galeazzi Orthopedic Institute, Milan,
Italy.

BACKGROUND: Budesonide and mesalazine (mesalamine) are commonly used in the
medical management of patients with mild to moderate Crohn's disease.
AIM: To assess their comparative efficacy and harm using the methodology of
network meta-analysis.
METHODS: A comprehensive search of Medline, Embase, the Cochrane Library and
ClinicalTrials.gov, through October 2014, was performed to identify randomised
controlled trials (RCTs) that recruited adult patients with active or quiescent
Crohn's disease, and compared budesonide or mesalazine with placebo, or against
each other, or different dosing strategies of one drug.
RESULTS: Twenty-five RCTs were combined using Bayesian network meta-analysis.
Budesonide 9 mg/day, or at higher doses (15 or 18 mg/day), was shown superior to
placebo for induction of remission [odds ratio (OR), 2.93; 95% credible interval
(CrI), 1.52-5.39, and OR, 3.28; CrI, 1.46-7.55 respectively] and ranks at the top
of the hierarchy of the competing treatments. For maintenance of remission,
budesonide 6 mg/day demonstrated superiority over placebo (OR, 1.69; CrI,
1.05-2.75), being also at the best ranking position among all compared treatment
strategies. No other comparisons (i.e. different doses of mesalazine vs. placebo
or budesonide, for induction or maintenance of remission) reached significance.
The occurrence of withdrawals due to adverse events was not shown different
between budesonide, mesalazine and placebo, in both the induction and maintenance
phases.
CONCLUSIONS: Budesonide, at the doses of 9 mg/day, or higher, for induction of
remission in active mild or moderate Crohn's disease, and at 6 mg/day for
maintenance of remission, appears to be the best treatment choice.

© 2015 John Wiley & Sons Ltd.

DOI: 10.1111/apt.13190
PMID: 25864873  [Indexed for MEDLINE]


289. Ann Hematol. 2015 Jun;94(6):1003-9. doi: 10.1007/s00277-015-2310-6. Epub 2015 Feb
14.

First-line treatments for chronic lymphocytic leukaemia: interpreting efficacy
data by network meta-analysis.

Messori A(1), Fadda V, Maratea D, Trippoli S.

Author information:
(1)HTA Unit, ESTAV Toscana Centro, Regional Health Service, 50100, Firenze,
Italy, andrea.messori.it@gmail.com.

When multiple treatments are available, network meta-analysis can synthesize
evidence and rank relative effectiveness. We applied this approach to current
treatments for previously untreated chronic lymphocytic leukaemia. Data search
was conducted in PubMed and websites of regulatory agencies (year 2000 through
present time). Our analysis included randomized controlled trials assessing
treatments for previously untreated chronic lymphocytic leukaemia. The endpoint
of the analysis was the rate of progression-free survival at 3 years. At least
two reviewers abstracted study data and outcomes. Agents examined for their
relative effectiveness included four monotherapies (chlorambucil, fludarabine,
bendamustine, alemtuzumab) and four combination treatments (cyclophosphamide +
fludarabine, cyclophosphamide + cladribine, cyclophosphamide + fludarabine +
rituximab, cyclophosphamide + fludarabine + alemtuzumab). A Bayesian network
meta-analysis was conducted to comparatively evaluate these treatments. Nine
trials (3620 patients) were included in the analysis. Odds ratio (with 95 %
credible intervals) was estimated for all direct and indirect comparisons.
Combinations treatments were found to be significantly more effective than
single-agent treatments. Ranking in effectiveness was as follows: (1)
cyclophosphamide + fludarabine + rituximab, (2) alemtuzumab, (3) cyclophosphamide
+ fludarabine + alemtuzumab, (4) cyclophosphamide + fludarabine and (at same
ranking) cyclophosphamide + cladribine, (6) fludarabine, (7) bendamustine and (8)
chlorambucil. Bendamustine fared worse in our analysis than in its pivotal trial.
Overall, the estimated rankings appeared to be robust according to probabilistic
analysis. Numerous indirect comparisons were assessed in the absence of RCTs. In
conclusion, we generated an updated synthesis of the effectiveness of these
treatments and we ranked them according to a Bayesian probabilistic model. In our
probabilistic analysis, cyclophosphamide + fludarabine + rituximab ranked first
in the base case while the worst-case scenario of this analysis placed this
treatment at a remarkable second place.

DOI: 10.1007/s00277-015-2310-6
PMID: 25677267  [Indexed for MEDLINE]


290. J Biomol Screen. 2015 Jun;20(5):588-96. doi: 10.1177/1087057114565080. Epub 2014
Dec 30.

Large scale meta-analysis of fragment-based screening campaigns: privileged
fragments and complementary technologies.

Kutchukian PS(1), Wassermann AM(2), Lindvall MK(3), Wright SK(2), Ottl J(4),
Jacob J(2), Scheufler C(4), Marzinzik A(4), Brooijmans N(5), Glick M(6).

Author information:
(1)Novartis Institutes for BioMedical Research, Cambridge, MA, USA Current
address: Merck, Boston, MA, USA.
(2)Novartis Institutes for BioMedical Research, Cambridge, MA, USA.
(3)Novartis Institutes for BioMedical Research, Emeryville, CA, USA.
(4)Novartis Institutes for BioMedical Research, Basel, Switzerland.
(5)Novartis Institutes for BioMedical Research, Cambridge, MA, USA Current
address: Blueprint Medicines, Cambridge, MA, USA.
(6)Novartis Institutes for BioMedical Research, Cambridge, MA, USA
Peter.Kutchukian@Merck.com Meir.Glick@Novartis.com.

A first step in fragment-based drug discovery (FBDD) often entails a
fragment-based screen (FBS) to identify fragment "hits." However, the integration
of conflicting results from orthogonal screens remains a challenge. Here we
present a meta-analysis of 35 fragment-based campaigns at Novartis, which
employed a generic 1400-fragment library against diverse target families using
various biophysical and biochemical techniques. By statistically interrogating
the multidimensional FBS data, we sought to investigate three questions: (1) What
makes a fragment amenable for FBS? (2) How do hits from different fragment
screening technologies and target classes compare with each other? (3) What is
the best way to pair FBS assay technologies? In doing so, we identified
substructures that were privileged for specific target classes, as well as
fragments that were privileged for authentic activity against many targets. We
also revealed some of the discrepancies between technologies. Finally, we
uncovered a simple rule of thumb in screening strategy: when choosing two
technologies for a campaign, pairing a biochemical and biophysical screen tends
to yield the greatest coverage of authentic hits.

© 2014 Society for Laboratory Automation and Screening.

DOI: 10.1177/1087057114565080
PMID: 25550355  [Indexed for MEDLINE]


291. Obes Rev. 2015 Jun;16(6):508-17. doi: 10.1111/obr.12274. Epub 2015 Mar 18.

Intraoperative mechanical ventilation strategies for obese patients: a systematic
review and network meta-analysis.

Wang C(1), Zhao N(1), Wang W(1), Guo L(1), Guo L(1), Chi C(1), Wang X(1), Pi
X(1), Cui Y(1), Li E(1).

Author information:
(1)Department of Anesthesiology, The First Affiliated Hospital of Harbin Medical
University, Harbin, China.

Several intraoperative ventilation strategies are available for obese patients.
However, the same ventilation interventions have exhibited different effects on
PaO2 /FIO2 concerning obese patients in different trials, and the issue remains
controversial. Therefore, we conducted a network meta-analysis to identify the
optimal mechanical ventilation strategy. We searched the Cochrane Central
Register of Controlled Trials (CENTRAL) in the Cochrane Library, Embase, MEDLINE,
CINAHL and Web of Science for studies published up to June 2014, and the PaO2
/FIO2 in obese patients given different mechanical ventilation strategies was
assessed. We assessed the studies for eligibility and extracted data and then
pooled the data and used a Bayesian fixed-effect model to combine direct
comparisons with indirect evidence. Eligible studies evaluated different
ventilation strategies for obese patients and reported the intraoperative PaO2
/FIO2 ratio, atelectasis and pulmonary compliance. Thirteen randomized controlled
trials were included for network meta-analysis, including 476 patients who
received 1 of 12 ventilation strategies. Volume-controlled ventilation with
higher PEEP plus single recruitment manoeuvres (VCV + higher PEEP + single RM)
was associated with the highest PaO2 /FiO2 ratio, improving intraoperative
pulmonary compliance and reducing the incidence of intraoperative atelectasis.

© 2015 World Obesity.

DOI: 10.1111/obr.12274
PMID: 25788167  [Indexed for MEDLINE]


292. Value Health. 2015 Jun;18(4):376-86. doi: 10.1016/j.jval.2015.04.002.

The Continuing Story of the Cost-Effectiveness of Photoselective Vaporization of
the Prostate versus Transuretheral Resection of the Prostate for the Treatment of
Symptomatic Benign Prostatic Obstruction.

Thomas JA(1), Tubaro A(2), Barber N(3), Thorpe A(4), Armstrong N(5), Bachmann
A(6), Van Hout B(7).

Author information:
(1)Department of Urology, Princess of Wales Hospital, Bridgend, Wales, UK.
(2)Department of Urology, Sant'Andrea Sapienza University, Rome, Italy.
(3)Department of Urology, Frimley Park Hospital, Frimley, Camberley, Surrey, UK.
(4)Freeman Hospital Newcastle, Newcastle upon Tyne, UK.
(5)Kleijnen Systematic Reviews, York, UK.
(6)Department of Urology, University of Basel, Basel, Switzerland.
(7)School for Health and Related Research, University of Sheffield, Sheffield,
UK. Electronic address: b.a.vanhout@sheffield.ac.uk.

BACKGROUND: In 2008, a UK assessment of technologies for benign prostatic
obstruction concluded negatively about photoselective vaporization of the
prostate (PVP), and the 2010 National Institute for Health and Care Excellence
guidance caused several UK institutions to abandon PVP.
OBJECTIVE: To reassess the costs and effects of PVP versus transurethral
resection of the prostate (TURP) on the basis of most recent data.
METHODS: The same model was used as in 2008. Transition probabilities were
estimated using a Bayesian approach updating the 2008 estimates with data from
two meta-analyses and data from GOLIATH, the latest and largest trial comparing
PVP with TURP. Utility estimates were from the 2008 assessment, and estimates of
resource utilization and costs were updated. Effectiveness was measured in
quality-adjusted life-years gained, and costs are in UK pounds. The balance
between costs and effects was addressed by multivariate sensitivity analysis.
RESULTS: If the 2010 National Institute for Health and Care Excellence analysis
would have updated the cost-effectiveness analysis with figures from its own
meta-analysis, it would have estimated the change in quality-adjusted life-years
at -0.01 (95% confidence interval [CI] -0.05 to 0.01) instead of at -0.11 (95% CI
-0.31 to -0.01) as in the 2008 analysis. The GOLIATH estimate of -0.01 (95% CI
-0.07 to 0.02) strengthens the conclusion of near equivalence. Estimates of
additional costs vary from £491 (£21-£1286) in 2008 to £111 (-£315 to £595) for
2010 and to £109 (-£204 to £504) for GOLIATH. PVP becomes cost saving if more
than 32% can be carried out as a day case in the United Kingdom.
CONCLUSIONS: The available evidence indicates that PVP can be a cost-effective
alternative for TURP in a potentially broad group of patients.

Copyright © 2015 International Society for Pharmacoeconomics and Outcomes
Research (ISPOR). Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.jval.2015.04.002
PMID: 26091591  [Indexed for MEDLINE]


293. Sci Rep. 2015 May 27;5:10593. doi: 10.1038/srep10593.

Comparison between 200 mg QD and 100 mg BID oral celecoxib in the treatment of
knee or hip osteoarthritis.

Zeng C(1), Wei J(2), Li H(1), Yang T(1), Gao SG(1), Li YS(1), Xiong YL(1), Xiao
WF(1), Luo W(1), Yang TB(2), Lei GH(1).

Author information:
(1)Department of Orthopaedics, Xiangya Hospital, Central South University,
Changsha, Hunan Province, China, 410008.
(2)Department of Epidemiology and Health Statistics, School of Public Health,
Central South University, Changsha, Hunan Province, China, 410008.

This network meta-analysis aimed to investigate the effectiveness and safety of
100 mg BID and 200 mg QD oral celecoxib in the treatment of OA of the knee or
hip. PubMed, Embase and Cochrane Library were searched through from inception to
August 2014. Bayesian network meta-analysis was used to combine direct and
indirect evidences on treatment effectiveness and safety. A total of 24 RCTs
covering 11696 patients were included. For the comparison in between the two
dosage regimens, 100 mg BID oral celecoxib exhibited a greater probability to be
the preferred one either in terms of pain intensity or function at the last
follow-up time point. For total gastrointestinal (GI) adverse effects (AEs), both
of the two dosage regimens demonstrated a higher incidence compared to the
placebo group. Further analyses of GI AEs revealed that only 200 mg QD was
associated with a significantly higher risk of abdominal pain when compared with
placebo. Furthermore, 100 mg BID showed a significantly lower incidence of skin
AEs when compared with 200 mg QD and placebo. Maybe 100 mg BID should be
considered as the preferred dosage regimen in the treatment of knee or hip OA.

DOI: 10.1038/srep10593
PMCID: PMC4445037
PMID: 26012738  [Indexed for MEDLINE]


294. World J Gastroenterol. 2015 May 21;21(19):6044-51. doi: 10.3748/wjg.v21.i19.6044.

Infliximab is superior to other biological agents for treatment of active
ulcerative colitis: A meta-analysis.

Mei WQ(1), Hu HZ(1), Liu Y(1), Li ZC(1), Wang WG(1).

Author information:
(1)Wei-Qun Mei, Hui-Zhen Hu, Wei-Guo Wang, Department of Gastroenterology, No.
117 Hospital of PLA, Hangzhou 310021, Zhejiang Province, China.

AIM: To compare the efficacy and safety of biological agents for the treatment of
active ulcerative colitis (UC).
METHODS: PubMed, MEDLINE, EMBASE and the Cochrane library were searched to screen
relevant articles from January 1996 to August 2014. The mixed treatment
comparison meta-analysis within a Bayesian framework was performed using
WinBUGS14 software. The proportions of patients reaching clinical response,
clinical remission and mucosal healing in induction and maintenance phases were
analyzed as efficacy indicators. Serious adverse events in maintenance phase were
analyzed as safety indicators.
RESULTS: The meta-analysis results showed that biological agents achieved better
clinical response, clinical remission and mucosal healing than placebo. Indirect
comparison indicated that in induction phase, infliximab was more effective than
adalimumab in inducing clinical response (OR = 0.41, 95%CI: 0.29-0.57), clinical
remission (OR = 0.33, 95%CI: 0.19-0.56) and mucosal healing (OR = 0.33, 95%CI:
0.19-0.56), and golimumab in inducing clinical response (OR = 0.66, 95%CI:
0.39-2.33) and mucosal healing (OR = 2.15, 95%CI: 1.18-4.22). No significant
difference was found between placebo and biological agents regarding their
safety.
CONCLUSION: All biological agents were superior to placebo for UC treatment in
both induction and maintenance phases with a similar safety profile, and
infliximab had a better clinical effect than the other biological agents.

DOI: 10.3748/wjg.v21.i19.6044
PMCID: PMC4438041
PMID: 26019471  [Indexed for MEDLINE]


295. PLoS One. 2015 May 20;10(5):e0127404. doi: 10.1371/journal.pone.0127404.
eCollection 2015.

Efficacy and Safety of HER2-Targeted Agents for Breast Cancer with
HER2-Overexpression: A Network Meta-Analysis.

Yu Q(1), Zhu Z(1), Liu Y(1), Zhang J(1), Li K(1).

Author information:
(1)Department of Public Health, Shantou University Medical College, No.22 Xinling
Road, Shantou, Guangdong 515041, China.

BACKGROUND: Clinical trials of human epidermal growth factor receptor 2
(HER2)-targeted agents added to standard treatment have been efficacious for
HER2-positive (HER2+) advanced breast cancer. To our knowledge, no meta-analysis
has evaluated HER2-targeted therapy including trastuzumab emtansine (T-DM1) and
pertuzumab for HER2-positive breast caner and ranked the targeted treatments. We
performed a network meta-analysis of both direct and indirect comparisons to
evaluate the effect of adding HER2-targeted agents to standard treatment and
examined side effects.
METHODS: We performed a Bayesian-framework network meta-analysis of randomized
controlled trials to compare 6 HER2-targeted treatment regimens and 1 naïve
standard treatment (NST, without any-targeted drugs) in targeted treatment of
HER2+ breast cancer in adults. These treatment regimens were T-DM1, LC
(lapatinib), HC (trastuzumab), PEC (pertuzumab), LHC (lapatinib and trastuzumab),
and PEHC (pertuzumab and trastuzumab). The main outcomes were overall survival
and response rates. We also examined side effects of rash, LVEF (left ventricular
ejection fraction), fatigue, and gastrointestinal disorders, and performed
subgroup analysis for the different treatment regimens in metastatic or advanced
breast cancer.
RESULTS: We identified 25 articles of 21 trials, with data for 11,276
participants. T-DM1 and PEHC were more efficient drug regimens with regard to
overall survival as compared with LHC, LC, HC and PEC. The incidence of
treatment-related rash occurs more frequently in the patients who received LC
treatment regimen than PEHC and T-DM1 and HC. In subgroup analysis, T-DM1 was
associated with increased overall survival as compared with LC and HC. PEHC was
associated with increased overall response as compared with LC, HC, and NST.
CONCLUSIONS: Overall, the regimen of T-DM1 as well as pertuzumab in combination
with trastuzumab and docetaxel is efficacious with fewer side effects as compared
with other regimens, especially for advanced HER2+ breast cancer.
IMPACT: This study suggests that both T-DM1 and PEHC therapy are potentially and
equally useful treatments for HER2+ breast cancer.

DOI: 10.1371/journal.pone.0127404
PMCID: PMC4439018
PMID: 25993646  [Indexed for MEDLINE]


296. Alcohol Clin Exp Res. 2015 May;39(5):919-31. doi: 10.1111/acer.12714.

Brief motivational interventions for college student drinking may not be as
powerful as we think: an individual participant-level data meta-analysis.

Huh D(1), Mun EY, Larimer ME, White HR, Ray AE, Rhew IC, Kim SY, Jiao Y, Atkins
DC.

Author information:
(1)Department of Psychiatry and Behavioral Sciences, University of Washington,
Seattle, Washington.

BACKGROUND: For over 2 decades, brief motivational interventions (BMIs) have been
implemented on college campuses to reduce heavy drinking and related negative
consequences. Such interventions include in-person motivational interviews (MIs),
often incorporating personalized feedback (PF), and stand-alone PF interventions
delivered via mail, computer, or the Web. Both narrative and meta-analytic
reviews using aggregate data from published studies suggest at least short-term
efficacy of BMIs, although overall effect sizes have been small.
METHODS: This study was an individual participant-level data (IPD) meta-analysis
of 17 randomized clinical trials evaluating BMIs. Unlike typical meta-analysis
based on summary data, IPD meta-analysis allows for an analysis that correctly
accommodates the sampling, sample characteristics, and distributions of the
pooled data. In particular, highly skewed distributions with many zeroes are
typical for drinking outcomes, but have not been adequately accounted for in
existing studies. Data are from Project INTEGRATE, one of the largest IPD
meta-analysis projects to date in alcohol intervention research, representing
6,713 individuals each with 2 to 5 repeated measures up to 12 months
postbaseline.
RESULTS: We used Bayesian multilevel over dispersed Poisson hurdle models to
estimate intervention effects on drinks per week and peak drinking, and Gaussian
models for alcohol problems. Estimates of overall intervention effects were very
small and not statistically significant for any of the outcomes. We further
conducted post hoc comparisons of 3 intervention types (individual MI with PF, PF
only, and group MI) versus control. There was a small, statistically significant
reduction in alcohol problems among participants who received an individual MI
with PF. Short-term and long-term results were similar.
CONCLUSIONS: This study questions the efficacy and magnitude of effects of BMIs
for college drinking prevention and intervention and suggests a need for the
development of more effective intervention strategies.

Copyright © 2015 by the Research Society on Alcoholism.

DOI: 10.1111/acer.12714
PMCID: PMC4502982
PMID: 25872599  [Indexed for MEDLINE]


297. Br J Anaesth. 2015 May;114(5):746-56. doi: 10.1093/bja/aeu446. Epub 2015 Feb 4.

A Bayesian network meta-analysis on the effect of inodilatory agents on
mortality.

Greco T(1), Calabrò MG(1), Covello RD(1), Greco M(1), Pasin L(1), Morelli A(2),
Landoni G(3), Zangrillo A(1).

Author information:
(1)Department of Anaesthesiology and Intensive Care, IRCCS San Raffaele
Scientific Institute, Via Olgettina 60, Milan 20132, Italy.
(2)Department of Anaesthesiology and Intensive Care, La Sapienza University,
Rome, Italy.
(3)Department of Anaesthesiology and Intensive Care, IRCCS San Raffaele
Scientific Institute, Via Olgettina 60, Milan 20132, Italy
landoni.giovanni@hsr.it.

BACKGROUND: Inodilators are commonly used in critically ill patients, but their
effect on survival has not been properly studied to date. The objective of this
work was to conduct a network meta-analysis on the effects of inodilators on
survival in adult cardiac surgery patients, and to compare and rank drugs that
have not been adequately compared in head-to-head trials.
METHODS: Relevant studies were independently searched in BioMedCentral,
MEDLINE/PubMed, Embase, and the Cochrane Central Register of clinical trials
(updated on May 1, 2014). The criteria for inclusion were: random allocation to
treatment with at least one group receiving dobutamine, enoximone, levosimendan,
or milrinone and at least another group receiving the above inodilators or
placebo, performed in cardiac surgical patients. The endpoint was to identify
differences in mortality at longest follow-up available.
RESULTS: The 46 included trials were published between 1995 and 2014 and
randomised 2647 patients. The Bayesian network meta-analysis found that only the
use of levosimendan was associated with a decrease in mortality when compared
with placebo (posterior mean of OR=0.48, 95% CrI 0.28 to 0.80). The posterior
distribution of the probability for each inodilator to be the best and the worst
drug showed that levosimendan is the best agent to improve survival after cardiac
surgery. The sensitivity analyses performed did not produce different
interpretative result.
CONCLUSION: Levosimendan seems to be the most efficacious inodilator to improve
survival in cardiac surgery.

© The Author 2015. Published by Oxford University Press on behalf of the British
Journal of Anaesthesia. All rights reserved. For Permissions, please email:
journals.permissions@oup.com.

DOI: 10.1093/bja/aeu446
PMID: 25652947  [Indexed for MEDLINE]


298. Contemp Clin Trials. 2015 May;42:51-9. doi: 10.1016/j.cct.2015.03.005. Epub 2015
Mar 21.

A multilevel approach to network meta-analysis within a frequentist framework.

Greco T(1), Edefonti V(2), Biondi-Zoccai G(3), Decarli A(4), Gasparini M(5),
Zangrillo A(6), Landoni G(6).

Author information:
(1)Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific
Institute, Milan, Italy; Laboratorio di Statistica Medica, Biometria ed
Epidemiologia "G. A. Maccacaro", Dipartimento di Scienze Cliniche e di Comunità,
University of Milan, Milan, Italy. Electronic address: greco.teresa@hotmail.it.
(2)Laboratorio di Statistica Medica, Biometria ed Epidemiologia "G. A.
Maccacaro", Dipartimento di Scienze Cliniche e di Comunità, University of Milan,
Milan, Italy.
(3)Department of Medico-Surgical Sciences and Biotechnologies, Sapienza
University of Rome, Latina, Italy; Meta-analysis and Evidence based medicine
Training in Cardiology (METCARDIO), Ospedaletti, Italy.
(4)Laboratorio di Statistica Medica, Biometria ed Epidemiologia "G. A.
Maccacaro", Dipartimento di Scienze Cliniche e di Comunità, University of Milan,
Milan, Italy; S. C. Statistica Medica, Biometria e Bioinformatica, Fondazione
IRCSS Istituto Nazionale Tumori di Milano, Milan, Italy.
(5)Department of Mathematical Sciences "G. L. Lagrange", Politecnico di Torino,
Turin, Italy.
(6)Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific
Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.

Meta-analysis is a powerful tool to summarize knowledge. Pairwise or network
meta-analysis may be carried out with multivariate models that account for the
dependence between treatment estimates and quantify the correlation across
studies. From a different perspective, meta-analysis may be viewed as a special
case of multilevel analysis having a hierarchical data structure. Hence, we
introduce an alternative frequentist approach, called multilevel network
meta-analysis, which also allows to account for publication bias and the presence
of inconsistency. We propose our approach for a three-level data structure
set-up: arms within studies at the first level, studies within study designs at
the second level and design configuration at the third level. This strategy
differs from the traditional frequentist modeling because it works directly on an
arm-based data structure. An advantage of using multilevel analysis is its
flexibility, since it naturally allows to add further levels to the model and to
accommodate for multiple outcome variables. Moreover, multilevel modeling may be
carried out with widely available statistical programs. Finally, we compare the
results from our approach with those from a Bayesian network meta-analysis on a
binary endpoint which examines the effect on mortality of some anesthetics at the
longest follow-up available. In addition, we compare results from the Bayesian
and multilevel network meta-analysis approaches on a publicly available
"Thrombolytic drugs" database. We also provide the reader with a blueprint of SAS
codes for fitting the proposed models, although our approach does not rely on any
specific software.

Copyright © 2015 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.cct.2015.03.005
PMID: 25804722  [Indexed for MEDLINE]


299. Exp Clin Endocrinol Diabetes. 2015 May;123(5):317-22. doi:
10.1055/s-0035-1548824. Epub 2015 May 19.

Comparative Efficacy of Four Treatments in Patients with Graves' Disease: a
Network Meta-analysis.

Ren Z(1), Qin L(1), Wang JQ(1), Li Y(1), Li J(1), Zhang RG(1).

Author information:
(1)Department of Nuclear Medicine, the First Centre Hospital of Tianjin, NanKai
District, People's Republic of China.

BACKGROUND: The question of which treatment should be preferred for the treatment
of Graves' disease is debatable, and pairwise meta-analyses could not obtain
hierarchies of these treatments. Our intention was to integrate the evidence to
provide hierarchies of the comparative efficacy of 4 treatments (radioiodine,
radioiodine+prednisone, antithyroid drugs and surgery).
METHODS: We conducted a Bayesian-framework network meta-analysis of randomized
controlled trials (RCTs) to compare 4 treatments in patients with Graves'
disease. The eligible RCTs were identified by searching Amed, the British Nursing
Index, Embase, PubMed, the Cochrane Central Register of Controlled Trials
(CENTRAL), Google scholar, SIGLE, the National Technical Information Service, the
National Research Register (UK) and the Current Controlled Trials databases. The
data for 2 outcomes (e.g., ophthalmopathy and recurrence) were independently
extracted by 2 authors.
RESULTS: A total of 4 RCTs were ultimately included. Radioiodine+prednisone
therapy showed statistical significance in reducing the incidence of new or
deteriorative ophthalmopathy comparing with the other 3 therapies. Compared with
radioiodine, therapy with antithyroid drugs therapy as well as surgery
significantly decreased the incidence of new or deteriorative ophthalmopathy.
Radioiodine therapy significantly reduced the rate of recurrence when compared to
therapy with antithyroid drugs or surgery. For decreasing the incidence of new or
deteriorative ophthalmopathy, the 4 treatments were ranked as follows:
radioiodine+prednisone therapy, therapy with antithyroid drugs, surgery and
radioiodine therapy. For reducing the rate of recurrence, 3 treatments were
ranked as follows: radioiodine therapy, therapy with antithyroid drugs and
surgery.
CONCLUSIONS: Radioiodine+prednisone therapy might have the least probability of
leading to an exacerbation or new appearance of ophthalmopathy, and radioiodine
therapy might have the least probability of causing a recurrence.

© Georg Thieme Verlag KG Stuttgart · New York.

DOI: 10.1055/s-0035-1548824
PMID: 25988881  [Indexed for MEDLINE]


300. J Am Geriatr Soc. 2015 May;63(5):1002-9. doi: 10.1111/jgs.13395. Epub 2015 May 6.

Comparative efficacy and safety of selective serotonin reuptake inhibitors and
serotonin-norepinephrine reuptake inhibitors in older adults: a network
meta-analysis.

Thorlund K(1)(2)(3), Druyts E(3)(4), Wu P(3), Balijepalli C(3), Keohane D(5),
Mills E(1)(3).

Author information:
(1)Stanford Prevention Research Center, Stanford University, Stanford,
California.
(2)Department of Clinical Epidemiology and Biostatistics, McMaster University,
Hamilton, Ontario, Canada.
(3)Redwood Outcomes, Vancouver, British Columbia, Canada.
(4)Department of Medicine, University of British Columbia, Vancouver, British
Columbia, Canada.
(5)Pfizer Inc., New York, New York.

Comment in
    Evid Based Ment Health. 2016 Nov;19(4):e26.

OBJECTIVES: To establish the comparative efficacy and safety of selective
serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors in
older adults using the network meta-analysis approach.
DESIGN: Systematic review and network meta-analysis.
PARTICIPANTS: Individuals aged 60 and older.
MEASUREMENTS: Data on partial response (defined as at least 50% reduction in
depression score from baseline) and safety (dizziness, vertigo, syncope, falls,
loss of consciousness) were extracted. A Bayesian network meta-analysis was
performed on the efficacy and safety outcomes, and relative risks (RRs) with 95%
credible intervals (CrIs) were produced.
RESULTS: Fifteen randomized controlled trials were eligible for inclusion in the
analysis. Citalopram, escitalopram, paroxetine, duloxetine, venlafaxine,
fluoxetine, and sertraline were represented. Reporting on partial response and
dizziness was sufficient to conduct a network meta-analysis. Reporting on other
outcomes was sparse. For partial response, sertraline (RR=1.28), paroxetine
(RR=1.48), and duloxetine (RR=1.62) were significantly better than placebo. The
remaining interventions yielded RRs lower than 1.20. For dizziness, duloxetine
(RR=3.18) and venlafaxine (RR=2.94) were statistically significantly worse than
placebo. Compared with placebo, sertraline had the lowest RR for dizziness (1.14)
and fluoxetine the second lowest (1.31). Citalopram, escitalopram, and paroxetine
all had RRs between 1.4 and 1.7.
CONCLUSION: There was clear evidence of the effectiveness of sertraline,
paroxetine, and duloxetine. There also appears to be a hierarchy of safety
associated with the different antidepressants, although there appears to be a
dearth of reporting of safety outcomes.

© 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics
Society.

DOI: 10.1111/jgs.13395
PMID: 25945410  [Indexed for MEDLINE]


301. J Clin Endocrinol Metab. 2015 May;100(5):1903-11. doi: 10.1210/jc.2014-4077. Epub
2015 Feb 19.

Comparative efficacy of radiofrequency and laser ablation for the treatment of
benign thyroid nodules: systematic review including traditional pooling and
bayesian network meta-analysis.

Ha EJ(1), Baek JH, Kim KW, Pyo J, Lee JH, Baek SH, Døssing H, Hegedüs L.

Author information:
(1)Department of Radiology (E.J.H.), Ajou University School of Medicine, Suwon
443-380, Korea; Department of Radiology and Research Institute of Radiology
(J.H.B., K.W.K., J.H.L.), University of Ulsan College of Medicine, Asan Medical
Center, Seoul 138-736, Korea; WHO Collaborating Centre for Pharmaceutical Policy
and Regulation, Department of Pharmaceutical Science (J.P.), Utrecht University,
Netherlands; Department of Clinical Epidemiology and Biostatistics (S.H.B.),
University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736,
Korea; and Departments of Otorhinolaryngology (H.D.) and Endocrinology (L.H.),
Odense University Hospital, DK-5000 Odense C, Denmark.

PURPOSE: To compare the efficacy of radiofrequency ablation (RFA) and laser
ablation (LA) for treatment of benign solid thyroid nodules, using a systematic
review including traditional pooling and Bayesian network meta-analysis.
MATERIALS AND METHODS: A comprehensive literature search in PubMed-MEDLINE,
EMBASE, and the Cochrane Library databases identified prospective studies
evaluating the percentage mean change [absolute mean change (mL)] in nodule
volume after RFA or LA. Studies from January 1, 2000, to November 1, 2013, were
included. Review of 128 potential papers, including a full-text review of 33,
identified 10 eligible papers covering a total of 184 patients for meta-analysis.
The percentage mean change [absolute mean change] in nodule volume over a 6-month
follow-up was compared between RFA and LA.
RESULTS: Based on the traditional frequentist approach, the pooled percentage
mean changes (95% confidence interval) of RFA and LA were 76.1% (70.1-82.1) and
49.9% (41.4-58.5), respectively, and the pooled absolute mean changes (95%
confidence interval) of RFA and LA were 8.9 mL (6.6-11.2) and 5.2 mL (4.3-6.1),
respectively. Based on the Bayesian network meta-analysis, RFA achieved a larger
pooled percentage mean change (95% credible interval) and absolute mean change
(95% credible interval) compared to LA [77.8% (67.7-88.0) vs 49.5% (26.7-72.4),
and 9.2 mL (5.8-11.9) vs 5.3 mL (2.1-8.5), respectively]. The RFA group has the
highest probability of having the most efficacious treatment (98.7%). There were
no major complications after either RFA or LA.
CONCLUSIONS: RFA appears to be superior to LA in reducing benign solid thyroid
nodule volume, despite the smaller number of treatment sessions without major
side effects.

DOI: 10.1210/jc.2014-4077
PMID: 25695887  [Indexed for MEDLINE]


302. J Manag Care Spec Pharm. 2015 May;21(5):409-23.

Comparative Efficacy of Novel DMARDs as Monotherapy and in Combination with
Methotrexate in Rheumatoid Arthritis Patients with Inadequate Response to
Conventional DMARDs: A Network Meta-Analysis.

Buckley F(1), Finckh A, Huizinga TW, Dejonckheere F, Jansen JP.

Author information:
(1)Department of HEOR and Strategic Market Access.

BACKGROUND: Given the availability of a number of alternative biologic treatment
options and other novel disease-modifying antirheumatic drugs (DMARDs) for the
treatment of patients with rheumatoid arthritis (RA), clinicians are faced with
an increasingly challenging choice regarding optimal treatment. Biologics are
usually combined with traditional DMARDs, primarily methotrexate (MTX), but some
biologics and tofacitinib (together referred to in this article as novel DMARDs)
have been shown to be efficacious as monotherapy as well. In real-world practice,
approximately one-third of RA patients receiving biologics are on monotherapy,
primarily because of intolerance of, or noncompliance with, MTX. Limited data,
however, are available analyzing the effectiveness of monotherapy compared with
combination therapy across novel DMARDs.
OBJECTIVE: To compare American College of Rheumatology (ACR) responses to
approved novel DMARDs used as monotherapy or as combination therapy with
methotrexate (MTX) at 24 weeks in RA patients who have shown inadequate response
to conventional DMARDs (DMARD-IR). 
METHODS: Through a systematic review of the literature, we identified randomized
controlled trials that assessed approved novel DMARDs used as monotherapy or as
combination therapy with MTX in DMARD-IR RA patients. Twenty-eight RCTs were
identified that evaluated abatacept, anakinra, adalimumab, certolizumab pegol,
etanercept, golimumab, infliximab, tocilizumab, or tofacitinib. ACR responses at
24 weeks were extracted and combined by means of Bayesian network meta-analyses. 
RESULTS: With the exception of anakinra plus MTX, which was less efficacious,
most novel DMARDs, when used in combination with MTX, demonstrated comparable ACR
responses. When novel DMARDs were used as monotherapies, greater ACR20/50/70
responses were observed with tocilizumab than with anti-tumor necrosis factor
agents (aTNF) or tofacitinib. Furthermore, ACR20/50/70 responses with tocilizumab
plus MTX were similar to those with tocilizumab monotherapy (odds ratio [OR] for
the indirect comparison = 1.08, 95% credible interval [CrI] = 0.40-2.84;
OR = 1.24, CrI = 0.44-3.61; OR = 0.95, CrI = 0.33-2.72, respectively), whereas
greater responses were observed with aTNF plus MTX than with aTNF monotherapy
(OR = 2.41, CrI = 0.51-11.61; OR = 2.85, CrI = 0.51-17.67; OR = 1.28,
CrI = 0.21-8.42, respectively). Relative efficacy estimates for the indirect
comparison of tofacitinib plus MTX with tofacitinib monotherapy were very
uncertain.
CONCLUSIONS: Results suggest that in combination with MTX most of the available
novel DMARDs have similar levels of efficacy in DMARD-IR patients. As
monotherapy, however, tocilizumab displayed higher ACR responses than aTNF or
tofacitinib. ACR responses with tocilizumab plus MTX were similar to those with
tocilizumab as monotherapy, whereas aTNF in combination with MTX demonstrated
greater ACR responses than aTNF as monotherapy.

DOI: 10.18553/jmcp.2015.21.5.409
PMID: 25943002  [Indexed for MEDLINE]


303. Lancet Glob Health. 2015 May;3(5):e271-8. doi: 10.1016/S2214-109X(14)70348-1.

Prevalence of symptoms of vaginal fistula in 19 sub-Saharan Africa countries: a
meta-analysis of national household survey data.

Maheu-Giroux M(1), Filippi V(2), Samadoulougou S(3), Castro MC(1), Maulet N(4),
Meda N(5), Kirakoya-Samadoulougou F(6).

Author information:
(1)Department of Global Health & Population, Harvard TH Chan School of Public
Health, Boston, MA, USA.
(2)London School of Hygiene & Tropical Medicine, London, UK.
(3)London School of Hygiene & Tropical Medicine, London, UK; Pôle Epidémiologie
et Biostatistique, Institut de Recherche Expérimentale et Clinique, Faculté de
Santé Publique, Université Catholique de Louvain, Brussels, Belgium.
(4)Institute of Health and Society, Université Catholique de Louvain, Brussels,
Belgium.
(5)Centre Muraz, Ministry of Health, Bobo-Dioulasso, Burkina Faso; Université de
Ouagadougou, Ouagadougou, Burkina Faso.
(6)London School of Hygiene & Tropical Medicine, London, UK. Electronic address:
fati.kirakoya@lshtm.ac.uk.

Comment in
    Lancet Glob Health. 2015 Aug;3(8):e442.
    Lancet Glob Health. 2015 Aug;3(8):e441.
    Lancet Glob Health. 2015 May;3(5):e243-4.

BACKGROUND: Vaginal fistula is a serious medical disorder characterised by an
abnormal opening between the vagina and the bladder or rectum, which results in
continuous leakage of urine or stool. The burden of this disorder in sub-Saharan
Africa is uncertain. We estimated the lifetime and point prevalence of symptoms
of vaginal fistula in this region using national household surveys based on
self-report of symptoms.
METHODS: We considered all Demographic and Health Surveys (DHS) and Multiple
Indicators Cluster Surveys (MICS) from sub-Saharan Africa and included data for
women of reproductive age (15-49 years). We estimated lifetime prevalence and
point prevalence of vaginal fistula with use of Bayesian hierarchical
meta-analysis.
FINDINGS: We included 19 surveys in our analysis, including 262,100 respondents.
Lifetime prevalence was 3.0 cases (95% credible interval 1.3-5.5) per 1000 women
of reproductive age. After imputation of missing data, point prevalence was 1.0
case (0.3-2.4) per 1000 women of reproductive age. Ethiopia had the largest
number of women who presently have symptoms of vaginal fistula.
INTERPRETATION: This study is the first to estimate the burden of vaginal fistula
in 19 sub-Saharan Africa countries using nationally representative survey data.
Point prevalence was slightly lower than previously estimated but these earlier
estimates are within the prevalence's credible intervals. Although vaginal
fistula is relatively rare, it is still too common in sub-Saharan Africa.
FUNDING: None.

Copyright © 2015 Maheu-Giroux et al. Open access article published under the
terms of CC BY. Published by .. All rights reserved.

DOI: 10.1016/S2214-109X(14)70348-1
PMID: 25889469  [Indexed for MEDLINE]


304. Medicine (Baltimore). 2015 May;94(18):e828. doi: 10.1097/MD.0000000000000828.

Nonsteroidal Anti-inflammatory Drugs as Prophylaxis for Heterotopic Ossification
after Total Hip Arthroplasty: A Systematic Review and Meta-Analysis.

Kan SL(1), Yang B, Ning GZ, Chen LX, Li YL, Gao SJ, Chen XY, Sun JC, Feng SQ.

Author information:
(1)From the Department of Orthopaedics, Tianjin Medical University General
Hospital, Heping District, Tianjin, China.

Comment in
    Orthopade. 2017 Mar;46(3):280-282.

Heterotopic ossification (HO) is a frequent complication after total hip
arthroplasty (THA). Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used
as routine prophylaxis for HO after THA. However, the efficacy of NSAIDs on HO,
particularly selective NSAIDs versus nonselective NSAIDs, is uncertain.We
searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, and
clinicaltrials.gov to identify randomized controlled trials with respect to HO
after THA. Two reviewers extracted the data and estimated the risk of bias. For
the ordered data, we followed the Bayesian framework to calculate the odds ratio
(OR) with a 95% credible interval (CrI). For the dichotomous data, the OR and 95%
confidence interval (CI) were calculated using Stata version 12.0. The subgroup
analyses and the Grading of Recommendations, Assessment, Development and
Evaluation (GRADE) approach were used.A total of 1856 articles were identified,
and 21 studies (5995 patients) were included. In the NSAIDs versus placebo
analysis, NSAIDs could decrease the incidence of HO, according to the Brooker
scale (OR = 2.786, 95% CrI 1.879-3.993) and Delee scale (OR = 9.987, 95% CrI
5.592-16.17). In the selective NSAIDs versus nonselective NSAIDs analysis, there
was no significant difference (OR = 0.7989, 95% CrI 0.5506-1.125) in the
prevention of HO. NSAIDs could increase discontinuation caused by
gastrointestinal side effects (DGSE) (OR = 1.28, 95% CI 1.00-1.63, P = 0.046)
more than a placebo. Selective NSAIDs could decrease DGSE (OR = 0.48, 95% CI
0.24-0.97, P = 0.042) compared with the nonselective NSAIDs. There was no
significant difference with respect to discontinuation caused by
non-gastrointestinal side effects (DNGSE) in NSAIDs versus a placebo (OR = 1.16,
95% CI 0.88-1.53, P = 0.297) and in selective NSAIDs versus nonselective NSAIDs
(OR = 0.83, 95% CI 0.50-1.37, P = 0.462).NSAIDs might reduce the incidence of HO
and increase DGSE in the short-term.

DOI: 10.1097/MD.0000000000000828
PMCID: PMC4602535
PMID: 25950691  [Indexed for MEDLINE]


305. PLoS One. 2015 Apr 13;10(4):e0123153. doi: 10.1371/journal.pone.0123153.
eCollection 2015.

Comparative efficacy and tolerability of three treatments in old people with
osteoporotic vertebral compression fracture: a network meta-analysis and
systematic review.

Chen LX(1), Li YL(1), Ning GZ(1), Li Y(1), Wu QL(1), Guo JX(1), Shi HY(1), Wang
XB(1), Zhou Y(1), Feng SQ(1).

Author information:
(1)Department of Orthopaedics, Tianjin Medical University General Hospital, 154
Anshan Road, Heping District, People's Republic of China.

PURPOSE: The question which kind of methods is most suitable for treating the old
people for osteoporotic vertebral compression fracture is still discussed and
pairwise meta-analyses cannot get hierarchies of these treatments. Our aim is to
integrate the evidence to provide hierarchies of the comparative efficacy
measured by the change of VAS (Visual Analogue Scale) and tolerability measured
by incidence of new fractures and risk of all-cause discontinuation on three
treatments (percutaneous vertebroplasty (PVP)、balloon kyphoplasty (BK) and
conservative treatment (CT)).
METHODS: We performed a Bayesian-framework network meta-analysis of randomized
controlled trials (RCTs) to compare three treatments for the old people with
osteoporotic vertebral compression fracture. The eligible RCTs were identified by
searching Amed, British Nursing Index, Embase, Pubmed, the Cochrane Central
Register of Controlled Trials (CENTRAL), Google scholar, SIGLE, the National
Technical Information Service, the National Research Register (UK) and the
Current Controlled Trials databases. Data from three outcomes (e.g. VAS, risk of
all-cause discontinuation and incidence of new fractures) were independently
extracted by two authors.
RESULTS: A total of five RCTs were finally included into this article. PVP and BK
significantly decreased VAS when compared with CT. BK had a significantly lower
risk of all-cause discontinuation contrast to CT. Three treatments (BK, PVP and
CT) had no significant differences in the incidence of new fractures.
CONCLUSIONS: PVP may be the best way to relieve pain, CT might lead to the lowest
incidence of new fractures and BK might had the lowest risk of all-cause
discontinuation in old people with osteoporotic vertebral compression fracture.
More large-scale and longer duration of follow-up studies are needed.

DOI: 10.1371/journal.pone.0123153
PMCID: PMC4395314
PMID: 25874802  [Indexed for MEDLINE]


306. Nutrients. 2015 Apr 10;7(4):2663-86. doi: 10.3390/nu7042663.

Assessing the association between natural food folate intake and blood folate
concentrations: a systematic review and Bayesian meta-analysis of trials and
observational studies.

Marchetta CM(1), Devine OJ(2), Crider KS(3), Tsang BL(4), Cordero AM(5), Qi
YP(6), Guo J(7), Berry RJ(8), Rosenthal J(9), Mulinare J(10), Mersereau P(11),
Hamner HC(12).

Author information:
(1)Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN 37831,
USA. claire.marchetta@gmail.com.
(2)Carter Consulting, Inc., Atlanta, GA 30345, USA. ojd1@cdc.gov.
(3)Division of Birth Defects and Developmental Disabilities (DBDDD), National
Center on Birth Defects and Developmental Disabilities (NCBDDD), Centers for
Disease Control and Prevention, Atlanta, GA 30329, USA. kvc3@cdc.gov.
(4)Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN 37831,
USA. bltsang@gmail.com.
(5)Division of Birth Defects and Developmental Disabilities (DBDDD), National
Center on Birth Defects and Developmental Disabilities (NCBDDD), Centers for
Disease Control and Prevention, Atlanta, GA 30329, USA. iqt8@cdc.gov.
(6)Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN 37831,
USA. rv7@cdc.gov.
(7)Acentia, Falls Church, VA 22042, USA. shashagj@gmail.com.
(8)Division of Birth Defects and Developmental Disabilities (DBDDD), National
Center on Birth Defects and Developmental Disabilities (NCBDDD), Centers for
Disease Control and Prevention, Atlanta, GA 30329, USA. rjb1@cdc.gov.
(9)Division of Birth Defects and Developmental Disabilities (DBDDD), National
Center on Birth Defects and Developmental Disabilities (NCBDDD), Centers for
Disease Control and Prevention, Atlanta, GA 30329, USA. jyr4@cdc.gov.
(10)Carter Consulting, Inc., Atlanta, GA 30345, USA. jxm1@cdc.gov.
(11)SciMetrika, LLC, Atlanta, GA 30329, USA. pmersereau@comcast.net.
(12)Division of Nutrition, Physical Activity, and Obesity (DNPAO), National
Center for Chronic Disease Prevention and Health Promotion (NCCDPHP), Centers for
Disease Control and Prevention, Atlanta, GA 30329, USA. hfc2@cdc.gov.

Folate is found naturally in foods or as synthetic folic acid in dietary
supplements and fortified foods. Adequate periconceptional folic acid intake can
prevent neural tube defects. Folate intake impacts blood folate concentration;
however, the dose-response between natural food folate and blood folate
concentrations has not been well described. We estimated this association among
healthy females. A systematic literature review identified studies (1 1992-3
2014) with both natural food folate intake alone and blood folate concentration
among females aged 12-49 years. Bayesian methods were used to estimate regression
model parameters describing the association between natural food folate intake
and subsequent blood folate concentration. Seven controlled trials and 29
observational studies met the inclusion criteria. For the six studies using
microbiologic assay (MA) included in the meta-analysis, we estimate that a 6%
(95% Credible Interval (CrI): 4%, 9%) increase in red blood cell (RBC) folate
concentration and a 7% (95% CrI: 1%, 12%) increase in serum/plasma folate
concentration can occur for every 10% increase in natural food folate intake.
Using modeled results, we estimate that a natural food folate intake of ≥ 450 μg
dietary folate equivalents (DFE)/day could achieve the lower bound of an RBC
folate concentration (~ 1050 nmol/L) associated with the lowest risk of a neural
tube defect. Natural food folate intake affects blood folate concentration and
adequate intakes could help women achieve a RBC folate concentration associated
with a risk of 6 neural tube defects/10,000 live births.

DOI: 10.3390/nu7042663
PMCID: PMC4425166
PMID: 25867949  [Indexed for MEDLINE]


307. AJR Am J Roentgenol. 2015 Apr;204(4):W439-48. doi: 10.2214/AJR.14.13373.

Dynamic contrast-enhanced MRI for the detection of prostate cancer:
meta-analysis.

Tan CH(1), Hobbs BP, Wei W, Kundra V.

Author information:
(1)1 Department of Diagnostic Radiology, Tan Tock Seng Hospital, 11 Jalan Tan
Tock Seng, Singapore 308433.

OBJECTIVE: The purpose of this study was to systematically review and
meta-analyze dynamic contrast-enhanced MRI (DCE-MRI) for the detection of
prostate cancer in comparison with standard evaluation with T2-weighted imaging.
MATERIALS AND METHODS: A PubMed electronic database search for the terms "dynamic
contrast-enhanced," "prostate," and "MRI" was completed for articles up to
September 17, 2013. All included studies had histopathologic correlation. Two by
two contingency data were constructed for each study. A binormal bayesian ROC
model was used to estimate and compare sensitivity, specificity, and AUC among
eligible modalities.
RESULTS: Both DCE-MRI (0.82-0.86) and diffusion-weighted MRI (DWI) (0.84-0.88)
yielded significantly better AUC than T2-weighted imaging (0.68-0.77). Moreover,
partial AUC for the combination of DCE-MRI, DWI, and T2-weighted imaging was
improved significantly (0.111; 0.103-0.119) when compared with DCE-MRI alone
(0.079; 0.072-0.085) and T2-weighted imaging alone (0.079; 0.074-0.084) but not
DWI alone (0.099; 0.091-0.108). Sensitivity and specificity were similar among
the four modalities.
CONCLUSION: DCE-MRI improves AUC of tumor detection overall compared with
T2-weighted imaging alone. Methods for DCE-MRI analysis require standardization,
but visual analysis performs similar to semiquantitative methods. A two-parameter
approach using DCE-MRI and T2-weighted imaging or DWI and T2-weighted imaging may
be sufficient, and the latter may be more favorable for most routine prostate
cancer imaging.

DOI: 10.2214/AJR.14.13373
PMCID: PMC5152763
PMID: 25794093  [Indexed for MEDLINE]


308. Ann Surg. 2015 Apr;261(4):662-9. doi: 10.1097/SLA.0000000000000935.

Immunoenhancing enteral and parenteral nutrition for gastrointestinal surgery: a
multiple-treatments meta-analysis.

Mazaki T(1), Ishii Y, Murai I.

Author information:
(1)*Division of Research Planning and Development, Nihon University School of
Medicine, Tokyo, Japan; and Divisions of †Surgical Oncology and ‡Physiology,
Graduate School of Medicine, Nihon University, Tokyo, Japan.

OBJECTIVE: Frequentist meta-analyses have demonstrated that immunoenhancing
parenteral nutrition (IMPN) and enteral nutrition (IMEN) reduce the incidence of
infection and shorten the length of hospital stays compared with standard
parenteral nutrition (SPN) and enteral nutrition (SEN). The aim of this study was
to evaluate which kind of nutrition-SPN, SEN, IMPN, and IMEN-is most efficacious
for reducing the incidence of complications after gastrointestinal surgery.
METHODS: An English literature search was carried out for randomized controlled
trials published from January 1990 to February 2013 that evaluated the clinical
efficacy of 4 kinds of nutrition after gastrointestinal surgery. A Bayesian
framework was used to calculate the odds ratio between each treatment and the
rank order.
RESULTS: Seventy-four studies (7572 participants) were included. According to the
surface below the cumulative ranking curve (SUCRA) ordering from the best to the
worst, IMEN was ranked first for reducing the incidence of 7 complications-any
infection (SUCRA = 0.86), overall complication (SUCRA = 0.88), mortality (SUCRA =
0.81), wound infection (SUCRA = 0.79), intra-abdominal abscess (SUCRA = 0.98),
anastomotic leak (SUCRA = 0.79), and sepsis (SUCRA = 0.92). Also, IMEN was ranked
second for pneumonia and urinary tract infection. IMPN was ranked first for
pneumonia (SUCRA = 0.81) and urinary tract infection (SUCRA = 0.86), third for
mortality, and fourth for both intra-abdominal abscess and anastomotic leak. SPN
showed an inferior efficacy for almost all outcomes.
CONCLUSIONS: This study suggests that IMEN outperformed other nutrition types for
reducing complications and IMEN should be considered the best available option.

DOI: 10.1097/SLA.0000000000000935
PMID: 25405556  [Indexed for MEDLINE]


309. Br J Surg. 2015 Apr;102(5):436-50. doi: 10.1002/bjs.9689. Epub 2015 Feb 23.

Meta-analysis of prognostic factors for amputation following surgical repair of
lower extremity vascular trauma.

Perkins ZB(1), Yet B, Glasgow S, Cole E, Marsh W, Brohi K, Rasmussen TE, Tai NR.

Author information:
(1)Centre for Trauma Sciences, Queen Mary, University of London, London, UK.

BACKGROUND: Lower extremity vascular trauma (LEVT) is a major cause of
amputation. A clear understanding of prognostic factors for amputation is
important to inform surgical decision-making, patient counselling and risk
stratification. The aim was to develop an understanding of prognostic factors for
amputation following surgical repair of LEVT.
METHODS: A systematic review was conducted to identify potential prognostic
factors. Bayesian meta-analysis was used to calculate an absolute (pooled
proportion) and relative (pooled odds ratio, OR) measure of the amputation risk
for each factor.
RESULTS: Forty-five studies, totalling 3187 discrete LEVT repairs, were included.
The overall amputation rate was 10·0 (95 per cent credible interval 7·4 to 13·1)
per cent. Significant prognostic factors for secondary amputation included:
associated major soft tissue injury (26 versus 8 per cent for no soft tissue
injury; OR 5·80), compartment syndrome (28 versus 6 per cent; OR 5·11), multiple
arterial injuries (18 versus 9 per cent; OR 4·85), duration of ischaemia
exceeding 6 h (24 versus 5 per cent; OR 4·40), associated fracture (14 versus 2
per cent; OR 4·30), mechanism of injury (blast 19 per cent, blunt 16 per cent,
penetrating 5 per cent), anatomical site of injury (iliac 18 per cent, popliteal
14 per cent, tibial 10 per cent, femoral 4 per cent), age over 55 years (16
versus 9 per cent; OR 3·03) and sex (men 7 per cent versus women 8 per cent; OR
0·64). Shock and nerve or venous injuries were not significant prognostic factors
for secondary amputation.
CONCLUSION: A significant proportion of patients who undergo lower extremity
vascular trauma repair will require secondary amputation. This meta-analysis
describes significant prognostic factors needed to inform surgical judgement,
risk assessment and patient counselling.

© 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.

DOI: 10.1002/bjs.9689
PMID: 25706113  [Indexed for MEDLINE]


310. Child Abuse Negl. 2015 Apr;42:135-45. doi: 10.1016/j.chiabu.2015.02.013. Epub
2015 Mar 5.

Attachment in institutionalized children: a review and meta-analysis.

Lionetti F(1), Pastore M(2), Barone L(3).

Author information:
(1)Department of Brain and Behavioral Sciences, University of Pavia, Italy.
Electronic address: francesca.lionetti@unipv.it.
(2)Department of Developmental and Social Psychology, University of Padova,
Italy.
(3)Department of Brain and Behavioral Sciences, University of Pavia, Italy.

In this article we review the literature on attachment patterns in
institutionalized children and then perform a meta-analysis on data from 10
attachment studies involving 399 children in institutional settings. We computed
the overall attachment distribution of secure, insecure, and disorganized rates
and explored the effect of a set of moderating variables (i.e., country of
institutionalization, attachment assessment procedure, age at entry, and age at
assessment). To overcome bias related to the small number of studies, we
conducted both classical and Bayesian meta-analysis and obtained comparable
results. Distribution of children's attachment patterns was: 18% secure, 28%
insecure, and 54% disorganized/cannot classify. Compared to their family-reared
peers, children living in an institution were found to be at greater risk for
insecure and disorganized attachment, with a similar medium effect size for both
distributions (d=0.77 and d=0.76, respectively). The following moderating
variables were associated with insecure attachment: representational assessment
procedures (d=0.63) and Eastern European countries of origin (d=1.13). Moderators
for disorganized attachment were: Eastern European countries of origin (d=1.12),
age at institution entry before the first birthday (d=0.93), and age at
assessment under three years of age (d=0.91). Implications for child development
and policies are discussed.

Copyright © 2015 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.chiabu.2015.02.013
PMID: 25747874  [Indexed for MEDLINE]


311. Eur J Radiol. 2015 Apr;84(4):652-61. doi: 10.1016/j.ejrad.2015.01.003. Epub 2015
Jan 16.

Qualitative elastography can replace thyroid nodule fine-needle aspiration in
patients with soft thyroid nodules. A systematic review and meta-analysis.

Nell S(1), Kist JW(1), Debray TP(2), de Keizer B(3), van Oostenbrugge TJ(1),
Borel Rinkes IH(1), Valk GD(4), Vriens MR(5).

Author information:
(1)Department of Surgery, University Medical Center Utrecht, The Netherlands.
(2)Julius Center for Health Sciences and Primary Care Utrecht, The Netherlands.
(3)Department of Radiology and Nuclear Medicine, University Medical Center
Utrecht, The Netherlands.
(4)Department of Endocrinology, University Medical Center Utrecht, The
Netherlands.
(5)Department of Surgery, University Medical Center Utrecht, The Netherlands.
Electronic address: mvriens@umcutrecht.nl.

CONTEXT: Only a minority of thyroid nodules is malignant; nevertheless, many
invasive diagnostic procedures are performed to distinguish between benign and
malignant nodules. Qualitative ultrasound elastography is a non-invasive
technique to evaluate thyroid nodules.
OBJECTIVE: To investigate the diagnostic value of qualitative elastography in
distinguishing benign from malignant thyroid nodules in patients referred for
fine-needle aspiration (FNA).
DATA SOURCES: A systematic literature search (PubMed, Embase and Cochrane
Library) was performed.
STUDY SELECTION: Included studies reported thyroid nodule elastography color
scores and the related cytologic or histologic findings in patients with a
thyroid nodule referred for FNA.
DATA EXTRACTION: Two independent reviewers extracted study data and assessed
study quality. Pooled sensitivities and specificities of different populations
were calculated using a bivariate Bayesian framework.
DATA SYNTHESIS: Twenty studies including thyroid nodules were analyzed. Pooled
results of elastography indicate a summary sensitivity of 85% (95% confidence
interval [CI], 79-90%) and specificity of 80% (95% CI, 73-86%). The respective
pooled negative predictive and positive predictive values were 97% (95% CI,
94-98%) and 40% (95% CI, 34-48%). The pretest probability of a benign nodule was
82%. Only 3.7% of the false-negative nodules was a follicular thyroid carcinoma.
A pooled negative predictive value of 99% (95% CI, 97-100%) was found when only
complete soft nodules (Asteria elastography 1) were classified as benign, which
included 14% of the studied population.
CONCLUSIONS: Elastography has a fair specificity and sensitivity for diagnostic
accuracy. Its major strength entails the detection of benignity, especially when
only completely soft nodules are qualified as benign. The outcomes of our
analysis show that FNA could safely be omitted in patients referred for analysis
of their thyroid nodule when elastography shows it to be completely soft (Asteria
elastography 1). This could prevent unnecessary invasive diagnostic procedures in
a substantial portion of patients.

Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

DOI: 10.1016/j.ejrad.2015.01.003
PMID: 25638577  [Indexed for MEDLINE]


312. Int J Cardiol. 2015 Apr 1;184:36-46. doi: 10.1016/j.ijcard.2015.01.081. Epub 2015
Jan 29.

The efficacy and safety of mechanical hemodynamic support in patients undergoing
high-risk percutaneous coronary intervention with or without cardiogenic shock:
Bayesian approach network meta-analysis of 13 randomized controlled trials.

Lee JM(1), Park J(1), Kang J(1), Jeon KH(1), Jung JH(1), Lee SE(1), Han JK(1),
Kim HL(2), Yang HM(1), Park KW(1), Kang HJ(1), Koo BK(1), Kim SH(2), Kim HS(3).

Author information:
(1)Department of Internal Medicine and Cardiovascular Center, Seoul National
University Hospital, Seoul, Republic of Korea.
(2)Department of Internal Medicine and Cardiovascular Center, Boramae Medical
Center, Seoul National University, Seoul, Republic of Korea.
(3)Department of Internal Medicine and Cardiovascular Center, Seoul National
University Hospital, Seoul, Republic of Korea; Molecular Medicine &
Biopharmaceutical Science, Graduate School of Convergence Science & Technology,
Seoul National University, Seoul, Republic of Korea. Electronic address:
usahyosoo@gmail.com.

BACKGROUND: Studies have reported conflicting results regarding efficacy of
mechanical hemodynamic support using intra-aortic balloon pump (IABP) or
percutaneous ventricular assisted device (pVAD) in patients undergoing high-risk
PCI. We performed a Bayesian network meta-analysis comparing the safety and
efficacy of mechanical hemodynamic support devices and medical therapy (MT).
METHODS AND RESULTS: RCTs comparing overall mortality of IABP versus MT or IABP
versus pVAD in high-risk PCI populations were included. The primary endpoint was
overall mortality, using the longest available follow-up in each study. This
analysis included 2843 patients from 13 trials. In network meta-analysis, overall
survival benefit was not significant with IABP (RR 0.84, 95% CrI 0.56-1.24) or
pVAD (RR 0.95, 95% CrI 0.42-2.06), compared with MT. IABP or pVAD also did not
show early survival benefit compared with MT. In terms of bleeding, pVAD was the
worst (versus IABP: RR 29.4, 95% CrI 5.99-221.0; versus MT: RR 41.7, 95% CrI
8.19-330.0), which was mainly driven by the higher incidence of bleeding in the
ECMO and TandemHeart, while IABP was worse than MT (RR 1.41, 95% CrI 1.01-2.08).
The incidence of acute limb ischemia or vascular complication was not different
between treatment groups.
CONCLUSIONS: In this meta-analysis, routine elective use of IABP or pVAD did not
reduce mortality, while it increased bleeding, compared with MT in high-risk PCI
population or even in the patients with cardiogenic shock. Thoughtful selection
of appropriate patients and balancing the risk and benefit should be the
prerequisites to the use of mechanical hemodynamic support devices.

Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

DOI: 10.1016/j.ijcard.2015.01.081
PMID: 25697869  [Indexed for MEDLINE]


313. Oncologist. 2015 Apr;20(4):440-9. doi: 10.1634/theoncologist.2014-0328. Epub 2015
Mar 2.

Systematic literature review and network meta-analysis comparing bone-targeted
agents for the prevention of skeletal-related events in cancer patients with bone
metastasis.

Wang Z(1), Qiao D(1), Lu Y(1), Curtis D(1), Wen X(1), Yao Y(1), Zhao H(2).

Author information:
(1)Department of Internal Oncology, Shanghai Jiao Tong University Affiliated
Sixth People's Hospital, Shanghai, People's Republic of China; Radiation
Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
(2)Department of Internal Oncology, Shanghai Jiao Tong University Affiliated
Sixth People's Hospital, Shanghai, People's Republic of China; Radiation
Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
zhao-hui@sjtu.edu.cn.

BACKGROUND: Complications from skeletal-related events (SREs) constitute a
challenge in the care of cancer patients with bone metastasis (BM).
OBJECTIVES: This study evaluated the comparative effectiveness of pamidronate,
ibandronate, zoledronate, and denosumab in reducing the morbidity of SREs in
cancer patients with BM.
METHODS: Medline (1948 to January 2014), Embase (1980 to January 2014), the
Cochrane Library (2014 issue 1), and Web of Science with Conference Proceedings
(1970 to January 2014) were searched. Only randomized controlled trials assessing
denosumab, bisphosphonates, or placebo in cancer patients with BM were included.
The primary outcomes were SREs and SREs by type. The network meta-analysis (NMA)
was performed with a random-effects Bayesian model.
RESULTS: The NMA included 14 trials with 10,192 patients. Denosumab was superior
to placebo in reducing the risk of SREs (odds ratio [OR]: 0.49; 95% confidence
interval [CI]: 0.31-0.75), followed by zoledronate (OR: 0.57; 95% CI: 0.41-0.77)
and pamidronate (OR: 0.55; 95% CI: 0.41-0.72). Ibandronate compared with placebo
could not reduce the risk of SREs. Denosumab was superior to placebo in reducing
the risk of pathologic fractures (OR: 0.50; 95% CI: 0.32-0.79), followed by
zoledronate (OR: 0.61; 95% CI: 0.43-0.86). Denosumab was superior to placebo in
reducing the risk of radiation (OR: 0.51; 95% CI: 0.35-0.75), followed by
pamidronate (OR: 0.67; 95% CI: 0.52-0.86) and zoledronate (OR: 0.70; 95% CI:
0.52-0.96).
CONCLUSION: This NMA showed that denosumab, zoledronate, and pamidronate were
generally effective in preventing SREs in cancer patients with BM. Denosumab and
zoledronate were also associated with reductions in the risk of pathologic
fractures and radiation compared with placebo. Denosumab was shown to be the most
effective of the bone-targeted agents.

©AlphaMed Press.

DOI: 10.1634/theoncologist.2014-0328
PMCID: PMC4391764
PMID: 25732263  [Indexed for MEDLINE]


314. PLoS One. 2015 Apr 1;10(4):e0120113. doi: 10.1371/journal.pone.0120113.
eCollection 2015.

Micronutrients in HIV: a Bayesian meta-analysis.

Carter GM(1), Indyk D(2), Johnson M(3), Andreae M(4), Suslov K(2), Busani S(2),
Esmaeili A(2), Sacks HS(2).

Author information:
(1)Foundation for Integrative AIDS Research, Brooklyn, NY, United States of
America.
(2)Icahn School of Medicine at Mount Sinai, New York, NY, United States of
America.
(3)Teachers College, Columbia University, New York, NY, United States of America.
(4)Department of Anesthesiology, Albert Einstein College of Medicine, Bronx, NY,
United States of America.

Erratum in
    PLoS One. 2016;11(1):e0148392.

BACKGROUND: Approximately 28.5 million people living with HIV are eligible for
treatment (CD4<500), but currently have no access to antiretroviral therapy.
Reduced serum level of micronutrients is common in HIV disease. Micronutrient
supplementation (MNS) may mitigate disease progression and mortality.
OBJECTIVES: We synthesized evidence on the effect of micronutrient
supplementation on mortality and rate of disease progression in HIV disease.
METHODS: We searched MEDLINE, EMBASE, the Cochrane Central, AMED and CINAHL
databases through December 2014, without language restriction, for studies of
greater than 3 micronutrients versus any or no comparator. We built a
hierarchical Bayesian random effects model to synthesize results. Inferences are
based on the posterior distribution of the population effects; posterior
distributions were approximated by Markov chain Monte Carlo in OpenBugs.
PRINCIPAL FINDINGS: From 2166 initial references, we selected 49 studies for full
review and identified eight reporting on disease progression and/or mortality.
Bayesian synthesis of data from 2,249 adults in three studies estimated the
relative risk of disease progression in subjects on MNS vs. control as 0.62 (95%
credible interval, 0.37, 0.96). Median number needed to treat is 8.4 (4.8, 29.9)
and the Bayes Factor 53.4. Based on data reporting on 4,095 adults reporting
mortality in 7 randomized controlled studies, the RR was 0.84 (0.38, 1.85), NNT
is 25 (4.3, ∞).
CONCLUSIONS: MNS significantly and substantially slows disease progression in
HIV+ adults not on ARV, and possibly reduces mortality. Micronutrient supplements
are effective in reducing progression with a posterior probability of 97.9%.
Considering MNS low cost and lack of adverse effects, MNS should be standard of
care for HIV+ adults not yet on ARV.

DOI: 10.1371/journal.pone.0120113
PMCID: PMC4382132
PMID: 25830916  [Indexed for MEDLINE]


315. QJM. 2015 Apr;108(4):299-306. doi: 10.1093/qjmed/hcu202. Epub 2014 Sep 19.

Network meta-analysis of direct-acting antivirals in combination with
peginterferon-ribavirin for previously untreated patients with hepatitis C
genotype 1 infection.

Druyts E(1), Lorenzi M(2), Toor K(2), Thorlund K(3), Mills EJ(3).

Author information:
(1)From the Faculty of Medicine, University of British Columbia, Vancouver,
British Columbia, Canada, Redwood Outcomes, Vancouver, British Columbia, Canada
and Stanford Prevention Research Centre, Stanford University, Stanford,
California, USA From the Faculty of Medicine, University of British Columbia,
Vancouver, British Columbia, Canada, Redwood Outcomes, Vancouver, British
Columbia, Canada and Stanford Prevention Research Centre, Stanford University,
Stanford, California, USA edruyts@redwoodoutcomes.com.
(2)From the Faculty of Medicine, University of British Columbia, Vancouver,
British Columbia, Canada, Redwood Outcomes, Vancouver, British Columbia, Canada
and Stanford Prevention Research Centre, Stanford University, Stanford,
California, USA.
(3)From the Faculty of Medicine, University of British Columbia, Vancouver,
British Columbia, Canada, Redwood Outcomes, Vancouver, British Columbia, Canada
and Stanford Prevention Research Centre, Stanford University, Stanford,
California, USA From the Faculty of Medicine, University of British Columbia,
Vancouver, British Columbia, Canada, Redwood Outcomes, Vancouver, British
Columbia, Canada and Stanford Prevention Research Centre, Stanford University,
Stanford, California, USA.

AIM: To conduct a network meta-analysis (NMA) to determine the comparative
efficacy, as measured by sustained virological response (SVR), between boceprevir
(BOC), telaprevir (TEL), faldaprevir (FAL), simeprevir (SIM) and sofosbuvir (SOF)
in combination with peginterferon-ribavirin (PR) against a control of PR.
DESIGN: A literature search was conducted to identify randomized controlled
trials (RCTs) including adult patients with hepatitis C virus genotype 1 who were
naive to any prior therapy. RCTs assessing standard duration therapy (SDT) or
response-guided therapy (RGT) BOC, TEL, FAL, SIM or SOF in combination with PR
against a control of PR were eligible for inclusion. All RCTs must have provided
SVR at either 12 or 24 weeks post-therapy cessation.
RESULTS: We included nine RCTs. All direct-acting antivirals (DAAs) were found to
perform better than PR. Additionally, SDT FAL was found to be better than the 240
mg RGT FAL regimen with the PR lead-in. A sensitivity analysis excluding RCTs
with only SVR at 12 weeks was consistent with the results of the primary
analysis. A sensitivity analysis removing an RCT assessing SIM that reported SVR
of >60% in the PR control group additionally found that RGT SIM was superior to
the 240 mg RGT FAL regimen with the PR lead-in.
DISCUSSION: Our analyses indicate that SDT and RGT regimens of DAAs plus PR do
not differ greatly in terms of SVR among treatment-naive hepatitis C genotype 1
patients. More advanced Bayesian network meta-analyses are likely needed to
incorporate a comprehensive evidence base, expanding beyond randomized clinical
trials.

© The Author 2014. Published by Oxford University Press on behalf of the
Association of Physicians. All rights reserved. For Permissions, please email:
journals.permissions@oup.com.

DOI: 10.1093/qjmed/hcu202
PMID: 25239762  [Indexed for MEDLINE]


316. Crit Care. 2015 Mar 20;19:108. doi: 10.1186/s13054-015-0843-7.

Mechanical ventilation modes for respiratory distress syndrome in infants: a
systematic review and network meta-analysis.

Wang C(1), Guo L(2), Chi C(3), Wang X(4), Guo L(5), Wang W(6), Zhao N(7), Wang
Y(8), Zhang Z(9), Li E(10).

Author information:
(1)Department of Anesthesiology, First Affiliated Hospital of Harbin Medical
University, No 23 Youzheng Str, Nangang District, Harbin, Heilongjiang, 150001,
China. changsongwang@aliyun.com.
(2)Department of Anesthesiology, First Affiliated Hospital of Harbin Medical
University, No 23 Youzheng Str, Nangang District, Harbin, Heilongjiang, 150001,
China. 780214870@qq.com.
(3)Department of Anesthesiology, First Affiliated Hospital of Harbin Medical
University, No 23 Youzheng Str, Nangang District, Harbin, Heilongjiang, 150001,
China. ccjnzb0602@163.com.
(4)Department of Anesthesiology, First Affiliated Hospital of Harbin Medical
University, No 23 Youzheng Str, Nangang District, Harbin, Heilongjiang, 150001,
China. 851787303@qq.com.
(5)Department of Anesthesiology, First Affiliated Hospital of Harbin Medical
University, No 23 Youzheng Str, Nangang District, Harbin, Heilongjiang, 150001,
China. 57077184@qq.com.
(6)Department of Anesthesiology, First Affiliated Hospital of Harbin Medical
University, No 23 Youzheng Str, Nangang District, Harbin, Heilongjiang, 150001,
China. 774523831@qq.com.
(7)Department of Anesthesiology, First Affiliated Hospital of Harbin Medical
University, No 23 Youzheng Str, Nangang District, Harbin, Heilongjiang, 150001,
China. 767721743@qq.com.
(8)Department of Implantology, Hospital of Stomatology, Harbin Medical
University, No 23 Youzheng Str, Nangang District, Harbin, Heilongjiang, 150001,
China. ellenchi@163.com.
(9)Department of Anesthesiology, The Third Affiliated Hospital of Harbin Medical
University, No 150 Haping Str, Nangang District, Harbin, Heilongjiang, 150001,
China. chichunjie0602@gmail.com.
(10)Department of Anesthesiology, First Affiliated Hospital of Harbin Medical
University, No 23 Youzheng Str, Nangang District, Harbin, Heilongjiang, 150001,
China. enyouli@aliyun.com.

INTRODUCTION: The effects of different mechanical ventilation (MV) modes on
mortality outcome in infants with respiratory distress syndrome (RDS) are not
well known.
METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL)
in the Cochrane Library, EMBASE, MEDLINE, CINAHL, and Web of Science for studies
published through April 2014 that assessed mortality in infants with RDS given
different MV modes. We assessed studies for eligibility, extracted data, and
subsequently pooled the data. A Bayesian fixed-effects model was used to combine
direct comparisons with indirect evidence. We also performed sensitivity analyses
and rankings of the competing treatment modes.
RESULTS: In total, 20 randomized controlled trials were included for the network
meta-analysis, which consisted of 2,832 patients who received one of 16
ventilation modes. Compared with synchronized intermittent mandatory ventilation
(SIMV) + pressure support ventilation (PSV), time-cycled pressure-limited
ventilation (TCPL) (hazard ratio (HR) 0.290; 95% confidence interval (CI) 0.071
to 0.972), high-frequency oscillatory ventilation (HFOV) (HR 0.294; 95% CI 0.080
to 0.852), SIMV + volume-guarantee (VG) (HR 0.122; 95% CI 0.014 to 0.858), and
volume-controlled (V-C) (HR 0.139; 95% CI 0.024 to 0.677) ventilation modes are
associated with lower mortality. The combined results of available ventilation
modes were not significantly different in regard to the incidences of patent
ductus arteriosus and intraventricular hemorrhage.
CONCLUSION: Compared with the SIMV + PSV ventilation mode, the TCPL, HFOV,
SIMV + VG, and V-C ventilation modes are associated with lower mortality.

DOI: 10.1186/s13054-015-0843-7
PMCID: PMC4391657
PMID: 25881121  [Indexed for MEDLINE]


317. Arthritis Res Ther. 2015 Mar 19;17:66. doi: 10.1186/s13075-015-0554-0.

Relative benefit-risk comparing diclofenac to other traditional non-steroidal
anti-inflammatory drugs and cyclooxygenase-2 inhibitors in patients with
osteoarthritis or rheumatoid arthritis: a network meta-analysis.

van Walsem A(1), Pandhi S(2), Nixon RM(3), Guyot P(4), Karabis A(5), Moore RA(6).

Author information:
(1)Mapi, De Molen 84, 3995, AX, Houten, The Netherlands.
avanwalsem@mapigroup.com.
(2)Novartis Pharma AG, Lichtstrasse 35, CH-4002, Basel, Switzerland.
shaloo.pandhi@novartis.com.
(3)Novartis Pharma AG, Lichtstrasse 35, CH-4002, Basel, Switzerland.
richard.nixon@novartis.com.
(4)Mapi, De Molen 84, 3995, AX, Houten, The Netherlands. pguyot@mapigroup.com.
(5)Mapi, De Molen 84, 3995, AX, Houten, The Netherlands. akarabis@mapigroup.com.
(6)University of Oxford, Old Road, Headington, OX3 7LE, Oxford, UK.
andrew.moore@ndcn.ox.ac.uk.

INTRODUCTION: There is argument over the benefits and risks of drugs for treating
chronic musculoskeletal pain. This study compared the efficacy, safety, and
tolerability of diclofenac, ibuprofen, naproxen, celecoxib, and etoricoxib for
patients with pain caused by osteoarthritis (OA) or rheumatoid arthritis (RA).
METHODS: A systematic literature review used Medline and EMBASE to identify
randomised controlled trials. Efficacy outcomes assessed included: pain relief
measured by visual analogue scale (VAS); Western Ontario McMaster Universities
Arthritis Index (WOMAC) VAS or WOMAC Likert scale; physical functioning measured
by WOMAC VAS or Likert scale; and patient global assessment (PGA) of disease
severity measured on VAS or 5-point Likert scale. Safety outcomes included:
Antiplatelet Trialists' Collaboration (APTC), major cardiovascular (CV) and major
upper gastrointestinal (GI) events, and withdrawals. Data for each outcome were
synthesized by a Bayesian network meta-analysis (NMA). For efficacy assessments,
labelled doses for OA treatment were used for the base case while labelled doses
for RA treatment were also included in the sensitivity analysis. Pooled data
across dose ranges were used for safety.
RESULTS: Efficacy, safety, and tolerability data were found for 146,524 patients
in 176 studies included in the NMA. Diclofenac (150 mg/day) was likely to be more
effective in alleviating pain than celecoxib (200 mg/day), naproxen (1000
mg/day), and ibuprofen (2400 mg/day), and similar to etoricoxib (60 mg/day); a
lower dose of diclofenac (100 mg/day) was comparable to all other treatments in
alleviating pain. Improved physical function with diclofenac (100 and 150 mg/day)
was mostly comparable to all other treatments. PGA with diclofenac (100 and 150
mg/day) was likely to be more effective or comparable to all other treatments.
All active treatments were similar for APTC and major CV events. Major upper GI
events with diclofenac were lower compared to naproxen and ibuprofen, comparable
to celecoxib, and higher than etoricoxib. Risk of withdrawal with diclofenac was
lower compared to ibuprofen, similar to celecoxib and naproxen, and higher than
etoricoxib.
CONCLUSIONS: The benefit-risk profile of diclofenac was comparable to other
treatments used for pain relief in OA and RA; benefits and risks vary in
individuals and need consideration when making treatment decisions.

DOI: 10.1186/s13075-015-0554-0
PMCID: PMC4411793
PMID: 25879879  [Indexed for MEDLINE]


318. BMC Infect Dis. 2015 Mar 17;15:128. doi: 10.1186/s12879-015-0855-6.

Systematic review and mixed treatment comparison meta-analysis of randomized
clinical trials of primary oral antifungal prophylaxis in allogeneic
hematopoietic cell transplant recipients.

Bow EJ(1), Vanness DJ(2), Slavin M(3), Cordonnier C(4), Cornely OA(5), Marks
DI(6), Pagliuca A(7), Solano C(8), Cragin L(9), Shaul AJ(10), Sorensen S(11),
Chambers R(12), Kantecki M(13), Weinstein D(14), Schlamm H(15).

Author information:
(1)CancerCare Manitoba, 675 McDermot Ave, Winnipeg, MB, Canada.
EJBow@cancercare.mb.ca.
(2)University of Wisconsin and Visiting Scientist at Evidera, Madison, Wisconsin,
USA. dvanness@wisc.edu.
(3)Royal Melbourne Hospital, Melbourne, Australia. Monica.Slavin@mh.org.au.
(4)Assistance Publique-Hopitaux de Paris, Hôpital Henri Mondor and Université
Paris-Est-Créteil, Creteil, France. carlcord@club-internet.fr.
(5)Department I of Internal Medicine, Clinical Trials Centre Cologne, ZKS Köln,
BMBF 01KN1106, Center for Integrated Oncology CIO KölnBonn, Cologne Excellence
Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD),
University of Cologne, Cologne, Germany. Oliver.Cornely@zks-koeln.de.
(6)University Hospitals Bristol NHS Foundation Trust, Bristol, UK.
david.marks@uhbristol.nhs.uk.
(7)King's College Hospital, London, UK. antonio.pagliuca@kcl.ac.uk.
(8)Hospital Clínico, INCLIVA Foundation, University of Valencia, Valencia, Spain.
solano_car@gva.es.
(9)Evidera, Bethesda, Maryland, USA. lael.bilzor@verizon.net.
(10)Evidera, Bethesda, Maryland, USA. mendoza.alissa@gmail.com.
(11)Evidera, Bethesda, Maryland, USA. Sonja.Sorensen@evidera.com.
(12)Pfizer, Collegeville, Pennsylvania, USA. richard.chambers@pfizer.com.
(13)Pfizer, Paris, France. Michal.Kantecki@Pfizer.com.
(14)Pfizer, Paris, France. douvedel@yahoo.fr.
(15)HTS Pharma Consulting, New York, New York, USA. HTSchlamm@att.net.

BACKGROUND: Antifungal prophylaxis is a promising strategy for reducing invasive
fungal infections (IFIs) in allogeneic hematopoietic cell transplant (alloHCT)
recipients, but the optimum prophylactic agent is unknown. We used mixed
treatment comparison (MTC) meta-analysis to compare clinical trials examining the
use of oral antifungals for prophylaxis in alloHCT recipients, with the goal of
informing medical decision-making.
METHODS: Randomized controlled trials (RCTs) of fluconazole, itraconazole,
posaconazole, and voriconazole for primary antifungal prophylaxis were identified
through a systematic literature review. Outcomes of interest (incidence of
IFI/invasive aspergillosis/invasive candidiasis, all-cause mortality, and use of
other antifungals) were extracted from eligible RCTs and incorporated into a
Bayesian hierarchical random-effects MTC.
RESULTS: Five eligible RCTs, randomizing 2147 patients in total, were included.
Relative to fluconazole, prophylaxis with itraconazole (odds ratio [OR]: 0.52;
interquartile range [IQR]: 0.35-0.76), posaconazole (OR: 0.56; IQR: 0.32-0.99),
and voriconazole (OR: 0.46; IQR: 0.28-0.73) reduced incidence of overall
proven/probable IFI. Posaconazole (OR: 0.31; IQR: 0.17-0.58) and voriconazole
(OR: 0.33; IQR: 0.17-0.58) prophylaxis reduced proven/probable invasive
aspergillosis more than itraconazole (OR: 0.68; IQR: 0.42-1.12). All-cause
mortality was similar across all mould-active agents.
CONCLUSION: As expected, mould-active azoles prevented IFIs, particularly
invasive aspergillosis, more effectively than fluconazole in alloHCT recipients.
The paucity of comparative efficacy data suggests that other factors such as
long-term tolerability, availability of intravenous formulations, local IFI
epidemiology, and drug costs may need to form the basis for selection among the
mould-active azoles.

DOI: 10.1186/s12879-015-0855-6
PMCID: PMC4374298
PMID: 25887385  [Indexed for MEDLINE]


319. BMJ Open. 2015 Mar 11;5(3):e006139. doi: 10.1136/bmjopen-2014-006139.

Glycaemic control efficacy of oral antidiabetic drugs in treating type 2
diabetes: a protocol for network meta-analysis.

Jia Y(1), Lao Y(1), Leung SW(2).

Author information:
(1)State Key Laboratory of Quality Research in Chinese Medicine, Institute of
Chinese Medical Sciences, University of Macau, Macao, China.
(2)State Key Laboratory of Quality Research in Chinese Medicine, Institute of
Chinese Medical Sciences, University of Macau, Macao, China School of
Informatics, University of Edinburgh, Edinburgh, UK.

INTRODUCTION: Past studies of network meta-analysis focused on evaluating drug
combinations in treating type 2 diabetes but not on evaluating antidiabetic drugs
in monotherapy. Clinical guidelines (eg, NICE (National Institute of Health and
Care Excellence) clinical guidelines 66 and 87) were based only on the findings
of individual clinical trials and pairwise meta-analysis in evaluating
monotherapy. This study aims to fill this gap of research by conducting a
Bayesian network meta-analysis to compare major antidiabetic drugs, including
metformin, glimepiride, glyburide, glipizide, repaglinide, nateglinide,
sitagliptin, vildagliptin, saxagliptin and SGLT-2 (sodium-glucose transporter-2)
inhibitors.
METHODS AND ANALYSES: Randomised controlled trials (RCTs) on the drug therapy of
type 2 diabetes with outcome measures including glycosylated haemoglobin or
fasting blood glucose will be included. The quality of included RTCs will be
evaluated according to the Cochrane Collaboration's risk of bias tool.
Traditional pairwise meta-analysis and Bayesian network meta-analysis will be
conducted to compare the efficacies of antidiabetic drugs. Sensitivity analysis
on the sample size of RCTs, meta-regression analysis on the follow-up periods,
dosages and baselines of outcome measure, contradiction analysis between pairwise
and network meta-analyses, and publication bias analysis, will be performed.
ETHICS AND DISSEMINATION: Ethical approval is not required because this study
includes no confidential personal data and interventions on the patients.
Pairwise and network meta-analyses are based on the published RCT reports of
eligible drugs in treating type 2 diabetes. The results of this study will be
disseminated by a peer-reviewed publication.
PROTOCOL REGISTRATION NUMBER: PROSPERO CRD42014010567.

Published by the BMJ Publishing Group Limited. For permission to use (where not
already granted under a licence) please go to
http://group.bmj.com/group/rights-licensing/permissions.

DOI: 10.1136/bmjopen-2014-006139
PMCID: PMC4360728
PMID: 25762228  [Indexed for MEDLINE]


320. Crit Care. 2015 Mar 10;19:79. doi: 10.1186/s13054-015-0815-y.

Safety evaluation on low-molecular-weight hydroxyethyl starch for volume
expansion therapy in pediatric patients: a meta-analysis of randomized controlled
trials.

Li L(1), Li Y(2), Xu X(3), Xu B(4), Ren R(5), Liu Y(6), Zhang J(7), He B(8).

Author information:
(1)Department of Pharmacy, Xinhua Hospital, Shanghai Jiaotong University School
of Medicine, Kongjiang Road 1665, Shanghai, 200092, China. llxlyy88@sina.com.
(2)Department of Surgery, Shanghai Jiaotong University Affiliated Sixth People's
Hospital, Yishan Road 600, Shanghai, 200233, China. llxlyy@sina.com.
(3)Department of Epidemiology, Shanghai Jiaotong University School of Medicine,
Kongjiang Road 1665, Shanghai, 200092, China. xiaoxingxu1@sina.com.
(4)Department of Anesthesiology and SICU, Xinhua Hospital, Shanghai Jiaotong
University School of Medicine, Kongjiang Road 1665, Shanghai, 200092, China.
xubo-mazui@163.com.
(5)Department of Anesthesiology and SICU, Xinhua Hospital, Shanghai Jiaotong
University School of Medicine, Kongjiang Road 1665, Shanghai, 200092, China.
lingximengfei@126.com.
(6)Department of Pharmacy, Xinhua Hospital, Shanghai Jiaotong University School
of Medicine, Kongjiang Road 1665, Shanghai, 200092, China. liuyan160@163.com.
(7)Department of Pharmacy, Xinhua Hospital, Shanghai Jiaotong University School
of Medicine, Kongjiang Road 1665, Shanghai, 200092, China. zj_boss@126.com.
(8)Department of Anesthesiology and SICU, Xinhua Hospital, Shanghai Jiaotong
University School of Medicine, Kongjiang Road 1665, Shanghai, 200092, China.
hebinicu@139.com.

INTRODUCTION: Hydroxyethyl starch (HES) has been widely used for volume
expansion, but its safety in adult patients has been questioned recently. The aim
of this meta-analysis is to see whether or not HES has any adverse effect in
pediatric patients.
METHODS: Randomized controlled trials (RCTs) involving pediatric patients who
received 6% low-molecular-weight HES, published before January 2014, were
searched for in Pubmed, Embase database and Cochrane Library. Two reviewers
independently extracted the valid data, including the mortality, renal function,
coagulation, blood loss, hemodynamic changes, and length of hospital and ICU
stay. All data were analyzed by I (2)-test, and the results of statistical
analysis were displayed in forest plots. Possible publication bias was tested by
funnel plots. Bayesian analysis was performed using WinBUGS with fixed and random
effects models.
RESULTS: A total of 13 RCTs involving 1,156 pediatric patients were finally
included in this meta-analysis. Compared with other fluids, HES did not
significantly decrease the mortality (RR = -0.01; 95%CI: 0.05 to 0.03; P = 0.54;
I(2) = 6%), creatinine level (I(2) -test: MD = 1.81; 95%CI: -0.35 to 3.98;
P = 0.10;I(2)  = 0%; Bayesian analysis: Fixed effect model MD = 1.77; 95%CI:
-0.07 to 3.6; Random effects model MD = 1.78; 95%CI: -1.86 to 5.33), activated
partial thromboplastin time (MD = 0.01; 95%CI: -1.05 to 1.07; P = 0.99;
I(2) = 42%), and blood loss (MD = 17.72; 95%CI: -41.27 to 5.82; P = 0.10;
I(2) = 0%) in pediatric patients. However, HES significantly decreased the blood
platelet count (MD = 20.99; 95%CI: -32.08 to -9.90; P = 0.0002; I(2) = 28%) and
increased the length of ICU stay (MD = 0.94; 95%CI: 0.18 to 1.70; P = 0.02;
I(2) = 46%).
CONCLUSIONS: Volume expansion with 6% HES significantly decreased the platelet
count and increased the length of ICU stay, also might have an adverse effect on
renal function. Therefore HES is not recommended for pediatric patients, which
safety needs more high quality RCTs and studies to confirm in future.

DOI: 10.1186/s13054-015-0815-y
PMCID: PMC4391127
PMID: 25887704  [Indexed for MEDLINE]


321. Can J Cardiol. 2015 Mar;31(3):260-9. doi: 10.1016/j.cjca.2014.12.012. Epub 2014
Dec 15.

Transcatheter reduction of paravalvular leaks: a systematic review and
meta-analysis.

Millán X(1), Skaf S(1), Joseph L(2), Ruiz C(3), García E(4), Smolka G(5), Noble
S(6), Cruz-González I(7), Arzamendi D(8), Serra A(8), Kliger C(3), Sia YT(9),
Asgar A(1), Ibrahim R(1), Jolicœur EM(10).

Author information:
(1)Department of Medicine, Montreal Heart Institute, Université de Montréal,
Montreal, Québec, Canada.
(2)Division of Clinical Epidemiology, McGill University Health Centre, Montreal,
Québec, Canada.
(3)Division of Structural and Congenital Heart Disease, Lenox Hill Heart and
Vascular Institute-North Shore LIJ Health System, New York, New York, USA.
(4)Division of Interventional Cardiology, Hospital Universitario Clínico San
Carlos, Madrid, Spain.
(5)Division of Cardiology, Medical University of Silesia, Katowice, Poland.
(6)Department of Medical Specialties, Cardiology Division, Université de Genève,
Geneva, Switzerland.
(7)Division of Interventional Cardiology, Hospital Universitario de Salamanca,
Salamanca, Spain.
(8)Division of Interventional Cardiology, Hospital de la Santa Creu i Sant Pau,
Universitat Autònoma de Barcelona, Barcelona, Spain.
(9)Centre Hospitalier Universitaire de Montréal, Université de Montréal,
Montreal, Québec, Canada.
(10)Department of Medicine, Montreal Heart Institute, Université de Montréal,
Montreal, Québec, Canada. Electronic address: marc.jolicoeur@icm-mhi.org.

BACKGROUND: Significant paravalvular leak (PVL) after surgical valve replacement
can result in intractable congestive heart failure and hemolytic anemia. Because
repeat surgery is performed in only few patients, transcatheter reduction of PVL
is emerging as an alternative option, but its safety and efficacy remain
uncertain. In this study we sought to assess whether a successful transcatheter
PVL reduction is associated with an improvement in clinical outcomes.
METHODS: We identified 12 clinical studies that compared successful and failed
transcatheter PVL reductions in a total of 362 patients. A Bayesian hierarchical
meta-analysis was performed using cardiac mortality as a primary end point. The
combined occurrence of improvement in New York Heart Association functional class
or hemolytic anemia and the need for repeat surgery, were used as secondary end
points.
RESULTS: A successful transcatheter PVL reduction was associated with a lower
cardiac mortality rate (odds ratio [OR], 0.08; 95% credible interval [CrI],
0.01-0.90) and with a superior improvement in functional class or hemolytic
anemia, compared with a failed intervention (OR, 9.95; 95% CrI, 2.10-66.73).
Fewer repeat surgeries were also observed after successful procedures (OR, 0.08;
95% CrI, 0.01-0.40).
CONCLUSIONS: A successful transcatheter PVL reduction is associated with reduced
all-cause mortality and improved functional class in patients deemed unsuitable
for surgical correction.

Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All
rights reserved.

DOI: 10.1016/j.cjca.2014.12.012
PMID: 25746018  [Indexed for MEDLINE]


322. Circ Cardiovasc Qual Outcomes. 2015 Mar;8(2):179-86. doi:
10.1161/CIRCOUTCOMES.114.001306. Epub 2015 Feb 10.

Survival benefit of the primary prevention implantable cardioverter-defibrillator
among older patients: does age matter? An analysis of pooled data from 5 clinical
trials.

Hess PL(1), Al-Khatib SM(2), Han JY(2), Edwards R(2), Bardy GH(2), Bigger JT(2),
Buxton A(2), Cappato R(2), Dorian P(2), Hallstrom A(2), Kadish AH(2), Kudenchuk
PJ(2), Lee KL(2), Mark DB(2), Moss AJ(2), Steinman R(2), Inoue LY(2), Sanders
G(2).

Author information:
(1)From the Duke Clinical Research Institute, Durham, NC (P.L.H., S.M.A., R.E.,
K.L.L., D.B.M., G.S.); University of Washington, Seattle (J.Y.H., G.H.B., A.H.,
P.J.K., L.Y.T.I.); Columbia University, New York, NY (J.T.B., R.S.); Beth Israel
Deaconess Medical Center, Boston, MA (A.B.); I.R.C.C.S. Policlinico San Donato,
Milan, Italy (R.C.); University of Toronto, Ontario, Canada (P.D.); Northwestern
Feinberg School of Medicine, Chicago, IL (A.H.K.); and University of Rochester,
Rochester, NY (A.J.M.). p.hess@duke.edu.
(2)From the Duke Clinical Research Institute, Durham, NC (P.L.H., S.M.A., R.E.,
K.L.L., D.B.M., G.S.); University of Washington, Seattle (J.Y.H., G.H.B., A.H.,
P.J.K., L.Y.T.I.); Columbia University, New York, NY (J.T.B., R.S.); Beth Israel
Deaconess Medical Center, Boston, MA (A.B.); I.R.C.C.S. Policlinico San Donato,
Milan, Italy (R.C.); University of Toronto, Ontario, Canada (P.D.); Northwestern
Feinberg School of Medicine, Chicago, IL (A.H.K.); and University of Rochester,
Rochester, NY (A.J.M.).

BACKGROUND: The impact of patient age on the risks of death or rehospitalization
after primary prevention implantable cardioverter-defibrillator (ICD) placement
is uncertain.
METHODS AND RESULTS: Data from 5 major ICD trials were merged: the Multicenter
Automatic Defibrillator Implantation Trial I (MADIT-I), the Multicenter
UnSustained Tachycardia Trial (MUSTT), the Multicenter Automatic Defibrillator
Implantation Trial II (MADIT-II), the Defibrillators in Nonischemic
Cardiomyopathy Treatment Evaluation Trial (DEFINITE), and the Sudden Cardiac
Death in Heart Failure Trial (SCD-HeFT). Median age at enrollment was 62
(interquartile range 53-70) years. Compared with their younger counterparts,
older patients had a greater burden of comorbid illness. In unadjusted
exploratory analyses, ICD recipients were less likely to die than nonrecipients
in all age groups: among patients aged <55 years: hazard ratio 0.48, 95%
posterior credible interval 0.33 to 0.69; among patients aged 55 to 64 years:
hazard ratio 0.69, 95% posterior credible interval 0.53 to 0.90; among patients
aged 65 to 74 years: hazard ratio 0.67, 95% posterior credible interval, 0.53 to
0.85; and among patients aged ≥75 years: hazard ratio 0.54, 95% posterior
credible interval 0.37 to 0.78. Sample sizes were limited among patients aged ≥75
years. In adjusted Bayesian-Weibull modeling, point estimates indicate ICD
efficacy persists but is attenuated with increasing age. There was evidence of an
interaction between age and ICD treatment on survival (two-sided posterior tail
probability of no interaction <0.01). Using an adjusted Bayesian logistic
regression model, there was no evidence of an interaction between age and ICD
treatment on rehospitalization (two-sided posterior tail probability of no
interaction 0.44).
CONCLUSIONS: In this analysis, the survival benefit of the ICD exists but is
attenuated with increasing age. The latter finding may be because of the higher
burden of comorbid illness, competing causes of death, or limited sample size of
older patients. There was no evidence that age modifies the association between
ICD treatment and rehospitalization.

© 2015 American Heart Association, Inc.

DOI: 10.1161/CIRCOUTCOMES.114.001306
PMCID: PMC4408540
PMID: 25669833  [Indexed for MEDLINE]


323. Gastrointest Endosc. 2015 Mar;81(3):700-709.e3. doi: 10.1016/j.gie.2014.10.033.

Comparing the effectiveness of competing tests for reducing colorectal cancer
mortality: a network meta-analysis.

Elmunzer BJ(1), Singal AG(2), Sussman JB(3), Deshpande AR(4), Sussman DA(4),
Conte ML(5), Dwamena BA(6), Rogers MA(7), Schoenfeld PS(8), Inadomi JM(9), Saini
SD(8), Waljee AK(8).

Author information:
(1)Department of Internal Medicine, Division of Gastroenterology and Hepatology,
University of Michigan Health System, Ann Arbor, Michigan, USA.
(2)Department of Internal Medicine, Division of Digestive and Liver Diseases and
the Harold C. Simmons Cancer Center, University of Texas Southwestern Medical
Center, Dallas, Texas, USA.
(3)Center for Clinical Management Research, Ann Arbor Veterans Affairs Healthcare
System, Ann Arbor, Michigan, USA; Department of Internal Medicine, Division of
General Internal Medicine, University of Michigan Health System, Ann Arbor,
Michigan, USA.
(4)Department of Internal Medicine, Division of Gastroenterology, University of
Miami Miller School of Medicine, Miami, Florida, USA.
(5)University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
(6)Department of Radiology, Division of Nuclear Medicine, University of Michigan
Health System, Ann Arbor, Michigan, USA.
(7)Department of Internal Medicine, Division of General Internal Medicine,
University of Michigan Health System, Ann Arbor, Michigan, USA.
(8)Department of Internal Medicine, Division of Gastroenterology and Hepatology,
University of Michigan Health System, Ann Arbor, Michigan, USA; Center for
Clinical Management Research, Ann Arbor Veterans Affairs Healthcare System, Ann
Arbor, Michigan, USA.
(9)Department of Medicine, Division of Gastroenterology, University of Washington
School of Medicine, Seattle, Washington, USA.

Comment in
    Gastrointest Endosc. 2015 Mar;81(3):710-2.

BACKGROUND: Comparative effectiveness data pertaining to competing colorectal
cancer (CRC) screening tests do not exist but are necessary to guide clinical
decision making and policy.
OBJECTIVE: To perform a comparative synthesis of clinical outcomes studies
evaluating the effects of competing tests on CRC-related mortality.
DESIGN: Traditional and network meta-analyses. Two reviewers identified studies
evaluating the effect of guaiac-based fecal occult blood testing (gFOBT),
flexible sigmoidoscopy (FS), or colonoscopy on CRC-related mortality.
INTERVENTIONS: gFOBT, FS, colonoscopy.
MAIN OUTCOME MEASUREMENTS: Traditional meta-analysis was performed to produce
pooled estimates of the effect of each modality on CRC mortality. Bayesian
network meta-analysis (NMA) was performed to indirectly compare the effectiveness
of screening modalities. Multiple sensitivity analyses were performed.
RESULTS: Traditional meta-analysis revealed that, compared with no intervention,
colonoscopy reduced CRC-related mortality by 57% (relative risk [RR] 0.43; 95%
confidence interval [CI], 0.33-0.58), whereas FS reduced CRC-related mortality by
40% (RR 0.60; 95% CI, 0.45-0.78), and gFOBT reduced CRC-related mortality by 18%
(RR 0.82; 95% CI, 0.76-0.88). NMA demonstrated nonsignificant trends favoring
colonoscopy over FS (RR 0.71; 95% CI, 0.45-1.11) and FS over gFOBT (RR 0.74; 95%
CI, 0.51-1.09) for reducing CRC-related deaths. NMA-based simulations, however,
revealed that colonoscopy has a 94% probability of being the most effective test
for reducing CRC mortality and a 99% probability of being most effective when the
analysis is restricted to screening studies.
LIMITATIONS: Randomized trials and observational studies were combined within the
same analysis.
CONCLUSION: Clinical outcomes studies demonstrate that gFOBT, FS, and colonoscopy
are all effective in reducing CRC-related mortality. Network meta-analysis
suggests that colonoscopy is the most effective test.

Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by
Elsevier Inc. All rights reserved.

DOI: 10.1016/j.gie.2014.10.033
PMCID: PMC4766592
PMID: 25708757  [Indexed for MEDLINE]


324. J Allergy Clin Immunol Pract. 2015 Mar-Apr;3(2):256-266.e3. doi:
10.1016/j.jaip.2014.09.018. Epub 2014 Nov 20.

Network meta-analysis shows commercialized subcutaneous and sublingual grass
products have comparable efficacy.

Nelson H(1), Cartier S(2), Allen-Ramey F(3), Lawton S(4), Calderon MA(5).

Author information:
(1)National Jewish Health, Denver, Colo. Electronic address:
nelsonh@njhealth.org.
(2)Optum Burlington, ON, Canada.
(3)Merck & Co, Inc, Whitehouse Station, NJ.
(4)ALK Hørsholm, Denmark.
(5)Imperial College London, Section of Allergy and Clinical Immunology, National
Heart and Lung Institute, Royal Hospital Brompton, London, United Kingdom.

Comment in
    J Allergy Clin Immunol Pract. 2015 Mar-Apr;3(2):267-8.

BACKGROUND: Subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT)
have been shown to effectively treat grass pollen allergies, although direct
comparisons are sparse.
OBJECTIVE: To estimate the relative efficacy of SLIT tablets compared with SCIT
and SLIT drops in commercially available products though network meta-analysis.
METHODS: A literature search of MEDLINE, Embase, and Cochrane Library
publications. Randomized, double-blind clinical trials of SCIT, SLIT drops, and
SLIT tablets for grass pollen were included. Bayesian network meta-analyses
estimated the standardized mean difference (SMD) across 3 immunotherapy
modalities on allergic rhinoconjunctivitis symptom and medication score data from
publications or received from authors. Both fixed and random effects models were
investigated.
RESULTS: Thirty-seven studies were included in meta-analyses for symptom scores
and 31 studies for medication scores. In the random effects model, SCIT and SLIT
tablets were significantly different from placebo for symptom scores: SMDs (95%
CI) of -0.32 (-0.45 to -0.18) and -0.32 (-0.41 to -0.23), respectively. No
significant difference was identified for SLIT drops compared with placebo
(SMD, -0.17; -0.37 to 0.04). For medication scores, significant differences
compared with placebo were observed for SCIT (SMD, -0.33; 95% CI, -0.52
to -0.13), SLIT tablets (SMD, -0.23; 95% CI, -0.29 to -0.17), and SLIT drops
(SMD, -0.44; 95% CI, -0.83 to -0.06). Network meta-analysis revealed no
significant differences in SMDs (95% credible interval) for symptom scores
(0.0145 [-0.19 to 0.23]) or medication scores (0.133 [-0.31 to 0.57]) between
SLIT tablets and SCIT, or for symptom scores (-0.175 [-0.37 to 0.02]) and
medication scores (0.188 [-0.18 to 0.56]) between SLIT tablets and SLIT drops.
CONCLUSIONS: The comparisons for grass pollen immunotherapy products
commercialized in at least 1 country indicate comparable reductions in allergic
rhinoconjunctivitis symptoms and supplemental medication use for SLIT tablets and
SCIT in the first pollen season.

Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by
Elsevier Inc. All rights reserved.

DOI: 10.1016/j.jaip.2014.09.018
PMID: 25609326  [Indexed for MEDLINE]


325. J Comp Eff Res. 2015 Mar;4(2):101-14. doi: 10.2217/cer.14.69.

A meta-analysis platform methodology for determining the comparative
effectiveness of antihepatitis C virus regimens.

Broglio KR(1), Daar ES, Quintana M, Yuan Y, Kalsekar A, Spellberg B, Lewis RJ,
Akker Dv, Detry MA, Le T, Berry SM.

Author information:
(1)Berry Consultants, LLC, Austin, TX 78746, USA.

AIM: Many hepatitis C virus regimens are unlikely to be compared head to head. In
more difficult to treat populations where there is no standard of care, trials
are single arm. We describe a flexible meta-analysis platform in this setting.
METHODS: Our meta-analysis is literature based. We illustrate our methodology and
show how inference can be extended to single-arm trials.
RESULTS: As an example, in the single arm setting, a regimen with response rates
of 84, 72 and 54% in genotype 1a across treatment naive, previous partial
responders and previous null responders, respectively, would have 95% probability
of superiority to IFN-α + RBV + TPV.
CONCLUSION: This is a rigorous approach to comparative effectiveness that
accounts for varying patient populations and plans for the incorporation of
emerging treatments.

DOI: 10.2217/cer.14.69
PMID: 25825840  [Indexed for MEDLINE]


326. JACC Cardiovasc Interv. 2015 Mar;8(3):382-394. doi: 10.1016/j.jcin.2014.09.023.
Epub 2015 Feb 18.

Comparison among drug-eluting balloon, drug-eluting stent, and plain balloon
angioplasty for the treatment of in-stent restenosis: a network meta-analysis of
11 randomized, controlled trials.

Lee JM(1), Park J(1), Kang J(1), Jeon KH(1), Jung JH(1), Lee SE(1), Han JK(1),
Kim HL(2), Yang HM(1), Park KW(1), Kang HJ(1), Koo BK(1), Kim HS(3).

Author information:
(1)Department of Internal Medicine and Cardiovascular Center, Seoul National
University Hospital, Seoul, South Korea.
(2)Cardiovascular Center, Seoul National University Boramae Hospital, Seoul,
South Korea.
(3)Department of Internal Medicine and Cardiovascular Center, Seoul National
University Hospital, Seoul, South Korea; Molecular Medicine & Biopharmaceutical
Science, Graduate School of Convergence Science & Technology, Seoul National
University, Seoul, South Korea. Electronic address: usahyosoo@gmail.com.

Comment in
    JACC Cardiovasc Interv. 2015 Mar;8(3):395-7.

OBJECTIVES: A Bayesian network meta-analysis was performed comparing the efficacy
and safety of drug-eluting balloons (DEB), drug-eluting stents (DES), or plain
old balloon angioplasty (POBA) for treatment of in-stent restenosis (ISR).
BACKGROUND: Optimal treatment options for ISR have not been well established.
METHODS: Randomized, controlled trials comparing DEB, DES, and POBA for the
treatment of ISR after percutaneous coronary intervention with bare metal stent
or DES were included. The primary outcome was target lesion revascularization
(TLR). The pairwise posterior median odds ratio (OR) with 95% credible interval
(CrI) was the effect measure.
RESULTS: This analysis included 2,059 patients from 11 RCTs. The risk of TLR was
markedly lower in patients treated with DEB (OR: 0.22, 95% CrI: 0.10 to 0.42) or
DES (OR: 0.24, 95% CrI: 0.11 to 0.47) than in those treated with POBA in a
random-effects model. In a comparison of DEB and DES, the risk of TLR (OR: 0.92,
95% CrI: 0.43 to 1.90) was similar. The risk of MI or all-cause mortality was
lowest in the DEB group compared with the DES and POBA groups, which did not meet
statistical significance. The risk of major adverse cardiac events, which was
mainly driven by TLR, was also significantly lower in the DEB or and DES group
(OR: 0.28, 95% CrI: 0.14 to 0.53) than in the POBA group, but it was similar
between the DEB and DES groups (OR: 0.84, 95% CrI: 0.45 to 1.50). The probability
of being ranked as the best treatment was 59.9% (DEB), 40.1% (DES), and 0.1%
(POBA) in terms of TLR, whereas it was 63.0% (DEB), 35.3% (POBA), and 1.7% (DES)
in terms of MI.
CONCLUSIONS: Local drug delivery by DEB or DES for ISR lesions was markedly
better than POBA in preventing TLR, but not for MI or mortality. Among the 2
different strategies of drug delivery for ISR lesions, treatment with DEB showed
a trend of less development of MI than did treatment with DES.

Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier
Inc. All rights reserved.

DOI: 10.1016/j.jcin.2014.09.023
PMID: 25703886  [Indexed for MEDLINE]


327. Medicine (Baltimore). 2015 Mar;94(11):e595. doi: 10.1097/MD.0000000000000595.

Interventions for treating displaced midshaft clavicular fractures: a Bayesian
network meta-analysis of randomized controlled trials.

Wang J(1), Meng XH, Guo ZM, Wu YH, Zhao JG.

Author information:
(1)From the Department of Orthopaedic Surgery (JW, Z-MG, Y-HW), Tianjin Hospital;
Graduate School (X-HM), Tianjin University of Traditional Chinese Medicine; and
Department of Orthopaedic Surgery (J-GZ), Clinical College of Orthopaedic
Surgery, Tianjin Medical University, Tianjin, China.

Displaced midshaft clavicle fractures are frequent injuries. There are 3
treatment methods including conservative treatment, plate fixation, and
intramedullary pin fixation. However, which is the best treatment remains a topic
of debate.To establish the optimum treatment for displaced midshaft clavicular
fractures, we did a network meta-analysis to compare 3 treatments in terms of
postoperative nonunion and infection.We searched PubMed, the Cochrane Library,
and Embase for relevant randomized controlled trials (RCTs) until the end of
October 2014. Two investigators independently reviewed the abstract and full text
of eligible studies and extracted information. We used WinBUGS 1.4 (Imperial
College School of Medicine at St Mary's, London) to perform our Bayesian network
meta-analysis. We used the graphical tools in STATA12 (StataCorp, Texas) to
present the results of statistical analyses of WinBUGS14. Nonunion and infection
were presented as odd ratios (ORs) with 95% confidence intervals (CIs). We also
presented the results using surface under the cumulative ranking curve (SUCRA). A
higher SUCRA value suggests better results for respective treatment
method.Thirteen RCTs were included in our network meta-analysis, with a total of
894 patients randomized to receive 1 of 3 treatments. Nonunion rates were 0.9%,
2.4%, and 11.4% for intramedullary pin fixation, plate fixation, and conservative
method, respectively. Nonunion occurred more commonly in patients treated with
conservative method than in patients treated with either plate fixation (OR,
0.18; 95% CI, 0.05-0.46) or intramedullary pin fixation (OR, 0.12; 95% CI,
0.01-0.50). There was no significant difference between plate and intramedullary
pin fixation in nonunion (OR, 3.64; 95% CI, 0.31-17.27). Furthermore, SUCRA
probabilities were 87.8%, 62.0%, and 0.2% for intramedullary pin fixation, plate
fixation, and conservative method, respectively. Infection rates were 3.6% and
3.9% for intramedullary pin fixation and plate fixation, respectively. There was
no significant difference between plate and intramedullary pin fixation in
infection (OR, 3.64; 95% CI, 0.31-17.27). SUCRA probabilities were 46.5% and 8.5%
for intramedullary pin and plate fixation, respectively.Our network meta-analysis
suggested that intramedullary pin fixation is the optimum treatment method for
displaced midshaft clavicle fracture because of the low probabilities of nonunion
and infection.

DOI: 10.1097/MD.0000000000000595
PMCID: PMC4602486
PMID: 25789948  [Indexed for MEDLINE]


328. Medicine (Baltimore). 2015 Mar;94(10):e510. doi: 10.1097/MD.0000000000000510.

Treatments for shoulder impingement syndrome: a PRISMA systematic review and
network meta-analysis.

Dong W(1), Goost H, Lin XB, Burger C, Paul C, Wang ZL, Zhang TY, Jiang ZC, Welle
K, Kabir K.

Author information:
(1)From the Department of Orthopedic and Trauma Surgery (WD, Z-LW, T-YZ), Central
Hospital of PetroChina, Langfang, Hebei, China; Department of Orthopedic and
Trauma Surgery (WD, CB, KW, KK), University Hospital Bonn, Bonn; Department of
Orthopedic and Trauma Surgery (HG), Hospital Wermelskirchen, Wermelskirchen,
Germany; Department of Orthopedic and Trauma Surgery (X-BL), Rizhao People's
Hospital, Rizhao, Shandong, China; Department of Orthopedic and Trauma Surgery
(CP), Evangelic Wald-Krankenhaus, Bonn, Germany; and Department of Fundamental
Science (Z-CJ), North China Institute of Aerospace Engineering, Langfang, Hebei,
China.

Many treatments for shoulder impingement syndrome (SIS) are available in clinical
practice; some of which have already been compared with other treatments by
various investigators. However, a comprehensive treatment comparison is lacking.
Several widely used electronic databases were searched for eligible studies. The
outcome measurements were the pain score and the Constant-Murley score (CMS).
Direct comparisons were performed using the conventional pair-wise meta-analysis
method, while a network meta-analysis based on the Bayesian model was used to
calculate the results of all potentially possible comparisons and rank
probabilities. Included in the meta-analysis procedure were 33 randomized
controlled trials involving 2300 patients. Good agreement was demonstrated
between the results of the pair-wise meta-analyses and the network meta-analyses.
Regarding nonoperative treatments, with respect to the pain score, combined
treatments composed of exercise and other therapies tended to yield better
effects than single-intervention therapies. Localized drug injections that were
combined with exercise showed better treatment effects than any other treatments,
whereas worse effects were observed when such injections were used alone.
Regarding the CMS, most combined treatments based on exercise also demonstrated
better effects than exercise alone. Regarding surgical treatments, according to
the pain score and the CMS, arthroscopic subacromial decompression (ASD) together
with treatments derived from it, such as ASD combined with radiofrequency and
arthroscopic bursectomy, showed better effects than open subacromial
decompression (OSD) and OSD combined with the injection of platelet-leukocyte
gel. Exercise therapy also demonstrated good performance. Results for
inconsistency, sensitivity analysis, and meta-regression all supported the
robustness and reliability of these network meta-analyses. Exercise and other
exercise-based therapies, such as kinesio taping, specific exercises, and
acupuncture, are ideal treatments for patients at an early stage of SIS. However,
low-level laser therapy and the localized injection of nonsteroidal
anti-inflammatory drugs are not recommended. For patients who have a long-term
disease course, operative treatments may be considered, with standard ASD surgery
preferred over arthroscopic bursectomy and the open surgical technique for
subacromial decompression. Notwithstanding, the choice of surgery should be made
cautiously because similar outcomes may also be achieved by the implementation of
exercise therapy.

DOI: 10.1097/MD.0000000000000510
PMCID: PMC4602475
PMID: 25761173  [Indexed for MEDLINE]


329. Lancet. 2015 Feb 28;385(9970):792-8. doi: 10.1016/S0140-6736(14)62052-3. Epub
2014 Nov 16.

Extended duration dual antiplatelet therapy and mortality: a systematic review
and meta-analysis.

Elmariah S(1), Mauri L(2), Doros G(3), Galper BZ(4), O'Neill KE(4), Steg PG(5),
Kereiakes DJ(6), Yeh RW(7).

Author information:
(1)Cardiology Division, Department of Medicine, Massachusetts General Hospital,
Harvard Medical School, Boston, MA, USA; Harvard Clinical Research Institute,
Boston, MA, USA.
(2)Division of Cardiovascular Medicine, Department of Medicine, Brigham and
Women's Hospital, Harvard Medical School, Boston, MA, USA; Harvard Clinical
Research Institute, Boston, MA, USA.
(3)Harvard Clinical Research Institute, Boston, MA, USA; Department of
Biostatistics, Boston University School of Public Health, Boston, MA, USA.
(4)Division of Cardiovascular Medicine, Department of Medicine, Brigham and
Women's Hospital, Harvard Medical School, Boston, MA, USA.
(5)Université Paris-Diderot, Sorbonne Paris-Cité, Paris, France; Département
Hospitalo-Universitaire FIRE (Fibrosis, Inflammation and Remodeling), INSERM
U-1148 and Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France;
National Heart Lung Institute, Imperial College, Royal Brompton Hospital, London,
UK.
(6)The Lindner Research Center, The Christ Hospital Heart and Vascular Center,
Cincinnati, OH, USA.
(7)Cardiology Division, Department of Medicine, Massachusetts General Hospital,
Harvard Medical School, Boston, MA, USA; Harvard Clinical Research Institute,
Boston, MA, USA. Electronic address: ryeh@mgh.harvard.edu.

Erratum in
    Lancet. 2015 May 9;385(9980):1834.

Comment in
    Lancet. 2015 Feb 28;385(9970):756-7.
    Nat Rev Cardiol. 2015 Jan;12(1):1.
    Lancet. 2015 May 30;385(9983):2149.
    Lancet. 2015 May 30;385(9983):2149-50.

BACKGROUND: Treatment with aspirin and a P2Y12 inhibitor is commonly used in
patients with cardiovascular disorders. The overall effect of such treatment on
all-cause mortality is unknown. In the Dual Antiplatelet Therapy (DAPT) Study,
continuation of dual antiplatelet therapy beyond 12 months after coronary
stenting was associated with an unexpected increase in non-cardiovascular death.
In view of the potential public health importance of these findings, we aimed to
assess the effect of extended duration dual antiplatelet therapy on mortality by
doing a meta-analysis of all randomised, controlled trials of treatment duration
in various cardiovascular disorders.
METHODS: We searched Medline, Embase, and Cochrane Central Register of Controlled
Trials (CENTRAL) to identify randomised controlled trials assessing the effect of
extended duration versus no or short duration dual antiplatelet therapy,
published before Oct 1, 2014. We did a meta-analysis to pool results with a
hierarchical Bayesian random-effects model. The primary outcomes were hazard
ratios comparing rates of all-cause, cardiovascular, and non-cardiovascular
death.
FINDINGS: Including the DAPT Study, we identified 14 eligible trials that
randomly assigned 69,644 participants to different durations of dual antiplatelet
therapy. Compared with aspirin alone or short duration dual antiplatelet therapy
(≤6 months), continued treatment was not associated with a difference in
all-cause mortality (hazard ratio [HR] 1·05, 95% credible interval [CrI]
0·96-1·19; p=0·33). Similarly, cardiovascular (1·01, 0·93-1·12; p=0·81) and
non-cardiovascular mortality (1·04, 0·90-1·26; p=0·66) were no different with
extended duration versus short duration dual antiplatelet therapy or aspirin
alone.
INTERPRETATION: Extended duration dual antiplatelet therapy was not associated
with a difference in the risk of all-cause, cardiovascular, or non-cardiovascular
death compared with aspirin alone or short duration dual antiplatelet therapy.
FUNDING: None.

Copyright © 2015 Elsevier Ltd. All rights reserved.

DOI: 10.1016/S0140-6736(14)62052-3
PMCID: PMC4386690
PMID: 25467565  [Indexed for MEDLINE]


330. Syst Rev. 2015 Feb 27;4:19. doi: 10.1186/s13643-015-0005-7.

The pharmacological and non-pharmacological treatment of attention deficit
hyperactivity disorder in children and adolescents: protocol for a systematic
review and network meta-analysis of randomized controlled trials.

Catalá-López F(1), Hutton B(2)(3), Núñez-Beltrán A(4), Mayhew AD(5), Page MJ(6),
Ridao M(7)(8), Tobías A(9), Catalá MA(10), Tabarés-Seisdedos R(11), Moher
D(12)(13).

Author information:
(1)Fundación Instituto de Investigación en Servicios de Salud, Valencia, Spain.
ferran_catala@hotmail.com.
(2)Clinical Epidemiology Program, Ottawa Hospital Research Institute (OHRI),
Ottawa, ON, Canada. bhutton@ohri.ca.
(3)Department of Epidemiology and Community Medicine, Faculty of Medicine,
University of Ottawa, Ottawa, ON, Canada. bhutton@ohri.ca.
(4)Centro de Atención Integral a Drogodependientes (CAID) Norte, Regional Health
Council, Madrid, Spain. anunezbeltran@hotmail.com.
(5)Clinical Epidemiology Program, Ottawa Hospital Research Institute (OHRI),
Ottawa, ON, Canada. almayhew@ohri.ca.
(6)Australasian Cochrane Centre, School of Public Health and Preventive Medicine,
Monash University, Melbourne, Australia. matthew.page@monash.edu.
(7)Instituto Aragonés de Ciencias de la Salud (IACS), Red de Investigación en
Servicios de Salud en Enfermedades Crónicas (REDISSEC), Zaragoza, Spain.
ridao_man@gva.es.
(8)FISABIO-Salud Pública, Valencia, Spain. ridao_man@gva.es.
(9)Spanish Council for Scientific Research (CSIC), Barcelona, Spain.
aurelio.tobias@idaea.csic.es.
(10)University of Valencia, Valencia, Spain. miguel.a.catala@uv.es.
(11)University of Valencia/CIBERSAM, and Instituto de Investigación Sanitaria de
Valencia (INCLIVA), Valencia, Spain. rafael.tabares@uv.es.
(12)Clinical Epidemiology Program, Ottawa Hospital Research Institute (OHRI),
Ottawa, ON, Canada. dmoher@ohri.ca.
(13)Department of Epidemiology and Community Medicine, Faculty of Medicine,
University of Ottawa, Ottawa, ON, Canada. dmoher@ohri.ca.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the most
common neurodevelopmental disorders of children and adolescents, with a
significant impact on health services and the community in terms of economic and
social burdens. The objective of this systematic review will be to evaluate the
comparative efficacy and safety of pharmacological and non-pharmacological
treatments in children and adolescents with ADHD.
METHODS: Searches involving PubMed/MEDLINE and the Cochrane Database of
Systematic Reviews will be used to identify related systematic reviews and
relevant randomized trials. Search results will be supplemented by reports from
the regulatory and health technology agencies, clinical trials registers and by
data requested from trialists and/or pharmaceutical companies. We will consider
studies evaluating pharmacological interventions (e.g. stimulants,
non-stimulants, antidepressants), psychological interventions (e.g. behavioural
interventions, cognitive training and neurofeedback) and complementary and
alternative medicine interventions (e.g. dietary interventions, supplement with
fatty acids, vitamins, minerals, aminoacids, herbal treatment, homeopathy, and
mind-body interventions including massage, chiropractic, acupuncture, yoga,
meditation, Tai chi). Eligible control conditions will be placebo, waitlist, no
treatment and usual care. Randomized controlled trials of a minimum of 3 weeks
duration will be included. The primary outcomes of interest will be the
proportion of patients who responded to treatment and who dropped out of the
allocated treatment, respectively. Secondary outcomes will include treatment
discontinuation due to adverse events, as well as the occurrences of serious
adverse events and specific adverse events (decreased weight, anorexia, insomnia
and sleep disturbances, anxiety, syncope and cardiovascular events). Two
reviewers will independently screen references identified by the literature
search, as well as potentially relevant full-text articles in duplicate. Data
will be abstracted and risk of bias will be appraised by two team members
independently. Conflicts at all levels of screening and abstraction will be
resolved through discussion. Random-effects pairwise meta-analyses and Bayesian
network meta-analyses will be conducted where appropriate.
DISCUSSION: This systematic review and network meta-analysis will compare the
efficacy and safety of treatments used for ADHD in children and adolescents. The
findings will assist patients, clinicians and healthcare providers to make
evidence-based decisions regarding treatment selection.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014015008 .

DOI: 10.1186/s13643-015-0005-7
PMCID: PMC4357151
PMID: 25875125  [Indexed for MEDLINE]


331. BMJ Open. 2015 Feb 13;5(2):e005918. doi: 10.1136/bmjopen-2014-005918.

Psychotherapy for depression in children and adolescents: study protocol for a
systematic review and network meta-analysis.

Qin B(1), Zhou X(1), Michael KD(2), Liu Y(1), Whittington C(3), Cohen D(4), Zhang
Y(1), Xie P(1).

Author information:
(1)Department of Neurology, The First Affiliated Hospital of Chongqing Medical
University, Chongqing, China.
(2)Department of Psychology, Appalachian State University, Boone, North Carolina,
USA.
(3)Centre for Outcomes Research and Effectiveness, Research Department of
Clinical, Educational & Health Psychology, University College London, London, UK.
(4)Sorbonne Universités; and the Department of Child and Adolescent Psychiatry,
Institut des Systèmes Intelligents et de Robotiques, UPMC Univ Paris 06, UMR
7222, AP-HP, Hôpital Pitié-Salpétrière, Paris, France.

INTRODUCTION: Depression is common among children and adolescents and is
associated with significantly negative effects. A number of structured
psychosocial treatments are administered for depression in children and
adolescents; however, evidence of their effectiveness is not clear. We describe
the protocol of a systematic review and network meta-analysis to evaluate the
efficacy, quality of life, tolerability and acceptability of the use of
psychological intervention for this young population.
METHODS AND ANALYSIS: We will search PubMed, EMBASE, CENTRAL (the Cochrane
Central Register of Controlled Trials), Web of Science, PsycINFO, CINAHL, LiLACS,
Dissertation Abstracts, European Association for Grey Literature Exploitation
(EAGLE) and the National Technical Information Service (NTIS) from inception to
July 2014. There will be no restrictions on language, publication year or
publication type. Only randomised clinical trials (RCTs) with psychosocial
treatments for depression in children and adolescents will be considered. The
primary outcome of efficacy will be the mean overall change of the total score in
continuous depression severity scales from baseline to end point. Data will be
independently extracted by two reviewers. Traditional pairwise meta-analyses will
be performed for studies that directly compared different treatment arms. Then we
will perform a Bayesian network meta-analyses to compare the relative efficacy,
quality of life, tolerability and acceptability of different psychological
intervention. Subgroup analyses will be performed by the age of participants and
the duration of psychotherapy, and sensitivity analyses will be conducted to
assess the robustness of the findings.
ETHICS AND DISSEMINATION: No ethical issues are foreseen. The results will be
published in a peer-reviewed journal and disseminated electronically and in
print. The meta-analysis may be updated to inform and guide management of
depression in children and adolescents.
TRIALS REGISTRATION NUMBER: PROSPERO CRD42014010014.

Published by the BMJ Publishing Group Limited. For permission to use (where not
already granted under a licence) please go to
http://group.bmj.com/group/rights-licensing/permissions.

DOI: 10.1136/bmjopen-2014-005918
PMCID: PMC4330321
PMID: 25681311  [Indexed for MEDLINE]


332. Cochrane Database Syst Rev. 2015 Feb 6;(2):CD009944. doi:
10.1002/14651858.CD009944.pub2.

Diagnostic accuracy of endoscopic ultrasonography (EUS) for the preoperative
locoregional staging of primary gastric cancer.

Mocellin S(1), Pasquali S.

Author information:
(1)Meta-Analysis Unit, Department of Surgery,Oncology and Gastroenterology,
University of Padova, Via Giustiniani 2, Padova, Veneto, 35128, Italy.
simone.mocellin@unipd.it. mocellins@hotmail.com.

BACKGROUND: Endoscopic ultrasound (EUS) is proposed as an accurate diagnostic
device for the locoregional staging of gastric cancer, which is crucial to
developing a correct therapeutic strategy and ultimately to providing patients
with the best chance of cure. However, despite a number of studies addressing
this issue, there is no consensus on the role of EUS in routine clinical
practice.
OBJECTIVES: To provide both a comprehensive overview and a quantitative analysis
of the published data regarding the ability of EUS to preoperatively define the
locoregional disease spread (i.e., primary tumor depth (T-stage) and regional
lymph node status (N-stage)) in people with primary gastric carcinoma.
SEARCH METHODS: We performed a systematic search to identify articles that
examined the diagnostic accuracy of EUS (the index test) in the evaluation of
primary gastric cancer depth of invasion (T-stage, according to the AJCC/UICC TNM
staging system categories T1, T2, T3 and T4) and regional lymph node status
(N-stage, disease-free (N0) versus metastatic (N+)) using histopathology as the
reference standard. To this end, we searched the following databases: the
Cochrane Library (the Cochrane Central Register of Controlled Trials (CENTRAL)),
MEDLINE, EMBASE, NIHR Prospero Register, MEDION, Aggressive Research Intelligence
Facility (ARIF), ClinicalTrials.gov, Current Controlled Trials MetaRegister, and
World Health Organization International Clinical Trials Registry Platform (WHO
ICTRP), from 1988 to January 2015.
SELECTION CRITERIA: We included studies that met the following main inclusion
criteria: 1) a minimum sample size of 10 patients with histologically-proven
primary carcinoma of the stomach (target condition); 2) comparison of EUS (index
test) with pathology evaluation (reference standard) in terms of primary tumor
(T-stage) and regional lymph nodes (N-stage). We excluded reports with possible
overlap with the selected studies.
DATA COLLECTION AND ANALYSIS: For each study, two review authors extracted a
standard set of data, using a dedicated data extraction form. We assessed data
quality using a standard procedure according to the Quality Assessment of
Diagnostic Accuracy Studies (QUADAS-2) criteria. We performed diagnostic accuracy
meta-analysis using the hierarchical bivariate method.
MAIN RESULTS: We identified 66 articles (published between 1988 and 2012) that
were eligible according to the inclusion criteria. We collected the data on 7747
patients with gastric cancer who were staged with EUS. Overall the quality of the
included studies was good: in particular, only five studies presented a high risk
of index test interpretation bias and two studies presented a high risk of
selection bias.For primary tumor (T) stage, results were stratified according to
the depth of invasion of the gastric wall. The meta-analysis of 50 studies (n =
4397) showed that the summary sensitivity and specificity of EUS in
discriminating T1 to T2 (superficial) versus T3 to T4 (advanced) gastric
carcinomas were 0.86 (95% confidence interval (CI) 0.81 to 0.90) and 0.90 (95% CI
0.87 to 0.93) respectively. For the diagnostic capacity of EUS to distinguish T1
(early gastric cancer, EGC) versus T2 (muscle-infiltrating) tumors, the
meta-analysis of 46 studies (n = 2742) showed that the summary sensitivity and
specificity were 0.85 (95% CI 0.78 to 0.91) and 0.90 (95% CI 0.85 to 0.93)
respectively. When we addressed the capacity of EUS to distinguish between T1a
(mucosal) versus T1b (submucosal) cancers the meta-analysis of 20 studies (n =
3321) showed that the summary sensitivity and specificity were 0.87 (95% CI 0.81
to 0.92) and 0.75 (95% CI 0.62 to 0.84) respectively. Finally, for the metastatic
involvement of lymph nodes (N-stage), the meta-analysis of 44 studies (n = 3573)
showed that the summary sensitivity and specificity were 0.83 (95% CI 0.79 to
0.87) and 0.67 (95% CI 0.61 to 0.72), respectively.Overall, as demonstrated also
by the Bayesian nomograms, which enable readers to calculate post-test
probabilities for any target condition prevalence, the EUS accuracy can be
considered clinically useful to guide physicians in the locoregional staging of
people with gastric cancer. However, it should be noted that between-study
heterogeneity was not negligible: unfortunately, we could not identify any
consistent source of the observed heterogeneity. Therefore, all accuracy measures
reported in the present work and summarizing the available evidence should be
interpreted cautiously. Moreover, we must emphasize that the analysis of positive
and negative likelihood values revealed that EUS diagnostic performance cannot be
considered optimal either for disease confirmation or for exclusion, especially
for the ability of EUS to distinguish T1a (mucosal) versus T1b (submucosal)
cancers and positive versus negative lymph node status.
AUTHORS' CONCLUSIONS: By analyzing the data from the largest series ever
considered, we found that the diagnostic accuracy of EUS might be considered
clinically useful to guide physicians in the locoregional staging of people with
gastric carcinoma. However, the heterogeneity of the results warrants special
caution, as well as further investigation for the identification of factors
influencing the outcome of this diagnostic tool. Moreover, physicians should be
warned that EUS performance is lower in diagnosing superficial tumors (T1a versus
T1b) and lymph node status (positive versus negative). Overall, we observed large
heterogeneity and its source needs to be understood before any definitive
conclusion can be drawn about the use of EUS can be proposed in routine clinical
settings.

DOI: 10.1002/14651858.CD009944.pub2
PMID: 25914908  [Indexed for MEDLINE]


333. BMJ. 2015 Feb 5;350:h217. doi: 10.1136/bmj.h217.

Labour induction with prostaglandins: a systematic review and network
meta-analysis.

Alfirevic Z(1), Keeney E(2), Dowswell T(3), Welton NJ(2), Dias S(2), Jones LV(3),
Navaratnam K(3), Caldwell DM(2).

Author information:
(1)Centre for Women's Health Research, University of Liverpool and Liverpool
Women's Hospital, Liverpool L8 7SS, UK zarko@liv.ac.uk.
(2)School of Social and Community Medicine, University of Bristol, Bristol BS8
2PS, UK.
(3)Centre for Women's Health Research, University of Liverpool and Liverpool
Women's Hospital, Liverpool L8 7SS, UK.

OBJECTIVES: To assess the effectiveness and safety of prostaglandins used for
labour induction.
DESIGN: Systematic review with Bayesian network meta-analysis
DATA SOURCES: The Cochrane Pregnancy and Childbirth Group's Database of Trials
(which incorporates the results of a broad generic search for all pregnancy and
postpartum trials). Sources included are CENTRAL, Medline, Embase, NHS Economic
Evaluation Database, CINAHL, relevant journals, conference proceedings, and
registries of ongoing trials.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised clinical trials of
prostaglandin or prostaglandin analogues used for third trimester cervical
ripening or labour induction versus placebo or no treatment, alternative
prostaglandin dose or administration, or a different type of prostaglandin. We
included studies recruiting women with a viable fetus, but had no other
restrictions relating to indication for labour induction or language of
publication. Outcomes assessed were serious neonatal morbidity (trialist defined)
or perinatal death; serious maternal morbidity (trialist defined) or death;
vaginal delivery not achieved within 24 hours, caesarean section, and uterine
hyperstimulation with fetal heart rate changes.
RESULTS: 280 randomised clinical trials were included (48 068 women) in the
review. Maternal and neonatal mortality and serious morbidity were rarely
reported and are summarized narratively. Unresolved inconsistency was observed
for the hyperstimulation outcome. Relative to placebo, the odds of failing to
achieve a vaginal delivery were lowest for vaginal misoprostol (≥50 µg) (odds
ratio 0.06 (95% credible interval 0.02 to 0.12)), with a 39% absolute probability
of event (95% credible interval 1% to 94%). Compared with placebo, odds of
caesarean section were lowest for titrated oral misoprostol solution (<50 µg)
(odds ratio 0.65 (0.49 to 0.83)), with an absolute probability of event of 15%
(3% to 40%).
CONCLUSIONS: Low dose(<50 µg) titrated oral misoprostol solution had the lowest
probability of caesarean section, whereas vaginal misprostol (≥50 µg) had the
highest probability of achieving a vaginal delivery within 24 hours. These
findings have important implications for a series of current national and
international guidelines for induction of labour and future research in this
area.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2013:CRD42013005116.

© Alfirevic et al 2015.


PMCID: PMC4353287
PMID: 25656228  [Indexed for MEDLINE]


334. Am J Prev Med. 2015 Feb;48(2):195-204. doi: 10.1016/j.amepre.2014.09.002. Epub
2014 Oct 14.

Diabetes and congenital heart defects: a systematic review, meta-analysis, and
modeling project.

Simeone RM(1), Devine OJ(2), Marcinkevage JA(3), Gilboa SM(2), Razzaghi H(3),
Bardenheier BH(4), Sharma AJ(5), Honein MA(2).

Author information:
(1)National Center on Birth Defects and Developmental Disabilities; Oak Ridge
Institute for Science and Education, Oak Ridge, Tennessee. Electronic address:
rsimeone@cdc.gov.
(2)National Center on Birth Defects and Developmental Disabilities.
(3)National Center on Birth Defects and Developmental Disabilities; Oak Ridge
Institute for Science and Education, Oak Ridge, Tennessee.
(4)National Center for Chronic Disease Prevention and Health Promotion, CDC.
(5)National Center for Chronic Disease Prevention and Health Promotion, CDC; U.S.
Public Health Service Commissioned Corps, Atlanta, Georgia.

CONTEXT: Maternal pregestational diabetes (PGDM) is a risk factor for development
of congenital heart defects (CHDs). Glycemic control before pregnancy reduces the
risk of CHDs. A meta-analysis was used to estimate summary ORs and mathematical
modeling was used to estimate population attributable fractions (PAFs) and the
annual number of CHDs in the U.S. potentially preventable by establishing
glycemic control before pregnancy.
EVIDENCE ACQUISITION: A systematic search of the literature through December 2012
was conducted in 2012 and 2013. Case-control or cohort studies were included.
Data were abstracted from 12 studies for a meta-analysis of all CHDs.
EVIDENCE SYNTHESIS: Summary estimates of the association between PGDM and CHDs
and 95% credible intervals (95% CrIs) were developed using Bayesian
random-effects meta-analyses for all CHDs and specific CHD subtypes. Posterior
estimates of this association were combined with estimates of CHD prevalence to
produce estimates of PAFs and annual prevented cases. Ninety-five percent
uncertainty intervals (95% UIs) for estimates of the annual number of preventable
cases were developed using Monte Carlo simulation. Analyses were conducted in
2013. The summary OR estimate for the association between PGDM and CHDs was 3.8
(95% CrI=3.0, 4.9). Approximately 2670 (95% UI=1795, 3795) cases of CHDs could
potentially be prevented annually if all women in the U.S. with PGDM achieved
glycemic control before pregnancy.
CONCLUSIONS: Estimates from this analysis suggest that preconception care of
women with PGDM could have a measureable impact by reducing the number of infants
born with CHDs.

Published by Elsevier Inc.

DOI: 10.1016/j.amepre.2014.09.002
PMCID: PMC4455032
PMID: 25326416  [Indexed for MEDLINE]


335. Cancer Treat Rev. 2015 Feb;41(2):77-93. doi: 10.1016/j.ctrv.2014.11.004. Epub
2014 Dec 4.

A network meta-analysis of progression free survival and overall survival in
first-line treatment of chronic lymphocytic leukemia.

Ladyzynski P(1), Molik M(2), Foltynski P(3).

Author information:
(1)Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy
of Sciences, 4 Trojdena Street, 02-109 Warsaw, Poland. Electronic address:
pladyzynski@ibib.waw.pl.
(2)Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy
of Sciences, 4 Trojdena Street, 02-109 Warsaw, Poland. Electronic address:
mmolik@ibib.waw.pl.
(3)Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy
of Sciences, 4 Trojdena Street, 02-109 Warsaw, Poland. Electronic address:
pfoltynski@ibib.waw.pl.

BACKGROUND: A limited evidence exists regarding comparisons of clinical
effectiveness of available therapies for first-line treatment of chronic
lymphocytic leukemia (CLL).
METHODS: We compared available therapies for treatment-naïve, symptomatic CLL
regarding progression free survival (PFS) and overall survival (OS) in all the
identified random control trials and in subgroups composed of younger/fit and
older/unfit patients, using a Bayesian network meta-analysis.
RESULTS: In younger/fit patients we obtained median of projected mean PFS of: 19,
26, 31, 43, 51 and 75months for chlorambucil, fludarabine, alemtuzumab,
fludarabine with cyclophosphamide (FC), bendamustine and fludarabine with
cyclophosphamide and rituximab (FCR), respectively. We noted median OS of: 59,
66, 66, 70months for FC, chlorambucil, FCR and fludarabine, respectively. In
older/unfit patients we noted PFS of: 16, 17, 24, 30, 60months for chlorambucil,
fludarabine and chlorambucil with ofatumumab (OClb) or rituximab (RClb) or
obinutuzumab (GClb), respectively. We obtained median OS of: 44, 58, 59 and
90months for fludarabine, RClb, chlorambucil and GClb, respectively.
CONCLUSIONS: Our results suggest that: (1) FCR has higher potential of preventing
CLL progression in younger/fit patients over four therapy options, which were
subject of previous meta-analysis but also over bendamustine; (2) in these
patients FCR does not entail prolonging of OS in comparison with chlorambucil and
it is outperformed by fludarabine; (3) in older/unfit patients GClb demonstrates
longer projected PFS than all assessed comparators; (4) in this group GClb has
also the highest potential of increasing OS.

Copyright © 2014 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.ctrv.2014.11.004
PMID: 25512118  [Indexed for MEDLINE]


336. Gastroenterology. 2015 Feb;148(2):344-54.e5; quiz e14-5. doi:
10.1053/j.gastro.2014.10.011. Epub 2014 Oct 16.

Comparative effectiveness of immunosuppressants and biologics for inducing and
maintaining remission in Crohn's disease: a network meta-analysis.

Hazlewood GS(1), Rezaie A(2), Borman M(1), Panaccione R(1), Ghosh S(1), Seow
CH(3), Kuenzig E(4), Tomlinson G(5), Siegel CA(6), Melmed GY(2), Kaplan GG(7).

Author information:
(1)Department of Medicine, University of Calgary, Calgary, Alberta, Canada.
(2)Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California.
(3)Department of Medicine, University of Calgary, Calgary, Alberta, Canada;
Departmet of Community Health Sciences, University of Calgary, Calgary, Alberta,
Canada.
(4)Departmet of Community Health Sciences, University of Calgary, Calgary,
Alberta, Canada.
(5)University Health Network, University of Toronto, Toronto, Ontario, Canada.
(6)Department of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New
Hampshire.
(7)Department of Medicine, University of Calgary, Calgary, Alberta, Canada;
Departmet of Community Health Sciences, University of Calgary, Calgary, Alberta,
Canada. Electronic address: ggkaplan@ucalgary.ca.

Comment in
    Gastroenterology. 2015 Jun;148(7):1484.
    Gastroenterology. 2015 Jun;148(7):1483-4.

BACKGROUND & AIMS: There is controversy regarding the best treatment for patients
with Crohn's disease because of the lack of direct comparative trials. We
compared therapies for induction and maintenance of remission in patients with
Crohn's disease, based on direct and indirect evidence.
METHODS: We performed systematic reviews of MEDLINE, EMBASE, and Cochrane Central
databases, through June 2014. We identified randomized controlled trials (N = 39)
comparing methotrexate, azathioprine/6-mercaptopurine, infliximab, adalimumab,
certolizumab, vedolizumab, or combined therapies with placebo or an active agent
for induction and maintenance of remission in adult patients with Crohn's
disease. Pairwise treatment effects were estimated through a Bayesian
random-effects network meta-analysis and reported as odds ratios (OR) with a 95%
credible interval (CrI).
RESULTS: Infliximab, the combination of infliximab and azathioprine (infliximab +
azathioprine), adalimumab, and vedolizumab were superior to placebo for induction
of remission. In pair-wise comparisons of anti-tumor necrosis factor agents,
infliximab + azathioprine (OR, 3.1; 95% CrI, 1.4-7.7) and adalimumab (OR, 2.1;
95% CrI, 1.0-4.6) were superior to certolizumab for induction of remission. All
treatments were superior to placebo for maintaining remission, except for the
combination of infliximab and methotrexate. Adalimumab, infliximab, and
infliximab + azathioprine were superior to azathioprine/6-mercaptopurine:
adalimumab (OR, 2.9; 95% CrI, 1.6-5.1), infliximab (OR, 1.6; 95% CrI, 1.0-2.5),
infliximab + azathioprine (OR, 3.0; 95% CrI, 1.7-5.5) for maintenance of
remission. Adalimumab and infliximab + azathioprine were superior to
certolizumab: adalimumab (OR, 2.5; 95% CrI, 1.4-4.6) and infliximab +
azathioprine (OR, 2.6; 95% CrI, 1.3-6.0). Adalimumab was superior to vedolizumab
(OR, 2.4; 95% CrI, 1.2-4.6).
CONCLUSIONS: Based on a network meta-analysis, adalimumab and infliximab +
azathioprine are the most effective therapies for induction and maintenance of
remission of Crohn's disease.

Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

DOI: 10.1053/j.gastro.2014.10.011
PMID: 25448924  [Indexed for MEDLINE]


337. J Endocrinol Invest. 2015 Feb;38(2):189-92. doi: 10.1007/s40618-014-0211-5. Epub
2014 Nov 21.

Gastrointestinal and renal side effects of bisphosphonates: differentiating
between no proof of difference and proof of no difference.

Fadda V(1), Maratea D(1), Trippoli S(1), Messori A(2).

Author information:
(1)HTA unit, Area Vasta Centro Toscana, Regional Health System, Via San Salvi 12,
50100, Florence, Italy.
(2)HTA unit, Area Vasta Centro Toscana, Regional Health System, Via San Salvi 12,
50100, Florence, Italy. andrea.messori.it@gmail.com.

BACKGROUND: This study was aimed at comparing the safety of bisphosphonates in
women with osteoporosis by application of equivalence testing.
METHODS: Gastrointestinal and renal side effects were evaluated based on
information published in randomized controlled trials.
RESULTS: The data on gastrointestinal side effects (47 trials) indicated that
alendronate, risedronate etidronate, and zolendronate have similar rates of the
adverse effects; application of Bayesian network meta-analysis showed that
equivalence was demonstrated according to margins around ±10%. The data on renal
safety were more sparse and suffered from the use of different outcome measures;
hence, a single trial could be evaluated. This trial showed a similar effect of
alendronate and risedronate on renal function at 12 months; equivalence was based
on differences between the two agents in renal function with margins of less than
±10.4 ml/min.
CONCLUSION: Our study provided quantitative information to determine to what
extent bisphosphonates can be considered equivalent in terms of gastrointestinal
and renal side effects.

DOI: 10.1007/s40618-014-0211-5
PMID: 25412945  [Indexed for MEDLINE]


338. New Phytol. 2015 Feb;205(3):1071-5. doi: 10.1111/nph.13238. Epub 2014 Dec 31.

Relatedness is a poor predictor of negative plant-soil feedbacks.

Mehrabi Z(1), Tuck SL.

Author information:
(1)Long Term Ecology Laboratory, Department of Zoology, University of Oxford,
Oxford, OX1 3PS, UK.

Understanding the mechanisms underlying negative plant-soil feedbacks remains a
critical challenge in plant ecology. If closely related species are more similar,
then phylogeny could be used as a predictor for plant species interactions,
simplifying our understanding of how plant-soil feedbacks structure plant
communities, underlie invasive species dynamics, or reduce agricultural
productivity. Here, we test the utility of phylogeny for predicting plant-soil
feedbacks by undertaking a hierarchical Bayesian meta-analysis on all available
pairwise plant-soil feedback experiments conducted over the last two decades,
including 133 plant species in 329 pairwise interactions. We found that the sign
and magnitude of plant-soil feedback effects were not explained by the
phylogenetic distance separating interacting species. This result was consistent
across different life forms, life cycles, provenances, and phylogenetic scales.
Our analysis shows that, contrary to widespread assumption, relatedness is a poor
predictor of plant-soil feedback effects.

© 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

DOI: 10.1111/nph.13238
PMCID: PMC4303931
PMID: 25557183  [Indexed for MEDLINE]


339. Osteoarthritis Cartilage. 2015 Feb;23(2):189-202. doi:
10.1016/j.joca.2014.11.014. Epub 2014 Nov 26.

Electrical stimulation for pain relief in knee osteoarthritis: systematic review
and network meta-analysis.

Zeng C(1), Li H(1), Yang T(1), Deng ZH(1), Yang Y(1), Zhang Y(1), Lei GH(2).

Author information:
(1)Department of Orthopaedics, Xiangya Hospital, Central South University,
Changsha, Hunan Province, China.
(2)Department of Orthopaedics, Xiangya Hospital, Central South University,
Changsha, Hunan Province, China. Electronic address: lgh9640@sina.cn.

OBJECTIVE: To investigate the efficacy of different electrical stimulation (ES)
therapies in pain relief of patients with knee osteoarthritis (OA).
METHOD: Electronic databases including MEDLINE, Embase and Cochrane Library were
searched through for randomized controlled trials (RCTs) comparing any ES
therapies with control interventions (sham or blank) or with each other. Bayesian
network meta-analysis was used to combine both the direct and indirect evidence
on treatment effectiveness.
RESULTS: 27 trials and six kinds of ES therapies, including high-frequency
transcutaneous electrical nerve stimulation (h-TENS), low-frequency
transcutaneous electrical nerve stimulation (l-TENS), neuromuscular electrical
stimulation (NMES), interferential current (IFC), pulsed electrical stimulation
(PES), and noninvasive interactive neurostimulation (NIN), were included. IFC is
the only significantly effective treatment in terms of both pain intensity and
change pain score at last follow-up time point when compared with the control
group. Meanwhile, IFC showed the greatest probability of being the best option
among the six treatment methods in pain relief. These estimates barely changed in
sensitivity analysis. However, the evidence of heterogeneity and the limitation
in sample size of some studies could be a potential threat to the validity of
results.
CONCLUSION: IFC seems to be the most promising pain relief treatment for the
management of knee OA. However, evidence was limited due to the heterogeneity and
small number of included trials. Although the recommendation level of the other
ES therapies is either uncertain (h-TENS) or not appropriate (l-TENS, NMES, PES
and NIN) for pain relief, it is likely that none of the interventions is
dangerous.
LEVEL OF EVIDENCE: LevelⅡ, systematic review and network meta-analysis of RCTs.

Copyright © 2014. Published by Elsevier Ltd.

DOI: 10.1016/j.joca.2014.11.014
PMID: 25497083  [Indexed for MEDLINE]


340. Ann Intern Med. 2015 Jan 6;162(1):46-54. doi: 10.7326/M14-1231.

Comparative effectiveness of pharmacologic interventions for knee osteoarthritis:
a systematic review and network meta-analysis.

Bannuru RR, Schmid CH, Kent DM, Vaysbrot EE, Wong JB, McAlindon TE.

Comment in
    Ann Intern Med. 2015 May 5;162(9):672.
    Ann Intern Med. 2015 May 5;162(9):672.
    Ann Intern Med. 2015 Jan 6;162(1):71-2.
    Evid Based Med. 2015 Oct;20(5):173.

BACKGROUND: The relative efficacy of available treatments of knee osteoarthritis
(OA) must be determined for rational treatment algorithms to be formulated.
PURPOSE: To examine the efficacy of treatments of primary knee OA using a network
meta-analysis design, which estimates relative effects of all treatments against
each other.
DATA SOURCES: MEDLINE, EMBASE, Web of Science, Google Scholar, Cochrane Central
Register of Controlled Trials from inception through 15 August 2014, and
unpublished data.
STUDY SELECTION: Randomized trials of adults with knee OA comparing 2 or more of
the following: acetaminophen, diclofenac, ibuprofen, naproxen, celecoxib,
intra-articular (IA) corticosteroids, IA hyaluronic acid, oral placebo, and IA
placebo.
DATA EXTRACTION: Two reviewers independently abstracted study data and assessed
study quality. Standardized mean differences were calculated for pain, function,
and stiffness at 3-month follow-up.
DATA SYNTHESIS: Network meta-analysis was performed using a Bayesian
random-effects model; 137 studies comprising 33,243 participants were identified.
For pain, all interventions significantly outperformed oral placebo, with effect
sizes from 0.63 (95% credible interval [CrI], 0.39 to 0.88) for the most
efficacious treatment (hyaluronic acid) to 0.18 (CrI, 0.04 to 0.33) for the least
efficacious treatment (acetaminophen). For function, all interventions except IA
corticosteroids were significantly superior to oral placebo. For stiffness, most
of the treatments did not significantly differ from one another.
LIMITATION: Lack of long-term data, inadequate reporting of safety data, possible
publication bias, and few head-to-head comparisons.
CONCLUSION: This method allowed comparison of common treatments of knee OA
according to their relative efficacy. Intra-articular treatments were superior to
nonsteroidal anti-inflammatory drugs, possibly because of the integrated IA
placebo effect. Small but robust differences were observed between active
treatments. All treatments except acetaminophen showed clinically significant
improvement from baseline pain. This information, along with the safety profiles
and relative costs of included treatments, will be helpful for individualized
patient care decisions.
PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

DOI: 10.7326/M14-1231
PMID: 25560713  [Indexed for MEDLINE]


341. Ann Oncol. 2015 Jan;26(1):205-11. doi: 10.1093/annonc/mdu507. Epub 2014 Oct 29.

A Bayesian network meta-analysis comparing concurrent chemoradiotherapy followed
by adjuvant chemotherapy, concurrent chemoradiotherapy alone and radiotherapy
alone in patients with locoregionally advanced nasopharyngeal carcinoma.

Chen YP(1), Wang ZX(2), Chen L(1), Liu X(1), Tang LL(1), Mao YP(1), Li WF(1), Lin
AH(3), Sun Y(1), Ma J(4).

Author information:
(1)State Key Laboratory of Oncology in South China, Department of Radiation
Oncology, Sun Yat-sen University Cancer Center, Guangzhou.
(2)Zhongshan School of Medicine.
(3)Department of Medical Statistics and Epidemiology, School of Public Health,
Sun Yat-sen University, Guangzhou, People's Republic of China.
(4)State Key Laboratory of Oncology in South China, Department of Radiation
Oncology, Sun Yat-sen University Cancer Center, Guangzhou
majun2@mail.sysu.edu.cn.

BACKGROUND: Given the lack of studies, whether the addition of adjuvant
chemotherapy (AC) to concurrent chemoradiotherapy (CCRT) is superior to CCRT
alone for locoregionally advanced nasopharyngeal carcinoma (NPC) remains unclear.
The main objective of this Bayesian network meta-analysis was to determine the
efficacy of CCRT + AC when compared with CCRT alone.
PATIENTS AND METHODS: We systematically searched databases and extracted data
from randomized, controlled trials involving NPC patients randomly assigned to
receive CCRT + AC, CCRT, or radiotherapy (RT). Overall survival (OS),
locoregional recurrence-free survival (LRFS), and distant metastasis-free
survival (DMFS) with hazard ratios (HRs) were investigated. A Bayesian network
for different outcomes was established to incorporate all evidence. Multiple
treatment comparisons based on the network integrated the efficacy of CCRT + AC,
CCRT, and RT.
RESULTS: Eight studies involving 2144 patients were analyzed. In the network
meta-analysis, CCRT + AC and CCRT were both significantly better than RT alone
for all outcomes, except that no significant difference was found between CCRT
and RT for LRFS. Though ranking probabilities showed that CCRT + AC was ranked
superior to CCRT for OS, LRFS, and DMFS, no significant differences were found
between CCRT+AC and CCRT for all outcomes [OS: HR = 0.86, 95% credible interval
(CrI) 0.60-1.16; LRFS: HR = 0.72, 95% CrI 0.43-1.15; DMFS: HR = 0.86, 95% CrI
0.62-1.16].
CONCLUSIONS: No significant improvement was found following CCRT + AC compared
with CCRT alone. Whether the omission of additional AC can reduce toxic effects
without adversely affecting survival in patients with locoregionally advanced NPC
should be further explored, in addition to the precise patient status that would
benefit from AC following CCRT.

© The Author 2014. Published by Oxford University Press on behalf of the European
Society for Medical Oncology. All rights reserved. For permissions, please email:
journals.permissions@oup.com.

DOI: 10.1093/annonc/mdu507
PMID: 25355717  [Indexed for MEDLINE]


342. Cad Saude Publica. 2015 Jan;31(1):26-38.

[Meta analysis of the use of Bayesian networks in breast cancer diagnosis].

[Article in Portuguese]

Simões PW, Silva GD, Moretti GP, Simon CS, Winnikow EP, Nassar SM, Medeiros LR,
Rosa MI.

The aim of this study was to determine the accuracy of Bayesian networks in
supporting breast cancer diagnoses. Systematic review and meta-analysis were
carried out, including articles and papers published between January 1990 and
March 2013. We included prospective and retrospective cross-sectional studies of
the accuracy of diagnoses of breast lesions (target conditions) made using
Bayesian networks (index test). Four primary studies that included 1,223 breast
lesions were analyzed, 89.52% (444/496) of the breast cancer cases and 6.33%
(46/727) of the benign lesions were positive based on the Bayesian network
analysis. The area under the curve (AUC) for the summary receiver operating
characteristic curve (SROC) was 0.97, with a Q* value of 0.92. Using Bayesian
networks to diagnose malignant lesions increased the pretest probability of a
true positive from 40.03% to 90.05% and decreased the probability of a false
negative to 6.44%. Therefore, our results demonstrated that Bayesian networks
provide an accurate and non-invasive method to support breast cancer diagnosis.


PMID: 25715289  [Indexed for MEDLINE]


343. Diabetes Technol Ther. 2015 Jan;17(1):35-42. doi: 10.1089/dia.2014.0188.

Gastrointestinal adverse events of glucagon-like peptide-1 receptor agonists in
patients with type 2 diabetes: a systematic review and network meta-analysis.

Sun F(1), Chai S, Yu K, Quan X, Yang Z, Wu S, Zhang Y, Ji L, Wang J, Shi L.

Author information:
(1)1 Department of Epidemiology and Biostatistics, School of Public Health,
Peking University Health Science Centre , Beijing, People's Republic of China .

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a new
class of drugs used in the treatment of type 2 diabetes mellitus (T2DM).
Gastrointestinal (GI) adverse events (AEs) are the most frequently reported
treatment-related AEs for GLP-1 RAs. We aim to evaluate the effect of GLP-1 RAs
on the incidence of GI AEs of T2DM.
MATERIALS AND METHODS: The overview of the GI events of GLP-1 RAs has been
performed on relevant publications through the literature search, such as
MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov The manufacturer was
contacted regarding unpublished data. We analyzed direct and indirect comparisons
of different treatments using Bayesian network meta-analysis.
RESULTS: Taspoglutide 30 mg once weekly (TAS30QW) and lixisenatide 30 μg twice
daily (LIX30BID) were ranked the top two drugs in terms of GI AEs versus placebo.
The odds ratios of nausea and vomiting for TAS30QW were 11.8 (95% confidence
interval [CI], 2.89, 46.9) and 51.7 (95% CI, 7.07, 415), respectively, and that
of diarrhea was 4.93 (95% CI, 1.75, 14.7) for LIX30BID.
CONCLUSIONS: Our study found all GLP-1 RA dose regimens significantly increased
the incidence of GI AEs, compared with placebo or conventional treatment. The
occurrence of GI AEs was different with diverse dose regimens of GLP-1 RAs.
TAS30QW had the maximum probability to occur nausea and vomiting, whereas
LIX30BID had the maximum probability to cause development of diarrhea versus
other treatments.

DOI: 10.1089/dia.2014.0188
PMCID: PMC4290796
PMID: 25375397  [Indexed for MEDLINE]


344. Expert Opin Drug Saf. 2015 Jan;14(1):7-20. doi: 10.1517/14740338.2014.971009.
Epub 2014 Oct 14.

Safety and efficacy of non-vitamin K oral anticoagulants in non-valvular atrial
fibrillation: a Bayesian meta-analysis approach.

Verdecchia P(1), Angeli F, Bartolini C, De Filippo V, Aita A, Di Giacomo L,
Poltronieri C, Lip GY, Reboldi G.

Author information:
(1)Hospital of Assisi, Department of Medicine , Via Valentin Müller 1, 06081
Assisi , Italy +075 8139301 ; verdec@tin.it.

INTRODUCTION: Choosing between different non-vitamin K antagonist oral
anticoagulants (NOACs) in non-valvular atrial fibrillation (NVAF) is difficult
due to the absence of head to head comparative studies. We performed a Bayesian
meta-analysis to explore similarities and differences between different NOACs and
to rank treatments overall for safety and efficacy outcomes.
AREAS COVERED: Through a systematic literature search we identified randomized
controlled Phase III trials of dabigatran, rivaroxaban, apixaban, and edoxaban
versus adjusted-dose warfarin in patients with NVAF.
EXPERT OPINION: Warfarin ranked worst for all-cause mortality and intracranial
bleedings and had a nil probability of ranking first for any outcome. The risk of
major bleeding versus warfarin was lower with apixaban, dabigatran 110 mg, and
both doses of edoxaban. All agents reduced the risk of intracranial bleeding
versus warfarin. Edoxaban 30 mg was the best among the treatments being compared
for major and gastrointestinal bleeding. Dabigatran 150 mg was the best for
stroke and systemic embolism. This study suggests that NOACs are generally
preferable to warfarin in patients with NVAF. However, safety and efficacy
differences do exist among NOACs, which might drive their use in specific subsets
of AF patients, allowing prescribers to tailor treatment to distinct patient
profiles.

DOI: 10.1517/14740338.2014.971009
PMID: 25311731  [Indexed for MEDLINE]


345. Expert Opin Pharmacother. 2015;16(13):1915-27. doi:
10.1517/14656566.2015.1058359.

First-line treatment in the management of advanced renal cell carcinoma:
systematic review and network meta-analysis.

Larkin J(1), Paine A, Foley G, Mitchell S, Chen C.

Author information:
(1)Royal Marsden NHS Foundation Trust , London SW3 6JJ , UK.

OBJECTIVES: To conduct a systematic review and network meta-analysis (NMA) to
assess effectiveness of first-line treatments for advanced renal cell carcinoma
(RCC).
METHODS: Database searches were conducted to identify randomized controlled
trials (RCTs) reporting results for eligible treatments. A fixed-effect Bayesian
NMA was conducted to assess the relative effectiveness of treatments, with
progression-free survival (PFS) reported as hazard ratios (HRs) and 95% credible
intervals (CrIs).
RESULTS: Eleven unique RCTs were suitable for inclusion in the NMA. In the base
case, in terms of PFS, sunitinib was superior compared with bevacizumab + IFN-α
(HR = 0.79, 95% CrI: 0.64 - 0.96), everolimus (HR = 0.70, 95% CrI: 0.56 - 0.87),
sorafenib (HR = 0.56, 95% CrI: 0.40 - 0.77) and temsirolimus + bevacizumab (HR =
0.74, 95% CrI: 0.56 - 0.96). Although, the point values for the mean and median
HRs were < 1.0, there was no significant difference in PFS between sunitinib and
axitinib, pazopanib or tivozanib. Although sensitivity analyses impacted the
results of the NMA, no treatment was significantly more efficacious than
sunitinib.
CONCLUSION: Results from this analysis suggest that there is no treatment
superior to the current benchmark treatment, sunitinib, in the management of
advanced RCC in the first-line setting.

DOI: 10.1517/14656566.2015.1058359
PMID: 26194211  [Indexed for MEDLINE]


346. Expert Rev Pharmacoecon Outcomes Res. 2015;15(5):813-22. doi:
10.1586/14737167.2015.1076338. Epub 2015 Aug 13.

Economic resources consumption structure in severe hypoglycemia episodes: a
systematic review and meta-analysis.

Jakubczyk M(1), Rdzanek E(2), Niewada M(3), Czech M(4)(5).

Author information:
(1)a 1 Decision Analysis and Support Unit, Warsaw School of Economics, Al.
Niepodległości 162, Warsaw, Poland.
(2)b 2 HealthQuest spółka z ograniczoną odpowiedzialnością Sp. K, 02-554 Warsaw,
Poland.
(3)c 3 Department of Experimental and Clinical Pharmacology, Medical University
of Warsaw, Warsaw, Poland.
(4)d 4 Novo Nordisk Pharma sp. z o.o., Warsaw, Poland.
(5)e 5 Department of Pharmacoeconomics, Medical University of Warsaw, Warsaw,
Poland.

Diabetes mellitus (DM) is associated with severe hypoglycemia events (SHEs) that
vary in severity and resource consumption. Here we perform a systematic review in
Medline of studies evaluating SHE-related health resource use. Eligible studies
investigated patients with DM and included ≥10 SHEs. We also assessed studies
identified in another systematic review, and through references from the included
studies. We identified 14 relevant studies and used data from 11 (encompassing
6075 patients). Study results were interpreted to fit our definitions, which
sometimes required assumptions. SHE type structure was synthesized using Bayesian
modeling. Estimating Type 1 & 2 DM separately revealed only small differences;
therefore, we used joint results. Of the analyzed SHEs, 9.97% were
hospital-treated, 22.3% medical professional-treated, and 67.73% family-treated.
These meta-analysis results help in understanding the structure of resource
consumption following SHE and can be used in economic studies.

DOI: 10.1586/14737167.2015.1076338
PMID: 26289736  [Indexed for MEDLINE]


347. Gastroenterology. 2015 Jan;148(1):64-76.e2; quiz e14. doi:
10.1053/j.gastro.2014.09.031. Epub 2014 Sep 26.

Comparative efficacy of pharmacologic interventions in preventing relapse of
Crohn's disease after surgery: a systematic review and network meta-analysis.

Singh S(1), Garg SK(2), Pardi DS(3), Wang Z(4), Murad MH(4), Loftus EV Jr(3).

Author information:
(1)Division of Gastroenterology and Hepatology, Department of Internal Medicine,
Mayo Clinic, Rochester, Minnesota. Electronic address: singh.siddharth2@mayo.edu.
(2)Department of Surgery, University of Minnesota, Minneapolis, Minnesota.
(3)Division of Gastroenterology and Hepatology, Department of Internal Medicine,
Mayo Clinic, Rochester, Minnesota.
(4)Knowledge and Evaluation Research Unit, Robert D. and Patricia E. Kern Center
for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota.

Comment in
    Z Gastroenterol. 2015 Aug;53(8):843-5.

BACKGROUND & AIMS: There are several drugs that might decrease the risk of
relapse of Crohn's disease (CD) after surgery, but it is unclear whether one is
superior to others. We estimated the comparative efficacy of different
pharmacologic interventions for postoperative prophylaxis of CD, through a
network meta-analysis of randomized controlled trials.
METHODS: We conducted a systematic search of the literature through March 2014.
We identified randomized controlled trials that compared the abilities of
mesalamine, antibiotics, budesonide, immunomodulators, anti-tumor necrosis factor
α (anti-TNF) (started within 3 months of surgery), and/or placebo or no
intervention to prevent clinical and/or endoscopic relapse of CD in adults after
surgical resection. We used Bayesian network meta-analysis to combine direct and
indirect evidence and estimate the relative effects of treatment.
RESULTS: We identified 21 trials comprising 2006 participants comparing 7
treatment strategies. In a network meta-analysis, compared with placebo,
mesalamine (relative risk [RR], 0.60; 95% credible interval [CrI], 0.37-0.88),
antibiotics (RR, 0.26; 95% CrI, 0.08-0.61), immunomodulator monotherapy (RR,
0.36; 95% CrI, 0.17-0.63), immunomodulator with antibiotics (RR, 0.11; 95% CrI,
0.02-0.51), and anti-TNF monotherapy (RR, 0.04; 95% CrI, 0.00-0.14), but not
budesonide (RR, 0.93; 95% CrI, 0.40-1.84), reduced the risk of clinical relapse.
Likewise, compared with placebo, antibiotics (RR, 0.41; 95% CrI, 0.15-0.92),
immunomodulator monotherapy (RR, 0.33; 95% CrI, 0.13-0.68), immunomodulator with
antibiotics (RR, 0.16; 95% CrI, 0.04-0.48), and anti-TNF monotherapy (RR, 0.01;
95% CrI, 0.00-0.05), but neither mesalamine (RR, 0.67; 95% CrI, 0.39-1.08) nor
budesonide (RR, 0.86; 95% CrI, 0.61-1.22), reduced the risk of endoscopic
relapse. Anti-TNF monotherapy was the most effective pharmacologic intervention
for postoperative prophylaxis, with large effect sizes relative to all other
strategies (clinical relapse: RR, 0.02-0.20; endoscopic relapse: RR, 0.005-0.04).
CONCLUSIONS: Based on Bayesian network meta-analysis combining direct and
indirect treatment comparisons, anti-TNF monotherapy appears to be the most
effective strategy for postoperative prophylaxis for CD.

Copyright © 2015. Published by Elsevier Inc.

DOI: 10.1053/j.gastro.2014.09.031
PMCID: PMC4274207
PMID: 25263803  [Indexed for MEDLINE]


348. J Dent. 2015 Jan;43(1):1-15. doi: 10.1016/j.jdent.2014.10.004. Epub 2014 Oct 22.

Effects of using different criteria for caries removal: a systematic review and
network meta-analysis.

Schwendicke F(1), Paris S(2), Tu YK(3).

Author information:
(1)Department of Operative and Preventive Dentistry, Charité -
Universitätsmedizin Berlin, Aßmannshauser Str. 4-6, 14199 Berlin, Germany.
Electronic address: falk.schwendicke@charite.de.
(2)Department of Operative and Preventive Dentistry, Charité -
Universitätsmedizin Berlin, Aßmannshauser Str. 4-6, 14199 Berlin, Germany.
(3)Institute of Epidemiology & Preventive Medicine, College of Public Health,
National Taiwan University, Taipei, Taiwan.

OBJECTIVES: Conventionally, caries excavation is performed until only hard
dentine remains, while more selective and reliable criteria might be available.
We aimed at systematically comparing the effects of using different excavation
criteria via network meta-analysis.
SOURCES: Electronic databases were searched for randomised or non-randomised
clinical trials (RCTs/NRCTs) evaluating excavation of cavitated lesions.
DATA: Criteria were divided into six groups: Excavation until pulpo-proximal
dentine on the cavity floor was (1) either hard on probing, (2) slightly softened
on probing, (3) not stainable by caries-detector-dye, or until (4) self-limiting
polymer burs, (5) fluorescence-assisted devices or (6) chemo-mechanical gels
indicated termination of the excavation. Evaluation of risk of complications,
risk of pain/discomfort, excavation time, and number of remaining bacteria were
then undertaken using Bayesian network meta-analysis.
STUDY SELECTION: 28 studies (19 RCTs, 9 NRCTs) with 1782 patients (2555 lesions),
most of them investigating primary teeth, were included. Risk of complications
was highest when excavating until only non-stainable dentine remained, and lowest
when not attempting to remove all softened dentine. Risk of pain significantly
decreased if self-limiting chemo-mechanical excavation or fluorescence-assisted
lasers were used instead of excavating until all dentine was hard. When not
attempting to remove all softened dentine, the time required for excavation was
shortest, whilst the greatest number bacteria remained.
CONCLUSIONS: Not attempting to remove all softened or stainable dentine might
reduce the risk of complications. Data regarding self-limiting excavation is
insufficient for definitive conclusions. Excavation criteria should be validated
against clinically relevant outcomes.
CLINICAL SIGNIFICANCE: Given current evidence, dentists might not need to attempt
excavation until only hard dentin remains in proximity to the pulp. Instead,
their choice of excavation criterion or method should be guided by clinical
requirements and outcomes.

Copyright © 2014 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.jdent.2014.10.004
PMID: 25456612  [Indexed for MEDLINE]


349. Lancet Infect Dis. 2015 Jan;15(1):74-84. doi: 10.1016/S1473-3099(14)71004-7. Epub
2014 Dec 3.

Spatial and temporal distribution of soil-transmitted helminth infection in
sub-Saharan Africa: a systematic review and geostatistical meta-analysis.

Karagiannis-Voules DA(1), Biedermann P(1), Ekpo UF(2), Garba A(3), Langer E(1),
Mathieu E(4), Midzi N(5), Mwinzi P(6), Polderman AM(7), Raso G(1), Sacko M(8),
Talla I(9), Tchuenté LA(10), Touré S(11), Winkler MS(1), Utzinger J(1), Vounatsou
P(12).

Author information:
(1)Department of Epidemiology and Public Health, Swiss Tropical and Public Health
Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
(2)Department of Biological Sciences, Federal University of Agriculture,
Abeokuta, Nigeria.
(3)Réseau International Schistosomiases, Environnement, Aménagements et Lutte,
Niamey, Niger.
(4)Center for Global Health, Centers for Disease Control and Prevention, Atlanta,
GA, USA.
(5)Department of Medical Microbiology, College of Health Sciences, University of
Zimbabwe, Harare, Zimbabwe.
(6)Centre for Global Health Research, Kenya Medical Research Institute, Kisumu,
Kenya.
(7)Department of Parasitology, Leiden University Medical Centre, Leiden,
Netherlands.
(8)Institut National de Recherche en Santé Publique, Bamako, Mali.
(9)Direction de la Lutte contre la Maladie, Ministère de la Santé, Dakar,
Senegal.
(10)Laboratory of Parasitology and Ecology, University of Yaoundé I, Yaoundé,
Cameroon; Center for Schistosomiasis and Parasitology, Yaoundé, Cameroon.
(11)Programme National de Lutte contre la Schistosomiase, Ministère de la Santé,
Ouagadougou, Burkina Faso.
(12)Department of Epidemiology and Public Health, Swiss Tropical and Public
Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.
Electronic address: penelope.vounatsou@unibas.ch.

Comment in
    Lancet Infect Dis. 2015 Jan;15(1):9-11.

BACKGROUND: Interest is growing in predictive risk mapping for neglected tropical
diseases (NTDs), particularly to scale up preventive chemotherapy, surveillance,
and elimination efforts. Soil-transmitted helminths (hookworm, Ascaris
lumbricoides, and Trichuris trichiura) are the most widespread NTDs, but broad
geographical analyses are scarce. We aimed to predict the spatial and temporal
distribution of soil-transmitted helminth infections, including the number of
infected people and treatment needs, across sub-Saharan Africa.
METHODS: We systematically searched PubMed, Web of Knowledge, and African Journal
Online from inception to Dec 31, 2013, without language restrictions, to identify
georeferenced surveys. We extracted data from household surveys on sources of
drinking water, sanitation, and women's level of education. Bayesian
geostatistical models were used to align the data in space and estimate risk of
with hookworm, A lumbricoides, and T trichiura over a grid of roughly 1 million
pixels at a spatial resolution of 5 × 5 km. We calculated anthelmintic treatment
needs on the basis of WHO guidelines (treatment of all school-aged children once
per year where prevalence in this population is 20-50% or twice per year if
prevalence is greater than 50%).
FINDINGS: We identified 459 relevant survey reports that referenced 6040 unique
locations. We estimate that the prevalence of hookworm, A lumbricoides, and T
trichiura among school-aged children from 2000 onwards was 16·5%, 6·6%, and 4·4%.
These estimates are between 52% and 74% lower than those in surveys done before
2000, and have become similar to values for the entire communities. We estimated
that 126 million doses of anthelmintic treatments are required per year.
INTERPRETATION: Patterns of soil-transmitted helminth infection in sub-Saharan
Africa have changed and the prevalence of infection has declined substantially in
this millennium, probably due to socioeconomic development and large-scale
deworming programmes. The global control strategy should be reassessed, with
emphasis given also to adults to progress towards local elimination.
FUNDING: Swiss National Science Foundation and European Research Council.

Copyright © 2015 Elsevier Ltd. All rights reserved.

DOI: 10.1016/S1473-3099(14)71004-7
PMID: 25486852  [Indexed for MEDLINE]


350. Psychol Med. 2015 Jan;45(2):299-317. doi: 10.1017/S0033291714001305. Epub 2014
Jul 18.

A network meta-analysis on comparative efficacy and all-cause discontinuation of
antimanic treatments in acute bipolar mania.

Yildiz A(1), Nikodem M(2), Vieta E(3), Correll CU(4), Baldessarini RJ(3).

Author information:
(1)Department of Psychiatry,Dokuz Eylül University,Izmir,Turkey.
(2)Faculty of Applied Mathematics,AGH University of Science and
Technology,Krakow,Poland.
(3)International Consortium for Bipolar Disorder Research & Psychopharmacology
Program, McLean Division of Massachusetts General Hospital,Boston, MA,USA.
(4)Division of Psychiatry Research, Department of Psychiatry,Zucker Hillside
Hospital,New York, NY,USA.

BACKGROUND: Evidence synthesis methods enabling direct and indirect comparisons
over the entire set of relevant clinical data produce quantitative point
estimates for the treatments contrasts between competing interventions, and
provide a hierarchical rank ordering between them. We aimed to provide
evidence-based guidance on the efficacy and all-cause discontinuation of
antimanic treatments.
METHOD: We conducted a network meta-analysis within a Bayesian framework. We
searched all standard literature databases without language restrictions up to 15
January 2014 to identify reports of short-term, randomized, blinded trials of
putative antimanic drugs as monotherapy for adults with bipolar-I mania.
RESULTS: Altogether, 14256 manic patients randomized to one of 18 active
treatments or placebo provided 95 direct comparisons on 128 data points. For the
primary outcome, standardized mean difference as Hedges' g (standardized mean
difference; SMD), the hierarchies indicated by surface under the cumulative
ranking (SUCRA) probabilities were in agreement with the point estimates for all
antimanic drugs identified as effective. For the 12 effective antimanic drugs on
clinical use, SMDs against placebo ranged from 0.32 to 0.66 without superiority
of one over another, except for risperidone v. aripiprazole and valproate.
Aripiprazole, olanzapine, quetiapine, risperidone, and valproate had less
all-cause discontinuation rates than placebo. Sensitivity analysis by drug class
indicated similar efficacy profiles for haloperidol, second-generation
antipsychotics, and mood stabilizers.
CONCLUSIONS: Hierarchical rank ordering by comparative efficacy and risk of
all-cause discontinuations should help to guide antimanic treatment choices by
clinicians, healthcare policy makers, and guideline developers.

DOI: 10.1017/S0033291714001305
PMID: 25036226  [Indexed for MEDLINE]


351. Value Health. 2015 Jan;18(1):116-26. doi: 10.1016/j.jval.2014.10.006.

Network meta-analysis: development of a three-level hierarchical modeling
approach incorporating dose-related constraints.

Owen RK(1), Tincello DG(2), Keith RA(3).

Author information:
(1)Department of Health Sciences, University of Leicester, Leicester, UK.
Electronic address: rhiannon.owen@leicester.ac.uk.
(2)Reproductive Science Section, Department of Cancer Studies and Molecular
Medicine, University of Leicester, Leicester, UK.
(3)Department of Health Sciences, University of Leicester, Leicester, UK.

BACKGROUND: Network meta-analysis (NMA) is commonly used in evidence synthesis;
however, in situations in which there are a large number of treatment options,
which may be subdivided into classes, and relatively few trials, NMAs produce
considerable uncertainty in the estimated treatment effects, and consequently,
identification of the most beneficial intervention remains inconclusive.
OBJECTIVE: To develop and demonstrate the use of evidence synthesis methods to
evaluate extensive treatment networks with a limited number of trials, making use
of classes.
METHODS: Using Bayesian Markov chain Monte Carlo methods, we build on the
existing work of a random effects NMA to develop a three-level hierarchical NMA
model that accounts for the exchangeability between treatments within the same
class as well as for the residual between-study heterogeneity. We demonstrate the
application of these methods to a continuous and binary outcome, using a
motivating example of overactive bladder. We illustrate methods for incorporating
ordering constraints in increasing doses, model selection, and assessing
inconsistency between the direct and indirect evidence.
RESULTS: The methods were applied to a data set obtained from a systematic
literature review of trials for overactive bladder, evaluating the mean reduction
in incontinence episodes from baseline and the number of patients reporting one
or more adverse events. The data set involved 72 trials comparing 34
interventions that were categorized into nine classes of interventions, including
placebo.
CONCLUSIONS: Bayesian three-level hierarchical NMAs have the potential to
increase the precision in the effect estimates while maintaining the
interpretability of the individual interventions for decision making.

Copyright © 2015 International Society for Pharmacoeconomics and Outcomes
Research (ISPOR). Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.jval.2014.10.006
PMID: 25595242  [Indexed for MEDLINE]
