

1. 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.

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.

PMID: 25975452  [PubMed - indexed for MEDLINE]


2. 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.

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.

PMID: 25777667  [PubMed - indexed for MEDLINE]


3. 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.

PMID: 25677267  [PubMed - indexed for MEDLINE]


4. 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.

PMID: 25652947  [PubMed - indexed for MEDLINE]


5. 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.

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.

PMID: 25945410  [PubMed - indexed for MEDLINE]


6. 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.

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.

PMID: 25950691  [PubMed - indexed for MEDLINE]


7. 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.

PMID: 25794093  [PubMed - indexed for MEDLINE]


8. 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.

PMID: 25405556  [PubMed - indexed for MEDLINE]


9. 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.

PMID: 25706113  [PubMed - indexed for MEDLINE]


10. 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.

PMID: 25746018  [PubMed - indexed for MEDLINE]


11. 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.

PMID: 25789948  [PubMed - indexed for MEDLINE]


12. 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.

PMID: 25761173  [PubMed - indexed for MEDLINE]


13. 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
    Nat Rev Cardiol. 2015 Jan;12(1):1.
    Lancet. 2015 May 30;385(9983):2149.
    Lancet. 2015 Feb 28;385(9970):756-7.
    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.

PMCID: PMC4386690 [Available on 2016-02-28]
PMID: 25467565  [PubMed - indexed for MEDLINE]


14. 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.

PMID: 25914908  [PubMed - indexed for MEDLINE]


15. 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  [PubMed - indexed for MEDLINE]


16. 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.

PMID: 25512118  [PubMed - indexed for MEDLINE]


17. 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.

PMID: 25448924  [PubMed - indexed for MEDLINE]


18. 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.

PMID: 25497083  [PubMed - indexed for MEDLINE]


19. 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.

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.

PMID: 25560713  [PubMed - indexed for MEDLINE]



21. 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.

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.

PMCID: PMC4274207 [Available on 2016-01-01]
PMID: 25263803  [PubMed - indexed for MEDLINE]


22. 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.

PMID: 25486852  [PubMed - indexed for MEDLINE]


23. 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.

PMID: 25595242  [PubMed - indexed for MEDLINE]


24. Hum Mol Genet. 2014 Dec 20;23(25):6944-60. doi: 10.1093/hmg/ddu401. Epub 2014 Aug
5.

Trans-ethnic meta-analysis of white blood cell phenotypes.

Keller MF(1), Reiner AP(2), Okada Y(3), van Rooij FJ(4), Johnson AD(5), Chen
MH(6), Smith AV(7), Morris AP(8), Tanaka T(9), Ferrucci L(9), Zonderman AB(10),
Lettre G(11), Harris T(12), Garcia M(12), Bandinelli S(13), Qayyum R(14), Yanek
LR(14), Becker DM(14), Becker LC(15), Kooperberg C(16), Keating B(17), Reis
J(18), Tang H(19), Boerwinkle E(20), Kamatani Y(21), Matsuda K(22), Kamatani
N(21), Nakamura Y(23), Kubo M(24), Liu S(25), Dehghan A(4), Felix JF(4), Hofman
A(4), Uitterlinden AG(26), van Duijn CM(4), Franco OH(27), Longo DL(28),
Singleton AB(29), Psaty BM(30), Evans MK(31), Cupples LA(32), Rotter JI(33),
O'Donnell CJ(5), Takahashi A(21), Wilson JG(34), Ganesh SK(35), Nalls MA(36);
CHARGE Hematology; COGENT; BioBank Japan Project (RIKEN) Working Groups.

Collaborators: Arepalli S, Bandinelli S, Biffi A, Bis JC, Boerwinkle E,
Chakravarti A, Chen MH, Chong S, Coresh J, Couper DJ, Cupples L, Dehghan A,
Do'ring A, Eiriksdottir G, Felix JF, Ferrucci L, Folsom AR, Fox CS, Frayling TM,
Ganesh SK, Garcia M, Garner SF, Gasparini P, Gieger C, Glazer NL, Gouskova NA,
Greinacher A, Gudnason V, Harris TB, Hernandez DG, Hofman A, Illig T, Kamatani Y,
Kamatani N, Kubo M, Kuhnel B, Lagou V, Lettre G, Levi D, Lin J, Liu Y, Longo DL,
Lumley T, Mangino M, Matsuda K, Meisinger C, Melzer D, Menzel S, Moore M,
Nakamura Y, Nalls MA, Nauck M, O'Donnell CJ, Okada Y, Oostra BA, Ouwehand WH,
Patel KV, Pirastu N, Pistis G, Prokisch H, Prokopenko I, Psaty BM, Reiner AP,
Rendon A, Sambrook J, Singleton AB, Smith AV, Soranzo N, Spector TD, Stephens J,
Stumvoll M, Takahashi A, Tanaka T, Tanaka T, Taylor K, Teumer A, Thein SL,
To'njes A, Toniolo D, Tsunoda T, Uitterlinden AG, van Duijn CM, van Rooij FJ,
Vo'lker U, Vo'lzke H, Wichmann H-, Wiggins KL, Wilson JG, Witteman JC, Wood AR,
Yamamoto K, Yang Q, Zakai NA, Arepalli S, Austin MA, Becker DM, Britton A, Chen
Z, Couper D, Curb J, Dean E, Eaton CB, Evans MK, Folsom AR, Fornage M, Ganesh SK,
Grant SF, Harris TB, Hernandez D, Kamatini N, Keating BJ, Kubo M, LaCroix A,
Lange LA, Lettre G, Liu S, Liu Y, Lohman K, Mathias R, Meng Y, Mohler ER 3rd,
Musani S, Nakamura Y, Nalls MA, O'Donnell CJ, Okada Y, Palmer CD, Papanicolaou
GJ, Patel KV, Reiner AP, Singleton AB, Snively BM, Takahashi A, Tang H, Taylor HA
Jr, Taylor K, Thomson C, Wilson JG, Yanek LR, Yang L, Ziv E, Zonderman AB, Higasa
K, Hirota T, Hosono N, Kamatani Y, Kamatani N, Kubo M, Kumasaka N, Matsuda K,
Nakamura Y, Ohmiya H, Okada Y, Takahashi A, Tamari M, Tanaka T, Tanaka T, Tsunoda
T, Yamaguchi-Kabata Y, Yamamoto K.

White blood cell (WBC) count is a common clinical measure used as a predictor of
certain aspects of human health, including immunity and infection status. WBC
count is also a complex trait that varies among individuals and ancestry groups.
Differences in linkage disequilibrium structure and heterogeneity in allelic
effects are expected to play a role in the associations observed between
populations. Prior genome-wide association study (GWAS) meta-analyses have
identified genomic loci associated with WBC and its subtypes, but much of the
heritability of these phenotypes remains unexplained. Using GWAS summary
statistics for over 50 000 individuals from three diverse populations (Japanese,
African-American and European ancestry), a Bayesian model methodology was
employed to account for heterogeneity between ancestry groups. This approach was
used to perform a trans-ethnic meta-analysis of total WBC, neutrophil and
monocyte counts. Ten previously known associations were replicated and six new
loci were identified, including several regions harboring genes related to
inflammation and immune cell function. Ninety-five percent credible interval
regions were calculated to narrow the association signals and fine-map the
putatively causal variants within loci. Finally, a conditional analysis was
performed on the most significant SNPs identified by the trans-ethnic
meta-analysis (MA), and nine secondary signals within loci previously associated
with WBC or its subtypes were identified. This work illustrates the potential of
trans-ethnic analysis and ascribes a critical role to multi-ethnic cohorts and
consortia in exploring complex phenotypes with respect to variants that lie
outside the European-biased GWAS pool.

Published by Oxford University Press 2014. This work is written by (a) US
Government employee(s) and is in the public domain in the US.

PMCID: PMC4245044 [Available on 2015-12-20]
PMID: 25096241  [PubMed - indexed for MEDLINE]


25. Am J Transplant. 2014 Dec;14(12):2765-76. doi: 10.1111/ajt.12925. Epub 2014 Nov
13.

Antifungal prophylaxis in liver transplantation: a systematic review and network
meta-analysis.

Evans JD(1), Morris PJ, Knight SR.

Author information:
(1)Department of Medicine, Cambridge University, Cambridge, UK; Centre for
Evidence in Transplantation, Royal College of Surgeons of England and the London
School of Hygiene and Tropical Medicine, London, UK.

Invasive fungal infections (IFIs) cause significant morbidity and mortality in
liver transplant recipients, but the need and best agent for prophylaxis is
uncertain. A comprehensive literature search was performed to identify randomized
controlled trials comparing regimens for antifungal prophylaxis in liver
transplant recipients. Direct comparisons were made between treatments using
random-effects meta-analysis and a Bayesian network meta-analysis was performed
for the primary end point of proven IFI. Fourteen studies met inclusion criteria,
reporting comparisons of fluconazole, liposomal amphotericin B (L-AmB),
itraconazole, micafungin and placebo. Overall, antifungal prophylaxis reduced the
rate of proven IFI (odds ratio [OR] 0.37, confidence interval [CI] 0.19-0.72,
p = 0.003), suspected or proven IFI (OR 0.40, CI 0.25-0.66, p = 0.0003) and
mortality due to IFI (OR 0.32, CI 0.10-0.83, p = 0.02) when compared to placebo.
All-cause mortality was not significantly affected. There was no difference in
risk of adverse events requiring cessation of prophylaxis (OR 1.11, 95% CI
0.48-2.55, p = 0.81). In the network meta-analysis an equivalent reduction in the
rate of IFI was seen with fluconazole (OR 0.21, CI 0.06-0.57) and L-AmB (OR 0.21,
CI 0.05-0.71) compared with placebo. Routine prophylaxis with fluconazole or
L-AmB reduces the incidence of IFI following liver transplantation, and the
available evidence suggests that the two are equivalent in efficacy.

© Copyright 2014 The American Society of Transplantation and the American Society
of Transplant Surgeons.

PMID: 25395336  [PubMed - indexed for MEDLINE]


26. Mayo Clin Proc. 2014 Dec;89(12):1621-35. doi: 10.1016/j.mayocp.2014.08.019. Epub
2014 Oct 29.

Comparative efficacy of biologic therapy in biologic-naïve patients with Crohn
disease: 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, Mayo Clinic, Rochester, MN.
Electronic address: singh.siddharth2@mayo.edu. (2)Department of Surgery,
University of Minnesota, Minneapolis. (3)Division of Gastroenterology and
Hepatology, Mayo Clinic, Rochester, MN. (4)Knowledge and Evaluation Research
Unit, Robert D. and Patricia E. Kern Center for the Science of Health Care
Delivery, Mayo Clinic, Rochester, MN.

OBJECTIVE: To study the comparative efficacy of biologic therapy in the
management of biologic-naïve patients with Crohn disease (CD).
PATIENTS AND METHODS: We conducted a systematic review of randomized controlled
trials published from January 1, 1985, through September 30, 2013, comparing
biologic agents (infliximab [IFX], adalimumab [ADA], certolizumab pegol,
natalizumab, vedolizumab, and ustekinumab) with each other or placebo for
inducing and maintaining clinical remission in adults with moderate to severe CD.
To increase comparability across trials, we focused on a subset of biologic-naïve
patients for the induction end point and on responders to induction therapy for
the maintenance end point. We followed a Bayesian network meta-analysis approach.
RESULTS: We identified 17 randomized controlled trials of good methodological
quality comparing 6 biologic agents with placebo, with no direct comparison of
biologic agents. In network meta-analysis, we observed that IFX (relative risk
[RR], 6.11; 95% credible interval [CrI], 2.49-18.29) and ADA (RR, 2.98; 95% CrI,
1.12-8.18), but not certolizumab pegol (RR, 1.48; 95% CrI, 0.76-2.93),
natalizumab (RR, 1.36; 95% CrI, 0.69-2.86), vedolizumab (RR, 1.40; 95% CrI,
0.63-3.28), and ustekinumab (RR, 0.61; 95% CrI, 0.15-2.49), were more likely to
induce remission than placebo. Similar results were observed for maintenance of
remission. Infliximab had the highest probability of being ranked as the most
efficacious agent for induction (86%) and ADA for maintenance of remission (48%).
CONCLUSION: On the basis of network meta-analysis, IFX may be most efficacious
agent for inducing remission in CD in biologic-naïve patients. In the absence of
head-to-head treatment comparison, the confidence in these estimates is low.
Future comparative efficacy studies are warranted.

Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by
Elsevier Inc. All rights reserved.

PMID: 25441399  [PubMed - indexed for MEDLINE]


27. Neuropsychol Rev. 2014 Dec;24(4):428-44. doi: 10.1007/s11065-014-9271-8. Epub
2014 Sep 25.

Blast-related mild traumatic brain injury: a Bayesian random-effects
meta-analysis on the cognitive outcomes of concussion among military personnel.

Karr JE(1), Areshenkoff CN, Duggan EC, Garcia-Barrera MA.

Author information:
(1)Department of Psychology, University of Victoria, P.O. Box 1700, Victoria, BC,
V8W 2Y2, Canada, jkarr@uvic.ca.

Throughout their careers, many soldiers experience repeated blasts exposures from
improvised explosive devices, which often involve head injury. Consequentially,
blast-related mild Traumatic Brain Injury (mTBI) has become prevalent in modern
conflicts, often occuring co-morbidly with psychiatric illness (e.g.,
post-traumatic stress disorder [PTSD]). In turn, a growing body of research has
begun to explore the cognitive and psychiatric sequelae of blast-related mTBI.
The current meta-analysis aimed to evaluate the chronic effects of blast-related
mTBI on cognitive performance. A systematic review identified 9 studies reporting
12 samples meeting eligibility criteria. A Bayesian random-effects meta-analysis
was conducted with cognitive construct and PTSD symptoms explored as moderators.
The overall posterior mean effect size and Highest Density Interval (HDI) came to
d = -0.12 [-0.21, -0.04], with executive function (-0.16 [-0.31, 0.00]), verbal
delayed memory (-0.19 [-0.44, 0.06]) and processing speed (-0.11 [-0.26, 0.01])
presenting as the most sensitive cognitive domains to blast-related mTBI. When
dividing executive function into diverse sub-constructs (i.e., working memory,
inhibition, set-shifting), set-shifting presented the largest effect size (-0.33
[-0.55, -0.05]). PTSD symptoms did not predict cognitive effects sizes, β PTSD
 = -0.02 [-0.23, 0.20]. The results indicate a subtle, but chronic cognitive
impairment following mTBI, especially in set-shifting, a relevant aspect of
executive attention. These findings are consistent with past meta-analyses on
multiple mTBI and correspond with past neuroimaging research on the cognitive
correlates of white matter damage common in mTBI. However, all studies had
cross-sectional designs, which resulted in universally low quality ratings and
limited the conclusions inferable from this meta-analysis.

PMID: 25253505  [PubMed - indexed for MEDLINE]




29. Ann Intern Med. 2014 Nov 18;161(10):724-32. doi: 10.7326/M14-0808.

Coronary revascularization in diabetic patients: a systematic review and Bayesian
network meta-analysis.

Tu B, Rich B, Labos C, Brophy JM.

Comment in
    Ann Intern Med. 2015 Mar 17;162(6):JC8.

BACKGROUND: The optimal revascularization technique in diabetic patients is an
important unresolved question.
PURPOSE: To compare long-term outcomes between the revascularization techniques
of percutaneous coronary intervention (PCI) and coronary artery bypass grafting
(CABG).
DATA SOURCES: English-language publications in PubMed, the Cochrane Central
Register of Controlled Trials, Ovid, and EMBASE between 1 January 1990 and 1 June
2014.
STUDY SELECTION: Two investigators independently reviewed randomized, controlled
trials comparing PCI (with drug-eluting or bare-metal stents) with CABG in adults
with diabetes with multivessel or left main coronary artery disease.
DATA EXTRACTION: Study design, quality, patient characteristics, length of
follow-up, and outcomes were extracted. For duplicate publications, outcomes were
obtained from the publication with the longest follow-up.
DATA SYNTHESIS: 40 studies were combined using a Bayesian network meta-analysis
that accounted for the variation in stent choice. The primary outcome, a
composite of all-cause mortality, nonfatal myocardial infarction, and stroke,
increased with PCI (odds ratio [OR], 1.33 [95% credible interval {CrI}, 1.01 to
1.65]). Percutaneous coronary intervention resulted in increased mortality (OR,
1.44 [CrI, 1.05 to 1.91]), no change in the number of myocardial infarctions (OR,
1.33 [CrI, 0.86 to 1.95]), and fewer strokes (OR, 0.56 [CrI, 0.36 to 0.88]).
LIMITATIONS: Study design and length of follow-up were heterogeneous, and results
were driven primarily by a single study. Costs and nonvascular complications of
the interventions were not examined.
CONCLUSION: Coronary artery bypass grafting seems to be the preferred
revascularization technique in diabetics, especially if long-term survival is
anticipated. However, because of residual uncertainties and increased risk for
stroke with CABG, clinical judgment is required when choosing a revascularization
technique in patients with diabetes.
PRIMARY FUNDING SOURCE: Fonds de recherche du Québec-Santé.

PMID: 25402514  [PubMed - indexed for MEDLINE]




31. Epidemiology. 2014 Nov;25(6):835-42. doi: 10.1097/EDE.0000000000000162.

Outdoor fine particles and nonfatal strokes: systematic review and meta-analysis.

Shin HH(1), Fann N, Burnett RT, Cohen A, Hubbell BJ.

Author information:
(1)From the aEnvironmental Health Science and Research Bureau, Health Canada,
Ottawa, ON, Canada; bDepartment of Mathematics and Statistics, Queen's
University, Kingston, ON, Canada; cHealth and Environmental Impacts Division,
Office of Air Quality Planning and Standards, U.S. Environmental Protection
Agency, NC; and dHealth Effects Institute, Boston, MA.

BACKGROUND: Epidemiologic studies find that long- and short-term exposure to fine
particles (PM2.5) is associated with adverse cardiovascular outcomes, including
ischemic and hemorrhagic strokes. However, few systematic reviews or
meta-analyses have synthesized these results.
METHODS: We reviewed epidemiologic studies that estimated the risks of nonfatal
strokes attributable to ambient PM2.5. To pool risks among studies we used a
random-effects model and 2 Bayesian approaches. The first Bayesian approach
assumes a normal prior that allows risks to be zero, positive or negative. The
second assumes a gamma prior, where risks can only be positive. This second
approach is proposed when the number of studies pooled is small, and there is
toxicological or clinical literature to support a causal relation.
RESULTS: We identified 20 studies suitable for quantitative meta-analysis.
Evidence for publication bias is limited. The frequentist meta-analysis produced
pooled risk ratios of 1.06 (95% confidence interval = 1.00-1.13) and 1.007
(1.003-1.010) for long- and short-term effects, respectively. The Bayesian
meta-analysis found a posterior mean risk ratio of 1.08 (95% posterior interval =
0.96-1.26) and 1.008 (1.003-1.013) from a normal prior, and of 1.05 (1.02-1.10)
and 1.008 (1.004-1.013) from a gamma prior, for long- and short-term effects,
respectively, per 10 μg/m PM2.5.
CONCLUSIONS: Sufficient evidence exists to develop a concentration-response
relation for short- and long-term exposures to PM2.5 and stroke incidence.
Long-term exposures to PM2.5 result in a higher risk ratio than short-term
exposures, regardless of the pooling method. The evidence for short-term
PM2.5-related ischemic stroke is especially strong.

PMCID: PMC4222795
PMID: 25188557  [PubMed - indexed for MEDLINE]


32. Ophthalmology. 2014 Nov;121(11):2081-90. doi: 10.1016/j.ophtha.2014.05.013. Epub
2014 Jun 26.

Global prevalence of glaucoma and projections of glaucoma burden through 2040: a
systematic review and meta-analysis.

Tham YC(1), Li X(2), Wong TY(1), Quigley HA(3), Aung T(1), Cheng CY(4).

Author information:
(1)Singapore Eye Research Institute, Singapore National Eye Centre, Singapore;
Department of Ophthalmology, Yong Loo Lin School of Medicine, National University
of Singapore and National University Health System, Singapore. (2)Singapore Eye
Research Institute, Singapore National Eye Centre, Singapore; Department of
Statistics and Applied Probability, National University of Singapore, Singapore.
(3)Glaucoma Service and Dana Center for Preventive Ophthalmology, Wilmer
Ophthalmological Institute, Johns Hopkins School of Medicine, Baltimore,
Maryland. (4)Singapore Eye Research Institute, Singapore National Eye Centre,
Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National
University of Singapore and National University Health System, Singapore; Saw
Swee Hock School of Public Health, National University of Singapore and National
University Health System, Singapore; Duke-NUS Graduate Medical School, Singapore.
Electronic address: ching-yu_cheng@nuhs.edu.sg.

PURPOSE: Glaucoma is the leading cause of global irreversible blindness. Present
estimates of global glaucoma prevalence are not up-to-date and focused mainly on
European ancestry populations. We systematically examined the global prevalence
of primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG),
and projected the number of affected people in 2020 and 2040.
DESIGN: Systematic review and meta-analysis.
PARTICIPANTS: Data from 50 population-based studies (3770 POAG cases among
140,496 examined individuals and 786 PACG cases among 112 398 examined
individuals).
METHODS: We searched PubMed, Medline, and Web of Science for population-based
studies of glaucoma prevalence published up to March 25, 2013. Hierarchical
Bayesian approach was used to estimate the pooled glaucoma prevalence of the
population aged 40-80 years along with 95% credible intervals (CrIs). Projections
of glaucoma were estimated based on the United Nations World Population
Prospects. Bayesian meta-regression models were performed to assess the
association between the prevalence of POAG and the relevant factors.
MAIN OUTCOME MEASURES: Prevalence and projection numbers of glaucoma cases.
RESULTS: The global prevalence of glaucoma for population aged 40-80 years is
3.54% (95% CrI, 2.09-5.82). The prevalence of POAG is highest in Africa (4.20%;
95% CrI, 2.08-7.35), and the prevalence of PACG is highest in Asia (1.09%; 95%
CrI, 0.43-2.32). In 2013, the number of people (aged 40-80 years) with glaucoma
worldwide was estimated to be 64.3 million, increasing to 76.0 million in 2020
and 111.8 million in 2040. In the Bayesian meta-regression model, men were more
likely to have POAG than women (odds ratio [OR], 1.36; 95% CrI, 1.23-1.52), and
after adjusting for age, gender, habitation type, response rate, and year of
study, people of African ancestry were more likely to have POAG than people of
European ancestry (OR, 2.80; 95% CrI, 1.83-4.06), and people living in urban
areas were more likely to have POAG than those in rural areas (OR, 1.58; 95% CrI,
1.19-2.04).
CONCLUSIONS: The number of people with glaucoma worldwide will increase to 111.8
million in 2040, disproportionally affecting people residing in Asia and Africa.
These estimates are important in guiding the designs of glaucoma screening,
treatment, and related public health strategies.

Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc.
All rights reserved.

PMID: 24974815  [PubMed - indexed for MEDLINE]


33. Syst Rev. 2014 Oct 30;3:130. doi: 10.1186/2046-4053-3-130.

Impact of long-term lifestyle programmes on weight loss and cardiovascular risk
factors in overweight/obese participants: a systematic review and network
meta-analysis.

Schwingshackl L(1), Dias S, Hoffmann G.

Author information:
(1)Faculty of Life Sciences, Department of Nutritional Sciences, University of
Vienna, Althanstraße 14 UZA II, A-1090 Vienna, Austria.
lukas.schwingshackl@univie.ac.at.

BACKGROUND: The aim of this meta-analysis was to compare the long-term efficacy
of diet plus exercise (D+E) vs. diet (D), D+E vs. exercise (E) and D vs. E on
anthropometric outcomes and cardiovascular risk factors in overweight and obese
participants.
METHODS: Electronic searches were performed in MEDLINE and the Cochrane Central
Register of controlled trials. Inclusion criteria were as follows: body mass
index≥25 kg/m2 and a minimum intervention period including follow-up of ≥12
months. Outcomes of interest were as follows: anthropometric parameters, blood
lipids, blood pressure and cardiorespiratory fitness. Pooled effects were
calculated using pairwise random effects and Bayesian random effects network
meta-analysis. Results of the corresponding fixed effects models were compared in
sensitivity analyses.
RESULTS: Overall, 22 trials (24 reports) met the inclusion criteria and 21
(including 3,521 participants) of them were included in the quantitative
analysis. As compared with D, D+E resulted in a significantly more pronounced
reduction in body weight [mean differences (MD): -1.38 kg, 95% confidence
interval (CI) -1.98 to -0.79], and fat mass (MD: -1.65 kg, 95% CI -2.81 to
-0.49], respectively. When comparing D+E with E, MD in change of body weight
(-4.13 kg, 95% CI -5.62 to -2.64), waist circumference (-3.00 cm, 95% CI -5.81 to
-0.20), and fat mass (-3.60 kg, 95% CI -6.15 to -1.05) was in favour of combined
diet and exercise, respectively. Comparing E vs. D, diet resulted in a
significantly more pronounced decrease in body weight (MD: -2.93 kg, 95% CI -4.18
to -1.68), and fat mass (MD: -2.20 kg, 95% CI -3.75 to -0.66). D+E yielded also
the greatest reductions with respect to blood lipids and blood pressure when
compared to single applications of D and E, respectively. Results from the
network meta-analyses confirmed these findings.
CONCLUSIONS: Moderate-quality evidence from the present network meta-analysis
suggests that D+E can be highly recommended for long-term obesity management.
Furthermore, the evidence suggests a moderate superiority of D over E with
respect to anthropometric outcomes.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42013003906.

PMCID: PMC4227972
PMID: 25358395  [PubMed - indexed for MEDLINE]


34. Angiogenesis. 2014 Oct;17(4):909-20. doi: 10.1007/s10456-014-9438-1. Epub 2014
Jul 11.

Genetic variability of VEGF pathway genes in six randomized phase III trials
assessing the addition of bevacizumab to standard therapy.

de Haas S(1), Delmar P, Bansal AT, Moisse M, Miles DW, Leighl N, Escudier B, Van
Cutsem E, Carmeliet P, Scherer SJ, Pallaud C, Lambrechts D.

Author information:
(1)F. Hoffmann-La Roche, Basel, Switzerland.

BACKGROUND: Despite extensive translational research, no validated biomarkers
predictive of bevacizumab treatment outcome have been identified.
METHODS: We performed a meta-analysis of individual patient data from six
randomized phase III trials in colorectal, pancreatic, lung, renal, breast, and
gastric cancer to explore the potential relationships between 195 common genetic
variants in the vascular endothelial growth factor (VEGF) pathway and bevacizumab
treatment outcome.
RESULTS: The analysis included 1,402 patients (716 bevacizumab-treated and 686
placebo-treated). Twenty variants were associated (P < 0.05) with
progression-free survival (PFS) in bevacizumab-treated patients. Of these, 4
variants in EPAS1 survived correction for multiple testing (q < 0.05).
Genotype-by-treatment interaction tests revealed that, across these 20 variants,
3 variants in VEGF-C (rs12510099), EPAS1 (rs4953344), and IL8RA (rs2234671) were
potentially predictive (P < 0.05), but not resistant to multiple testing (q >
0.05). A weak genotype-by-treatment interaction effect was also observed for
rs699946 in VEGF-A, whereas Bayesian genewise analysis revealed that genetic
variability in VHL was associated with PFS in the bevacizumab arm (q < 0.05).
Variants in VEGF-A, EPAS1, and VHL were located in expression quantitative loci
derived from lymphoblastoid cell lines, indicating that they affect the
expression levels of their respective gene.
CONCLUSIONS: This large genetic analysis suggests that variants in VEGF-A, EPAS1,
IL8RA, VHL, and VEGF-C have potential value in predicting bevacizumab treatment
outcome across tumor types. Although these associations did not survive
correction for multiple testing in a genotype-by-interaction analysis, they are
among the strongest predictive effects reported to date for genetic variants and
bevacizumab efficacy.

PMID: 25012543  [PubMed - indexed for MEDLINE]


35. Int J Parasitol. 2014 Oct 1;44(11):765-74. doi: 10.1016/j.ijpara.2014.05.009.
Epub 2014 Jun 30.

Sensitivity of diagnostic tests for human soil-transmitted helminth infections: a
meta-analysis in the absence of a true gold standard.

Nikolay B(1), Brooker SJ(2), Pullan RL(2).

Author information:
(1)Faculty of Infectious and Tropical Diseases, London School of Hygiene &
Tropical Medicine, Keppel Street, WC1E 7HT London, United Kingdom. Electronic
address: birgit.nikolay@lshtm.ac.uk. (2)Faculty of Infectious and Tropical
Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, WC1E 7HT
London, United Kingdom.

Reliable, sensitive and practical diagnostic tests are an essential tool in
disease control programmes for mapping, impact evaluation and surveillance. To
provide a robust global assessment of the relative performance of available
diagnostic tools for the detection of soil-transmitted helminths, we conducted a
meta-analysis comparing the sensitivities and the quantitative performance of the
most commonly used copro-microscopic diagnostic methods for soil-transmitted
helminths, namely Kato-Katz, direct microscopy, formol-ether concentration,
McMaster, FLOTAC and Mini-FLOTAC. In the absence of a perfect reference standard,
we employed a Bayesian latent class analysis to estimate the true, unobserved
sensitivity of compared diagnostic tests for each of the soil-transmitted
helminth species Ascaris lumbricoides, Trichuris trichiura and the hookworms. To
investigate the influence of varying transmission settings we subsequently
stratified the analysis by intensity of infection. Overall, sensitivity estimates
varied between the different methods, ranging from 42.8% for direct microscopy to
92.7% for FLOTAC. The widely used double slide Kato-Katz method had a sensitivity
of 74-95% for the three soil-transmitted helminth species at high infection
intensity, however sensitivity dropped to 53-80% in low intensity settings, being
lowest for hookworm and A. lumbricoides. The highest sensitivity, overall and in
both intensity groups, was observed for the FLOTAC method, whereas the
sensitivity of the Mini-FLOTAC method was comparable with the Kato-Katz method.
FLOTAC average egg count estimates were significantly lower compared with
Kato-Katz, while the compared McMaster counts varied. In conclusion, we
demonstrate that the Kato-Katz and Mini-FLOTAC methods had comparable
sensitivities. We further show that test sensitivity of the Kato-Katz method is
reduced in low transmission settings.

Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

PMCID: PMC4186778
PMID: 24992655  [PubMed - indexed for MEDLINE]


36. J Clin Periodontol. 2014 Oct;41(10):1015-25. doi: 10.1111/jcpe.12292. Epub 2014
Aug 11.

A systematic review and Bayesian network meta-analysis of randomized clinical
trials on non-surgical treatments for peri-implantitis.

Faggion CM Jr(1), Listl S, Frühauf N, Chang HJ, Tu YK.

Author information:
(1)Department of Periodontology, Faculty of Dentistry, University of Münster,
Münster, Germany.

BACKGROUND/AIM: It remains unclear which type of non-surgical treatment is most
appropriate as first-line intervention against peri-implantitis. This systematic
review and Bayesian network meta-analysis aimed to compare the clinical effect of
various non-surgical peri-implantitis therapies.
METHODS: The PubMed, SCOPUS, CINAHL, DARE and Web of Knowledge databases were
searched in duplicate for randomized controlled trials (RCTs) up to and including
01 January 2014. Additional relevant literature was identified using
handsearching of reference lists within published systematic reviews, and
screenings of OpenGrey, ClinicalTrials.gov and Controlled-Trials.com. Probing
pocket depth (PPD) was the outcome measure assessed. Multilevel mixed modelling
was used to perform the network meta-analysis, and Markov Chain Monte Carlo
simulation to obtain random effects.
RESULTS: Eleven studies were included in the network meta-analysis. Debridement
in conjunction with antibiotics achieved the greatest additional PPD reduction in
comparison to debridement only (0.490 mm; 95% credible interval: -0.647;1.252).
The highest probabilities of being the most effective interventions were achieved
by Vector system (p = 20.60%), debridement plus periochip (p = 20.00%) and
photodynamic therapy (p = 18.90%).
CONCLUSION: The differences between various non-surgical treatments were
relatively small with large credible intervals. On the basis of currently
available RCTs, there is insufficient evidence to support that any particular
non-surgical treatment for peri-implantitis showed better performance than
debridement alone.

© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PMID: 25039292  [PubMed - indexed for MEDLINE]


37. J Crit Care. 2014 Oct;29(5):706-10. doi: 10.1016/j.jcrc.2014.04.011. Epub 2014
Apr 26.

Mortality benefit of vasopressor and inotropic agents in septic shock: a Bayesian
network meta-analysis of randomized controlled trials.

Oba Y(1), Lone NA(2).

Author information:
(1)University of Missouri, School of Medicine, Division of Pulmonary, Critical
Care and Environmental Medicine, Columbia, MO, USA. Electronic address:
obay@health.missouri.edu. (2)University of Missouri, School of Medicine, Division
of Pulmonary, Critical Care and Environmental Medicine, Columbia, MO, USA.

OBJECTIVE: The choice of vasopressor in septic shock has been a matter of debate.
The purpose of this study was to systematically review overall evidence of
vasopressor and inotropic agents in septic shock using a Bayesian network
meta-analysis.
METHODS: Databases, including Medline, Scopus, CINAHL, and Google Scholar were
searched to identify relevant studies. Eligible studies were randomized
controlled trials that reported mortality rates on the use of vasopressors and
inotropes in patients with septic shock. We chose to use 28-day mortality as the
outcome assessment criterion.
RESULTS: Fourteen studies with a total of 2811 patients were included in the
analysis. Norepinephrine (NE) and NE + low-dose vasopressin but not epinephrine
(EPI) were associated with significantly reduced mortality compared with
dopamine. (Odds ratio, 0.80 [95% credibility interval, 0.65-0.99], 0.69
[0.48-0.98], and 0.56 [0.26-1.18], respectively). The addition of an inotropic
agent such as dobutamine or dopexamine did not reduce mortality compared with EPI
or NE alone.
CONCLUSIONS: Our results support the use of NE with or without low-dose
vasopressin as the first-line vasopressor therapy in septic shock. No concrete
evidence exists to support the use of EPI over dopamine as the second-line agent
or the addition of an inotropic agent.

Copyright © 2014 Elsevier Inc. All rights reserved.

PMID: 24857641  [PubMed - indexed for MEDLINE]


38. Med Decis Making. 2014 Oct;34(7):899-910. doi: 10.1177/0272989X14537558. Epub
2014 Jun 16.

A Bayesian mixed-treatment comparison meta-analysis of treatments for alcohol
dependence and implications for planning future trials.

DeSantis SM(1), Zhu H(2).

Author information:
(1)Division of Biostatistics, School of Public Health, University of Texas Health
Science Center, Houston, TX, USA (SMD, HZ) stacia.m.desantis@uth.tmc.edu.
(2)Division of Biostatistics, School of Public Health, University of Texas Health
Science Center, Houston, TX, USA (SMD, HZ).

BACKGROUND: Several treatments for alcohol dependence have been tested in
randomized controlled trials, giving rise to systematic reviews with a network of
evidence structure, or mixed treatment comparisons (MTCs). Within the network,
there are few direct comparisons of active treatments. Thus far, this network has
not been adequately analyzed. For example, "indirect comparisons" between
treatments (e.g., the comparison of treatments B:C obtained via estimates from
A:B and A:C trials) have not been incorporated into estimates of treatment
effects. This has implications for the planning of future randomized controlled
trials.
METHODS: We applied recent developments in Bayesian MTC meta-analysis to analyze
the network of evidence. Using these results, we proposed a methodology to
inform, design, and power a hypothetical trial in the context of an updated
meta-analysis for treatments that have been infrequently compared and therefore
whose effect sizes are not well informed by a meta-analysis.
RESULTS: An MTC meta-analysis provides more accurate estimates than a pairwise
meta-analysis and uncovers decisive differences between active treatments that
have been infrequently directly compared. Weighting across all outcomes indicates
that a combination (naltrexone + acamprosate) treatment has the highest posterior
probability of being the "best" treatment. If a new clinical trial were to be
conducted of a combination therapy versus acamprosate alone, there is no feasible
sample size that would result in a decisive meta-analysis.
CONCLUSIONS: An MTC meta-analysis should be used to estimate treatment effects in
networks in which direct and indirect evidence are consistent and to inform the
design of future studies.

© The Author(s) 2014.

PMCID: PMC4318856 [Available on 2015-10-01]
PMID: 24935915  [PubMed - indexed for MEDLINE]


39. J Natl Cancer Inst. 2014 Sep 15;106(9). pii: dju203. doi: 10.1093/jnci/dju203.
Print 2014 Sep.

Comparative effectiveness of neoadjuvant therapy for HER2-positive breast cancer:
a network meta-analysis.

Nagayama A(1), Hayashida T(2), Jinno H(1), Takahashi M(1), Seki T(1), Matsumoto
A(1), Murata T(1), Ashrafian H(1), Athanasiou T(1), Okabayashi K(2), Kitagawa
Y(1).

Author information:
(1)Department of Surgery, Keio University School of Medicine, Tokyo, Japan (AN,
TH, HJ, MT, TS, AM, TM, KO, YK); Department of Surgery and Cancer, Imperial
College London, London, UK (HA, TA). (2)Department of Surgery, Keio University
School of Medicine, Tokyo, Japan (AN, TH, HJ, MT, TS, AM, TM, KO, YK); Department
of Surgery and Cancer, Imperial College London, London, UK (HA, TA).
tetsu@z7.keio.jp okabayashikoji@gmail.com.

Comment in
    J Natl Cancer Inst. 2015 Apr;107(4). pii: djv038. doi: 10.1093/jnci/djv038.
    J Natl Cancer Inst. 2014 Sep;106(9). pii: dju259. doi: 10.1093/jnci/dju259.
    J Natl Cancer Inst. 2015 Apr;107(4). pii: djv039. doi: 10.1093/jnci/djv039.

BACKGROUND: The growing number of antihuman epidermal growth factor receptor-2
(HER2) agents suggests the need for defining the optimal choice of neoadjuvant
therapy for HER2-positive breast cancer. This study aims to assess the efficacy
and safety of neoadjuvant therapy for HER2-positive breast cancer.
METHODS: Randomized trials that compared different anti-HER2 regimens in the
neoadjuvant setting were included. The odds ratio (OR) for pathological complete
response (pCR), treatment completion, and safety was utilized for pooling effect
sizes. Network meta-analysis using a Bayesian statistical model was performed to
combine the direct and indirect evidence of neoadjuvant therapy for HER2-positive
breast cancer. All statistical tests were two-sided.
RESULTS: A database search identified 1047 articles, with 10 studies meeting the
eligibility criteria. A total of 2247 patients in seven different treatment arms
were assessed. Anti-HER2 agents evaluated included trastuzumab (tzmb), lapatinib
(lpnb), and pertuzumab (pzmb). Network meta-analysis showed no statistically
significant difference between dual targeting treatment arms; however, lpnb
reduced treatment completion due to adverse events. Patients in dual targeting
arms had statistically significantly more pCR than those in other treatment arms
(chemotherapy [CT] + tzmb + pzmb vs CT + tzmb, OR = 2.29, 95% credibility
interval = 1.02 to 5.02, P = .02). The surface under the cumulative ranking
probability curve indicated that CT + tzmb + pzmb had the highest probability of
being the best treatment arm in terms of pCR.
CONCLUSIONS: This study indicates that combining two anti-HER2 agents with CT is
the most effective treatment modality in the neoadjuvant setting for
HER2-positive breast cancer.

© The Author 2014. Published by Oxford University Press. All rights reserved. For
Permissions, please e-mail: journals.permissions@oup.com.

PMID: 25224562  [PubMed - indexed for MEDLINE]


40. JAMA. 2014 Sep 3;312(9):923-33. doi: 10.1001/jama.2014.10397.

Comparison of weight loss among named diet programs in overweight and obese
adults: a meta-analysis.

Johnston BC(1), Kanters S(2), Bandayrel K(3), Wu P(4), Naji F(5), Siemieniuk
RA(6), Ball GD(7), Busse JW(8), Thorlund K(9), Guyatt G(10), Jansen JP(11), Mills
EJ(12).

Author information:
(1)Hospital for Sick Children Research Institute, Toronto, Ontario,
Canada2Institute of Health Policy, Management and Evaluation, University of
Toronto, Toronto, Ontario, Canada3Department of Clinical Epidemiology and
Biostatistics, McMaster University, Hami. (2)School of Population and Public
Health, University of British Columbia, Vancouver, Canada6Faculty of Health
Sciences, University of Ottawa, Ottawa, Ontario, Canada7Redwood Outcomes,
Vancouver, British Columbia, Canada. (3)Hospital for Sick Children Research
Institute, Toronto, Ontario, Canada4Department of Anesthesia and Pain Medicine,
Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
(4)Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada.
(5)Michael G. DeGroote School of Medicine, McMaster University, Hamilton,
Ontario, Canada. (6)Department of Medicine, University of Toronto, Toronto,
Ontario, Canada. (7)Department of Pediatrics, University of Alberta, Edmonton,
Canada11Department of Agricultural, Food and Nutritional Science, University of
Alberta, Edmonton, Canada. (8)Department of Clinical Epidemiology and
Biostatistics, McMaster University, Hamilton, Ontario, Canada12Michael G.
DeGroote Institute for Pain Research and Care, McMaster University, Hamilton,
Ontario, Canada13Department of Anesthesia, McMaster University. (9)Department of
Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario,
Canada7Redwood Outcomes, Vancouver, British Columbia, Canada14Stanford Prevention
Research Center, Stanford University School of Medicine, Stanford University.
(10)Department of Clinical Epidemiology and Biostatistics, McMaster University,
Hamilton, Ontario, Canada. (11)Redwood Outcomes, Vancouver, British Columbia,
Canada15Department of Public Health and Community Medicine, Tufts University,
Boston, Massachusetts. (12)Redwood Outcomes, Vancouver, British Columbia,
Canada14Stanford Prevention Research Center, Stanford University School of
Medicine, Stanford University, Stanford, California.

Comment in
    JAMA. 2014 Sep 3;312(9):900-1.
    Evid Based Med. 2015 Jun;20(3):103-4.

IMPORTANCE: Many claims have been made regarding the superiority of one diet or
another for inducing weight loss. Which diet is best remains unclear.
OBJECTIVE: To determine weight loss outcomes for popular diets based on diet
class (macronutrient composition) and named diet.
DATA SOURCES: Search of 6 electronic databases: AMED, CDSR, CENTRAL, CINAHL,
EMBASE, and MEDLINE from inception of each database to April 2014.
STUDY SELECTION: Overweight or obese adults (body mass index ≥25) randomized to a
popular self-administered named diet and reporting weight or body mass index data
at 3-month follow-up or longer.
DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data on
populations, interventions, outcomes, risk of bias, and quality of evidence. A
Bayesian framework was used to perform a series of random-effects network
meta-analyses with meta-regression to estimate the relative effectiveness of diet
classes and programs for change in weight and body mass index from baseline. Our
analyses adjusted for behavioral support and exercise.
MAIN OUTCOMES AND MEASURES: Weight loss and body mass index at 6- and 12-month
follow-up (±3 months for both periods).
RESULTS: Among 59 eligible articles reporting 48 unique randomized trials
(including 7286 individuals) and compared with no diet, the largest weight loss
was associated with low-carbohydrate diets (8.73 kg [95% credible interval {CI},
7.27 to 10.20 kg] at 6-month follow-up and 7.25 kg [95% CI, 5.33 to 9.25 kg] at
12-month follow-up) and low-fat diets (7.99 kg [95% CI, 6.01 to 9.92 kg] at
6-month follow-up and 7.27 kg [95% CI, 5.26 to 9.34 kg] at 12-month follow-up).
Weight loss differences between individual diets were minimal. For example, the
Atkins diet resulted in a 1.71 kg greater weight loss than the Zone diet at
6-month follow-up. Between 6- and 12-month follow-up, the influence of behavioral
support (3.23 kg [95% CI, 2.23 to 4.23 kg] at 6-month follow-up vs 1.08 kg [95%
CI, -1.82 to 3.96 kg] at 12-month follow-up) and exercise (0.64 kg [95% CI, -0.35
to 1.66 kg] vs 2.13 kg [95% CI, 0.43 to 3.85 kg], respectively) on weight loss
differed.
CONCLUSIONS AND RELEVANCE: Significant weight loss was observed with any
low-carbohydrate or low-fat diet. Weight loss differences between individual
named diets were small. This supports the practice of recommending any diet that
a patient will adhere to in order to lose weight.

PMID: 25182101  [PubMed - indexed for MEDLINE]


41. Am J Clin Nutr. 2014 Sep;100(3):746-55. doi: 10.3945/ajcn.113.082602. Epub 2014
Jul 23.

Cardiovascular disease and vitamin D supplementation: trial analysis, systematic
review, and meta-analysis.

Ford JA(1), MacLennan GS(1), Avenell A(1), Bolland M(1), Grey A(1), Witham M(1);
RECORD Trial Group.

Collaborators: Grant AM, Avenell A, Campbell MK, McDonald AM, MacLennan GS,
McPherson GC, Anderson FH, Cooper C, Francis RM, Donaldson C, Gillespie WJ,
Robinson CM, Torgerson DJ, Wallace WA.

Author information:
(1)From the Health Services Research Unit, University of Aberdeen, Aberdeen,
United Kingdom (JAF, GSM, and AA); the Department of Medicine, University of
Auckland, Auckland, New Zealand (MB and AG); and the Section of Aging and Health,
University of Dundee, Dundee, United Kingdom (MW).

BACKGROUND: Low 25-hydroxyvitamin D status has been associated with increased
cardiovascular events in epidemiologic studies.
OBJECTIVE: We assessed whether vitamin D supplementation reduces cardiac failure,
myocardial infarction (MI), and stroke through an analysis of the Randomised
Evaluation of Calcium Or vitamin D (RECORD) randomized controlled trial (RCT), a
systematic review, and a meta-analysis.
DESIGN: Two analyses were undertaken. The first analysis was a trial analysis.
The RECORD was a factorial RCT that compared vitamin D₃ (800 IU/d), calcium (1000
mg/d), vitamin D plus calcium, and a placebo. Cardiovascular events were
collected throughout the trial and 3-y posttrial follow-up. Data were analyzed by
using Cox regression. The second analysis was a systematic review. MEDLINE,
EMBASE, CENTRAL, conference abstracts, and ongoing trials were searched for RCTs
that evaluated vitamin D from 1980 to 2013. RCTs with ≥1 y of follow-up and
participants mean or median age ≥60 y were included. Meta-analyses were based on
a Bayesian fixed-effects model by using a complementary log-log link function to
account for varying lengths of follow-up.
RESULTS: In the trial analysis, we showed that, for the 5292 participants in the
RECORD trial, HRs (95% CIs) for vitamin D compared with no vitamin D for cardiac
failure, MI, and stroke were 0.75 (0.58, 0.97), 0.97 (0.75,1.26), and 1.06 (0.8,
1.32), respectively. Twenty-one studies met the inclusion criteria for the
systematic review (n = 13,033). Estimated HRs (credible intervals) for vitamin D
compared with the placebo or control for on-study events for cardiac failure, MI,
and stroke were 0.82 (0.58, 1.15), 0.96 ( 0.83, 1.10), and 1.07 (0.91, 1.29),
respectively.
CONCLUSION: Vitamin D supplementation might protect against cardiac failure in
older people but does not appear to protect against MI or stroke.

© 2014 American Society for Nutrition.

PMID: 25057156  [PubMed - indexed for MEDLINE]


42. Diabetologia. 2014 Sep;57(9):1789-97. doi: 10.1007/s00125-014-3303-z. Epub 2014
Jul 5.

Impact of different training modalities on glycaemic control and blood lipids in
patients with type 2 diabetes: a systematic review and network meta-analysis.

Schwingshackl L(1), Missbach B, Dias S, König J, Hoffmann G.

Author information:
(1)Department of Nutritional Sciences, Faculty of Life Sciences, University of
Vienna, Althanstraße 14 (UZAII), 1090, Vienna, Austria,
lukas.schwingshackl@univie.ac.at.

AIMS/HYPOTHESIS: This study aimed to systematically review randomised controlled
trials comparing the effects of aerobic exercise training (AET), resistance
training (RT) and combined training (CT) on glycaemic control and blood lipids in
patients with type 2 diabetes mellitus.
METHODS: Searches were performed in MEDLINE, EMBASE and the Cochrane Library.
Inclusion criteria were: type 2 diabetes mellitus, adult, supervised training and
a minimum intervention period of 8 weeks. Pooled effects were calculated by
fixed/random effect pairwise and Bayesian fixed/random effects network
meta-analyses.
RESULTS: A total of 14 trials enrolling 915 participants were included. AET was
more effective than RT in improving HbA1c levels (mean difference [MD] -0.20%
[-2.2 mmol/mol]; 95% CI -0.32, -0.08; p = 0.0007, 10 trials/515 participants) and
fasting glucose (MD -0.9 mmol/l; 95% CI -1.71, -0.09; p = 0.03, 8 trials/245
participants). Compared with AET, CT resulted in a significantly more pronounced
reduction in HbA1c (MD -0.17% [-1.87 mmol/mol]; 95% CI -0.31, -0.03; p = 0.02, 9
trials/493 participants). Compared with RT, the MD of the change in HbA1c (MD
-0.62%, [-6.82 mmol/mol]; 95% CI -0.95, -0.30; p = 0.0002, 5 trials/362
participants], fasting glucose (MD -1.99 mmol/l; 95% CI -3.07, -0.90; p = 0.0003,
3 trials/99 participants) and triacylglycerols (MD -0.28 mmol/l; 95% CI -0.46,
-0.10; p = 0.003, 4 trials/213 participants) were all in favour of CT. The
exclusion of trials with a high risk of bias yielded only non-significant
results.
CONCLUSIONS/INTERPRETATION: The present data suggest that CT might be the most
efficacious exercise modality to improve glycaemic control and blood lipids.
Interpretation with respect to clinical relevance is limited by the low quality
of the studies included and the limited information on the clinically important
outcomes or adverse effects of exercise.

PMID: 24996616  [PubMed - indexed for MEDLINE]


43. J Clin Endocrinol Metab. 2014 Sep;99(9):3070-9. doi: 10.1210/jc.2014-1162. Epub
2014 May 13.

Effect of odanacatib on BMD and fractures: estimates from Bayesian univariate and
bivariate meta-analyses.

Gajic-Veljanoski O(1), Tomlinson G, Srighanthan J, Adachi JD, Josse R, Brown JP,
Cheung AM.

Author information:
(1)Osteoporosis Program (O.G.-V., J.S., A.M.C.), University Health Network/Mt
Sinai Hospital, Toronto, ON M5G 2C4, Canada; Institute of Health Policy,
Management and Evaluation (G.T., A.M.C.), and Department of Medicine (G.T., R.J.,
A.M.C.), University of Toronto, Toronto, ON M5T 3M6, Canada; St Joseph's
Healthcare and McMaster University (J.D.A.), Hamilton, ON L8N 1Y2, Canada; St
Michael's Hospital (R.J.), Toronto, ON M5C 2T2, Canada; and Centre Hospitalier
Universitaire de Québec Research Centre and Laval University (J.P.B.), Quebec, QC
G1V 4G2, Canada.

CONTEXT: Odanacatib (ODN), a selective cathepsin-K inhibitor, was found to
increase bone mineral density (BMD); the effect on fractures is based on adverse
event reports.
OBJECTIVE: To estimate current effects and predict future effects of ODN on BMD
and fractures.
DATA SOURCES: Electronic databases (Medline, EMBASE, Cochrane Library),
conference proceedings, and bibliographies.
STUDY SELECTION: Trials that compared ODN 50 mg/wk to placebo for at least 1 year
and reported changes in BMD or fractures. Meta-analysis: Two bone outcomes were
pooled as independent and as joint outcomes in Bayesian univariate and bivariate
random-effects models.
DATA SYNTHESIS: Of 32 potentially eligible articles, six citations describing
four trials (993 patients) were included. ODN for 3 years increased mean BMD at
the lumbar spine by 5.0% (95% credible interval [CrI], 2.7, 7.5), total hip by
3.6% (95% CrI, 1.6, 5.9), and femoral neck (FN) by 3.6% (95% CrI, 1.6, 5.7). In a
future trial of 3-year duration, the predicted mean increase in BMD, adjusted for
the effect on fractures, was 4.9% for lumbar spine (95% CrI, 2.5, 7.4), 3.4% for
total hip (95% CrI, 1.7, 5.2), and 3.5% for FN (95% CrI, 1.8, 5.3). After
accounting for the effect on FN BMD, ODN for 3 years was associated with a
population odds ratio of 0.38 (95% CrI, 0.1, 0.8). In a future trial, the odds
ratio was 0.41 (95% CrI, 0.1, 1.1). The probability of benefit on fractures was
96-99%. The estimates remained robust in sensitivity analyses.
CONCLUSIONS: Our analyses suggest that ODN will increase BMD and decrease all
fractures in the fracture outcome trial; however, direct demonstration of this
antifracture efficacy is needed.

PMID: 24823462  [PubMed - indexed for MEDLINE]


44. CNS Drugs. 2014 Aug;28(8):699-712. doi: 10.1007/s40263-014-0169-z.

Comparative efficacy and risk of harms of immediate- versus extended-release
second-generation antidepressants: a systematic review with network
meta-analysis.

Nussbaumer B(1), Morgan LC, Reichenpfader U, Greenblatt A, Hansen RA, Van Noord
M, Lux L, Gaynes BN, Gartlehner G.

Author information:
(1)Department for Evidence-Based Medicine and Clinical Epidemiology, Danube
University Krems, Dr.-Karl-Dorrek Strasse 30, 3500, Krems, Austria,
barbara.nussbaumer@donau-uni.ac.at.

BACKGROUND: Major depressive disorder (MDD) has detrimental effects on an
individual's personal life, leads to increased risk of comorbidities, and places
an enormous economic burden on society. Several 'second-generation'
antidepressants are available as both immediate-release (IR) and extended-release
formulations. The advantage of extended-release formulations may be the
potentially improved adherence and a lower risk of adverse events.
OBJECTIVE: We conducted a systematic review to assess the comparative efficacy,
risk of harms, and patients' adherence of IR and extended-release antidepressants
for the treatment of MDD.
DATA SOURCE: English-language abstracts were retrieved from PubMed, EMBASE, the
Cochrane Library, PsycINFO, and International Pharmaceutical Abstracts from 1980
to October 2012, as well as from reference lists of pertinent review articles and
grey literature searches.
ELIGIBILITY CRITERIA: We included head-to-head randomized controlled trials
(RCTs) of at least 6 weeks' duration that compared an IR formulation with an
extended-release formulation of the same antidepressant in adult patients with
MDD. We also included placebo-controlled trials to conduct a network
meta-analysis. To assess harms and adherence, in addition to RCTs, we searched
for observational studies with ≥1,000 participants and a follow-up of ≥12 weeks.
STUDY APPRAISAL AND SYNTHESIS METHODS: We dually reviewed abstracts and full
texts and assessed quality ratings. Lacking head-to-head evidence for many
comparisons of interest, we conducted network meta-analyses using Bayesian
methods. Our outcome measure of choice was response on the Hamilton Depression
Rating Scale.
RESULTS: We located seven head-to-head trials and 94 placebo- and
active-controlled trials for network meta-analysis. Overall, our analyses
indicate that IR and extended-release formulations do not differ substantially
with respect to efficacy and risk of harms. The evidence is mixed with respect to
differences in adherence, indicating lower adherence for IR formulations.
LIMITATIONS: The lack of head-to-head comparisons for many drugs compromises our
conclusions. Network meta-analyses have methodological limitations that need to
be taken into consideration when interpreting findings.
CONCLUSION: Available evidence currently shows no clear differences between the
two formulations and therefore we cannot recommend a first choice. However, if
adherence or compliance with one medication is an issue, then clinicians and
patients should consider the alternative medication. If adherence or costs are a
problem with one formulation, consideration of the other formulation to provide
an adequate treatment trial is reasonable.

PMID: 24794101  [PubMed - indexed for MEDLINE]


45. Curr Med Res Opin. 2014 Aug;30(8):1473-87. doi: 10.1185/03007995.2014.898140.
Epub 2014 Apr 3.

A network meta-analysis of the efficacy of belatacept, cyclosporine and
tacrolimus for immunosuppression therapy in adult renal transplant recipients.

Goring SM(1), Levy AR, Ghement I, Kalsekar A, Eyawo O, L'Italien GJ, Kasiske B.

Author information:
(1)Oxford Outcomes Ltd , Vancouver, BC , Canada.

Belatacept is a first in-class co-stimulation blocker developed for primary
maintenance immunosuppression following renal transplantation. The objective of
this study was to estimate the efficacy of belatacept relative to tacrolimus and
cyclosporine among adults receiving a single kidney transplant. A systematic
review was conducted of randomized clinical trials (RCTs) published between
January 1990 and December 2013 using EMBASE, MEDLINE, the Cochrane Central
Register of Controlled Trials, and unpublished study reports from two belatacept
RCTs. Bayesian network meta-analysis (NMA) methods were used to compare the
efficacy measures, mortality, graft loss, acute rejection and glomerular
filtration rate (GFR). Heterogeneity was quantified using statistical metrics and
potential sources were evaluated using meta-regression and subgroup analysis. A
total of 28 RCTs comparing tacrolimus with cyclosporine, and three comparing
belatacept with cyclosporine, were identified. All three agents provided
comparable graft and patient survival, despite a higher risk of acute rejection
associated with belatacept and cyclosporine. Belatacept was associated with
significant improvement in GFR versus cyclosporine. Compared with tacrolimus,
this difference was clinically meaningful yet statistically non-significant. The
probability of being the best treatment was highest for belatacept for graft
survival (68%), patient survival (97%) and renal function (89%), and highest for
tacrolimus for acute rejection (99%).Variability in donor, recipient, and trial
characteristics was present in the included RCTs; however, minimal statistical
heterogeneity was detected in the analysis of acute rejection, graft or patient
survival, and none of the characteristics were found to be significantly
associated with relative effect. Although the direction of effect of
immunosuppressants on GFR was consistent across RCTs, precise estimation of its
magnitude was limited by a small number of RCTs and heterogeneity in relative
effect sizes. Clinicians often seek an alternative to CNIs due to their
nephrotoxic effects. The results of this indirect comparison indicate that
belatacept is an effective immunosuppressive agent in renal transplantation among
adults.

PMID: 24628478  [PubMed - indexed for MEDLINE]


46. Lung Cancer. 2014 Aug;85(2):230-8. doi: 10.1016/j.lungcan.2014.05.007. Epub 2014
May 21.

Afatinib in the treatment of EGFR mutation-positive NSCLC--a network
meta-analysis.

Popat S(1), Mok T(2), Yang JC(3), Wu YL(4), Lungershausen J(5), Stammberger U(5),
Griebsch I(5), Fonseca T(6), Paz-Ares L(7).

Author information:
(1)Royal Marsden Hospital, London, UK. Electronic address:
sanjay.popat@rmh.nhs.uk. (2)State Key Laboratory of Southern China, Hong Kong
Cancer Institute, The Chinese University of Hong Kong, Hong Kong. (3)National
Taiwan University, Taipei, Taiwan. (4)Guangdong Lung Cancer Institute, Guangdong
General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.
(5)Boehringer Ingelheim GmbH, Ingelheim, Germany. (6)IMS Health, London, UK.
(7)Instituto de Biomedicina de Sevilla - IBIS (University Hospital Virgen del
Rocío, US, CSIC), Seville, Spain.

OBJECTIVES: Epidermal growth factor receptor (EGFR) mutation-positive non-small
cell lung cancer (NSCLC) is a specific lung cancer subtype characterized by
sensitivity to treatment with EGFR tyrosine kinase inhibitors (TKIs). Two
reversible EGFR TKIs (gefitinib, erlotinib) and the irreversible ErbB family
blocker afatinib are currently approved for treatment of EGFR mutation-positive
NSCLC, but no head-to-head trials have been reported to date. We aimed to assess
the relative efficacy of the three drugs by conducting a network meta-analysis
(NMA).
MATERIALS AND METHODS: A systematic literature review was conducted to identify
all the available evidence. Outcomes of interest were progression-free survival
(PFS) and overall survival. For PFS, results by investigator review were
considered as not all trials assessed PFS independently. Results were analyzed
using Bayesian methods.
RESULTS: The literature search identified 246 articles that were assessed for
eligibility, of which 21 studies were included in the NMA, including eight trials
performed in an EGFR mutation-positive population. The estimated PFS HR (95%
credible interval, CrI) for afatinib compared with gefitinib was 0.70 (0.40-1.16)
and compared with erlotinib was 0.86 (0.50-1.50) in the total population. The
estimated probability of being best for afatinib over all other treatments for
PFS was 70% versus 27% for erlotinib and 3% for gefitinib; the estimated
probability of chemotherapy being the best treatment was 0%. Estimated HR (95%
CrI) in patients with common mutations was 0.73 (0.42-1.24) for afatinib compared
with erlotinib and 0.60 (0.34-0.99) for afatinib compared with gefitinib. OS
findings were not significantly different between treatments.
CONCLUSIONS: In the absence of direct head-to-head trial data comparing efficacy
between the three EGFR TKIs, our analysis suggests that afatinib is a viable
treatment alternative to erlotinib or gefitinib in terms of PFS. A direct
trial-based comparison of the efficacy of these agents is warranted to clarify
their relative benefits.

Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

PMID: 24929780  [PubMed - indexed for MEDLINE]


47. Osteoarthritis Cartilage. 2014 Aug;22(8):1090-9. doi: 10.1016/j.joca.2014.06.028.
Epub 2014 Jul 4.

Effectiveness of continuous and pulsed ultrasound for the management of knee
osteoarthritis: a systematic review and network meta-analysis.

Zeng C(1), Li H(2), Yang T(2), Deng ZH(2), Yang Y(2), Zhang Y(2), Ding X(2), Lei
GH(3).

Author information:
(1)Department of Orthopaedics, Xiangya Hospital, Central South University,
Changsha, Hunan Province, China. Electronic address: zengchao19880505@sina.com.
(2)Department of Orthopaedics, Xiangya Hospital, Central South University,
Changsha, Hunan Province, China. (3)Department of Orthopaedics, Xiangya Hospital,
Central South University, Changsha, Hunan Province, China. Electronic address:
lgh9640@sina.cn.

BACKGROUND: To investigate the efficacy of continuous and pulsed ultrasound (US)
in the management of knee osteoarthritis (OA).
DESIGN: This systematic review and network meta-analysis covered 12 trials in
total. Electronic databases including MEDLINE, Embase and Cochrane Library were
searched through to identify randomized controlled trials comparing the two modes
of US with control interventions (sham or blank) or with each other. Bayesian
network meta-analysis was used to integrate both the direct and indirect
evidences on treatment effectiveness.
RESULTS: Pulsed US (PUS) is more effective in both pain relief and function
improvement when compared with the control group; but for continuous US (CUS),
there is only a significant difference in pain relief in comparison with the
control group. In addition, no matter in terms of pain intensity or function at
the last follow-up time point, PUS always exhibited a greater probability of
being the preferred mode. However, the evidence of heterogeneity and the
limitation in sample size of some studies could be a potential threat to the
validity of results.
CONCLUSIONS: Our findings indicated that PUS, with a greater probability of being
the preferred mode, is more effective in both pain relief and function
improvement when compared with the control group. However, CUS could only be
considered as a pain relief treatment in the management of knee OA. The findings
also confirmed that none of these modes is dangerous.
LEVEL OF EVIDENCE: Level II, systematic review and network meta-analysis of
randomized controlled trials.

Copyright © 2014 Osteoarthritis Research Society International. Published by
Elsevier Ltd. All rights reserved.

PMID: 24999112  [PubMed - indexed for MEDLINE]


48. Health Qual Life Outcomes. 2014 Jul 3;12:102. doi: 10.1186/1477-7525-12-102.

Comparative efficacy of biologics as monotherapy and in combination with
methotrexate on patient reported outcomes (PROs) in rheumatoid arthritis patients
with an inadequate response to conventional DMARDs--a systematic review and
network meta-analysis.

Jansen JP, Buckley F(1), Dejonckheere F, Ogale S.

Author information:
(1)Mapi Group, 180 Canal Street, Suite 503, Boston, MA 02114, USA.
fbuckley@mapigroup.com.

OBJECTIVE: To compare biologics as monotherapy or in combination with
methotrexate (MTX) in terms of patient reported outcomes (PROs) in RA patients
with an inadequate response to conventional DMARDs (DMARD-IR).
METHODS: With a systematic literature review 17 RCTs were identified that
evaluated adalimumab, certolizumab pegol, etanercept, golimumab, infliximab,
abatacept, anakinra or tocilizumab. Treatment effects in terms of pain (0-100
mm), patient's global assessment of disease activity (PGA; 0-100 mm), Health
Assessment-Questionnaire (HAQ) disability index (DI; 0-3), and the physical
component summary (PCS) of the SF36 Health Survey (0-100) at 24 weeks were
combined by means of Bayesian network meta-analyses.
RESULTS: With tocilizumab monotherapy, greater improvements in pain
(difference = -11.1; (95% Credible Interval -21.3, -0.1)) and PGA (-10.3 (-20.4,
0.8)) were observed than with aTNF monotherapy. Tocilizumab was at least as
efficacious as aTNF in HAQ-DI improvements (-0.16; (-0.37, 0.05)). aTNF + MTX
(-17.9 (-23.1, -13.0) & -19.1 (-24.2, -14.4)), abatacept + MTX (-23.0 (-47.3, 1.
5) & -13.6 (-28.4, 2.0)) and tocilizumab + MTX (-16.0 (-26.3, -6.3) & -15.1
(-25.1, -5.7)) showed comparable reductions in pain and PGA relative to MTX.
Efficacy of anakinra + MTX was much smaller as compared to other biologics. The
greatest improvements in HAQ-DI relative to MTX were observed with aTNF + MTX
(-0.30 (-0.37, -0.22)) and tocilizumab + MTX (-0.27 (-0.42, -0.12)), followed by
abatacept + MTX (-0.21 (-0.37, -0.05)) and anakinra + MTX (-0.11 (-0.26, 0.05)).
The improvements in SF36-PCS with abatacept + MTX, aTNF + MTX and
tocilizumab + MTX were comparable. There is a >90% probability that aTNF + MTX
results in a greater improvement in pain (-12.4), PGA (-16.1) and HAQ-DI (-0.21)
than aTNF as monotherapy. Efficacy of tocilizumab + MTX showed comparable
improvements in PROs as tocilizumab monotherapy.
CONCLUSIONS: Based on a network meta-analysis involving indirect comparison of
trial findings, the following observations were made for DMARD-IR patients. In
monotherapy, tocilizumab was associated with a greater improvement in pain and
self-reported disease activity than aTNF, and was at least as efficacious
regarding functional ability. The improvements in PROs with aTNF, abatacept and
tocilizumab in combination with MTX were comparable. Improvements in PROs with
tocilizumab as monotherapy were similar to that of tocilizumab + MTX, whereas
aTNF as monotherapy was likely to be less efficacious than aTNF + MTX.

PMCID: PMC4101713
PMID: 24988902  [PubMed - indexed for MEDLINE]


49. J Crohns Colitis. 2014 Jul;8(7):571-81. doi: 10.1016/j.crohns.2014.01.010. Epub
2014 Feb 1.

Adalimumab versus infliximab for the treatment of moderate to severe ulcerative
colitis in adult patients naïve to anti-TNF therapy: an indirect treatment
comparison meta-analysis.

Thorlund K(1), Druyts E(2), Mills EJ(3), Fedorak RN(4), Marshall JK(5).

Author information:
(1)Department of Clinical Epidemiology and Biostatistics, McMaster University,
Hamilton, Ontario, Canada; Stanford Prevention Research Center, Stanford
University, Stanford, CA, United States. Electronic address: thorluk@mcmaster.ca.
(2)Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada.
(3)Stanford Prevention Research Center, Stanford University, Stanford, CA, United
States; Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario,
Canada. (4)Division of Gastroenterology, University of Alberta, Canada.
(5)Division of Gastroenterology, McMaster University, Hamilton, Ontario, Canada.

OBJECTIVE: To compare the efficacy of adalimumab and infliximab for the treatment
of moderate to severe ulcerative colitis using indirect treatment comparison
meta-analysis.
METHODS: A systematic review and Bayesian indirect treatment comparison
meta-analyses were performed for seven patient-important clinical outcomes at 8
weeks and 52 weeks. Odds ratio (OR) estimates and associated 95% credible
intervals (CrIs) were produced.
RESULTS: Five eligible RCTs informed clinical remission, response, mucosal
healing, quality of life, colectomy, serious adverse events, and discontinuation
due to adverse events at 8 weeks and 52 weeks. At 8 weeks of induction therapy,
clinical remission (OR=0.42, 95% CrI 0.17-0.97), clinical response (OR=0.45, 95%
CrI 0.23-0.89) and mucosal healing (OR=0.46, 95% CrI 0.25-0.86) statistically
favored infliximab. However, after 52 weeks of maintenance therapy OR estimates
showed no significant difference between infliximab and adalimumab. For serious
adverse events and discontinuations due to adverse events, adalimumab and
infliximab were similar to placebo. Further, the indirect treatment comparison of
adalimumab and infliximab yielded odds ratios close to 1.00 with wide credible
intervals.
CONCLUSION: The findings of this indirect treatment comparison meta-analysis
suggest that both infliximab and adalimumab are superior to placebo in the
treatment of moderate to moderately severe ulcerative colitis. While infliximab
is statistically more effective than adalimumab in the induction of remission,
response and mucosal healing at 8 weeks, infliximab and adalimumab are comparable
in efficacy at 52 weeks of maintenance treatment.

Copyright © 2014 European Crohn's and Colitis Organisation. Published by Elsevier
B.V. All rights reserved.

PMID: 24491514  [PubMed - indexed for MEDLINE]


50. Joint Bone Spine. 2014 Jul;81(4):337-41. doi: 10.1016/j.jbspin.2013.11.006. Epub
2013 Dec 31.

Non-biologic remission maintenance therapy in adult patients with ANCA-associated
vasculitis: a systematic review and network meta-analysis.

Hazlewood GS(1), Metzler C(2), Tomlinson GA(3), Gross WL(4), Feldman BM(5),
Guillevin L(6), Pagnoux C(7).

Author information:
(1)Department of Internal Medicine, University of Calgary, 3330 Hospital Dr NW,
Calgary, Alberta, T2N1N1 Canada. Electronic address: glenhazlewood@gmail.com.
(2)University of Lubeck, Bad Branstedy, Germany. (3)University Health Network,
University of Toronto, 200 Elizabeth Street, Toronto, ON, Canada. (4)Medical
University at Lubeck, Lubeck, Germany. (5)The Hospital for Sick Children,
University of Toronto, 555 University Avenue, Toronto, ON, Canada. (6)Department
of Internal Medicine, Cochin Hospital, Assistance publique-Hôpitaux de Paris,
université Paris-Descartes, 27, rue du Faubourg-Saint-Jacques, 75014 Paris,
France. (7)Mount Sinai Hospital, University of Toronto, 60 Murray Street, 2nd
Floor, Room 222, Toronto, Ontario, Canada.

OBJECTIVE: To determine the comparative efficacy of non-biologic treatments for
remission maintenance in ANCA-associated vasculitis.
METHODS: We identified all randomized trials comparing leflunomide, azathioprine,
methotrexate or mycophenolate mofetil in adult patients with granulomatosis with
polyangiitis or microscopic polyangiitis. Relapse-free survival was compared
through hazard ratios (HR) using a Bayesian fixed-effects network meta-analysis.
Multiple sensitivity analyses were performed to explore biases identified in one
trial using original trial data.
RESULTS: Three trials were available (leflunomide-methotrexate, methotrexate-
azathioprine, azathioprine-mycophenolate). Mycophenolate was inferior to all
treatments, although the 95% credible interval (CrI) of the HR relative to
methotrexate crossed 1. Leflunomide was superior to azathioprine (HR 0.43 [95%
CrI: 0.14-1.3]) and methotrexate (HR 0.47 [95% CrI: 0.18-1.2]), although the 95%
CrI also crossed 1. There was a 90% probability that leflunomide was the best
treatment. After down weighting the effect of leflunomide vs. methotrexate for
early trial termination and slow MTX dose escalation, there remained a 55%
probability leflunomide was best.
CONCLUSION: Based on indirect evidence, leflunomide is effective in maintaining
remission in granulomatosis with polyangiitis or microscopic polyangiitis
relative to other non-biologic treatments. Further randomized trials of
leflunomide are needed for confirmation.

Copyright © 2013 Société française de rhumatologie. Published by Elsevier SAS.
All rights reserved.

PMID: 24387970  [PubMed - indexed for MEDLINE]


51. BMC Cancer. 2014 Jun 27;14:471. doi: 10.1186/1471-2407-14-471.

Chemotherapy regimens for advanced pancreatic cancer: a systematic review and
network meta-analysis.

Gresham GK(1), Wells GA, Gill S, Cameron C, Jonker DJ.

Author information:
(1)Department of Epidemiology and Community Medicine, University of Ottawa,
Ottawa, Ontario, Canada. ggresha3@jhu.edu.

BACKGROUND: Advanced pancreatic cancer confers poor prognosis and treatment
advancement has been slow. Recent randomized clinical trials (RCTs) have
demonstrated survival benefits for combination therapy compared to gemcitabine
alone. However, the comparative benefits and harms of available combination
chemotherapy treatments are not clear. We therefore conducted a systematic review
and Bayesian network meta-analysis to assess the comparative safety and efficacy
of chemotherapy regimens for the treatment of advanced pancreatic cancer.
METHODS: MEDLINE, PubMed, EMBASE, Cochrane Central Registry of Clinical trials
and abstracts from major scientific meetings were searched for RCTs published
from 2002 to 2013. Key outcomes were overall survival (OS), progression free
survival (PFS), and safety including grade 3-4 febrile neutropenia, neutropenia,
vomiting, diarrhea, fatigue and sensory neuropathy. Bayesian network
meta-analyses were conducted to calculate survival and safety outcomes using
gemcitabine (GEM) as the reference comparator. Effect estimates and 95% credible
intervals were calculated for each comparison. Mean ranks and the probability of
being best were obtained for each treatment analyzed in the network
meta-analysis.
RESULTS: The search identified 23 studies involving 19 different treatment
regimens and 9,989 patients. FOLFIRINOX, GEM/cisplatin/epirubicin/5FU (PEFG),
GEM/NAB-paclitaxel (NAB-P), GEM/erlotinib+/-bevacizumab, GEM/capecitabine, and
GEM/oxaliplatin were associated with statistically significant improvements in OS
and PFS relative to gemcitabine alone and several other treatments. They were
amongst the top ranked for survival outcomes amongst other treatments included.
No significant differences were found for other combination chemotherapy
treatments. Effect estimates from indirect comparisons matched closely to
estimates derived from pairwise comparisons. Overall, combination therapies had
greater risk for evaluated grade 3-4 toxicities over gemcitabine alone.
CONCLUSIONS: In the absence of head-to-head comparisons, we performed a
mixed-treatment analysis to achieve high-quality information on the effectiveness
and safety of each treatment. This study suggests that some combination therapies
may offer greater benefits in the treatment of advanced pancreatic cancer than
others. To more fully elucidate the comparative benefits and harms of different
combination chemotherapy regimens, rigorously conducted comparative studies, or
network meta-analysis of patient-level data are required.

PMCID: PMC4097092
PMID: 24972449  [PubMed - indexed for MEDLINE]


52. BMJ. 2014 Jun 23;348:g3859. doi: 10.1136/bmj.g3859.

Revascularisation versus medical treatment in patients with stable coronary
artery disease: network meta-analysis.

Windecker S, Stortecky S, Stefanini GG, da Costa BR, Rutjes AW, Di Nisio M,
Silletta MG, Maione A, Alfonso F, Clemmensen PM, Collet JP, Cremer J, Falk V,
Filippatos G, Hamm C, Head S, Kappetein AP, Kastrati A, Knuuti J, Landmesser U,
Laufer G, Neumann FJ, Richter D, Schauerte P, Sousa Uva M, Taggart DP, Torracca
L, Valgimigli M, Wijns W, Witkowski A, Kolh P, Jüni P.

Erratum in
    BMJ. 349:g4605. daCosta, Bruno R [corrected to da Costa, Bruno R]; Siletta, Maria
G [corrected to Silletta, Maria G]; Juni, Peter [corrected to Jüni, Peter].

Comment in
    BMJ. 2014;348:g4099.
    Ann Intern Med. 2014 Oct 21;161(8):JC10.

OBJECTIVE: To investigate whether revascularisation improves prognosis compared
with medical treatment among patients with stable coronary artery disease.
DESIGN: Bayesian network meta-analyses to combine direct within trial comparisons
between treatments with indirect evidence from other trials while maintaining
randomisation.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES: A strategy of initial medical
treatment compared with revascularisation by coronary artery bypass grafting or
Food and Drug Administration approved techniques for percutaneous
revascularization: balloon angioplasty, bare metal stent, early generation
paclitaxel eluting stent, sirolimus eluting stent, and zotarolimus eluting
(Endeavor) stent, and new generation everolimus eluting stent, and zotarolimus
eluting (Resolute) stent among patients with stable coronary artery disease.
DATA SOURCES: Medline and Embase from 1980 to 2013 for randomised trials
comparing medical treatment with revascularisation.
MAIN OUTCOME MEASURE: All cause mortality.
RESULTS: 100 trials in 93,553 patients with 262,090 patient years of follow-up
were included. Coronary artery bypass grafting was associated with a survival
benefit (rate ratio 0.80, 95% credibility interval 0.70 to 0.91) compared with
medical treatment. New generation drug eluting stents (everolimus: 0.75, 0.59 to
0.96; zotarolimus (Resolute): 0.65, 0.42 to 1.00) but not balloon angioplasty
(0.85, 0.68 to 1.04), bare metal stents (0.92, 0.79 to 1.05), or early generation
drug eluting stents (paclitaxel: 0.92, 0.75 to 1.12; sirolimus: 0.91, 0.75 to
1.10; zotarolimus (Endeavor): 0.88, 0.69 to 1.10) were associated with improved
survival compared with medical treatment. Coronary artery bypass grafting reduced
the risk of myocardial infarction compared with medical treatment (0.79, 0.63 to
0.99), and everolimus eluting stents showed a trend towards a reduced risk of
myocardial infarction (0.75, 0.55 to 1.01). The risk of subsequent
revascularisation was noticeably reduced by coronary artery bypass grafting
(0.16, 0.13 to 0.20) followed by new generation drug eluting stents (zotarolimus
(Resolute): 0.26, 0.17 to 0.40; everolimus: 0.27, 0.21 to 0.35), early generation
drug eluting stents (zotarolimus (Endeavor): 0.37, 0.28 to 0.50; sirolimus: 0.29,
0.24 to 0.36; paclitaxel: 0.44, 0.35 to 0.54), and bare metal stents (0.69, 0.59
to 0.81) compared with medical treatment.
CONCLUSION: Among patients with stable coronary artery disease, coronary artery
bypass grafting reduces the risk of death, myocardial infarction, and subsequent
revascularisation compared with medical treatment. All stent based coronary
revascularisation technologies reduce the need for revascularisation to a
variable degree. Our results provide evidence for improved survival with new
generation drug eluting stents but no other percutaneous revascularisation
technology compared with medical treatment.

© Windecker et al 2014.

PMCID: PMC4066935
PMID: 24958153  [PubMed - indexed for MEDLINE]


53. Aliment Pharmacol Ther. 2014 Jun;39(12):1349-62. doi: 10.1111/apt.12749. Epub
2014 Apr 20.

Systematic review with network meta-analysis: the efficacy of anti-TNF agents for
the treatment of Crohn's disease.

Stidham RW(1), Lee TC, Higgins PD, Deshpande AR, Sussman DA, Singal AG, Elmunzer
BJ, Saini SD, Vijan S, Waljee AK.

Author information:
(1)Division of Gastroenterology and Hepatology, Department of Internal Medicine,
University of Michigan Health System, Ann Arbor, MI, USA.

BACKGROUND: Anti-tumour necrosis factor-alpha agents (anti-TNF) are effective
therapies for the treatment of Crohn's disease (CD), but their comparative
efficacy is unknown.
AIM: To perform a network meta-analysis comparing the efficacy of anti-TNF
therapies in CD.
METHODS: After screening 506 studies, reviewers extracted information on 10
studies. Traditional meta-analysis (TMA) was used to compare each anti-TNF agent
to placebo. Bayesian network meta-analysis (NMA) was performed to compare the
effects of anti-TNF agents to placebo. In addition, sample sizes for comparative
efficacy trials were calculated.
RESULTS: Compared to placebo, TMA revealed that anti-TNF agents result in a
higher likelihood of induction of remission and response (RR: 1.66, 95% CI:
1.17-2.36 and RR: 1.43, 95% CI: 1.17-1.73, respectively) as well as maintenance
of remission and response (RR: 1.78, 95% CI: 1.51-2.09 and RR: 1.68, 95% CI:
1.46-1.93, respectively). NMA found nonsignificant trends between infliximab and
adalimumab or certolizumab pegol. Among subcutaneous therapies, NMA demonstrated
superiority of adalimumab to certolizumab pegol for induction of remission (RR:
2.93, 95% CrI: 1.21-7.75). Sample size calculations suggest that adequately
powered head-to-head comparative efficacy trials would require greater than 3000
patients.
CONCLUSIONS: All anti-TNF agents are effective for induction and maintenance of
response and remission in the treatment of CD. Although adalimumab is superior to
certolizumab pegol for induction of remission, there is no evidence of clinical
superiority among anti-TNF agents. Head-to-head trials among the anti-TNF agents
are impractical in terms of size and cost.

© 2014 John Wiley & Sons Ltd.

PMID: 24749763  [PubMed - indexed for MEDLINE]


54. Chest. 2014 Jun;145(6):1286-97.

Use of inhaled corticosteroids in patients with COPD and the risk of TB and
influenza: A systematic review and meta-analysis of randomized controlled trials.
a systematic review and meta-analysis of randomized controlled trials.

Dong YH, Chang CH, Lin Wu FL, Shen LJ, Calverley PM, Löfdahl CG, Lai MS, Mahler
DA.

Comment in
    Chest. 2014 Dec;146(6):e212.
    Chest. 2014 Dec;146(6):e212-3.

Background: The use of inhaled corticosteroids (ICSs) is associated with an
increased risk of pneumonia in patients with COPD. However, the risks of other
respiratory infections, such as TB and influenza, remain unclear.Methods: Through
a comprehensive literature search of MEDLINE, EMBASE, CINAHL, Cochrane Library,
and ClinicalTrials.gov from inception to July 2013, we identified randomized
controlled trials of ICS therapy lasting at least 6 months. We conducted
meta-analyses by the Peto, Mantel-Haenszel, and Bayesian approaches to generate
summary estimates comparing ICS with non-ICS treatment on the risk of TB and
influenza.Results: Twenty-fi ve trials (22,898 subjects) for TB and 26 trials
(23,616 subjects) for influenza were included. Compared with non-ICS treatment,
ICS treatment was associated with a significantly higher risk of TB (Peto OR,
2.29; 95% CI, 1.04-5.03) but not influenza (Peto OR, 1.24;95% CI, 0.94-1.63).
Results were similar with each meta-analytic approach. Furthermore, the number
needed to harm to cause one additional TB event was lower for patients with COPD
treated with ICSs in endemic areas than for those in nonendemic areas (909 vs
1,667, respectively).Conclusions: This study raises safety concerns about the
risk of TB and influenza associated with ICS use in patients with COPD, which
deserve further investigation.

PMID: 24504044  [PubMed - indexed for MEDLINE]


55. Curr Med Res Opin. 2014 Jun;30(6):971-95. doi: 10.1185/03007995.2013.860020. Epub
2014 Feb 28.

Comparative efficacy, acceptability, and safety of medicinal,
cognitive-behavioral therapy, and placebo treatments for acute major depressive
disorder in children and adolescents: a multiple-treatments meta-analysis.

Ma D(1), Zhang Z, Zhang X, Li L.

Author information:
(1)Affiliated ZhongDa Hospital and the Institution Neuropsychiatry of Southeast
University , Nanjing , China.

BACKGROUND: New generation antidepressant therapies, including
serotonin-norepinephrine reuptake inhibitor (SNRIs) and selective serotonin
reuptake inhibitors (SSRIs) were introduced in the late 1980s; however, few
comprehensive studies compared the benefits and risks of various contemporary
treatments for major depressive disorder (MDD) in pediatric patients.
OBJECTIVE: Multiple-treatments meta-analysis (MTM) was conducted to assess
efficacy, acceptability, and safety of contemporary interventions in children and
adolescents with MDD.
METHODS: Cochrane Library, AMED, CINAHL, EMBASE, LiLACS, MEDLINE, PSYCINFO,
PSYNDEX, and Journal of Medicine and Pharmacy databases were searched for
randomized controlled trials (RCTs) comparing medicinal interventions
(citalopram, escitalopram, fluoxetine, mirtazapine, paroxetine, sertraline,
venlafaxine), cognitive behavioral therapy (CBT), combined fluoxetine with CBT,
and placebo treatment for acute MDD from January 1988 to March 2013. Treatment
success, dropout rate, and suicidal ideation/attempt outcomes were measured.
Bayesian methods were used to conduct a MTM including age and funding subgroups.
RESULTS: A total of 21 RCTs (4969 participants) were identified. Combined
fluoxetine/CBT exhibited the highest efficacy, with fluoxetine alone superior to
CBT, paroxetine, sertraline, citalopram, escitalopram, and placebo treatment.
Sertraline, paroxetine, escitalopram, and venlafaxine showed superior
acceptability to fluoxetine and combined fluoxetine/CBT. Combined fluoxetine/CBT
combination was less safe, though CBT was safer than fluoxetine alone. Combined
fluoxetine/CBT, fluoxetine, and mirtazapine exhibited the highest efficacy;
sertraline, escitalopram, venlafaxine, and paroxetine were the best tolerated;
and mirtazapine and venlafaxine were the safest.
CONCLUSIONS: Sertraline and mirtazapine exhibited optimally balanced efficacy,
acceptability, and safety for first-line acute treatment of child and adolescent
MDD.

PMID: 24188102  [PubMed - indexed for MEDLINE]


56. J Hum Nutr Diet. 2014 Jun;27(3):280-97. doi: 10.1111/jhn.12138. Epub 2013 Jun 22.

A Mediterranean diet improves HbA1c but not fasting blood glucose compared to
alternative dietary strategies: a network meta-analysis.

Carter P(1), Achana F, Troughton J, Gray LJ, Khunti K, Davies MJ.

Author information:
(1)Diabetes Research Unit, Leicester Diabetes Centre, Leicester General Hospital,
University of Leicester, Leicester, UK.

BACKGROUND: Overweight or obese individuals with type 2 diabetes are encouraged
to lose weight for optimal glucose management, yet many find this difficult.
Determining whether alterations in dietary patterns irrespective of weight loss
can aid glucose control has not been fully investigated.
METHODS: We conducted a systematic review and meta-analysis aiming to determine
the effects of a Mediterranean diet compared to other dietary interventions on
glycaemic control irrespective of weight loss. Electronic databases were searched
for controlled trials that included a Mediterranean diet intervention. The
interventions included all major components of the Mediterranean diet and were
carried out in free-living individuals at high risk or diagnosed with type 2
diabetes. Network meta-analysis compared all interventions with one another at
the same time as maintaining randomisation. Analyses were conducted within a
Bayesian framework.
RESULTS: Eight studies met the inclusion criteria, seven examined fasting blood
glucose (n = 972), six examined fasting insulin (n = 1330) and three examined
HbA1c (n = 487). None of the interventions were significantly better than the
others in lowering glucose parameters. The Mediterranean diet reduced HbA1c
significantly compared to usual care but not compared to the Palaeolithic diet.
CONCLUSIONS: The effect of alterations in dietary practice irrespective of weight
loss on glycaemic control cannot be concluded from the present review. The need
for further research in this area is apparent because no firm conclusions about
relative effectiveness of interventions could be drawn as a result of the paucity
of the evidence.

© 2013 The British Dietetic Association Ltd.

PMID: 23790149  [PubMed - indexed for MEDLINE]




58. BMJ. 2014 May 13;348:g3009. doi: 10.1136/bmj.g3009.

Comparative effectiveness of long term drug treatment strategies to prevent
asthma exacerbations: network meta-analysis.

Loymans RJ(1), Gemperli A(2), Cohen J(3), Rubinstein SM(4), Sterk PJ(5), Reddel
HK(6), Jüni P(7), ter Riet G(3).

Author information:
(1)Department of General Practice, Academic Medical Center, University of
Amsterdam, PO box 22700, 1105 DE, Amsterdam, Netherlands r.j.loijmans@amc.nl.
(2)Division of Clinical Epidemiology and Biostatistics, Institute of Social and
Preventive Medicine, University of Bern, Berne, Switzerland Department of Health
Sciences and Health Policy, University of Lucerne, Lucerne, Switzerland Swiss
Paraplegic Research, Nottwil, Switzerland. (3)Department of General Practice,
Academic Medical Center, University of Amsterdam, PO box 22700, 1105 DE,
Amsterdam, Netherlands. (4)Department of Health Sciences, Section Health
Economics and Health Technology Assessment, VU University Amsterdam, Amsterdam,
Netherlands. (5)Department of Respiratory Medicine, Academic Medical Center,
University of Amsterdam, Amsterdam, Netherlands. (6)Clinical Management Group,
Woolcock Institute of Medical Research, University of Sydney, Sydney, NSW,
Australia. (7)Division of Clinical Epidemiology and Biostatistics, Institute of
Social and Preventive Medicine, University of Bern, Berne, Switzerland.

Comment in
    BMJ. 2014;348:g3148.

OBJECTIVE: To determine the comparative effectiveness and safety of current
maintenance strategies in preventing exacerbations of asthma.
DESIGN: Systematic review and network meta-analysis using Bayesian statistics.
DATA SOURCES: Cochrane systematic reviews on chronic asthma, complemented by an
updated search when appropriate. ELIGIBILITY CRITERIA TRIALS OF Adults with
asthma randomised to maintenance treatments of at least 24 weeks duration and
that reported on asthma exacerbations in full text. Low dose inhaled
corticosteroid treatment was the comparator strategy. The primary effectiveness
outcome was the rate of severe exacerbations. The secondary outcome was the
composite of moderate or severe exacerbations. The rate of withdrawal was
analysed as a safety outcome.
RESULTS: 64 trials with 59,622 patient years of follow-up comparing 15 strategies
and placebo were included. For prevention of severe exacerbations, combined
inhaled corticosteroids and long acting β agonists as maintenance and reliever
treatment and combined inhaled corticosteroids and long acting β agonists in a
fixed daily dose performed equally well and were ranked first for effectiveness.
The rate ratios compared with low dose inhaled corticosteroids were 0.44 (95%
credible interval 0.29 to 0.66) and 0.51 (0.35 to 0.77), respectively. Other
combined strategies were not superior to inhaled corticosteroids and all single
drug treatments were inferior to single low dose inhaled corticosteroids. Safety
was best for conventional best (guideline based) practice and combined
maintenance and reliever therapy.
CONCLUSIONS: Strategies with combined inhaled corticosteroids and long acting β
agonists are most effective and safe in preventing severe exacerbations of
asthma, although some heterogeneity was observed in this network meta-analysis of
full text reports.

© Loymans et al 2014.

PMCID: PMC4019015
PMID: 24919052  [PubMed - indexed for MEDLINE]


59. Diabetes Obes Metab. 2014 May;16(5):433-42. doi: 10.1111/dom.12239. Epub 2013 Dec
16.

Dapagliflozin compared with other oral anti-diabetes treatments when added to
metformin monotherapy: a systematic review and network meta-analysis.

Goring S(1), Hawkins N, Wygant G, Roudaut M, Townsend R, Wood I, Barnett AH.

Author information:
(1)Oxford Outcomes, Vancouver, Canada.

AIMS: Indirect evidence from randomized controlled trials (RCTs) was used to
estimate the effect of dapagliflozin, a new agent with a novel mechanism of
action (SGLT-2 inhibition), relative to other anti-diabetes therapies after 1
year of treatment.
METHODS: A systematic literature review and Bayesian network meta-analysis (NMA)
of RCTs involving anti-diabetes treatments added to metformin were conducted.
RCTs enrolling subjects with type 2 diabetes inadequately controlled on metformin
monotherapy were included. Comparators included dipeptidyl peptidase-4 (DPP-4)
inhibitors, thiazolidinediones (TZDs), sulphonylureas, glucagon-like peptide-1
(GLP-1) analogues and dapagliflozin. Outcomes of interest were mean change from
baseline HbA1c, weight and systolic blood pressure, and incidence of
hypoglycaemia.
RESULTS: From 4270 abstracts, six RCTs were included in the primary analysis; no
RCTs involving GLP-1 analogues met primary inclusion criteria. All RCTs were
actively controlled with sulphonylureas. The mean change in HbA1c from baseline
was similar across comparators. The treatment effect (95% credible interval) of
dapagliflozin on HbA1c was -0.08% (-0.25, 0.10) relative to DPP-4 inhibitors,
-0.02% (-0.24, 0.21) relative to TZDs and 0.00% (-0.16, 0.16) relative to
sulphonylureas. Non-sulphonylureas showed significantly lower risk of
hypoglycaemia relative to sulphonylureas. Dapagliflozin had a significant effect
on weight change: the relative difference was -2.74 kg (-5.35, -0.10) compared
with DPP-4 inhibitors, and -4.67 kg (-7.03, -2.35) compared with sulphonylureas.
Systolic blood pressure was not meta-analysed due to infrequent reporting.
CONCLUSION: Compared with DPP-4 inhibitors, TZDs and sulphonylureas,
dapagliflozin offers similar HbA1c control after 1 year, with similar or reduced
risk of hypoglycaemia and the additional benefit of weight loss, when added to
metformin.

© 2013 John Wiley & Sons Ltd.

PMID: 24237939  [PubMed - indexed for MEDLINE]


60. Eur Heart J. 2014 May;35(17):1147-58. doi: 10.1093/eurheartj/eht570. Epub 2014
Jan 23.

Biodegradable-polymer drug-eluting stents vs. bare metal stents vs.
durable-polymer drug-eluting stents: a systematic review and Bayesian approach
network meta-analysis.

Kang SH(1), Park KW, Kang DY, Lim WH, Park KT, Han JK, Kang HJ, Koo BK, Oh BH,
Park YB, Kandzari DE, Cohen DJ, Hwang SS, Kim HS.

Author information:
(1)Department of Internal Medicine and Cardiovascular Center, Seoul National
University Hospital, 28 Yeongeon-Dong, Chongno-gu, Seoul 110-744, Korea.

Comment in
    Eur Heart J. 2014 May;35(17):1098-100.

BACKGROUND: The aim of this study was to compare the safety and efficacy of
biodegradable-polymer (BP) drug-eluting stents (DES), bare metal stents (BMS),
and durable-polymer DES in patients undergoing coronary revascularization, we
performed a systematic review and network meta-analysis using a Bayesian
framework.
METHODS AND RESULTS: Study stents included BMS, paclitaxel-eluting (PES),
sirolimus-eluting (SES), endeavor zotarolimus-eluting (ZES-E), cobalt-chromium
everolimus-eluting (CoCr-EES), platinium-chromium everolimus-eluting (PtCr-EES),
resolute zotarolimus-eluting (ZES-R), and BP biolimus-eluting stents (BP-BES).
After a systematic electronic search, 113 trials with 90 584 patients were
selected. The principal endpoint was definite or probable stent thrombosis (ST)
defined according to the Academic Research Consortium within 1 year.
RESULTS: Biodegradable polymer-biolimus-eluting stents [OR, 0.56; 95% credible
interval (CrI), 0.33-0.90], SES (OR, 0.53; 95% CrI, 0.38-0.73), CoCr-EES (OR,
0.34; 95% CrI, 0.23-0.52), and PtCr-EES (OR, 0.31; 95% CrI, 0.10-0.90) were all
superior to BMS in terms of definite or probable ST within 1 year.
Cobalt-chromium everolimus-eluting stents demonstrated the lowest risk of ST of
all stents at all times after stent implantation. Biodegradable
polymer-biolimus-eluting stents was associated with a higher risk of definite or
probable ST than CoCr-EES (OR, 1.72; 95% CrI, 1.04-2.98). All DES reduced the
need for repeat revascularization, and all but PES reduced the risk of myocardial
infarction compared with BMS.
CONCLUSIONS: All DESs but PES and ZES-E were superior to BMS in terms of ST
within 1 year. Cobalt-chromium everolimus-eluting stents was safer than any DES
even including BP-BES. Our results suggest that not only the biodegradability of
polymer, but the optimal combination of stent alloy, design, strut thickness,
polymer, and drug all combined determine the safety of DES.

PMID: 24459196  [PubMed - indexed for MEDLINE]


61. Eur J Health Econ. 2014 May;15 Suppl 1:S45-52. doi: 10.1007/s10198-014-0593-5.
Epub 2014 May 16.

Comparative efficacy and safety of biosimilar infliximab and other biological
treatments in ankylosing spondylitis: systematic literature review and
meta-analysis.

Baji P(1), Péntek M, Szántó S, Géher P, Gulácsi L, Balogh O, Brodszky V.

Author information:
(1)Department of Health Economics, Corvinus University of Budapest, Fővám tér 8,
1093, Budapest, Hungary, petra.baji@uni-corvinus.hu.

OBJECTIVES: To compare the efficacy and safety of infliximab-biosimilar with
other biological drugs for the treatment of active ankylosing spondylitis (AS).
METHODS: Systematic literature review for randomized controlled trials (RCTs)
with adalimumab, etanercept, golimumab, infliximab and infliximab-biosimilar in
AS was performed and indirect meta-analysis (Bayesian mixed treatment comparison)
was carried out. The proportion of patients reaching 20% improvement by the
assessment of Spondyloarthritis International Society response criteria (ASAS20)
at weeks 12 and 24 was used as efficacy endpoints, and the occurrence of serious
adverse events at week 24 was applied to compare the safety of the biologicals.
RESULTS: Altogether, 13 RCTs, identified by the systematic literature search,
were included in the analysis. Results on the ASAS20 efficacy endpoint were
reported for week 12 in 12 RCTs involving 2,395 patients, and for week 24 in 5
RCTs comprising 1,337 patients. All the five biological agents proved to be
significantly superior to placebo. Infliximab showed the highest odds ratio (OR)
of 7.2 (95% CI 3.68-13.19) compared to placebo, followed by infliximab-biosimilar
with OR 6.25 (95% CI 2.55-13.14), both assessed at week 24. No significant
difference was found between infliximab-biosimilar and other biological
treatments regarding their efficacy and safety.
CONCLUSIONS: This is the first study which includes a biosimilar drug in the
meta-analysis of biological treatments in AS. The results have proven the similar
efficacy and safety profile of infliximab-biosimilar treatment compared to other
biologicals.

PMCID: PMC4046080
PMID: 24832835  [PubMed - indexed for MEDLINE]




63. J Am Heart Assoc. 2014 Apr 14;3(2):e000759. doi: 10.1161/JAHA.113.000759.

Relations of change in plasma levels of LDL-C, non-HDL-C and apoB with risk
reduction from statin therapy: a meta-analysis of randomized trials.

Thanassoulis G(1), Williams K, Ye K, Brook R, Couture P, Lawler PR, de Graaf J,
Furberg CD, Sniderman A.

Author information:
(1)Preventive and Genomic Cardiology, McGill University Health Centre, Department
of Medicine, Montreal, Quebec, Canada.

BACKGROUND: Identifying the best markers to judge the adequacy of lipid-lowering
treatment is increasingly important for coronary heart disease (CHD) prevention
given that several novel, potent lipid-lowering therapies are in development.
Reductions in LDL-C, non-HDL-C, or apoB can all be used but which most closely
relates to benefit, as defined by the reduction in events on statin treatment, is
not established.
METHODS AND RESULTS: We performed a random-effects frequentist and Bayesian
meta-analysis of 7 placebo-controlled statin trials in which LDL-C, non-HDL-C,
and apoB values were available at baseline and at 1-year follow-up. Summary level
data for change in LDL-C, non-HDL-C, and apoB were related to the relative risk
reduction from statin therapy in each trial. In frequentist meta-analyses, the
mean CHD risk reduction (95% CI) per standard deviation decrease in each marker
across these 7 trials were 20.1% (15.6%, 24.3%) for LDL-C; 20.0% (15.2%, 24.7%)
for non-HDL-C; and 24.4% (19.2%, 29.2%) for apoB. Compared within each trial,
risk reduction per change in apoB averaged 21.6% (12.0%, 31.2%) greater than
changes in LDL-C (P<0.001) and 24.3% (22.4%, 26.2%) greater than changes in
non-HDL-C (P<0.001). Similarly, in Bayesian meta-analyses using various prior
distributions, Bayes factors (BFs) favored reduction in apoB as more closely
related to risk reduction from statins compared with LDL-C or non-HDL-C (BFs
ranging from 484 to 2380).
CONCLUSIONS: Using both a frequentist and Bayesian approach, relative risk
reduction across 7 major placebo-controlled statin trials was more closely
related to reductions in apoB than to reductions in either non-HDL-C or LDL-C.

PMCID: PMC4187506
PMID: 24732920  [PubMed - indexed for MEDLINE]


64. Aliment Pharmacol Ther. 2014 Apr;39(7):660-71. doi: 10.1111/apt.12644. Epub 2014
Feb 9.

Systematic review with network meta-analysis: the efficacy of anti-tumour
necrosis factor-alpha agents for the treatment of ulcerative colitis.

Stidham RW(1), Lee TC, Higgins PD, Deshpande AR, Sussman DA, Singal AG, Elmunzer
BJ, Saini SD, Vijan S, Waljee AK.

Author information:
(1)Division of Gastroenterology and Hepatology, Department of Internal Medicine,
University of Michigan Health System, Ann Arbor, MI, USA.

Erratum in
    Aliment Pharmacol Ther. 2015 Jul;42(1):130.

Comment in
    Aliment Pharmacol Ther. 2014 May;39(10):1244.
    Aliment Pharmacol Ther. 2014 Jun;39(12):1433-4.
    Aliment Pharmacol Ther. 2014 May;39(10):1242-4.
    Aliment Pharmacol Ther. 2014 Jun;39(12):1432-3.

BACKGROUND: Antibodies against tumour necrosis factor-alpha (anti-TNF) are
effective therapies in the treatment of ulcerative colitis (UC), but their
comparative efficacy is unknown.
AIM: To perform a network meta-analysis comparing the efficacy of anti-TNF agents
in UC.
METHODS: After screening 506 studies, reviewers extracted information on seven
studies. Traditional meta-analysis (TMA) was used to compare each anti-TNF agent
to placebo. Bayesian network meta-analysis (NMA) was performed to compare the
effects of anti-TNF agents to placebo. In addition, sample sizes for comparative
efficacy trials were calculated.
RESULTS: Compared to placebo, TMA revealed that anti-TNF agents result in a
higher likelihood of induction of remission and response (RR: 2.45, 95% CI:
1.72-3.47 and RR: 1.65, 95% CI: 1.37-1.99 respectively) as well as maintenance of
remission and response (RR: 2.00, 95% CI: 1.52-2.62 and RR: 1.76, 95% CI:
1.46-2.14 respectively). Individually, infliximab, adalimumab and goliumumab
resulted in a higher likelihood of induction and maintenance for both remission
and response. NMA found nonsignificant trends in comparisons of the individual
agents. The required sample sizes for direct head-to-head trials between
infliximab and adalimumab for induction and maintenance are 174 and 204 subjects
respectively.
CONCLUSIONS: This study demonstrates that, compared to placebo, infliximab,
adalimumab and golimumab are all effective for the induction and maintenance of
remission in ulcerative colitis. However, network meta-analysis demonstrates that
no single agent is clinically superior to the others and therefore, other factors
such as cost, safety, route of administration and patient preference should
dictate our choice of anti-TNF agents. A randomised comparative efficacy trial
between infliximab and adalimumab in UC is of practical size and should be
performed.

© 2014 John Wiley & Sons Ltd.

PMID: 24506179  [PubMed - indexed for MEDLINE]


65. Cephalalgia. 2014 Apr;34(4):258-67. doi: 10.1177/0333102413508661. Epub 2013 Oct
9.

Comparative efficacy of triptans for the abortive treatment of migraine: a
multiple treatment comparison meta-analysis.

Thorlund K(1), Mills EJ, Wu P, Ramos E, Chatterjee A, Druyts E, Goadsby PJ.

Author information:
(1)Department of Clinical Epidemiology & Biostatistics, McMaster University,
Canada.

BACKGROUND: Migraine is the most common neurological condition in developed
countries. The abortive treatment of migraine attacks is important both for
quality of life and costs associated with illness. Triptans, serotonin 5-HT1B/1D
receptor agonists, effectively relieve the pain, disability, and associated
symptoms of migraine while improving health-related quality of life. Although a
number of direct head-to-head triptan comparisons have been made, data for all
possible permutations are not available, and unlikely to ever be so, although in
clinical practice such information would be useful.
OBJECTIVE: We aimed to determine the relative efficacy of all available triptans
to abort migraine headache among patients with previous adequate response to
migraine treatments.
METHODS: We included only double-blinded randomized clinical trials comparing
triptans to either placebo or another triptan. Our primary outcomes were
pain-free response at two hours and 24-hour sustained pain-free response, and our
secondary outcomes were headache response at two hours and 24-hour sustained
headache response. We used Bayesian multiple treatment comparison meta-analyses
of seven triptans used in adult patients to abort migraine attacks. We applied a
random-effects analysis with meta-regression adjusting for dose. Results are
reported as odds ratios with 95% credible intervals.
RESULTS: We included data from 74 randomized clinical trials. All triptans were
significantly superior to placebo for all outcomes, with the exception of
naratriptan for 24-hour sustained pain-free response. Eletriptan consistently
yielded the highest treatment effect estimates. For the two-hour endpoints,
eletriptan was statistically significantly superior to sumatriptan, almotriptan,
naratriptan, and frovatriptan for at least one of the two outcomes. Rizatriptan
yielded the second highest treatment effects followed by zolmitriptan. For the
24-hour endpoints, eletriptan was statistically significantly superior to
sumatriptan, rizatriptan, almotriptan, and naratriptan for at least one of the
two outcomes. Frovatriptan data were not available at that endpoint. Further, the
probability that eletriptan is the most likely of all triptans to produce a
favorable outcome was 68% for pain-free response at two hours, and 54% for
24-hour sustained pain-free response.
CONCLUSION: Triptans appear to offer differing treatment effects. In the
populations studied eletriptan was most likely to produce pain-free responses
that were sustained.

PMID: 24108308  [PubMed - indexed for MEDLINE]


66. J Neurol. 2014 Apr;261(4):655-62. doi: 10.1007/s00415-013-7053-5. Epub 2013 Jul
28.

Diagnosing flow residuals in coiled cerebral aneurysms by MR angiography:
meta-analysis.

Menke J(1), Schramm P, Sohns JM, Kallenberg K, Staab W.

Author information:
(1)Department of Diagnostic Radiology, University Hospital, Robert-Koch-Strasse
40, 37075, Goettingen, Germany, Menke-J@T-Online.de.

This meta-analysis summarizes the accuracy of magnetic resonance angiography
(MRA) for diagnosing residuals in coiled cerebral aneurysms by using the
threefold Roy classification (residuals: none, neck, or sac). Four databases were
searched from 2000 to June 2013 for eligible studies that compared MRA to digital
subtraction angiography (DSA) and reported 3 × 3 count data of threefold Roy
classification, or a reduced scheme of 2 × 2 count data. Bivariate and trivariate
Bayesian random-effects models were used for meta-analysis. Among 27 included
studies (2,119 coiled aneurysms in 1,809 patients) the average prevalence of
DSA-confirmed sac residuals was 18.2 % (range 0-43 %). The pooled sensitivity was
88.0 % (95 % CI 81.4-94.0) and specificity was 97.2 % (94.6-99.0 %) for assessing
sac residuals by MRA. In the trivariate meta-analysis, a "sac residual" finding
at MRA had a high positive likelihood ratio of 28.2 (14.0-79.0). A "neck
residual" finding had a moderate negative likelihood ratio of 0.246
(0.111-0.426), and the MRA finding of "no residual" had a good negative
likelihood ratio of 0.044 (0.013-0.096). Subgroup analyses identified no
significant influence of covariates on diagnostic accuracy (P > 0.05). In
conclusion, in coiled cerebral aneurysms MRA with application of the threefold
Roy classification is well suited for detecting or excluding sac residuals that
might require retreatment.

PMCID: PMC3973941
PMID: 23893001  [PubMed - indexed for MEDLINE]


67. J Vasc Surg. 2014 Apr;59(4):1123-1133.e8. doi: 10.1016/j.jvs.2014.01.041.

Bayesian network meta-analysis of nitinol stents, covered stents, drug-eluting
stents, and drug-coated balloons in the femoropopliteal artery.

Katsanos K(1), Spiliopoulos S(2), Karunanithy N(3), Krokidis M(4), Sabharwal
T(3), Taylor P(5).

Author information:
(1)Department of Interventional Radiology, Guy's and St. Thomas' Hospitals, NHS
Foundation Trust, King's Health Partners, London, United Kingdom. Electronic
address: konstantinos.katsanos@gstt.nhs.uk. (2)Department of Interventional
Radiology, Patras University Hospital, School of Medicine, Rion, Greece.
(3)Department of Interventional Radiology, Guy's and St. Thomas' Hospitals, NHS
Foundation Trust, King's Health Partners, London, United Kingdom. (4)Department
of Interventional Radiology, Addenbrooke's Hospital, Cambridge University
Hospitals, NHS Foundation Trust, Cambridge, United Kingdom. (5)Department of
Vascular Surgery, Guy's and St. Thomas' Hospitals, NHS Foundation Trust, King's
Health Partners, London, United Kingdom.

OBJECTIVE: Several randomized controlled trials (RCTs) have shown the superiority
of some of these technologies over balloon angioplasty, but direct comparisons
between these treatment options are lacking. The authors conducted a network
meta-analysis of RCTs comparing bare nitinol stents, covered nitinol stents,
paclitaxel- or sirolimus-eluting stents (PES or SES), and paclitaxel-coated
balloons (PCB) with plain balloon angioplasty or with each other in the
femoropopliteal artery (PROSPERO registry: CRD42013004845).
METHODS: Sixteen RCTs comprising 2532 patients with 4227 person-years of
follow-up were analyzed on an intention-to-treat basis. Bayesian random effects
Poisson and binomial models were used for mixed treatment comparisons (WinBUGS).
Clinical heterogeneity was accounted for by incorporating a meta-regression model
on trial-specific baseline risk. End points included technical success, vascular
restenosis, target lesion revascularization, and major amputations. Pairwise odds
ratios and rate ratios (ORs and RRs) of absolute treatment effects were
calculated, and the probabilities of each treatment being best are reported.
Summary estimates are reported as the posterior median and associated credible
intervals (CrIs) that serve the same purpose as confidence intervals in the
context of the Bayesian framework. Extensive sensitivity, meta-regression, and
network consistency analyses were performed to evaluate heterogeneity.
RESULTS: Technical success was highest with covered stents (pooled OR, 13.6; 95%
CrI, 3.3-31.1, probability best 82%) followed by uncovered stents (pooled OR,
7.0; 95% CrI, 2.6-129, probability best 18%) when compared with balloon
angioplasty (reference treatment). Vascular restenosis was lowest with PES (RR,
0.43; 95% CrI, 0.16-1.18, probability best 45%) followed by PCB (RR, 0.43; 95%
CrI, 0.26-0.67, probability best 42%). Target lesion revascularization was lowest
with PCB (RR, 0.36; 95% CrI, 0.23-0.55, probability best 56%) followed by PES
(RR, 0.42; 95% CrI, 0.16-1.06, probability best 33%). Major amputations were rare
in all treatment and control groups (pooled amputation rate of 0.7 events per 100
person-years).
CONCLUSIONS: Immediate technical success is better with the use of covered
stents, whereas paclitaxel-eluting stents and paclitaxel-coated balloons offer
the best long-term results in the femoropopliteal artery.

Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All
rights reserved.

PMID: 24661896  [PubMed - indexed for MEDLINE]


68. Osteoporos Int. 2014 Apr;25(4):1225-35. doi: 10.1007/s00198-013-2576-2. Epub 2013
Nov 28.

Comparative gastrointestinal safety of bisphosphonates in primary osteoporosis: a
network meta-analysis.

Tadrous M(1), Wong L, Mamdani MM, Juurlink DN, Krahn MD, Lévesque LE, Cadarette
SM.

Author information:
(1)Leslie Dan Faculty of Pharmacy, University of Toronto, 144 College Street,
Toronto, ON, M5S 3M2, Canada, mina.tadrous@utoronto.ca.

Comment in
    Osteoporos Int. 2014 Nov;25(11):2669.
    Osteoporos Int. 2014 Nov;25(11):2671-2.

We completed a network meta-analysis of published papers to compare
bisphosphonate gastrointestinal safety. We found that zoledronic acid had the
highest chance of causing gastrointestinal adverse events. Etidronate had the
highest chance of discontinuation due to an adverse event. No difference was
found for serious adverse events.INTRODUCTION: Bisphosphonates are first-line
treatment for osteoporosis. Gastrointestinal (GI) adverse events (AE) are the
primary reason for non-adherence. Little is known about the comparative GI safety
of bisphosphonates.
PURPOSE: Leverage published clinical trial data to examine the comparative GI
safety of bisphosphonates.
METHODS: We completed a systematic review of all English-language clinical trials
that assessed bisphosphonate safety and/or efficacy in primary osteoporosis
through to 2012. Randomized, blinded, and controlled studies were eligible. The
primary outcome was any GI-related AE. Subanalyses were completed for upper GI
symptoms, serious GI, nausea, esophageal-related events, and discontinuation due
to AE. A Bayesian-based network meta-analysis was completed to allow for indirect
comparisons. Results were reported as the probability that a specific drug had
the highest number of events.
RESULTS: We identified 50 studies: 32 alendronate, 12 risedronate, 5 etidronate,
and 7 zoledronic acid. Zoledronic acid had the highest probability of having the
highest number of any GI AE (91%) and nausea (70%). Etidronate (70%) and
zoledronic acid (28%) had the highest probability of having the greatest
attrition due to AE. Etidronate had the highest probability (56%) of having the
greatest number of upper GI symptoms among oral bisphosphonates.
CONCLUSION: Zoledronic acid had the highest probability of causing the greatest
number of GI AE, possibly related to nausea. These results question the
assumption that annual zoledronic acid will translate into better adherence.
Little difference was found between alendronate and risedronate for serious AE.
More research into real-world implications of the comparative safety of
bisphosphonates is needed.

PMID: 24287510  [PubMed - indexed for MEDLINE]


69. BMJ. 2014 Mar 31;348:g2197. doi: 10.1136/bmj.g2197.

Selective digestive or oropharyngeal decontamination and topical oropharyngeal
chlorhexidine for prevention of death in general intensive care: systematic
review and network meta-analysis.

Price R(1), MacLennan G, Glen J; SuDDICU Collaboration.

Author information:
(1)Intensive Care Unit, Royal Alexandra Hospital, Paisley PA2 9PN, UK.

Comment in
    Dtsch Med Wochenschr. 2014 May;139(19):980.
    Ann Intern Med. 2014 Aug 19;161(4):JC9.

OBJECTIVES: To determine the effect on mortality of selective digestive
decontamination, selective oropharyngeal decontamination, and topical
oropharyngeal chlorhexidine in adult patients in general intensive care units and
to compare these interventions with each other in a network meta-analysis.
DESIGN: Systematic review, conventional meta-analysis, and network meta-analysis.
Medline, Embase, and CENTRAL were searched to December 2012. Previous
meta-analyses, conference abstracts, and key journals were also searched. We used
pairwise meta-analyses to estimate direct evidence from intervention-control
trials and a network meta-analysis within a Bayesian framework to combine direct
and indirect evidence.
INCLUSION CRITERIA: Prospective randomised controlled trials that recruited adult
patients in general intensive care units and studied selective digestive
decontamination, selective oropharyngeal decontamination, or oropharyngeal
chlorhexidine compared with standard care or placebo.
RESULTS: Selective digestive decontamination had a favourable effect on
mortality, with a direct evidence odds ratio of 0.73 (95% confidence interval
0.64 to 0.84). The direct evidence odds ratio for selective oropharyngeal
decontamination was 0.85 (0.74 to 0.97). Chlorhexidine was associated with
increased mortality (odds ratio 1.25, 1.05 to 1.50). When each intervention was
compared with the other, both selective digestive decontamination and selective
oropharyngeal decontamination were superior to chlorhexidine. The difference
between selective digestive decontamination and selective oropharyngeal
decontamination was uncertain.
CONCLUSION: Selective digestive decontamination has a favourable effect on
mortality in adult patients in general intensive care units. In these patients,
the effect of selective oropharyngeal decontamination is less certain. Both
selective digestive decontamination and selective oropharyngeal decontamination
are superior to chlorhexidine, and there is a possibility that chlorhexidine is
associated with increased mortality.

PMCID: PMC3970764
PMID: 24687313  [PubMed - indexed for MEDLINE]




71. Int J Cardiol. 2014 Mar 15;172(2):375-80. doi: 10.1016/j.ijcard.2014.01.075. Epub
2014 Jan 24.

Nephropathy after administration of iso-osmolar and low-osmolar contrast media:
evidence from a network meta-analysis.

Biondi-Zoccai G(1), Lotrionte M(2), Thomsen HS(3), Romagnoli E(4), D'Ascenzo
F(5), Giordano A(6), Frati G(7).

Author information:
(1)Department of Medico-Surgical Sciences and Biotechnologies, Sapienza
University of Rome, Latina, Italy. Electronic address:
giuseppe.biondizoccai@uniroma1.it. (2)Heart Failure and Cardiac Rehabilitation
Unit, Columbus Integrated Complex, Rome, Italy. (3)Copenhagen University
Hospital, Herlev, Denmark. (4)Division of Cardiology, Policlinico Casilino, Rome,
Italy. (5)Division of Cardiology, University of Turin, Turin, Italy. (6)Unità
Operativa di Interventistica Cardiovascolare, Presidio Ospedaliero Pineta Grande,
Castel Volturno, Italy; Unità Operativa di Emodinamica, Casa di Salute Santa
Lucia, San Giuseppe Vesuviano, Italy. (7)Department of Medico-Surgical Sciences
and Biotechnologies, Sapienza University of Rome, Latina, Italy.

BACKGROUND/OBJECTIVES: Contrast-induced nephropathy (CIN) may be a severe
complication to the administration of iodine-based contrast media for diagnostic
or interventional procedure using radiation exposure. Whether there is a
difference in nephrotoxic potential between the various agents is uncertain. We
aimed to perform a systematic review and network meta-analysis of randomized
trials on iodine-based contrast agents.
METHODS: Randomized trials of low-osmolar or iso-osmolar contrast media were
searched in CENTRAL, Google Scholar, MEDLINE/PubMed, and Scopus. Risk of CIN was
appraised within a hierarchical Bayesian model computing absolute rates (AR) and
odds ratios (OR) with 95% credibility intervals, and probability of being best
(Pbest) for each agent.
RESULTS: A total of 42 trials (10048 patients) were included focusing on 7
different iodine-based contrast media. Risk of CIN was similarly low with
iodixanol (AR=5.7% [2.2%-13.9%], Pbest=18.8%), iomeprol (AR=6.0% [2.2%-15.4%],
Pbest=24.8%), iopamidol (AR=6.1% [2.2%-15.5%], Pbest=21.5%), and ioversol
(AR=6.0% [2.1%-16.4%], Pbest=31.3%). Conversely, CIN was twice as common with
iohexol (AR=11.2% [4.1%-29.5%], Pbest=0.1%) and ioxaglate (AR=11.0% [4.0%-26.9%],
Pbest<0.1%), with both proving less safe than iodixanol (respectively OR=2.18
[1.22-3.92] and 2.05 [1.26-3.29]), iomeprol (OR=2.08 [1.04-4.17] and 1.96
[1.06-3.48]) and iopamidol (OR=2.04 [1.15-3.85] and 1.92 [1.06-3.45]). Data on
iopromide were less conclusive (AR=6.9% [2.6%-17.1%], Pbest=3.6%).
CONCLUSIONS: Iodixanol, iomeprol, iopamidol and ioversol are iodine-based
contrast media with a similar renal safety profile. Iohexol and ioxaglate have a
poorer renal safety profile, whereas further data may be required on iopromide.

Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

PMID: 24502883  [PubMed - indexed for MEDLINE]


72. BMC Musculoskelet Disord. 2014 Mar 11;15:76. doi: 10.1186/1471-2474-15-76.

The efficacy of duloxetine, non-steroidal anti-inflammatory drugs, and opioids in
osteoarthritis: a systematic literature review and meta-analysis.

Myers J(1), Wielage RC, Han B, Price K, Gahn J, Paget MA, Happich M.

Author information:
(1)Medical Decision Modeling, Inc, 8909 Purdue Road, Suite 550, Indianapolis, IN,
USA. jam@mdm-inc.com.

BACKGROUND: This meta-analysis assessed the efficacy of duloxetine versus other
oral treatments used after failure of acetaminophen for management of patients
with osteoarthritis.
METHODS: A systematic literature review of English language articles was
performed in PUBMED, EMBASE, MedLine In-Process, Cochrane Library, and
ClinicalTrials.gov between January 1985 and March 2013. Randomized controlled
trials of duloxetine and all oral non-steroidal anti-inflammatory drugs and
opioids were included if treatment was ≥12 weeks and the Western Ontario and
McMaster Universities Index (WOMAC) total score was available. Studies were
assessed for quality using the assessment tool from the National Institute for
Health and Clinical Excellence guidelines for single technology appraisal
submissions.WOMAC baseline and change from baseline total scores were extracted
and standardized. A frequentist meta-analysis, meta-regression, and indirect
comparison were performed using the DerSimonian-Laird and Bucher methods.
Bayesian analyses with and without adjustment for study-level covariates were
performed using noninformative priors.
RESULTS: Thirty-two publications reported 34 trials (2 publications each reported
2 trials) that met inclusion criteria. The analyses found all treatments except
oxycodone (frequentist) and hydromorphone (frequentist and Bayesian) to be more
effective than placebo. Indirect comparisons to duloxetine found no significant
differences for most of the compounds. Some analyses showed evidence of a
difference with duloxetine for etoricoxib (better), tramadol and oxycodone
(worse), but without consistent results between analyses. Forest plots revealed
positive trends in overall efficacy improvement with baseline scores. Adjusting
for baseline, the probability duloxetine is superior to other treatments ranges
between 15% to 100%.Limitations of this study include the low number of studies
included in the analyses, the inclusion of only English language publications,
and possible ecological fallacy associated with patient level characteristics.
CONCLUSIONS: This analysis suggests no difference between duloxetine and other
post-first line oral treatments for osteoarthritis (OA) in total WOMAC score
after approximately 12 weeks of treatment. Significant results for 3 compounds (1
better and 2 worse) were not consistent across performed analyses.

PMCID: PMC4007556
PMID: 24618328  [PubMed - indexed for MEDLINE]


73. Curr Med Res Opin. 2014 Mar;30(3):367-80. doi: 10.1185/03007995.2013.837818. Epub
2013 Nov 19.

Comparison of the efficacy and safety of low molecular weight heparins for venous
thromboembolism prophylaxis in medically ill patients.

Dooley C(1), Kaur R, Sobieraj DM.

Author information:
(1)Hartford Hospital, Pharmacy , Hartford, CT , USA.

OBJECTIVE: To conduct a systematic review and mixed-treatment comparison (MTC)
meta-analysis to compare the efficacy and safety of low molecular weight heparins
(LMWHs) for venous thromboembolism (VTE) prophylaxis in hospitalized medically
ill patients. As a secondary objective we compared all therapies within the
network to each other.
METHODS: We conducted a systematic literature search for randomized trials that
evaluated pharmacologic VTE prophylaxis in hospitalized medically ill patients.
We conducted a traditional meta-analysis for all pairwise comparisons using a
random effects model, reporting relative risks (RRs) and 95% confidence intervals
for each outcome. To determine the relative efficacy and safety of included
therapies we conducted a MTC meta-analysis using a Bayesian framework, reporting
odds ratios (OR) and 95% credible intervals.
RESULTS: Twenty trials met inclusion criteria. Enoxaparin, dalteparin, nadroparin
and certoparin were the LMWHs evaluated although none in direct comparative
trials. Upon MTC, the relative efficacy of all LMWHs was similar in preventing
mortality and VTE as well as in the odds of major and minor bleeding. Dalteparin
was not included in the network to evaluate deep vein thrombosis (DVT) and
pulmonary embolism (PE) due to lack of reported data and the remaining LMWHs were
found to be similar in relative efficacy in preventing these outcomes.
LIMITATIONS: Traditional meta-analysis was not possible for many drug comparisons
made within the MTC. Heterogeneity was observed in several of the traditional
meta-analyses although this may be an inherent limitation of the studied
population. Overall rarity of events contributed to imprecise estimates
demonstrated by the wide confidence intervals.
CONCLUSIONS: Enoxaparin, dalteparin, nadroparin and certoparin are similar in
relative efficacy for the prevention of mortality and VTE and in the odds of
major or minor bleeding while enoxaparin, nadroparin and certoparin are similar
in relative efficacy for the prevention of PE and DVT in hospitalized medical
patients.

PMID: 23971722  [PubMed - indexed for MEDLINE]




75. Heart. 2014 Mar;100(5):396-405. doi: 10.1136/heartjnl-2013-304347. Epub 2013 Sep
5.

Current and new oral antithrombotics in non-valvular atrial fibrillation: a
network meta-analysis of 79 808 patients.

Dogliotti A(1), Paolasso E, Giugliano RP.

Author information:
(1)Unidad de Epidemiología Clínica y Estadística, Grupo Oroño, , Rosario,
Argentina.

Comment in
    Ann Intern Med. 2014 Feb 18;160(4):JC3.

BACKGROUND: Antithrombotic therapy reduces stroke, embolism and mortality in
patients with atrial fibrillation (AF); however, meta-analyses have focused on
pairwise comparisons of treatments.
OBJECTIVE: To synthesise the evidence from trials using a multiple treatment
comparison methods thereby permitting a broader comparison across multiple
therapies.
DESIGN, SETTING, PATIENTS: Randomised controlled trials in patients with AF of
antithrombotics were identified from MEDLINE, Embase, and Cochrane Central
Register of Controlled Trials through May 2012. We performed a random-effects
model within a Bayesian framework using Markov Chain Monte Carlo simulation to
calculate pooled OR and 95% credibility intervals (CrI). We also ranked therapies
by their likelihood of leading to the best results for the outcomes.
MAIN OUTCOME MEASURE: Multiple endpoints including stroke, embolism, death and
bleeding.
RESULTS: We identified 20 studies with 79 808 patients allocated to 8 treatments:
ASA, ASA plus clopidogrel, vitamin K antagonists (VKAs), dabigatran 110 mg,
dabigatran 150 mg, rivaroxaban, apixaban or placebo/control. Compared with
placebo/control, dabigatran 150 mg was associated with the lowest risk of stroke
(OR=0.25, 0.15-0.43), the composite of ischaemic stroke or systemic embolism
(OR=0.26, 0.12-0.54) and mortality (OR=0.53, 0.28-0.88). ASA plus clopidogrel was
associated with the highest risk of major bleeding (OR=3.65, 1.22-13.56). In
simulated comparisons, the novel oral anticoagulants ranked better than VKA or
antiplatelet therapies for prevention of stroke, ischaemic stroke or systemic
embolism and mortality.
CONCLUSIONS: In this network meta-analysis, novel oral anticoagulants were the
most promising treatments to reduce stroke, stroke or systemic embolism, and
all-cause mortality in patients with AF.

PMID: 24009224  [PubMed - indexed for MEDLINE]


76. J Clin Endocrinol Metab. 2014 Mar;99(3):923-31. doi: 10.1210/jc.2013-2409. Epub
2014 Jan 1.

The incidence and prevalence of thyroid dysfunction in Europe: a meta-analysis.

Garmendia Madariaga A(1), Santos Palacios S, Guillén-Grima F, Galofré JC.

Author information:
(1)Departments of Endocrinology and Nutrition (A.G.M., S.S.P., J.C.G.) and
Preventive Medicine (F.G.-G.), Clínica Universidad de Navarra, University of
Navarra, 31008 Pamplona, Spain; and Department of Health Sciences (F.G.-G.),
Public University of Navarra, 31008 Pamplona, Spain.

CONTEXT: Thyroid dysfunction is one of the leading endocrine disorders. Previous
data show that about half of the population with thyroid dysfunction remains
undiagnosed.
OBJECTIVE: Our objective was to estimate epidemiologic data on thyroid
dysfunction in Europe.
DATA SOURCES: PubMed, EMBASE, and SCOPUS databases were searched to identify
studies that evaluated the prevalence and/or incidence of thyroid dysfunction in
Europe published between 1975 and 2012.
STUDY SELECTION: Of the 541 identified abstracts examined, 178 were considered
for evaluation and 17 were included. Studies were excluded if they included
participants with an underlying disease or were limited by age or gender.
DATA EXTRACTION: Results were grouped into 3 categories: 1) prevalence of
undiagnosed thyroid dysfunction, 2) prevalence of thyroid dysfunction, and 3)
incidence of thyroid dysfunction. Extraction was conducted independently by 2
investigators.
DATA SYNTHESIS: An empirical Bayesian random-effects model was used. The
prevalence of undiagnosed thyroid dysfunction was assessed in 7 studies with a
mean result of 6.71% (95% credibility interval, 6.49%-6.93%): 4.94% (4.75%-5.13%)
and 1.72% (1.66%-1.88%) for undiagnosed hypothyroidism and hyperthyroidism,
respectively. The prevalence of both previously diagnosed and undiagnosed thyroid
dysfunction was assessed in 9 studies with a mean result of 3.82% (3.77%-3.86%):
3.05% (3.01%-3.09%) and 0.75% (0.73%-0.77%) for hypothyroidism and
hyperthyroidism, respectively. The incidence rate of thyroid dysfunction was
assessed in 7 studies with a mean result of 259.12 (254.39-263.9) per 100 000 per
year: 226.2 (222.26-230.17) and 51 (49.23-52.88) per 100 000 per year for
hypothyroidism and hyperthyroidism, respectively.
CONCLUSION: This meta-analysis provides extensive data on the prevalence and
incidence of thyroid dysfunction in Europe.

PMID: 24423323  [PubMed - indexed for MEDLINE]


77. J Clin Endocrinol Metab. 2014 Mar;99(3):757-67. doi: 10.1210/jc.2013-3450. Epub
2013 Dec 11.

Efficacy of vitamin D supplementation in depression in adults: a systematic
review.

Li G(1), Mbuagbaw L, Samaan Z, Falavigna M, Zhang S, Adachi JD, Cheng J,
Papaioannou A, Thabane L.

Author information:
(1)Department of Clinical Epidemiology and Biostatistics (G.L., L.M., S.Z., J.C.,
L.T.), and Department of Psychiatry and Behavioural Neurosciences (Z.S.),
Division of Geriatric Medicine, Department of Medicine (A.P.), McMaster
University, Hamilton, Ontario, Canada L8S 4L8; Post Graduate Program in
Epidemiology (M.F.), Universidade Federal do Rio Grande do Sul, Porto Alegre
90040-060, Brazil; and St Joseph's Hospital (J.D.A., J.C., L.T.), McMaster
University, Hamilton, Ontario, Canada L8N 4A6.

CONTEXT: Randomized controlled trials (RCTs) investigating the efficacy of
vitamin D (Vit D) in depression provided inconsistent results.
OBJECTIVE: We aim to summarize the evidence of RCTs to assess the efficacy of
oral Vit D supplementation in depression compared to placebo.
DATA SOURCES: We searched electronic databases, two conference proceedings, and
gray literature by contacting authors of included studies.
STUDY SELECTION: We selected parallel RCTs investigating the effect of oral Vit D
supplementation compared with placebo on depression in adults at risk of
depression, with depression symptoms or a primary diagnosis of depression.
DATA EXTRACTION: Two reviewers independently extracted data from relevant
literature.
DATA SYNTHESIS: Classical and Bayesian random-effects meta-analyses were used to
pool relative risk, odds ratio, and standardized mean difference. The quality of
evidence was assessed using the Grading of Recommendations Assessment,
Development and Evaluation tool.
RESULTS: Six RCTs were identified with 1203 participants (72% females) including
71 depressed patients; five of the studies involved adults at risk of depression,
and one trial used depressed patients. Results of the classical meta-analysis
showed no significant effect of Vit D supplementation on postintervention
depression scores (standardized mean difference = -0.14, 95% confidence interval
= -0.41 to 0.13, P = .32; odds ratio = 0.93, 95% confidence interval = 0.54 to
1.59, P = .79). The quality of evidence was low. No significant differences were
demonstrated in subgroup or sensitivity analyses. Similar results were found when
Bayesian meta-analyses were applied.
CONCLUSIONS: There is insufficient evidence to support the efficacy of Vit D
supplementation in depression symptoms, and more RCTs using depressed patients
are warranted.

PMID: 24423304  [PubMed - indexed for MEDLINE]




79. EuroIntervention. 2014 Feb;9(10):1225-34. doi: 10.4244/EIJV9I10A205.

A systematic review and meta-analysis of surgical outcomes following mitral valve
surgery in octogenarians: implications for transcatheter mitral valve
interventions.

Andalib A(1), Mamane S, Schiller I, Zakem A, Mylotte D, Martucci G, Lauzier P,
Alharbi W, Cecere R, Dorfmeister M, Lange R, Brophy J, Piazza N.

Author information:
(1)Department of Medicine, Division of Cardiology, Interventional Cardiology,
McGill University Health Centre, Montreal, Quebec, Canada.

Comment in
    EuroIntervention. 2014 Feb;9(10):1133-5.

AIMS: To evaluate the outcomes of mitral valve surgery in octogenarians with
severe symptomatic mitral regurgitation (MR).
METHODS AND RESULTS: We performed a systematic review and meta-analysis of data
on octogenarians who underwent mitral valve replacement (MVR) or mitral valve
repair (MVRpr). Our search yielded 16 retrospective studies. Using Bayesian
hierarchical models, we estimated the pooled proportion of 30-day mortality,
postoperative stroke, and long-term survival. The pooled proportion of 30-day
postoperative mortality was 13% following MVR (10 studies, 3,105 patients, 95%
credible interval [CI] 9-18%), and 7% following MVRpr (six studies, 2,642
patients, 95% CI: 3-12%). Furthermore, pooled proportions of postoperative stroke
were 4% (six studies, 2,945 patients, 95% CI: 3-7%) and 3% (three studies, 348
patients, 95% CI: 1-8%) for patients undergoing MVR and MVRpr, respectively.
Pooled survival rates at one and five years following MVR (four studies, 250
patients) were 67% (95% CI: 50-80%) and 29% (95% CI: 16-47%), and following MVRpr
(three studies, 333 patients) were 69% (95% CI: 50-83%) and 23% (95% CI: 12-39%),
respectively.
CONCLUSIONS: Surgical treatment of MR in octogenarians is associated with high
perioperative mortality and poor long-term survival with an uncertain benefit on
quality of life. These data highlight the importance of patient selection for
operative intervention and suggest that future transcatheter mitral valve
therapies such as transcatheter mitral valve repair (TMVr) and/or transcatheter
mitral valve implantation (TMVI), may provide an alternative therapeutic approach
in selected high-risk elderly patients.

PMID: 24035898  [PubMed - indexed for MEDLINE]


80. Pain Pract. 2014 Feb;14(2):167-84. doi: 10.1111/papr.12054. Epub 2013 Mar 28.

Systematic review and meta-analysis of pharmacological therapies for painful
diabetic peripheral neuropathy.

Snedecor SJ(1), Sudharshan L, Cappelleri JC, Sadosky A, Mehta S, Botteman M.

Author information:
(1)Pharmerit International, Bethesda, MD, USA.

BACKGROUND: Painful diabetic peripheral neuropathy (pDPN) is prevalent among
persons with diabetes and increases over time. Published guidelines recommend a
number of medications to treat this condition providing clinicians with a variety
of treatment options. This study provides a comprehensive systematic review and
meta-analysis of published pharmacologic therapies for pDPN.
METHODS: The published literature was systematically searched to identify
randomized, controlled trials of all available pharmacologic treatments for pDPN
(recommended or nonrecommended) reporting predefined efficacy and safety
outcomes. Bayesian fixed-effect mixed treatment comparison methods were used to
assess relative therapeutic efficacy and harms.
RESULTS: Data from 58 studies including 29 interventions and 11,883 patients were
analyzed. Pain reduction over that of placebo on the 11-point numeric rating
scale ranged from -3.29 for sodium valproate (95% credible interval [CrI] =
[-4.21, -2.36]) to 1.67 for Sativex (-0.47, 0.60). Estimates for most treatments
were clustered between 0 and -1.5 and were associated with more study data and
smaller CrIs. Pregabalin (≥ 300 mg/day) was the most effective on the 100-point
visual analog scale (-21.88; [-27.06, -16.68]); topiramate was the least (-3.09;
[-3.99, -2.18]). Relative risks (RRs) of 30% pain reduction ranged from 0.78
(Sativex) to 1.84 (lidocaine 5% plaster). Analysis of the RR ratio of these 2
treatments reveals marginal significance for Sativex (3.27; [1.07, 9.81]),
indicating the best treatment is only slightly better than the worst. Relative
risks of 50% pain reduction ranged from 0.98 (0.56, 1.52) (amitriptyline) to 2.25
(1.51, 3.00) (alpha-lipoic acid). RR ratio for these treatments was not
statistically different (3.39; [0.88, 3.34]). Fluoxetine had the lowest risk of
adverse events (0.94; [0.62, 1.23]); oxycodone had the highest (1.55; [1.45,
1.64]). Discontinuation RRs were clustered around 0.8 to 1.5, with those on the
extreme having greater uncertainty.
CONCLUSIONS: Selecting an appropriate pDPN therapy is key given the large number
of available treatments. Comparative results revealed relative equivalence among
many of the studied interventions having the largest overall sample sizes and
highlight the importance of standardization of methods to effectively assess
pain.

© 2013 The Authors Pain Practice © 2013 World Institute of Pain.

PMID: 23534696  [PubMed - indexed for MEDLINE]


81. BMC Musculoskelet Disord. 2014 Jan 20;15:26. doi: 10.1186/1471-2474-15-26.

Systematic review, network meta-analysis and economic evaluation of biological
therapy for the management of active psoriatic arthritis.

Cawson MR, Mitchell SA(1), Knight C, Wildey H, Spurden D, Bird A, Orme ME.

Author information:
(1)Abacus International, 6 Talisman Business Centre, Talisman Road, Bicester OX26
6HR, UK. stephen.mitchell@abacusint.com.

Comment in
    BMC Musculoskelet Disord. 2014;15:25.

BACKGROUND: An updated economic evaluation was conducted to compare the
cost-effectiveness of the four tumour necrosis factor (TNF)-α inhibitors
adalimumab, etanercept, golimumab and infliximab in active, progressive psoriatic
arthritis (PsA) where response to standard treatment has been inadequate.
METHODS: A systematic review was conducted to identify relevant, recently
published studies and the new trial data were synthesised, via a Bayesian network
meta-analysis (NMA), to estimate the relative efficacy of the TNF-α inhibitors in
terms of Psoriatic Arthritis Response Criteria (PsARC) response, Health
Assessment Questionnaire (HAQ) scores and Psoriasis Area and Severity Index
(PASI). A previously developed economic model was updated with the new
meta-analysis results and current cost data. The model was adapted to delineate
patients by PASI 50%, 75% and 90% response rates to differentiate between
psoriasis outcomes.
RESULTS: All four licensed TNF-α inhibitors were significantly more effective
than placebo in achieving PsARC response in patients with active PsA. Adalimumab,
etanercept and infliximab were significantly more effective than placebo in
improving HAQ scores in patients who had achieved a PsARC response and in
improving HAQ scores in PsARC non-responders. In an analysis using 1,000 model
simulations, on average etanercept was the most cost-effective treatment and, at
the National Institute for Health and Care Excellence willingness-to-pay
threshold of between £20,000 to £30,000, etanercept is the preferred option.
CONCLUSIONS: The economic analysis agrees with the conclusions from the previous
models, in that biologics are shown to be cost-effective for treating patients
with active PsA compared with the conventional management strategy. In
particular, etanercept is cost-effective compared with the other biologic
treatments.

PMCID: PMC3903562
PMID: 24444034  [PubMed - indexed for MEDLINE]


82. Acta Med Iran. 2014;52(4):256-64.

Prevalence of G6PD deficiency in Iran, a mata-analysis.

Moosazadeh M(1), Amiresmaili M(2), Aliramezany M(3).

Author information:
(1)Department of Epidemiology, Research Center for Modeling in Health, Institute
for Futures Studies in Health, Kerman University of Medical Sciences, Kerman,
Iran mohammadreza.amiresmaili@gmail.com. (2)Department of Health services
management, Research Center for Health Services Management, Institute for Futures
Studies in Health, Kerman University of Medical Sciences, Kerman, Iran
mohammadreza.amiresmaili@gmail.com. (3)Department of Cardiology, Medical
Informatics Research Center, Institute for Futures Studies in Health, Kerman
University of Medical Sciences, Kerman, Iran. mohammadreza.amiresmaili@gmail.com.

Search results show that numerous primary studies have been carried out in
different parts of Iran regarding prevalence of G6PD deficiency; if results of
these studies are combined, a reliable estimation of prevalence of this factor
will be achieved in Iran. Thus, present study, aimed to determine the prevalence
of G6PD deficiency by combining findings of qualified primary studies using
meta-analysis and taking into account heterogeneity considerations. Searching the
relevant keywords in Iranian and International databases, primary studies were
selected. After quality appraisal and applying inclusion and exclusion criteria,
relevant primary studies were selected. In each study, standard error of
prevalence of G6PD was calculated according to binominal distribution formula.
Finally, heterogeneity index was determined among studies using Cochran's test.
Prevalence of G6PD in Iran was estimated by STATA software ver 11 using fixed or
random effect model based on heterogeneity results. 148916 subjects in 36 primary
studies which entered this meta-analysis were examined. G6PD deficiency
prevalence was 6.7% in Iran (men: 8.8% and women: 2.2%). Also, this deficiency in
the present study was four times higher in men than in women. Its prevalence was
adjusted in different parts of Iran and it was shown that it was between 0.8 and
15.2 using Bayesian analysis. This meta-analysis showed that Iran is among
countries with high frequency of G6PD deficiency and there is a significant
difference in prevalence of G6PD in different parts of Iran. According to these
results, screening newborn children seems very vital. Carrying out other primary
studies regarding prevalence of G6PD seems unnecessary.

PMID: 24901854  [PubMed - indexed for MEDLINE]


83. Breast Cancer Res Treat. 2014 Jan;143(1):125-33. doi: 10.1007/s10549-013-2778-5.
Epub 2013 Nov 24.

Comparative efficacy of everolimus plus exemestane versus fulvestrant for
hormone-receptor-positive advanced breast cancer following progression/recurrence
after endocrine therapy: a network meta-analysis.

Bachelot T(1), McCool R, Duffy S, Glanville J, Varley D, Fleetwood K, Zhang J,
Jerusalem G.

Author information:
(1)Département de Cancérologie Médicale, Centre Léon Bérard, 28 rue Laënnec,
69008, Lyon Cedex 08, France, thomas.bachelot@lyon.unicancer.fr.

Postmenopausal women with advanced breast cancer recurring/progressing on or
after initial (adjuvant or first-line) endocrine therapy may be treated multiple
times with one of several endocrine or combinatorial targeted treatment options
before initiating chemotherapy. In the absence of direct head-to-head comparisons
of these treatment options, an indirect comparison can inform treatment choice.
This network meta-analysis compared the efficacy of everolimus plus exemestane
with that of fulvestrant 250 and 500 mg in the advanced breast cancer setting
following adjuvant or first-line endocrine therapy. The reported hazard ratios
(HRs) for progression-free survival (PFS) or time to progression from six studies
that formed a network to compare everolimus plus exemestane (BOLERO-2 trial) with
fulvestrant were analyzed by means of a Bayesian network meta-analysis. In the
primary comparison (PFS analysis based on the local review of disease progression
from BOLERO-2 with the data from the other studies), everolimus plus exemestane
appeared to be more efficacious than both fulvestrant 250 mg (HR = 0.47; 95 %
credible interval [CrI] 0.38-0.58) and 500 mg (HR = 0.59; 95 % CrI 0.45-0.77).
Similar results were obtained in an alternate comparison based on central review
of disease progression from BOLERO-2 with the data from the other studies
(HR = 0.40; 95 % CrI 0.31-0.51 and HR = 0.50; 95 % CrI 0.37-0.67, respectively),
and in a subgroup analysis of patients who had received prior aromatase inhibitor
therapy (HR = 0.47; 95 % CrI 0.38-0.58 and HR = 0.55; 95 % CrI 0.40-0.76,
respectively). These results suggest that everolimus plus exemestane may be more
efficacious than fulvestrant in patients with advanced breast cancer who progress
on or after adjuvant or first-line therapy with a nonsteroidal aromatase
inhibitor.

PMCID: PMC3889833
PMID: 24272078  [PubMed - indexed for MEDLINE]


84. Drug Saf. 2014 Jan;37(1):19-31. doi: 10.1007/s40264-013-0129-4.

Sexual dysfunction associated with second-generation antidepressants in patients
with major depressive disorder: results from a systematic review with network
meta-analysis.

Reichenpfader U(1), Gartlehner G, Morgan LC, Greenblatt A, Nussbaumer B, Hansen
RA, Van Noord M, Lux L, Gaynes BN.

Author information:
(1)Department for Evidence-based Medicine and Clinical Epidemiology, Danube
University Krems, Dr.-Karl-Dorrek-Str. 30, 3500, Krems, Austria,
ureichenpfader@hotmail.com.

BACKGROUND: Sexual dysfunction (SD) is prevalent in patients with major
depressive disorder (MDD) and is also associated with second-generation
antidepressants (SGADs) that are commonly used to treat the condition. Evidence
indicates under-reporting of SD in efficacy studies. SD associated with
antidepressant treatment is a serious side effect that may lead to early
termination of treatment and worsening of quality of life.
OBJECTIVES: Our objective was to systematically assess the harms of SD associated
with SGADs in adult patients with MDD by drug type.
METHODS: We retrieved English-language abstracts from PubMed, EMBASE, the
Cochrane Library, PsycINFO, and International Pharmaceutical Abstracts from 1980
to October 2012 as well as from reference lists of pertinent review articles and
grey literature searches. Two independent reviewers identified randomized
controlled trials (RCTs) of at least 6 weeks' duration and observational studies
with at least 1,000 participants.
STUDY SELECTION: Reviewers abstracted data on study design, conduct,
participants, interventions, outcomes and method of SD ascertainment, and rated
risk of bias. A senior reviewer checked and confirmed extracted data and
risk-of-bias ratings.
ANALYSES: Random effects network meta-analysis using Bayesian methods for data
from head-to-head trials and placebo-controlled comparisons; descriptive analyses
calculating weighted mean rates from individual trials and observational studies.
RESULTS/SYNTHESIS: Data from 63 studies of low and moderate risk of bias (58
RCTs, five observational studies) with more than 26,000 patients treated with
SGADs were included. Based on network meta-analyses of 66 pairwise comparisons
from 37 RCTs, most comparisons showed a similar risk of SD among included SGADs.
However, credible intervals were wide and included differences that would be
considered clinically relevant. We observed three main patterns: bupropion had a
statistically significantly lower risk of SD than some other SGADs, and both
escitalopram and paroxetine showed a statistically significantly higher risk of
SD than some other SGADs. We found reporting of harms related to SD inconsistent
and insufficient in some trials.
LIMITATIONS: Most trials were conducted in highly selected populations. Search
was restricted to English-language only.
CONCLUSION AND IMPLICATIONS: Because of the indirect nature of the comparisons,
the often wide credible intervals, and the high variation in magnitude of
outcome, we rated the overall strength of evidence with respect to our findings
as low. The current degree of evidence does not allow a precise estimate of
comparative risk of SD associated with a specific antidepressant. In the absence
of such evidence, clinicians need to be aware of SD as a common adverse event and
should discuss patients' preferences before initiating antidepressant therapy.

PMID: 24338044  [PubMed - indexed for MEDLINE]


85. Hum Vaccin Immunother. 2014;10(5):1421-4. doi: 10.4161/hv.28284. Epub 2014 Mar 7.

Bayesian network meta-analysis suggests a similar effectiveness between a
monovalent and a pentavalent rotavirus vaccine: a preliminary report of
re-analyses of data from a Cochrane Database Systematic Review.

Takeuchi M(1).

Author information:
(1)Department of Pediatrics; Kikkoman General Hospital; Noda, Chiba, Japan.

To assess the comparative effectiveness of a monovalent and a pentavalent
rotavirus vaccine (RV1 and RV5), a Bayesian network meta-analysis was conducted.
Data of randomized trials from the Cochrane Review in 2012 were extracted and
synthesized. For the prevention of severe rotavirus disease up to 2 years, no
statistical difference was found in the effectiveness between the 2 types of
vaccine (odds ratio: 2.23, 95% credible interval: 0.71-5.20). Similarly, the
comparative effectiveness of RV1 and RV5 appeared equivalent for other
rotavirus-associated outcome measures, such as prevention of severe disease up to
1 year and all severity of rotavirus infections for up to both 1- and 2-year
follow-ups. These results indicates that, overall, RV1 and RV5 offer similar
benefits to prevent rotavirus diseases; nonetheless, credible intervals are
generally wide, highlighting the necessity of further meta-analyses including
updated information or, ideally, controlled trials comparing both vaccines
directly.

PMID: 24608099  [PubMed - indexed for MEDLINE]


86. Int J Chron Obstruct Pulmon Dis. 2014 May 12;9:469-79. doi: 10.2147/COPD.S48492.
eCollection 2014.

Comparative efficacy of inhaled corticosteroid and long-acting beta agonist
combinations in preventing COPD exacerbations: a Bayesian network meta-analysis.

Oba Y(1), Lone NA(1).

Author information:
(1)University of Missouri, School of Medicine, Division of Pulmonary, Critical
Care and Environmental Medicine, Columbia, MO, USA.

BACKGROUND: A combination therapy with inhaled corticosteroid (ICS) and a
long-acting beta agonist (LABA) is recommended in severe chronic obstructive
pulmonary disease (COPD) patients experiencing frequent exacerbations. Currently,
there are five ICS/LABA combination products available on the market. The purpose
of this study was to systematically review the efficacy of various ICS/LABA
combinations with a network meta-analysis.
METHODS: Several databases and manufacturer's websites were searched for relevant
clinical trials. Randomized control trials, at least 12 weeks duration, comparing
an ICS/LABA combination with active control or placebo were included. Moderate
and severe exacerbations were chosen as the outcome assessment criteria. The
primary analyses were conducted with a Bayesian Markov chain Monte Carlo method.
RESULTS: Most of the ICS/LABA combinations reduced moderate-to-severe
exacerbations as compared with placebo and LABA, but none of them reduced severe
exacerbations. However, many studies excluded patients receiving long-term oxygen
therapy. Moderate-dose ICS was as effective as high-dose ICS in reducing
exacerbations when combined with LABA.
CONCLUSION: ICS/LABA combinations had a class effect with regard to the
prevention of COPD exacerbations. Moderate-dose ICS/LABA combination therapy
would be sufficient for COPD patients when indicated. The efficacy of ICS/LABA
combination therapy appeared modest and had no impact in reducing severe
exacerbations. Further studies are needed to evaluate the efficacy of ICS/LABA
combination therapy in severely affected COPD patients requiring long-term oxygen
therapy.

PMCID: PMC4026563
PMID: 24872685  [PubMed - indexed for MEDLINE]


87. Int J Surg. 2014;12(5):516-22. doi: 10.1016/j.ijsu.2014.02.010. Epub 2014 Feb 25.

A network meta-analysis on the efficacy of 5-aminosalicylates, immunomodulators
and biologics for the prevention of postoperative recurrence in Crohn's disease.

Yang Z(1), Ye X(2), Wu Q(1), Wu K(1), Fan D(3).

Author information:
(1)Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military
Medical University, 127 West Changle Road, Xi'an 710032, China. (2)Department of
Health Statistics, Second Military Medical University, Shanghai 200433, China.
(3)Xijing Hospital of Digestive Diseases, Xijing Hospital, Fourth Military
Medical University, 127 West Changle Road, Xi'an 710032, China. Electronic
address: daimingfan@fmmu.edu.cn.

BACKGROUND AND AIMS: A number of agents have been evaluated in clinical trials to
reduce the risk of postoperative recurrence in Crohn's disease (CD). The aim of
this study was to compare the efficacy of 5-aminosalicylates, immunomodulators
and biologics for postoperative prophylaxis of CD recurrence by using a network
meta-analytical approach.
METHODS: PubMed, Embase, and Cochrane Library were searched (update to November
2013) to identify randomized placebo-controlled, or head-to-head trials among the
three drug classes for prevention of postoperative CD relapse. The primary
endpoint for efficacy was endoscopic recurrence, and the secondary outcomes were
clinical recurrence and adverse events. We conducted a Bayesian network
meta-analysis with a mixed treatment comparisons to combine both direct and
indirect evidences.
RESULTS: Fifteen trials involving 1507 patients were included in this analysis.
Biological agents were associated with a large and significant reduction of both
endoscopic and clinical recurrence compared with placebo, 5-aminosalicylates, or
immunomodulators. Immunomodulators showed greater efficacy in terms of endoscopic
and clinical recurrence prophylaxis compared with 5-aminosalicylates or placebo,
but with higher incidence of adverse events. 5-aminosalicylates were superior to
placebo for prevention of clinical recurrence, without increasing the rate of
side effect.
CONCLUSIONS: 5-aminosalicylates, immunomodulators, and biologics are more
efficacious than placebo for postoperative CD prevention. Biologics are found to
be the most effective medications to prevent CD recurrence.

Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights
reserved.

PMID: 24576593  [PubMed - indexed for MEDLINE]


88. J Gen Intern Med. 2014 Jan;29(1):204-13. doi: 10.1007/s11606-013-2535-9. Epub
2013 Jul 26.

SSRIs for hot flashes: a systematic review and meta-analysis of randomized
trials.

Shams T(1), Firwana B, Habib F, Alshahrani A, Alnouh B, Murad MH, Ferwana M.

Author information:
(1)National and Gulf Center for Evidence-Based Health Practice, King Saud Bin
Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia,
ShamsT@ngha.med.sa.

BACKGROUND: Hot flashes are the most commonly reported vasomotor symptom during
the peri- and early post-menopausal period.
OBJECTIVES: To systematically review, appraise and summarize the evidence of the
impact of different SSRIs on peri-menopausal hot flashes in healthy women in
randomized, controlled trials.
METHODS: A comprehensive literature search was conducted of MEDLINE™, EMBASE, the
Cochrane Central Register of Controlled Trials, Web of Science and Scopus through
March 2013. Two independent reviewers selected studies and extracted data. Random
effects meta-analysis was used to pool outcomes across studies, and Bayesian
mixed treatment methods were used to rank SSRIs in terms of effectiveness.
RESULTS: We included a total of 11 randomized controlled trials with good
methodological quality enrolling 2,069 menopausal and post-menopausal women
(follow-up 1-9 months, mean age 36-76 years, mean time since menopause
2.3-6.6 years). Compared with placebo, SSRIs were associated with a statistically
significant decrease in hot flash frequency (difference in means -0.93; 95 % CI
-1.46 to -0.37; I(2) = 21 %) and severity assessed by various scales
(standardized difference in means -0.34; 95 % CI -0.59 to -0.10; I(2) = 47 %).
Adverse events did not differ from placebo. Mixed treatment comparison analysis
demonstrated the superiority of escitalopram compared to other SSRIs in terms of
efficacy.
CONCLUSION: SSRI use is associated with modest improvement in the severity and
frequency of hot flashes but can also be associated with the typical profile of
SSRI adverse effects.

PMCID: PMC3889979
PMID: 23888328  [PubMed - indexed for MEDLINE]


89. PLoS One. 2014 Oct 6;9(10):e108749. doi: 10.1371/journal.pone.0108749.
eCollection 2014.

A Bayesian meta-analysis of multiple treatment comparisons of systemic regimens
for advanced pancreatic cancer.

Chan K(1), Shah K(2), Lien K(2), Coyle D(3), Lam H(2), Ko YJ(2).

Author information:
(1)Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada;
Division of Biostatistics, Dalla Lana School of Public Health, University of
Toronto, Toronto, ON, Canada. (2)Sunnybrook Odette Cancer Centre, University of
Toronto, Toronto, ON, Canada. (3)University of Ottawa, Ottawa, ON, Canada.

BACKGROUND: For advanced pancreatic cancer, many regimens have been compared with
gemcitabine (G) as the standard arm in randomized controlled trials. Few regimens
have been directly compared with each other in randomized controlled trials and
the relative efficacy and safety among them remains unclear.
METHODS: A systematic review was performed through MEDLINE, EMBASE, Cochrane
Central Register of Controlled Trials, and ASCO meeting abstracts up to May 2013
to identify randomized controlled trials that included advanced pancreatic cancer
comparing the following regimens: G, G+5-fluorouracil, G+ capecitabine, G+S1, G+
cisplatin, G+ oxaliplatin, G+ erlotinib, G+ nab-paclitaxel, and FOLFIRINOX.
Overall survival and progression-free survival with 95% credible regions were
extracted using the Parmar method. A Bayesian multiple treatment comparisons was
performed to compare all regimens simultaneously.
RESULTS: Twenty-two studies were identified and 16 were included in the
meta-analysis. Median overall survival, progression free survival, and response
rates for G arms from all trials were similar, suggesting no significant clinical
heterogeneity. For overall survival, the mixed treatment comparisons found that
the probability that FOLFIRINOX was the best regimen was 83%, while it was 11%
for G+ nab-paclitaxel and 3% for G+ S1 and G+ erlotinib, respectively. The
overall survival hazard ratio for FOLFIRINOX versus G+ nab-paclitaxel was 0.79
[0.50-1.24], with no obvious difference in toxicities. The hazard ratios from
direct pairwise comparisons were consistent with the mixed treatment comparisons
results.
CONCLUSIONS: FOLFIRINOX appeared to be the best regimen for advanced pancreatic
cancer probabilistically, with a trend towards improvement in survival when
compared with other regimens by indirect comparisons.

PMCID: PMC4186762
PMID: 25286060  [PubMed - indexed for MEDLINE]


90. PLoS One. 2014 Sep 30;9(9):e108940. doi: 10.1371/journal.pone.0108940.
eCollection 2014.

Chemotherapy or targeted therapy as second-line treatment of advanced gastric
cancer. A systematic review and meta-analysis of published studies.

Iacovelli R(1), Pietrantonio F(2), Farcomeni A(3), Maggi C(2), Palazzo A(1),
Ricchini F(2), de Braud F(2), Di Bartolomeo M(2).

Author information:
(1)Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei
Tumori, Milan, Italy; PhD Program, Department of Radiology, Oncology and Human
Pathology, Sapienza University of Rome, Rome, Italy. (2)Department of Medical
Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
(3)Department of Public Health and Infectious Diseases, Statistics Section,
Sapienza University of Rome, Rome, Italy.

Chemotherapy is a cornerstone in treatments of gastric cancer, but despite its
benefit, less than 60% of patients receive salvage therapy in clinical practice.
We performed a systematic review and meta-analysis based on trial data on the
role of second-line treatment of advanced gastric cancer. MEDLINE/PubMed and
Cochrane Library were searched for randomized phase III trials that compared
active therapy to best supportive care in advanced gastric cancer. Data
extraction was conducted according to the PRISMA statement. Summary HR for OS was
calculated using a hierarchical Bayesian model and subgroup analysis was
performed based on baseline Eastern Cooperative Oncology Group Performance Status
(ECOG) performance status (0 vs. 1 or more). A total of 1,407 patients were
evaluable for efficacy, 908 were treated in the experimental arms, with
chemotherapy (231 pts) or with targeted therapies (677 pts). The risk of death
was decreased by 18% (HR = 0.82; 95% CI, 0.79-0.85; posterior probability HR≥1:
<0.00001) with active therapies. Chemotherapy and ramucirumab were able to
decrease this risk by 27% and 22%, respectively. No differences were found
between chemotherapy and ramucirumab. In patients with ECOG = 0 a greater benefit
was found for chemotherapy with a reduction of the risk of death by 43% and no
benefits were found for ramucirumab or everolimus. In patients with ECOG = 1 or
more a significant reduction of the risk of death by 32% was reported in patients
treated with ramucirumab, even if no significant difference was reported between
chemotherapy and ramucirumab. This analysis reports that active and available
therapies are able to prolong survival in patients with advanced gastric cancer
with a different outcome based on initial patient's performance status. New
trials based on a better patient stratification are awaited.

PMCID: PMC4182573
PMID: 25268988  [PubMed - indexed for MEDLINE]


91. PLoS One. 2014 Sep 4;9(9):e105653. doi: 10.1371/journal.pone.0105653. eCollection
2014.

48-week efficacy and safety of dolutegravir relative to commonly used third
agents in treatment-naive HIV-1-infected patients: a systematic review and
network meta-analysis.

Patel DA(1), Snedecor SJ(1), Tang WY(1), Sudharshan L(1), Lim JW(2), Cuffe R(3),
Pulgar S(4), Gilchrist KA(5), Camejo RR(6), Stephens J(1), Nichols G(4).

Author information:
(1)Pharmerit International, Bethesda, Maryland, United States of America.
(2)GlaxoSmithKline, Stockley Park, United Kingdom. (3)ViiV Healthcare, Middlesex,
United Kingdom. (4)GlaxoSmithKline, Research Triangle Park, North Carolina,
United States of America. (5)GlaxoSmithKline, Renaissance, Pennsylvania, United
States of America. (6)GlaxoSmithKline, Brentford, United Kingdom.

BACKGROUND: A network meta-analysis can provide estimates of relative efficacy
for treatments not directly studied in head-to-head randomized controlled trials.
We estimated the relative efficacy and safety of dolutegravir (DTG) versus third
agents currently recommended by guidelines, including ritonavir-boosted
atazanavir (ATV/r), ritonavir-boosted darunavir (DRV/r), efavirenz (EFV),
cobicistat-boosted elvitegravir (EVG/c), ritonavir-boosted lopinavir (LPV/r),
raltegravir (RAL), and rilpivirine (RPV), in treatment-naive HIV-1-infected
patients.
METHODS: A systematic review of published literature was conducted to identify
phase 3/4 randomized controlled clinical trials (up to August 2013) including at
least one third agent of interest in combination with a backbone nucleoside
reverse transcriptase inhibitor (NRTI) regimen. Bayesian fixed-effect network
meta-analysis models adjusting for the type of nucleoside reverse transcriptase
inhibitor backbone (tenofovir disoproxil fumarate/emtricitabine [TDF/FTC] or
abacavir/lamivudine [ABC/3TC]) were used to evaluate week 48 efficacy (HIV-RNA
suppression to <50 copies/mL and change in CD4+ cells/µL) and safety (lipid
changes, adverse events, and discontinuations due to adverse events) of DTG
relative to all other treatments. Sensitivity analyses assessing the impact of
NRTI treatment adjustment and random-effects models were performed.
RESULTS: Thirty-one studies including 17,000 patients were combined in the
analysis. Adjusting for the effect of NRTI backbone, treatment with DTG resulted
in significantly higher odds of virologic suppression (HIV RNA<50 copies/mL) and
increase in CD4+ cells/µL versus ATV/r, DRV/r, EFV, LPV/r, and RPV. Dolutegravir
had better or equivalent changes in total cholesterol, LDL, triglycerides, and
lower odds of adverse events and discontinuation due to adverse events compared
to all treatments. Random-effects and unadjusted models resulted in similar
conclusions.
CONCLUSION: Three clinical trials of DTG have demonstrated comparable or superior
efficacy and safety to DRV, RAL, and EFV in HIV-1-infected treatment-naive
patients. This network meta-analysis suggests DTG is also favorable or comparable
to other commonly used third agents (ATV/r, LPV/r, RPV, and EVG/c).

PMCID: PMC4154896
PMID: 25188312  [PubMed - indexed for MEDLINE]


92. PLoS One. 2014 Jun 3;9(6):e96829. doi: 10.1371/journal.pone.0096829. eCollection
2014.

A network meta-analysis of the relative efficacy of treatments for actinic
keratosis of the face or scalp in Europe.

Vegter S(1), Tolley K(2).

Author information:
(1)University of Groningen, Department of Pharmacy, Groningen, the Netherlands;
Vegter Health Economic Research, Groningen, the Netherlands. (2)Tolley Health
Economics Consultancy Ltd, Buxton, United Kingdom.

BACKGROUND: Several treatments are available for actinic keratosis (AK) on the
face and scalp. Most treatment modalities were compared to placebo and therefore
little is known on their relative efficacy.
OBJECTIVES: To compare the different treatments for mild to moderate AK on the
face and scalp available in clinical practice in Europe.
METHODS: A network meta-analysis (NMA) was performed on the outcome "complete
patient clearance". Ten treatment modalities were included: two 5-aminolaevulinic
acid photodynamic therapies (ALA-PDT), applied as gel (BF-200 ALA) or patch;
methyl-aminolevulinate photodynamic therapy (MAL-PDT); three modalities with
imiquimod (IMI), applied as a 4-week or 16-week course with 5% imiquimod, or a
2-3 week course with 3.75% imiquimod; cryotherapy; diclofenac 3% in 2.5%
hyaluronic acid; 0.5% 5-fluorouracil (5-FU); and ingenol mebutate (IMB). The only
data available for 5% 5-FU was from one small study and was determined to be too
limited to be reliably included in the analysis. For BF-200 ALA and MAL-PDT, data
from illumination with narrow-band lights were selected as these are typically
used in clinical practice. The NMA was performed with a random-effects Bayesian
model.
RESULTS: 25 trials on 5,562 patients were included in the NMA. All active
treatments were significantly better than placebo. BF-200 ALA showed the highest
efficacy compared to placebo to achieve total patient clearance. BF-200 ALA had
the highest probability to be the best treatment and the highest SUCRA score
(64.8% and 92.1%), followed by IMI 5% 4 weeks (10.1% and 74.2%) and 5-FU 0.5%
(7.2% and 66.8%).
CONCLUSIONS: This NMA showed that BF-200 ALA, using narrow-band lights, was the
most efficacious treatment for mild to moderate AK on the face and scalp. This
analysis is relevant for clinical decision making and health technology
assessment, assisting the improved management of AK.

PMCID: PMC4043670
PMID: 24892649  [PubMed - indexed for MEDLINE]


93. PLoS One. 2014 Feb 13;9(2):e88440. doi: 10.1371/journal.pone.0088440. eCollection
2014.

Efficacy and safety of therapies for acute ischemic stroke in China: a network
meta-analysis of 13289 patients from 145 randomized controlled trials.

Yang B(1), Shi J(1), Chen X(1), Ma B(1), Sun H(1).

Author information:
(1)Department of Clinical Epidemiology, Institute of Cardiovascular Diseases and
Center of Evidence Based Medicine, The First Affiliated Hospital, China Medical
University, Shenyang, China.

BACKGROUND: Many of these therapies have been compared against placebos, but have
not been directly compared against each other. To evaluate the efficacy and
safety of several commonly used drugs for AIS directly or indirectly.
METHODS: A systematic literature review was performed to identify randomized
controlled trials (RCTs) published prior to April 2013 for AIS therapies. The
primary outcome measures were the National Institutes of Health Stroke Scale
(NIHSS) scores and the clinical effective rate. A fixed-effects meta-analysis and
meta-regression are performed; lastly, performed a mixed treatment comparison was
performed through the Bayesian methods.
RESULTS: Outcome of efficacy of therapies for acute ischemic stroke are as
followed: All of the therapies mentioned above yielded results a more effective
result than placebo, Sodium ozagrel (RR 3.86, 95%CI 3.18-4.61); Sodium ozagrel +
edaravone (RR 9.60, 95%CI 7.04-13.06); Edaravone (RR 4.07, 95%CI 3.30-5.01);
Edaravone + Kininogenase (RR 15.33, 95%CI 10.03-23.05). The significant
difference in efficacy between edaravone monotherapy and Sodium ozagrel +
edaravone was evident (RR 0.43, 95%CI 0.08-0.61) and was also significant between
efficacy of edaravone + Kininogenase and Sodium ozagrel (RR 4.00, 95%CI
2.47-6.24). The differences between the risk and benefit were not significant
when comparing Sodium ozagrel and edaravone or edaravone + Kininogenase and
Sodium ozagrel + Edaravone for AIS. Outcome of the defect of neurological
function: Placebo served a significant difference in treating the defects of
neurological function compared with Sodium ozagrel (WMD = -3.11, 95%CI -4.43 to
-1.79), Sodium ozagrel + edaravone (WMD = -6.25, 95%CI -7.96 to -4.54) and
Edaravone + Kininogenase (WMD =  -3.47, 95%CI -5.73 to -1.21).
CONCLUSIONS: It provides that the efficacy of edaravone monotherapy in treatment
was not more effective than Sodium ozagrel + edaravone.The efficacy of edaravone
+ Kininogenase monotherapy in treatment was more effective than Sodium ozagrel.
Edaravone + Kininogenase and Sodium ozagrel + Edaravone appeared the most
effective treatments. And Sodium ozagrel, Sodium ozagrel + edaravone, Edaravone +
Kininogenase can improve the nerve dysfunction.

PMCID: PMC3923787
PMID: 24551100  [PubMed - indexed for MEDLINE]


94. PLoS One. 2014 Feb 12;9(2):e85245. doi: 10.1371/journal.pone.0085245. eCollection
2014.

Network meta-analysis of erlotinib, gefitinib, afatinib and icotinib in patients
with advanced non-small-cell lung cancer harboring EGFR mutations.

Liang W(1), Wu X(1), Fang W(1), Zhao Y(1), Yang Y(1), Hu Z(1), Xue C(1), Zhang
J(1), Zhang J(1), Ma Y(1), Zhou T(1), Yan Y(1), Hou X(1), Qin T(1), Dinglin X(1),
Tian Y(1), Huang P(1), Huang Y(1), Zhao H(1), Zhang L(1).

Author information:
(1)State Key Laboratory of Oncology in South China, Collaborative Innovation
Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou,
Guangdong, China.

BACKGROUND: Several EGFR-tyrosine kinase inhibitors (EGFR-TKIs) including
erlotinib, gefitinib, afatinib and icotinib are currently available as treatment
for patients with advanced non-small-cell lung cancer (NSCLC) who harbor EGFR
mutations. However, no head to head trials between these TKIs in mutated
populations have been reported, which provides room for indirect and integrated
comparisons.
METHODS: We searched electronic databases for eligible literatures. Pooled data
on objective response rate (ORR), progression free survival (PFS), overall
survival (OS) were calculated. Appropriate networks for different outcomes were
established to incorporate all evidences. Multiple-treatments comparisons (MTCs)
based on Bayesian network integrated the efficacy and specific toxicities of all
included treatments.
RESULTS: Twelve phase III RCTs that investigated EGFR-TKIs involving 1821
participants with EGFR mutation were included. For mutant patients, the weighted
pooled ORR and 1-year PFS of EGFR-TKIs were significant superior to that of
standard chemotherapy (ORR: 66.6% vs. 30.9%, OR 5.46, 95%CI 3.59 to 8.30,
P<0.00001; 1-year PFS: 42.9% vs. 9.7%, OR 7.83, 95%CI 4.50 to 13.61; P<0.00001)
through direct meta-analysis. In the network meta-analyses, no statistically
significant differences in efficacy were found between these four TKIs with
respect to all outcome measures. Trend analyses of rank probabilities revealed
that the cumulative probabilities of being the most efficacious treatments were
(ORR, 1-year PFS, 1-year OS, 2-year OS): erlotinib (51%, 38%, 14%, 19%),
gefitinib (1%, 6%, 5%, 16%), afatinib (29%, 27%, 30%, 27%) and icotinib (19%,
29%, NA, NA), respectively. However, afatinib and erlotinib showed significant
severer rash and diarrhea compared with gefitinib and icotinib.
CONCLUSIONS: The current study indicated that erlotinib, gefitinib, afatinib and
icotinib shared equivalent efficacy but presented different efficacy-toxicity
pattern for EGFR-mutated patients. Erlotinib and afatinib revealed potentially
better efficacy but significant higher toxicities compared with gefitinib and
icotinib.

PMCID: PMC3922700
PMID: 24533047  [PubMed - indexed for MEDLINE]


95. PLoS One. 2014 Jan 23;9(1):e86136. doi: 10.1371/journal.pone.0086136. eCollection
2014.

Age-dependent prevalence of nasopharyngeal carriage of streptococcus pneumoniae
before conjugate vaccine introduction: a prediction model based on a
meta-analysis.

Le Polain de Waroux O(1), Flasche S(1), Prieto-Merino D(2), Edmunds WJ(1).

Author information:
(1)Department of Infectious Disease Epidemiology, London School of Hygiene and
Tropical Medicine, London, United Kingdom. (2)Department of Medical Statistics,
London School of Hygiene and Tropical Medicine, London, United Kingdom.

INTRODUCTION: Data on the prevalence of nasopharyngeal carriage of S.pneumoniae
in all age groups are important to help predict the impact of introducing
pneumococcal conjugate vaccines (PCV) into routine infant immunization, given the
important indirect effect of the vaccine. Yet most carriage studies are limited
to children under five years of age. We here explore the association between
carriage prevalence and serotype distribution in children aged ≥5 years and in
adults compared to children.
METHODS: We conducted a systematic review of studies providing carriage estimates
across age groups in healthy populations not previously exposed to PCV, using
MEDLINE and Embase. We used Bayesian linear meta-regression models to predict the
overall carriage prevalence as well as the prevalence and distribution of vaccine
and nonvaccine type (VT and NVT) serotypes in older age groups as a function of
that in <5 y olds.
RESULTS: Twenty-nine studies compromising of 20,391 individuals were included in
the analysis. In all studies nasopharyngeal carriage decreased with increasing
age. We found a strong positive linear association between the carriage
prevalence in pre-school childen (<5 y) and both that in school aged children
(5-17 y olds) and in adults. The proportion of VT serotypes isolated from
carriers was consistently lower in older age groups and on average about 73% that
of children <5 y among 5-17 y olds and adults respectively. We provide a
prediction model to infer the carriage prevalence and serotype distribution in
5-17 y olds and adults as a function of that in children <5 years of age.
CONCLUSION: Such predictions are helpful for assessing the potential
population-wide effects of vaccination programmes, e.g. via transmission models,
and thus assist in the design of future pneumococcal conjugate vaccination
strategies.

PMCID: PMC3900487
PMID: 24465920  [PubMed - indexed for MEDLINE]


96. Stat Med. 2013 Dec 30;32(30):5398-413. doi: 10.1002/sim.5959. Epub 2013 Sep 4.

Bayesian meta-analysis of diagnostic tests allowing for imperfect reference
standards.

Menten J(1), Boelaert M, Lesaffre E.

Author information:
(1)Clinical Trials Unit, Institute of Tropical Medicine, Antwerp, Belgium;
L-Biostat, KULeuven, Leuven, Belgium.

There is an increasing interest in meta-analyses of rapid diagnostic tests (RDTs)
for infectious diseases. To avoid spectrum bias, these meta-analyses should focus
on phase IV studies performed in the target population. For many infectious
diseases, these target populations attend primary health care centers in
resource-constrained settings where it is difficult to perform gold standard
diagnostic tests. As a consequence, phase IV diagnostic studies often use
imperfect reference standards, which may result in biased meta-analyses of the
diagnostic accuracy of novel RDTs. We extend the standard bivariate model for the
meta-analysis of diagnostic studies to correct for differing and imperfect
reference standards in the primary studies and to accommodate data from studies
that try to overcome the absence of a true gold standard through the use of
latent class analysis. Using Bayesian methods, improved estimates of sensitivity
and specificity are possible, especially when prior information is available on
the diagnostic accuracy of the reference test. In this analysis, the deviance
information criterion can be used to detect conflicts between the prior
information and observed data. When applying the model to a dataset of the
diagnostic accuracy of an RDT for visceral leishmaniasis, the standard
meta-analytic methods appeared to underestimate the specificity of the RDT.

Copyright © 2013 John Wiley & Sons, Ltd.

PMID: 24003003  [PubMed - indexed for MEDLINE]


97. Aliment Pharmacol Ther. 2013 Dec;38(11-12):1325-37. doi: 10.1111/apt.12534. Epub
2013 Oct 20.

Systematic review with network meta-analysis: pharmacological prophylaxis against
post-ERCP pancreatitis.

Akshintala VS(1), Hutfless SM, Colantuoni E, Kim KJ, Khashab MA, Li T, Elmunzer
BJ, Puhan MA, Sinha A, Kamal A, Lennon AM, Okolo PI, Palakurthy MK, Kalloo AN,
Singh VK.

Author information:
(1)Division of Gastroenterology, Johns Hopkins Medical Institutions, Baltimore,
MD, USA.

BACKGROUND: The efficacy of many pharmacological agents for preventing post-ERCP
pancreatitis (PEP) has been evaluated in randomised controlled trials (RCTs), but
it is unclear which agent(s) should be used in clinical practice. Network
meta-analyses of RCTs are used to simultaneously compare several agents to
determine their relative efficacy and identify priority agents for comparison in
future RCTs.
AIM: To evaluate pharmacological agents for the prevention of PEP by conducting a
network meta-analysis of RCTs.
METHODS: We searched MEDLINE, EMBASE and Cochrane Library databases for RCTs that
evaluated the efficacy of agents for preventing PEP. RCTs were simultaneously
analysed using random-effects network meta-analysis under the Bayesian framework
to identify the best agents. The efficacy of agents was ordered according to the
probability of being ranked as any of the top three best performing agents.
RESULTS: The network meta-analysis included 99 RCTs evaluating 16 agents in 25
313 patients. Topical epinephrine (adrenaline) was the most efficacious agent
with 85.9% probability of ranking among the top three agents, followed by
nafamostat (51.4%), antibiotics (44.5%) and NSAIDs (42.8%). However, in a
sensitivity analysis including only rectal NSAIDs, NSAIDs moved from fourth rank
to second (58.1%). Patients receiving topical epinephrine, compared with placebo,
had a 75% reduced risk of PEP (OR 0.25, 95% probability interval 0.06-0.66).
CONCLUSIONS: Topical epinephrine and rectal NSAIDs are the most efficacious
agents for preventing post-ERCP pancreatitis, based on existing RCTs.
Combinations of these agents, which act on different steps in the pathogenesis of
post-ERCP pancreatitis, should be evaluated in future trials.

© 2013 John Wiley & Sons Ltd.

PMID: 24138390  [PubMed - indexed for MEDLINE]


98. Br J Anaesth. 2013 Dec;111(6):886-96. doi: 10.1093/bja/aet231. Epub 2013 Jul 12.

Anaesthetic drugs and survival: a Bayesian network meta-analysis of randomized
trials in cardiac surgery.

Landoni G(1), Greco T, Biondi-Zoccai G, Nigro Neto C, Febres D, Pintaudi M, Pasin
L, Cabrini L, Finco G, Zangrillo A.

Author information:
(1)Anesthesia and Intensive Care Department, San Raffaele Scientific Institute,
Milan, Italy.

BACKGROUND: Many studies have compared desflurane, isoflurane, sevoflurane, total
i.v. anaesthesia (TIVA), or all in cardiac surgery to assess their effects on
patient survival.
METHODS: We performed standard pairwise and Bayesian network meta-analyses; the
latter allows indirect assessments if any of the anaesthetic agents were not
compared in head-to-head trials. Pertinent studies were identified using
BioMedCentral, MEDLINE/PubMed, Embase, and the Cochrane Library (last updated in
June 2012).
RESULTS: We identified 38 randomized trials with survival data published between
1991 and 2012, with most studies (63%) done in coronary artery bypass grafting
(CABG) patients with standard cardiopulmonary bypass. Standard meta-analysis
showed that the use of a volatile agent was associated with a reduction in
mortality when compared with TIVA at the longest follow-up available [25/1994
(1.3%) in the volatile group vs 43/1648 (2.6%) in the TIVA arm, odds ratio
(OR)=0.51, 95% confidence interval (CI) 0.33-0.81, P-value for effect=0.004,
number needed to treat 74, I(2)=0%] with results confirmed in trials with low
risk of bias, in large trials, and when including only CABG studies. Bayesian
network meta-analysis showed that sevoflurane (OR=0.31, 95% credible interval
0.14-0.64) and desflurane (OR=0.43, 95% credible interval 0.21-0.82) were
individually associated with a reduction in mortality when compared with TIVA.
CONCLUSIONS: Anaesthesia with volatile agents appears to reduce mortality after
cardiac surgery when compared with TIVA, especially when sevoflurane or
desflurane is used. A large, multicentre trial is warranted to confirm that
long-term survival is significantly affected by the choice of anaesthetic.

PMID: 23852263  [PubMed - indexed for MEDLINE]


99. JAMA Neurol. 2013 Dec;70(12):1486-90. doi: 10.1001/jamaneurol.2013.4021.

New oral anticoagulants and the risk of intracranial hemorrhage: traditional and
Bayesian meta-analysis and mixed treatment comparison of randomized trials of new
oral anticoagulants in atrial fibrillation.

Chatterjee S(1), Sardar P(2), Biondi-Zoccai G(3), Kumbhani DJ(4).

Author information:
(1)Division of Cardiology, Brown University, Providence, Rhode Island.
(2)Department of Medicine, New York Medical College-Metropolitan Hospital Center,
New York. (3)Department of Medico-Surgical Sciences and Biotechnologies, Sapienza
University of Rome, Latina, Italy. (4)Division of Cardiology, University of Texas
Southwestern Medical Center, Dallas.

Comment in
    JAMA Neurol. 2014 Mar;71(3):370-1.
    JAMA Neurol. 2014 Mar;71(3):371-2.
    JAMA. 2014 Dec 17;312(23):2562-3.
    JAMA Neurol. 2013 Dec;70(12):1483-4.
    Eur J Clin Pharmacol. 2014 Apr;70(4):505-6.
    JAMA Neurol. 2014 Mar;71(3):369-70.

IMPORTANCE: Randomized studies have shown a decreased risk of intracranial
hemorrhage (ICH) with use of novel oral anticoagulants (NOACs). However, it is
unclear whether the magnitude of benefit is similar for all NOACs currently
available.
OBJECTIVE: To perform a systematic review and meta-analysis to quantitatively
assess the rates of ICH within the framework of both conventional and Bayesian
statistics.
DATA SOURCES: The MEDLINE, CENTRAL, CINAHL, and EBSCO databases, supplemented
with conference abstracts, were searched up to December 1, 2012, with no language
restriction.
STUDY SELECTION: Randomized trials comparing NOACs vs a comparator and reporting
on ICH events.
DATA EXTRACTION AND SYNTHESIS: The NOACs were pooled to perform a comparison with
all comparators and among themselves in both traditional frequentist and Bayesian
random-effects models using vague priors and Markov chain Monte Carlo simulation
with Gibbs sampling, calculating pooled odds ratios and associated 95% confidence
intervals as well as numbers needed to treat and 95% credible intervals for the
Bayesian analysis.
MAIN OUTCOMES AND MEASURES: Intracranial hemorrhage events associated with NOACs
in comparison with comparators, expressed as odds ratios.
RESULTS: Six studies (1 administering dabigatran etexilate mesylate, 2
administering rivaroxaban, and 3 administering apixaban) enrolling a total of
57,491 patients were included for analysis. The NOACs significantly reduced the
risk of ICH against all comparators (odds ratio = 0.49; 95% CI, 0.36-0.65). Each
of the 3 drugs reduced the risk of ICH, with Bayesian indirect comparison
analysis not revealing a significant credible difference between the specific
medications.
CONCLUSIONS AND RELEVANCE: Novel oral anticoagulants are uniformly associated
with an overall reduced risk of ICH when used for stroke prevention in atrial
fibrillation. Any of the currently available NOACs can be considered first line
for patients at high risk for ICH.

PMID: 24166666  [PubMed - indexed for MEDLINE]


100. Langenbecks Arch Surg. 2013 Dec;398(8):1039-56. doi: 10.1007/s00423-013-1137-7.
Epub 2013 Nov 16.

ENERgized vessel sealing systems versus CONventional hemostasis techniques in
thyroid surgery--the ENERCON systematic review and network meta-analysis.

Contin P(1), Gooßen K, Grummich K, Jensen K, Schmitz-Winnenthal H, Büchler MW,
Diener MK.

Author information:
(1)Department of General-, Visceral- and Transplantation Surgery, University of
Heidelberg, Im Neuenheimer Feld 110, 69120, Heidelberg, Germany.

PURPOSE: Energized vessel-sealing systems have been proposed to save operation
time and reduce post-operative complications. The aim of the present systematic
review was to compare operation time and postoperative morbidity for ultrasonic
and electrothermal bipolar-activated devices with conventional hemostasis
techniques and with each other in open thyroidectomy.
METHODS: A systematic literature search (MEDLINE, Cochrane Library, EMBASE and
ISI Web of Science) was performed to identify randomised controlled trials (RCTs)
comparing conventional hemostasis techniques, ultrasonic devices (Harmonic®
scalpel) and/or electrothermal bipolar-activated vessel sealing systems
(Ligasure®) during open thyroidectomy. For the primary endpoint (operation time),
a network meta-analysis with Bayesian random effects model was performed.
Pairwise meta-analyses with random effects were calculated for primary and
secondary endpoints.
RESULTS: One hundred sixteen publications were evaluated for eligibility; 35 RCTs
(4,061 patients) were included. There was considerable methodological and
clinical heterogeneity of included trials. The Harmonic scalpel significantly
reduced operation time compared with conventional techniques (22.26 min, 22.7 min
in the inconsistency model). The use of Ligasure significantly reduced operation
time in total thyroidectomy (13.84 min in the consistency model, 12.18 min in the
inconsistency model). In direct comparison, operations with the Harmonic scalpel
were faster than with Ligasure (8.42 min in the consistency model, 2.45 min in
the inconsistency model). The rates of recurrent nerve palsy and postoperative
hypocalcaemia did not significantly differ in the intervention groups.
CONCLUSIONS: This meta-analysis shows superiority of ultrasonic devices in terms
of operation time compared with conventional hemostasis techniques in thyroid
surgery, with no detriment to safety outcomes.

PMID: 24240627  [PubMed - indexed for MEDLINE]


101. BMC Med. 2013 Nov 8;11:239. doi: 10.1186/1741-7015-11-239.

Diagnostic indicators of non-cardiovascular chest pain: a systematic review and
meta-analysis.

Wertli MM(1), Ruchti KB, Steurer J, Held U.

Author information:
(1)Horten Center for Patient Oriented Research and Knowledge Transfer, Department
of Internal Medicine, University of Zurich, Pestalozzistrasse 24, CH-8032,
Zurich, Switzerland. Maria.Wertli@usz.ch.

BACKGROUND: Non-cardiovascular chest pain (NCCP) has a high healthcare cost, but
insufficient guidelines exist for its diagnostic investigation. The objective of
the present work was to identify important diagnostic indicators and their
accuracy for specific and non-specific conditions underlying NCCP.
METHODS: A systematic review and meta-analysis were performed. In May 2012, six
databases were searched. Hand and bibliography searches were also conducted.
Studies evaluating a diagnostic test against a reference test in patients with
NCCP were included. Exclusion criteria were having <30 patients per group, and
evaluating diagnostic tests for acute cardiovascular disease. Diagnostic accuracy
is given in likelihood ratios (LR): very good (LR+ >10, LR- <0.1); good (LR + 5
to 10, LR- 0.1 to 0.2); fair (LR + 2 to 5, LR- 0.2 to 0.5); or poor (LR + 1 to 2,
LR- 0.5 to 1). Joined meta-analysis of the diagnostic test sensitivity and
specificity was performed by applying a hierarchical Bayesian model.
RESULTS: Out of 6,316 records, 260 were reviewed in full text, and 28 were
included: 20 investigating gastroesophageal reflux disorders (GERD), 3
musculoskeletal chest pain, and 5 psychiatric conditions. Study quality was good
in 15 studies and moderate in 13. GERD diagnosis was more likely with typical
GERD symptoms (LR + 2.70 and 2.75, LR- 0.42 and 0.78) than atypical GERD symptoms
(LR + 0.49, LR- 2.71). GERD was also more likely with a positive response to a
proton pump inhibitor (PPI) test (LR + 5.48, 7.13, and 8.56; LR- 0.24, 0.25, and
0.28); the posterior mean sensitivity and specificity of six studies were 0.89
(95% credible interval, 0.28 to 1) and 0.88 (95% credible interval, 0.26 to 1),
respectively. Panic and anxiety screening scores can identify individuals
requiring further testing for anxiety or panic disorders. Clinical findings in
musculoskeletal pain either had a fair to moderate LR + and a poor LR- or vice
versa.
CONCLUSIONS: In patients with NCCP, thorough clinical evaluation of the patient's
history, symptoms, and clinical findings can indicate the most appropriate
diagnostic tests. Treatment response to high-dose PPI treatment provides
important information regarding GERD, and should be considered early. Panic and
anxiety disorders are often undiagnosed and should be considered in the
differential diagnosis of chest pain.

PMCID: PMC4226211
PMID: 24207111  [PubMed - indexed for MEDLINE]


102. BMJ. 2013 Nov 6;347:f6530. doi: 10.1136/bmj.f6530.

Safety and efficacy outcomes of first and second generation durable polymer drug
eluting stents and biodegradable polymer biolimus eluting stents in clinical
practice: comprehensive network meta-analysis.

Navarese EP(1), Tandjung K, Claessen B, Andreotti F, Kowalewski M, Kandzari DE,
Kereiakes DJ, Waksman R, Mauri L, Meredith IT, Finn AV, Kim HS, Kubica J,
Suryapranata H, Aprami TM, Di Pasquale G, von Birgelen C, Kedhi E.

Author information:
(1)Department of Cardiology and Internal Medicine, Ludwik Rydygier Collegium
Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.

Comment in
    Nat Rev Cardiol. 2014 Jan;11(1):6.

OBJECTIVES: To investigate the safety and efficacy of durable polymer drug
eluting stents (DES) and biodegradable polymer biolimus eluting stents
(biolimus-ES).
DESIGN: Network meta-analysis of randomised controlled trials.
DATA SOURCES AND STUDY SELECTION: Medline, Google Scholar, Embase, and Cochrane
Central Register of Controlled Trials (CENTRAL) database search for randomised
controlled trials comparing at least two of durable polymer sirolimus eluting
stents (sirolimus-ES) and paclitaxel eluting stents (paclitaxel-ES), newer
durable polymer everolimus eluting stents (everolimus-ES), Endeavor and Resolute
zotarolimus eluting stents (zotarolimus-ES), and biodegradable polymer
biolimus-ES.
PRIMARY OUTCOMES: Safety (death, myocardial infarction, definite or probable
stent thrombosis) and efficacy (target lesion and target vessel
revascularisation) assessed at up to one year and beyond.
RESULTS: 60 randomised controlled trials were compared involving 63,242 patients
with stable coronary artery disease or acute coronary syndrome treated with a
DES. At one year, there were no differences in mortality among devices. Resolute
and Endeavor zotarolimus-ES, everolimus-ES, and sirolimus-ES, but not
biodegradable polymer biolimus-ES, were associated with significantly reduced
odds of myocardial infarction (by 29-34%) compared with paclitaxel-ES. Compared
with everolimus-ES, biodegradable polymer biolimus-ES were associated with
significantly increased odds of myocardial infarction (by 29%), while Endeavor
zotarolimus-ES and paclitaxel-ES were associated with significantly increased
odds of stent thrombosis. All investigated DES were similar with regards to
efficacy endpoints, except for Endeavor zotarolimus-ES and paclitaxel-ES, which
were associated with significantly increased the odds of target lesion and target
vessel revascularisations compared with other devices. Direction of results
beyond one year did not diverge from the findings for up to one year follow-up.
Bayesian probability curves showed a gradient in the magnitude of effect, with
everolimus-ES and Resolute zotarolimus-ES offering the highest safety profiles.
CONCLUSIONS: The newer durable polymer everolimus-ES and Resolute zotarolimus-ES
and the biodegradable polymer biolimus-ES maintain the efficacy of sirolimus-ES;
however, for safety endpoints, differences become apparent, with everolimus-ES
and Resolute zotarolimus-ES emerging as the safest stents to date.

PMCID: PMC3819044
PMID: 24196498  [PubMed - indexed for MEDLINE]


103. Intensive Care Med. 2013 Nov;39(11):1896-908. doi: 10.1007/s00134-013-3030-9.
Epub 2013 Aug 9.

Safety of off-label erythropoiesis stimulating agents in critically ill patients:
a meta-analysis.

Mesgarpour B(1), Heidinger BH, Schwameis M, Kienbacher C, Walsh C, Schmitz S,
Herkner H.

Author information:
(1)Department of Emergency Medicine, General Hospital, Medical University of
Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.

PURPOSE: Erythropoiesis stimulating agents (ESAs) are used to treat anemia in
critically ill patients. This indication is off-label, because it is not licensed
by regulatory authorities. Recently ESAs were suspected to harm critically ill
patients. Our objective was to assess the safety of ESAs in off-label indications
in critically ill patients.
METHODS: Eleven databases were searched up to April 2012. We considered
randomized controlled trials (RCTs) and controlled observational studies in any
language that compared off-label ESAs treatment with other effective
interventions, placebo or no treatment in critically ill patients. Two authors
independently screened and evaluated retrieved records, extracted data and
assessed risk of bias and quality of reporting.
RESULTS: We used frequentist and Bayesian models to combine studies, and
performed sensitivity and subgroup analyses. From 12,888 citations, we included
48 studies (34 RCTs; 14 observational), involving 944,856 participants. Harm
reporting was of medium to low quality. There was no statistically significant
increased risk of adverse events in general, serious adverse events, the most
frequently reported adverse events, and death in critically ill patients treated
with ESAs. These results were robust against risk of bias and analysis methods.
There is evidence that ESAs increase the risk of clinically relevant thrombotic
vascular events, and there is some less certain evidence that ESAs might increase
the risk for venous thromboembolism.
CONCLUSIONS: In critically ill patients, administration of ESAs is associated
with a significant increase in clinically relevant thrombotic vascular events but
not with other frequently reported adverse events and death.

PMID: 23928897  [PubMed - indexed for MEDLINE]


104. J Am Coll Surg. 2013 Nov;217(5):788-801.e1-4. doi:
10.1016/j.jamcollsurg.2013.07.386. Epub 2013 Sep 13.

Antibiotic prophylaxis for the prevention of surgical site infection after
tension-free hernia repair: a Bayesian and frequentist meta-analysis.

Mazaki T(1), Mado K, Masuda H, Shiono M.

Author information:
(1)Department of Surgery, Nihon University School of Medicine, Tokyo, Japan.
Electronic address: mazaki.takero@nihon-u.ac.jp.

BACKGROUND: Efficacy of antibiotic prophylaxis for the prevention of surgical
site infection (SSI) after open tension-free hernia repair remains controversial.
In light of additional data, the aim of this study was to determine whether
antibiotic prophylaxis reduces SSI after hernia repair.
STUDY DESIGN: We conducted a systematic review and meta-analysis to identify
randomized controlled trials comparing antibiotic prophylaxis and the subsequent
incidence of SSI after inguinal or femoral hernia repair. The primary outcomes
measure was the incidence of SSI. Subgroup analysis was evaluated by stratifying
the categories of SSI. The meta-analysis was performed using Bayesian and
frequentist methods.
RESULTS: Twelve studies were included in this meta-analysis; 1,902 patients
received antibiotic prophylaxis and the other 1,936 patients were allocated to
the control group. Incidence of SSI was 47 (pooled rate 3.0%) in the antibiotic
group and 91 (6.0%) in the control group. The number needed to treat to prevent 1
episode of SSI is 41. The Bayesian meta-analysis yielded a significant reduction
of SSI in the antibiotic group (odds ratio = 0.49; 95% credible interval
0.25-0.81). Subgroup analysis showed that an antibiotic prophylaxis was
beneficial for the prevention of superficial SSI (odds ratio = 0.40; 95% credible
interval 0.12-0.98), but not beneficial for prevention of deep SSI (odds ratio =
0.59; 95% credible interval 0.11-3.20). Also, the results were similar to those
with frequentist methods.
CONCLUSIONS: This meta-analysis suggests that antibiotic prophylaxis is
efficacious for the prevention of SSI after open mesh hernia repair.

Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All
rights reserved.

PMID: 24041559  [PubMed - indexed for MEDLINE]


105. Nutr Metab Cardiovasc Dis. 2013 Nov;23(11):1043-9. doi:
10.1016/j.numecd.2013.05.001. Epub 2013 Oct 5.

The SH2B1 obesity locus and abnormal glucose homeostasis: lack of evidence for
association from a meta-analysis in individuals of European ancestry.

Prudente S(1), Copetti M, Morini E, Mendonca C, Andreozzi F, Chandalia M, Baratta
R; DIAGRAM consortium, Pellegrini F, Mercuri L, Bailetti D, Abate N, Frittitta L,
Sesti G, Florez JC, Doria A, Trischitta V.

Collaborators: Voight BF, Scott LJ, Steinthorsdottir V, Morris AP, Dina C, Welch
RP, Zeggini E, Huth C, Aulchenko YS, Thorleifsson G, Mcculloch LJ, Ferreira T,
Grallert H, Amin N, Wu G, Willer CJ, Raychaudhuri S, Mccarroll SA, Langenberg C,
Hofmann OM, Dupuis J, Qi L, Segrè AV, van Hoek M, Navarro P, Ardlie K, Balkau B,
Benediktsson R, Bennett AJ, Blagieva R, Boerwinkle E, Bonnycastle LL, Boström KB,
Bravenboer B, Bumpstead S, Burtt NP, Charpentier G, Chines PS, Cornelis M, Couper
DJ, Crawford G, Doney AS, Elliott KS, Elliott AL, Erdos MR, Fox CS, Franklin CS,
Ganser M, Gieger C, Grarup N, Green T, Griffin S, Groves CJ, Guiducci C, Hadjadj
S, Hassanali N, Herder C, Isomaa B, Jackson AU, Johnson PR, Jørgensen T, Kao WH,
Klopp N, Kong A, Kraft P, Kuusisto J, Lauritzen T, Li M, Lieverse A, Lindgren CM,
Lyssenko V, Marre M, Meitinger T, Midthjell K, Morken MA, Narisu N, Nilsson P,
Owen KR, Payne F, Perry JR, Petersen AK, Platou C, Proença C, Prokopenko I,
Rathmann W, Rayner NW, Robertson NR, Rocheleau G, Roden M, Sampson MJ, Saxena R,
Shields BM, Shrader P, Sigurdsson G, Sparsø T, Strassburger K, Stringham HM, Sun
Q, Swift AJ, Thorand B, Tichet J, Tuomi T, van Dam RM, van Haeften TW, van Herpt
T, van Vliet-Ostaptchouk JV, Walters GB, Weedon MN, Wijmenga C, Witteman J,
Bergman RN, Cauchi S, Collins FS, Gloyn AL, Gyllensten U, Hansen T, Hide WA,
Hitman GA, Hofman A, Hunter DJ, Hveem K, Laakso M, Mohlke KL, Morris AD, Palmer
CN, Pramstaller PP, Rudan I, Sijbrands E, Stein LD, Tuomilehto J, Uitterlinden A,
Walker M, Wareham NJ, Watanabe RM, Abecasis GR, Boehm BO, Campbell H, Daly MJ,
Hattersley AT, Hu FB, Meigs JB, Pankow JS, Pedersen O, Wichmann HE, Barroso I,
Florez JC, Frayling TM, Groop L, Sladek R, Wilson JF, Illig T, Froguel P, van
duijn CM, Stefansson K, Altshuler D, Boehnke M, Mccarthy MI.

BACKGROUND/AIMS: The development of type 2 diabetes (T2D) is influenced both by
environmental and by genetic determinants. Obesity is an important risk factor
for T2D, mostly mediated by obesity-related insulin resistance. Obesity and
insulin resistance are also modulated by the genetic milieu; thus, genes
affecting risk of obesity and insulin resistance might also modulate risk of T2D.
Recently, 32 loci have been associated with body mass index (BMI) by genome-wide
studies, including one locus on chromosome 16p11 containing the SH2B1 gene.
Animal studies have suggested that SH2B1 is a physiological enhancer of the
insulin receptor and humans with rare deletions or mutations at SH2B1 are obese
with a disproportionately high insulin resistance. Thus, the role of SH2B1 in
both obesity and insulin resistance makes it a strong candidate for T2D. However,
published data on the role of SH2B1 variability on the risk for T2D are
conflicting, ranging from no effect at all to a robust association.
METHODS: The SH2B1 tag SNP rs4788102 (SNP, single nucleotide polymorphism) was
genotyped in 6978 individuals from six studies for abnormal glucose homeostasis
(AGH), including impaired fasting glucose, impaired glucose tolerance or T2D,
from the GENetics of Type 2 Diabetes in Italy and the United States (GENIUS T2D)
consortium. Data from these studies were then meta-analyzed, in a Bayesian
fashion, with those from DIAGRAM+ (n = 47,117) and four other published studies
(n = 39,448).
RESULTS: Variability at the SH2B1 obesity locus was not associated with AGH
either in the GENIUS consortium (overall odds ratio (OR) = 0.96; 0.89-1.04) or in
the meta-analysis (OR = 1.01; 0.98-1.05).
CONCLUSION: Our data exclude a role for the SH2B1 obesity locus in the modulation
of AGH.

Copyright © 2013 Elsevier B.V. All rights reserved.

PMID: 24103803  [PubMed - indexed for MEDLINE]


106. BMJ. 2013 Oct 24;347:f6008. doi: 10.1136/bmj.f6008.

Comparative effectiveness of renin-angiotensin system blockers and other
antihypertensive drugs in patients with diabetes: systematic review and bayesian
network meta-analysis.

Wu HY(1), Huang JW, Lin HJ, Liao WC, Peng YS, Hung KY, Wu KD, Tu YK, Chien KL.

Author information:
(1)Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei
City, Taiwan.

OBJECTIVE: To assess the effects of different classes of antihypertensive
treatments, including monotherapy and combination therapy, on survival and major
renal outcomes in patients with diabetes.
DESIGN: Systematic review and bayesian network meta-analysis of randomised
clinical trials.
DATA SOURCES: Electronic literature search of PubMed, Medline, Scopus, and the
Cochrane Library for studies published up to December 2011.
STUDY SELECTION: Randomised clinical trials of antihypertensive therapy
(angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers
(ARBs), α blockers, β blockers, calcium channel blockers, diuretics, and their
combinations) in patients with diabetes with a follow-up of at least 12 months,
reporting all cause mortality, requirement for dialysis, or doubling of serum
creatinine levels.
DATA EXTRACTION: Bayesian network meta-analysis combined direct and indirect
evidence to estimate the relative effects between treatments as well as the
probabilities of ranking for treatments based on their protective effects.
RESULTS: 63 trials with 36,917 participants were identified, including 2400
deaths, 766 patients who required dialysis, and 1099 patients whose serum
creatinine level had doubled. Compared with placebo, only ACE inhibitors
significantly reduced the doubling of serum creatinine levels (odds ratio 0.58,
95% credible interval 0.32 to 0.90), and only β blockers showed a significant
difference in mortality (odds ratio 7.13, 95% credible interval 1.37 to 41.39).
Comparisons among all treatments showed no statistical significance in the
outcome of dialysis. Although the beneficial effects of ACE inhibitors compared
with ARBs did not reach statistical significance, ACE inhibitors consistently
showed higher probabilities of being in the superior ranking positions among all
three outcomes. Although the protective effect of an ACE inhibitor plus calcium
channel blocker compared with placebo was not statistically significant, the
treatment ranking identified this combination therapy to have the greatest
probability (73.9%) for being the best treatment on reducing mortality, followed
by ACE inhibitor plus diuretic (12.5%), ACE inhibitors (2.0%), calcium channel
blockers (1.2%), and ARBs (0.4%).
CONCLUSIONS: Our analyses show the renoprotective effects and superiority of
using ACE inhibitors in patients with diabetes, and available evidence is not
able to show a better effect for ARBs compared with ACE inhibitors. Considering
the cost of drugs, our findings support the use of ACE inhibitors as the first
line antihypertensive agent in patients with diabetes. Calcium channel blockers
might be the preferred treatment in combination with ACE inhibitors if adequate
blood pressure control cannot be achieved by ACE inhibitors alone.

PMCID: PMC3807847
PMID: 24157497  [PubMed - indexed for MEDLINE]


107. Int J Cardiol. 2013 Oct 12;168(5):4931-4. doi: 10.1016/j.ijcard.2013.07.087. Epub
2013 Aug 2.

Can we predict which patients with ST-elevation myocardial infarction benefit
most from radial access? Evidence from frequentist and Bayesian meta-regressions
of randomized trials.

Biondi-Zoccai G(1), D'Ascenzo F, Mancone M, Romagnoli E, Agostoni P, Abbate A,
Sardella G, Frati G.

Author information:
(1)Department of Medico-Surgical Sciences and Biotechnology, Sapienza University
of Rome, Latina, Italy. Electronic address: giuseppe.biondizoccai@uniroma1.it.

PMID: 23916773  [PubMed - indexed for MEDLINE]


108. Respir Res. 2013 Oct 7;14:100. doi: 10.1186/1465-9921-14-100.

Comparative efficacy of long-acting bronchodilators for COPD: a network
meta-analysis.

Cope S(1), Donohue JF, Jansen JP, Kraemer M, Capkun-Niggli G, Baldwin M, Buckley
F, Ellis A, Jones P.

Author information:
(1)Division of Clinical Science, St George's University of London, London SW17
0RE, UK. pjones@sgul.ac.uk.

BACKGROUND: Clinicians are faced with an increasingly difficult choice regarding
the optimal bronchodilator for patients with chronic obstructive pulmonary
disease (COPD) given the number of new treatments. The objective of this study is
to evaluate the comparative efficacy of indacaterol 75/150/300 μg once daily
(OD), glycopyrronium bromide 50 μg OD, tiotropium bromide 18 μg/5 μg OD,
salmeterol 50 μg twice daily (BID), formoterol 12 μg BID, and placebo for
moderate to severe COPD.
METHODS: Forty randomized controlled trials were combined in a Bayesian network
meta-analysis. Outcomes of interest were trough and post-dose forced expiratory
volume in 1 second (FEV1), St. George's Respiratory Questionnaire (SGRQ) score
and responders (≥4 points), and Transition Dyspnea Index (TDI) score and
responders (≥1 point) at 6 months.
RESULTS: Indacaterol was associated with a higher trough FEV1 than other active
treatments (difference for indacaterol 150 μg and 300 μg versus placebo: 152 mL
(95% credible interval (CrI): 126, 179); 160 mL (95% CrI: 133, 187)) and the
greatest improvement in SGRQ score (difference for indacaterol 150 μg and 300 μg
versus placebo: -3.9 (95% CrI -5.2, -2.6); -3.6 (95% CrI -4.8, -2.3)).
Glycopyrronium and tiotropium 18 μg resulted in the next best estimates for both
outcomes with minor differences (difference for glycopyrronium versus tiotropium
for trough FEV1 and SGRQ: 18 mL (95% CrI: -16, 51); -0.55 (95% CrI: -2.04, 0.92).
CONCLUSION: In terms of trough FEV1 and SGRQ score indacaterol, glycopyrronium,
and tiotropium are expected to be the most effective bronchodilators.

PMCID: PMC4014806
PMID: 24093477  [PubMed - indexed for MEDLINE]


109. Cochrane Database Syst Rev. 2013 Oct 1;9:CD009259. doi:
10.1002/14651858.CD009259.pub2.

Flexible sigmoidoscopy versus faecal occult blood testing for colorectal cancer
screening in asymptomatic individuals.

Holme Ø, Bretthauer M, Fretheim A, Odgaard-Jensen J, Hoff G.

BACKGROUND: Colorectal cancer is the third most frequent cancer in the world. As
the sojourn time for this cancer is several years and a good prognosis is
associated with early stage diagnosis, screening has been implemented in a number
of countries. Both screening with faecal occult blood test and flexible
sigmoidoscopy have been shown to reduce mortality from colorectal cancer in
randomised controlled trials. The comparative effectiveness of these tests on
colorectal cancer mortality has, however, never been evaluated, and controversies
exist over which test to choose.
OBJECTIVES: To compare the effectiveness of screening for colorectal cancer with
flexible sigmoidoscopy to faecal occult blood testing.
SEARCH METHODS: We searched MEDLINE and EMBASE (November 16, 2012), the Cochrane
Central Register of Controlled Trials (CENTRAL) (2012, Issue 11) and reference
lists for eligible studies.
SELECTION CRITERIA: Randomised controlled trials comparing screening with
flexible sigmoidoscopy or faecal occult blood testing to each other or to no
screening. Only studies reporting mortality from colorectal cancer were included.
Faecal occult blood testing had to be repeated (annually or biennially).
DATA COLLECTION AND ANALYSIS: Data retrieval and assessment of risk of bias were
performed independently by two review authors. Standard meta-analyses using a
random-effects model were conducted for flexible sigmoidoscopy and faecal occult
blood testing (FOBT) separately and we calculated relative risks with 95%
confidence intervals (CI). We used a Bayesian approach (a contrast-based network
meta-analysis method) for indirect analyses and presented the results as
posterior median relative risk with 95% credibility intervals. We assessed the
quality of evidence using GRADE.
MAIN RESULTS: We identified nine studies comprising 338,467 individuals
randomised to screening and 405,919 individuals to the control groups. Five
studies compared flexible sigmoidoscopy to no screening and four studies compared
repetitive guaiac-based FOBT (annually and biennially) to no screening. We did
not consider that study risk of bias reduced our confidence in our results. We
did not identify any studies comparing the two screening methods directly. When
compared with no screening, colorectal cancer mortality was lower with flexible
sigmoidoscopy (relative risk 0.72; 95% CI 0.65 to 0.79, high quality evidence)
and FOBT (relative risk 0.86; 95% CI 0.80 to 0.92, high quality evidence). In the
analyses based on indirect comparison of the two screening methods, the relative
risk of dying from colorectal cancer was 0.85 (95% credibility interval 0.72 to
1.01, low quality evidence) for flexible sigmoidoscopy screening compared to
FOBT. No complications occurred after the FOBT test itself, but 0.03% of
participants suffered a major complication after follow-up. Among more than
60,000 flexible sigmoidoscopy screening procedures and almost 6000 work-up
colonoscopies, a major complication was recorded in 0.08% of participants.
Adverse event data should be interpreted with caution as the reporting of adverse
effects was incomplete.
AUTHORS' CONCLUSIONS: There is high quality evidence that both flexible
sigmoidoscopy and faecal occult blood testing reduce colorectal cancer mortality
when applied as screening tools. There is low quality indirect evidence that
screening with either approach reduces colorectal cancer deaths more than the
other. Major complications associated with screening require validation from
studies with more complete reporting of harms

PMID: 24085634  [PubMed - indexed for MEDLINE]


110. Int J Hematol. 2013 Oct;98(4):390-7. doi: 10.1007/s12185-013-1445-2. Epub 2013
Sep 21.

Evaluating the efficacy and safety of apixaban, a new oral anticoagulant, using
Bayesian meta-analysis.

Villa LA(1), Malone DC, Ross D.

Author information:
(1)Department of Pharmacy Practice and Science, The University of Arizona,
College of Pharmacy, 1295 North Martin Avenue, Tucson, AZ, 85721, USA,
villa@pharmacy.arizona.edu.

Apixaban is a direct inhibitor of factor Xa, and is a potential alternative for
the treatment of acute venous thromboembolism. This study sought to evaluate the
efficacy and safety of apixaban versus enoxaparin. A systematic search of the
literature for randomized controlled trials of apixaban thromboprophylaxis versus
enoxaparin was conducted using three databases: PubMed, EMBASE, and the Cochrane
library. Five studies that included a total of 12,938 patients were analyzed
using Bayesian random-effects meta-analysis. To evaluate efficacy, a composite of
venous thromboembolism and death during follow-up was measured. To evaluate
safety, major and total bleeding events were considered. The odds ratio (OR) for
the composite outcome of efficacy was 0.66 (95 % CI 0.33-1.29) for apixaban
compared to enoxaparin, while there was a similar risk of major bleeding (OR
1.03, 95 % CI 0.36-3.73) and total bleeding (OR 0.92, 95 % CI 0.64-1.20). These
results suggest a lack of clear superiority of apixaban relative to enoxaparin.
Apixaban is an oral alternative with similar efficacy and safety to existing
anticoagulant therapies.

PMID: 24057162  [PubMed - indexed for MEDLINE]




112. BMJ. 2013 Sep 20;347:f5555. doi: 10.1136/bmj.f5555.

Exercise for lower limb osteoarthritis: systematic review incorporating trial
sequential analysis and network meta-analysis.

Uthman OA(1), van der Windt DA, Jordan JL, Dziedzic KS, Healey EL, Peat GM,
Foster NE.

Author information:
(1)Arthritis Research UK Primary Care Centre, Keele University, Keele,
Staffordshire ST5 5BG, UK.

Comment in
    Evid Based Nurs. 2014 Oct;17(4):109.
    Ann Intern Med. 2013 Dec 17;159(12):JC7.

Republished in
    Br J Sports Med. 2014 Nov;48(21):1579.

OBJECTIVE: To determine whether there is sufficient evidence to conclude that
exercise interventions are more effective than no exercise control and to compare
the effectiveness of different exercise interventions in relieving pain and
improving function in patients with lower limb osteoarthritis.
DATA SOURCES: Nine electronic databases searched from inception to March 2012.
STUDY SELECTION: Randomised controlled trials comparing exercise interventions
with each other or with no exercise control for adults with knee or hip
osteoarthritis.
DATA EXTRACTION: Two reviewers evaluated eligibility and methodological quality.
Main outcomes extracted were pain intensity and limitation of function. Trial
sequential analysis was used to investigate reliability and conclusiveness of
available evidence for exercise interventions. Bayesian network meta-analysis was
used to combine both direct (within trial) and indirect (between trial) evidence
on treatment effectiveness.
RESULTS: 60 trials (44 knee, two hip, 14 mixed) covering 12 exercise
interventions and with 8218 patients met inclusion criteria. Sequential analysis
showed that as of 2002 sufficient evidence had been accrued to show significant
benefit of exercise interventions over no exercise control. For pain relief,
strengthening, flexibility plus strengthening, flexibility plus strengthening
plus aerobic, aquatic strengthening, and aquatic strengthening plus flexibility,
exercises were significantly more effective than no exercise control. A combined
intervention of strengthening, flexibility, and aerobic exercise was also
significantly more effective than no exercise control for improving limitation in
function (standardised mean difference -0.63, 95% credible interval -1.16 to
-0.10).
CONCLUSIONS: As of 2002 sufficient evidence had accumulated to show significant
benefit of exercise over no exercise in patients with osteoarthritis, and further
trials are unlikely to overturn this result. An approach combining exercises to
increase strength, flexibility, and aerobic capacity is likely to be most
effective in the management of lower limb osteoarthritis. The evidence is largely
from trials in patients with knee osteoarthritis.
PROTOCOL REGISTRATION: PROSPERO (www.crd.york.ac.uk/prospero/) No CRD42012002267.

PMCID: PMC3779121
PMID: 24055922  [PubMed - indexed for MEDLINE]


113. Lancet. 2013 Sep 14;382(9896):951-62. doi: 10.1016/S0140-6736(13)60733-3. Epub
2013 Jun 27.

Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia:
a multiple-treatments meta-analysis.

Leucht S(1), Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, Samara M,
Barbui C, Engel RR, Geddes JR, Kissling W, Stapf MP, Lässig B, Salanti G, Davis
JM.

Author information:
(1)Department of Psychiatry and Psychotherapy, Technische Universität München,
Klinikum rechts der Isar, Munich, Germany. stefan.leucht@lrz.tum.de

Erratum in
    Lancet. 2013 Sep 14;382(9896):940.

Comment in
    Lancet. 2013 Dec 7;382(9908):1874.
    Lancet. 2013 Dec 7;382(9908):1874-5.
    Lancet. 2013 Sep 14;382(9896):919-20.
    Lancet. 2013 Dec 7;382(9908):1873-4.
    Evid Based Ment Health. 2014 Feb;17(1):9.
    Ann Intern Med. 2013 Nov 19;159(10):JC7.

BACKGROUND: The question of which antipsychotic drug should be preferred for the
treatment of schizophrenia is controversial, and conventional pairwise
meta-analyses cannot provide a hierarchy based on the randomised evidence. We
aimed to integrate the available evidence to create hierarchies of the
comparative efficacy, risk of all-cause discontinuation, and major side-effects
of antipsychotic drugs.
METHODS: We did a Bayesian-framework, multiple-treatments meta-analysis (which
uses both direct and indirect comparisons) of randomised controlled trials to
compare 15 antipsychotic drugs and placebo in the acute treatment of
schizophrenia. We searched the Cochrane Schizophrenia Group's specialised
register, Medline, Embase, the Cochrane Central Register of Controlled Trials,
and ClinicalTrials.gov for reports published up to Sept 1, 2012. Search results
were supplemented by reports from the US Food and Drug Administration website and
by data requested from pharmaceutical companies. Blinded, randomised controlled
trials of patients with schizophrenia or related disorders were eligible. We
excluded trials done in patients with predominant negative symptoms, concomitant
medical illness, or treatment resistance, and those done in stable patients. Data
for seven outcomes were independently extracted by two reviewers. The primary
outcome was efficacy, as measured by mean overall change in symptoms. We also
examined all-cause discontinuation, weight gain, extrapyramidal side-effects,
prolactin increase, QTc prolongation, and sedation.
FINDINGS: We identified 212 suitable trials, with data for 43 049 participants.
All drugs were significantly more effective than placebo. The standardised mean
differences with 95% credible intervals were: clozapine 0·88, 0·73-1·03;
amisulpride 0·66, 0·53-0·78; olanzapine 0·59, 0·53-0·65; risperidone 0·56,
0·50-0·63; paliperidone 0·50, 0·39-0·60; zotepine 0·49, 0·31-0·66; haloperidol
0·45, 0·39-0·51; quetiapine 0·44, 0·35-0·52; aripiprazole 0·43, 0·34-0·52;
sertindole 0·39, 0·26-0·52; ziprasidone 0·39, 0·30-0·49; chlorpromazine 0·38,
0·23-0·54; asenapine 0·38, 0·25-0·51; lurasidone 0·33, 0·21-0·45; and iloperidone
0·33, 0·22-0·43. Odds ratios compared with placebo for all-cause discontinuation
ranged from 0·43 for the best drug (amisulpride) to 0·80 for the worst drug
(haloperidol); for extrapyramidal side-effects 0·30 (clozapine) to 4·76
(haloperidol); and for sedation 1·42 (amisulpride) to 8·82 (clozapine).
Standardised mean differences compared with placebo for weight gain varied from
-0·09 for the best drug (haloperidol) to -0·74 for the worst drug (olanzapine),
for prolactin increase 0·22 (aripiprazole) to -1·30 (paliperidone), and for QTc
prolongation 0·10 (lurasidone) to -0·90 (sertindole). Efficacy outcomes did not
change substantially after removal of placebo or haloperidol groups, or when
dose, percentage of withdrawals, extent of blinding, pharmaceutical industry
sponsorship, study duration, chronicity, and year of publication were accounted
for in meta-regressions and sensitivity analyses.
INTERPRETATION: Antipsychotics differed substantially in side-effects, and small
but robust differences were seen in efficacy. Our findings challenge the
straightforward classification of antipsychotics into first-generation and
second-generation groupings. Rather, hierarchies in the different domains should
help clinicians to adapt the choice of antipsychotic drug to the needs of
individual patients. These findings should be considered by mental health policy
makers and in the revision of clinical practice guidelines.
FUNDING: None.

Copyright © 2013 Elsevier Ltd. All rights reserved.

PMID: 23810019  [PubMed - indexed for MEDLINE]


114. Br J Surg. 2013 Sep;100(10):1271-9. doi: 10.1002/bjs.9193. Epub 2013 Jul 9.

Systematic review, meta-analysis and meta-regression of the effect of tranexamic
acid on surgical blood loss.

Ker K(1), Prieto-Merino D, Roberts I.

Author information:
(1)Clinical Trials Unit, London School of Hygiene and Tropical Medicine, Keppel
Street, London, WC1E 7HT, UK. katharine.ker@lshtm.ac.uk

Comment in
    Evid Based Med. 2014 Apr;19(2):e12.

BACKGROUND: Tranexamic acid (TXA) reduces blood transfusion in surgery but the
extent of the reduction in blood loss and how it relates to the dose of TXA is
unclear.
METHODS: A systematic review of randomized trials was performed. Data were
extracted on blood loss from trials comparing intravenous TXA with no TXA or
placebo in surgical patients. A Bayesian linear regression was used to describe
the relationship between the reduction in blood loss with TXA and the extent of
bleeding as measured by the mean blood loss in the control group. A meta-analysis
of the log-transformed data was conducted to quantify the effect of TXA on blood
loss, stratified by type of surgery, timing of TXA administration and trial
quality. Meta-regression was used to explore the effect of TXA dosage.
RESULTS: Data from 104 trials were examined. Although the absolute reduction in
blood loss with TXA increased as surgical bleeding increased, the percentage
reduction was similar. TXA reduced blood loss by 34 per cent (pooled ratio 0·66,
95 per cent confidence interval 0·65 to 0·67; P < 0·001). The percentage
reduction in blood loss with TXA differed by type of surgery, timing of TXA
administration and trial quality, but the differences were small. The effect of
TXA on blood loss did not vary over the range of doses assessed (5·5-300 mg/kg).
CONCLUSION: TXA reduces blood loss in surgical patients by about one-third. A
total dose of 1 g appears to be sufficient for most adults. There is no evidence
to support the use of high doses.

© 2013 British Journal of Surgery Society Ltd. Published by John Wiley & Sons
Ltd.

PMID: 23839785  [PubMed - indexed for MEDLINE]


115. Curr Drug Saf. 2013 Sep;8(4):236-45.

Relative survival benefit and morbidity with fluids in severe sepsis - a network
meta-analysis of alternative therapies.

Bansal M(1), Farrugia A, Balboni S, Martin G.

Author information:
(1)Plasma Protein Therapeutics Association, Global Access, 147 Old Solomons
Island Road Suite #100, Annapolis, MD 21401, USA. afarrugia@pptaglobal.org.

BACKGROUND: Fluid resuscitation is widely practiced in intensive care units for
the treatment of sepsis. A comparison of the evidence base of different fluids
may inform therapeutic choice.
METHODS: The risks of mortality and morbidity (the need for renal replacement
therapies (RRT)) were assessed in patients with severe sepsis. A network
meta-analysis compared trials for crystalloids, albumin and hydroxyethyl starch
(HES). A literature search of human randomized clinical trials was conducted in
databases, the bibliographies of other recent relevant systematic reviews and
data reported at recent conferences. Mortality outcomes and RRT data with the
longest follow up period were compared. A Bayesian network meta-analysis assessed
the risk of mortality and a pair-wise metaanalysis assessed RRT using
crystalloids as the reference treatment.
RESULTS: 13 studies were identified. A fixed-effects meta-analysis of mortality
data in the trials demonstrated an odds-ratio (OR) of 0.90 between crystalloids
and albumin, 1.25 between crystalloids and HES and 1.40 between albumin and HES.
The probability that albumin is associated with the highest survival was 96.4%
followed by crystalloid at 3.6%, with a negligible probability for HES. Sub-group
analyses demonstrated the robustness of this result to variations in fluid
composition, study source and origin of septic shock. A random-effects pairwise
comparison for the risk of RRT provided an OR of 1.52 favoring crystalloid over
HES.
CONCLUSION: Fluid therapy with albumin was associated with the highest survival
benefit. The higher morbidity with HES may affect mortality and requires
consideration by prescribers.

PMCID: PMC3856428
PMID: 23909705  [PubMed - indexed for MEDLINE]


116. J Gen Intern Med. 2013 Sep;28(9):1225-37. doi: 10.1007/s11606-013-2433-1. Epub
2013 Apr 17.

Preventive pharmacologic treatments for episodic migraine in adults.

Shamliyan TA(1), Choi JY, Ramakrishnan R, Miller JB, Wang SY, Taylor FR, Kane RL.

Author information:
(1)Minnesota Evidence-based Practice Center, Minneapolis, MN 55455, USA.
shaml005@umn.edu

Comment in
    Ann Intern Med. 2013 Oct 15;159(8):JC11.
    J Gen Intern Med. 2013 Sep;28(9):1125-6.

OBJECTIVES: Systematic review of preventive pharmacologic treatments for
community-dwelling adults with episodic migraine.
DATA SOURCES: Electronic databases through May 20, 2012.
ELIGIBILITY CRITERIA: English-language randomized controlled trials (RCTs) of
preventive drugs compared to placebo or active treatments examining rates of
≥50 % reduction in monthly migraine frequency or improvement in quality of life.
STUDY APPRAISAL AND SYNTHESIS METHODS: We assessed risk of bias and strength of
evidence and conducted random effects meta-analyses of absolute risk differences
and Bayesian network meta-analysis.
RESULTS: Of 5,244 retrieved references, 215 publications of RCTs provided mostly
low-strength evidence because of the risk of bias and imprecision. RCTs examined
59 drugs from 14 drug classes. All approved drugs, including topiramate (9 RCTs),
divalproex (3 RCTs), timolol (3 RCTs), and propranolol (4 RCTs); off-label beta
blockers metoprolol (4 RCTs), atenolol (1 RCT), nadolol (1 RCT), and acebutolol
(1 RCT); angiotensin-converting enzyme inhibitors captopril (1 RCT) and
lisinopril (1 RCT); and angiotensin II receptor blocker candesartan (1 RCT),
outperformed placebo in reducing monthly migraine frequency by ≥50 % in 200-400
patients per 1,000 treated. Adverse effects leading to treatment discontinuation
(68 RCTs) were greater with topiramate, off-label antiepileptics, and
antidepressants than with placebo. Limited direct evidence as well as frequentist
and exploratory network Bayesian meta-analysis showed no statistically
significant differences in benefits between approved drugs. Off-label
angiotensin-inhibiting drugs and beta-blockers were most effective and tolerable
for episodic migraine prevention.
LIMITATIONS: We did not quantify reporting bias or contact principal
investigators regarding unpublished trials.
CONCLUSIONS: Approved drugs prevented episodic migraine frequency by ≥50 % with
no statistically significant difference between them. Exploratory network
meta-analysis suggested that off-label angiotensin-inhibiting drugs and
beta-blockers had favorable benefit-to-harm ratios. Evidence is lacking for
long-term effects of drug treatments (i.e., trials of more than 3 months
duration), especially for quality of life.

PMCID: PMC3744311
PMID: 23592242  [PubMed - indexed for MEDLINE]


117. J Inherit Metab Dis. 2013 Sep;36(5):757-66. doi: 10.1007/s10545-012-9564-0. Epub
2012 Nov 30.

Estimating the probability of IQ impairment from blood phenylalanine for
phenylketonuria patients: a hierarchical meta-analysis.

Fonnesbeck CJ(1), McPheeters ML, Krishnaswami S, Lindegren ML, Reimschisel T.

Author information:
(1)Department of Biostatistics, Vanderbilt University Medical Center, 1161 21st
Ave South, S-2323 Medical Center North, Nashville, TN 37232-2158, USA.
chris.fonnesbeck@vanderbilt.edu

Though the control of blood phenylalanine (Phe) levels is essential for
minimizing impairment in individuals with phenylketonuria (PKU), the empirical
basis for the selection of specific blood Phe levels as targets has not been
evaluated. We evaluated the current evidence that particular Phe levels are
optimal for minimizing or avoiding cognitive impairment in individuals with PKU.
This work uses meta-estimates of blood Phe-IQ correlation to predict the
probability of low IQ for a range of Phe levels. We believe this metric is easily
interpretable by clinicians, and hence useful in making recommendations for Phe
intake. The median baseline association of Phe with IQ was estimated to be
negative, both in the context of historical (median = -0.026, 95 % BCI = [-0.040,
-0.013]) and concurrent (-0.007, [-0.014, 0.000]) measurement of Phe relative to
IQ. The estimated additive fixed effect of critical period Phe measurement was
also nominally negative for historical measurement (-0.010, [-0.022, 0.003]) and
positive for concurrent measurement (0.007, [-0.018, 0.035]). Probabilities
corresponding to historical measures of blood Phe demonstrated an increasing
chance of low IQ with increasing Phe, with a stronger association seen between
blood Phe measured during the critical period than later. In contrast,
concurrently-measured Phe was more weakly correlated with the probability of low
IQ, though the correlation is still positive, irrespective of whether Phe was
measured during the critical or non-critical period. This meta-analysis
illustrates the utility of a Bayesian hierarchical approach for not only
combining information from a set of candidate studies, but also for combining
different types of data to estimate parameters of interest.

PMID: 23197105  [PubMed - indexed for MEDLINE]


118. Lancet Oncol. 2013 Sep;14(10):943-52. doi: 10.1016/S1470-2045(13)70341-3. Epub
2013 Aug 13.

Effect of initial treatment strategy on survival of patients with advanced-stage
Hodgkin's lymphoma: a systematic review and network meta-analysis.

Skoetz N(1), Trelle S, Rancea M, Haverkamp H, Diehl V, Engert A, Borchmann P.

Author information:
(1)Cochrane Haematological Malignancies Group, University Hospital of Cologne,
Cologne, Germany.

Comment in
    Lancet Oncol. 2013 Sep;14(10):911-2.
    Lancet Oncol. 2013 Nov;14(12):e487-8.

BACKGROUND: Several treatment strategies are available for adults with
advanced-stage Hodgkin's lymphoma, but studies assessing two alternative
standards of care-increased dose bleomycin, etoposide, doxorubicin,
cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPescalated),
and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD)-were not powered
to test differences in overall survival. To guide treatment decisions in this
population of patients, we did a systematic review and network meta-analysis to
identify the best initial treatment strategy.
METHODS: We searched the Cochrane Library, Medline, and conference proceedings
for randomised controlled trials published between January, 1980, and June, 2013,
that assessed overall survival in patients with advanced-stage Hodgkin's lymphoma
given BEACOPPbaseline, BEACOPPescalated, BEACOPP variants, ABVD, cyclophosphamide
(mechlorethamine), vincristine, procarbazine, and prednisone (C[M]OPP), hybrid or
alternating chemotherapy regimens with ABVD as the backbone (eg, COPP/ABVD,
MOPP/ABVD), or doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin,
etoposide, and prednisone combined with radiation therapy (the Stanford V
regimen). We assessed studies for eligibility, extracted data, and assessed their
quality. We then pooled the data and used a Bayesian random-effects model to
combine direct comparisons with indirect evidence. We also reconstructed
individual patient survival data from published Kaplan-Meier curves and did
standard random-effects Poisson regression. Results are reported relative to
ABVD. The primary outcome was overall survival.
FINDINGS: We screened 2055 records and identified 75 papers covering 14 eligible
trials that assessed 11 different regimens in 9993 patients, providing 59 651
patient-years of follow-up. 1189 patients died, and the median follow-up was 5·9
years (IQR 4·9-6·7). Included studies were of high methodological quality, and
between-trial heterogeneity was negligible (τ(2)=0·01). Overall survival was
highest in patients who received six cycles of BEACOPPescalated (HR 0·38, 95%
credibility interval [CrI] 0·20-0·75). Compared with a 5 year survival of 88% for
ABVD, the survival benefit for six cycles of BEACOPPescalated is 7% (95% CrI
3-10)-ie, a 5 year survival of 95%. Reconstructed individual survival data showed
that, at 5 years, BEACOPPescalated has a 10% (95% CI 3-15) advantage over ABVD in
overall survival.
INTERPRETATION: Six cycles of BEACOPPescalated significantly improves overall
survival compared with ABVD and other regimens, and thus we recommend this
treatment strategy as standard of care for patients with access to the
appropriate supportive care.

Copyright © 2013 Elsevier Ltd. All rights reserved.

PMID: 23948348  [PubMed - indexed for MEDLINE]


119. Thyroid. 2013 Sep;23(9):1138-50. doi: 10.1089/thy.2012.0588. Epub 2013 Aug 27.

Which hemostatic device in thyroid surgery? A network meta-analysis of surgical
technologies.

Garas G(1), Okabayashi K, Ashrafian H, Shetty K, Palazzo F, Tolley N, Darzi A,
Athanasiou T, Zacharakis E.

Author information:
(1)1 Department of Otorhinolaryngology and Head & Neck Surgery, Imperial College
London , London, United Kingdom .

Comment in
    Thyroid. 2014 Apr;24(4):779-80.
    Thyroid. 2013 Sep;23(9):1047-8.
    Thyroid. 2014 Apr;24(4):778-9.

BACKGROUND: Energy-based hemostatic devices are increasingly being used in
thyroid surgery. However, there are several limitations with regard to the
existing evidence and a paucity of guidelines on the subject. The goal of this
review is to employ the novel evidence synthesis technique of a network
meta-analysis to assess the comparative effectiveness of surgical technologies in
thyroid surgery and contribute to enhanced governance in the field of thyroid
surgery.
METHODS: Articles published between January 2000 and June 2012 were identified
from Embase, Medline, Cochrane Library, and PubMed databases. Randomized
controlled trials of any size comparing the use of ultrasonic coagulation
(harmonic scalpel) or Ligasure either head-to-head or against the "clamp-and-tie"
technique were included. Two reviewers independently critically appraised and
extracted the data from each study. The number of patients who experienced
postoperative events was extracted in dichotomous format or continuous outcomes.
Odds ratios were calculated by a Bayesian network meta-analysis, and
metaregression was used for pair-wise comparisons. Indirect and direct
comparisons were performed and inconsistency was assessed.
RESULTS: Thirty-five randomized controlled trials with 2856 patients were
included. Ultrasonic coagulation ranked first (followed by Ligasure and then
clamp-and-tie) with the lowest risk of postoperative hypoparathyroidism (odds
ratio 1.43 [95% confidence interval (CI) 0.77-2.67] and 0.70 [CI 0.43-1.13],
ultrasonic coagulation vs. Ligasure and ultrasonic coagulation vs. clamp-and-tie,
respectively), least blood loss (-0.25 [CI -0.84 to -0.35] and -1.22 [CI -1.85 to
-0.59]), and drain output (0.28 [CI -0.35 to -0.91] and -0.36 [CI -0.70 to
-0.03]). From a health technology viewpoint, ultrasonic coagulation was
associated with the shortest operative time (-0.66 [CI -1.17 to -0.14] and -1.29
[CI -1.59 to -1.00]) and hospital stay (-0.28 [CI -0.78 to 0.22] and -0.56 [CI
-1.28 to 0.15]). The only exception occurs with the clinically important
complication of recurrent laryngeal nerve paralysis, where the reverse trend
applies (1.36 [CI 0.25-7.46] and 1.74 [CI 0.94-3.26]).
CONCLUSIONS: The comparative effectiveness of ultrasonic coagulation in thyroid
surgery outcomes seems superior to other techniques with the exception of
recurrent laryngeal nerve injury. This network meta-analysis, one of a handful in
a surgical field, offers preliminary and robust evidence to guide clinical
decisions and policy makers to adopt safer thyroid operations.

PMID: 23470035  [PubMed - indexed for MEDLINE]




121. Br J Dermatol. 2013 Aug;169(2):250-9. doi: 10.1111/bjd.12343.

Network meta-analysis of the outcome 'participant complete clearance' in
nonimmunosuppressed participants of eight interventions for actinic keratosis: a
follow-up on a Cochrane review.

Gupta AK(1), Paquet M.

Author information:
(1)Department of Medicine, University of Toronto, Toronto, ON, Canada.
agupta@execulink.com

The conclusions of pairwise meta-analyses of interventions for actinic keratosis
(AK) are limited due to the lack of direct comparison between some interventions.
Consequently, we performed a network meta-analysis for eight treatments
[5-aminolaevulinic acid (ALA)-photodynamic therapy (PDT), cryotherapy, diclofenac
3% in 2·5% hyaluronic acid (DCF/HA), 5-fluorouracil (5-FU) 0·5% or 5·0%,
imiquimod (IMI) 5%, ingenol mebutate (IMB) 0·015-0·05%, methyl aminolaevulinate
(MAL)-PDT and placebo/vehicle (including placebo-PDT)] to determine their
relative efficacies. As part of a prior Cochrane systematic review, different
databases and grey literature were searched for randomized controlled trials up
to April 2012. The inclusion criteria were parallel-group studies with
nonimmunosuppressed participants: (i) reporting 'participant complete clearance'
and (ii) comparing at least two of the interventions. Thirty-two publications met
the criteria and they included the following number of individual or pooled
studies (n) and total number of participants (N) for the different interventions:
5-FU 0·5% (n = 4, N = 169), 5-FU 5·0% (n = 2, N = 44), ALA-PDT (n = 6, N = 739),
cryotherapy (n = 2, N = 174), DCF/HA (n = 5, N = 299), IMI (n = 14, N = 1411),
IMB (n = 3, N = 560), MAL-PDT (n = 7, N = 557) and placebo (n = 32, N = 2520).
Network analyses using a random-effects Bayesian model were carried out with the
software ADDIS v1.16.1. The interventions were ranked as follows based on
calculated probabilities and odd ratios: 5-FU > ALA-PDT ≈ IMI ≈ IMB ≈ MAL-PDT >
cryotherapy > DCF/HA > placebo. This efficacy ranking was obtained based on the
current available data on 'participant complete clearance' from randomized
controlled trials and the analysis model used. However, several other factors
should also be considered when prescribing a treatment for AK.

© 2013 Mediprobe Research Inc BJD © 2013 British Association of Dermatologists.

PMID: 23550994  [PubMed - indexed for MEDLINE]


122. Curr Med Res Opin. 2013 Aug;29(8):1001-13. doi: 10.1185/03007995.2013.803461.
Epub 2013 Jun 19.

The efficacy and tolerability of perampanel and other recently approved
anti-epileptic drugs for the treatment of refractory partial onset seizure: a
systematic review and Bayesian network meta-analysis.

Khan N(1), Shah D, Tongbram V, Verdian L, Hawkins N.

Author information:
(1)IMS Health, NY, USA.

OBJECTIVES: This paper compares the efficacy and tolerability of perampanel (PER)
relative to other recently approved anti-epileptic drug (AEDs) - lacosamide
(LCS), retigabine (RTG), and eslicarbazepine (ESL) for the adjunctive treatment
of partial onset seizures with or without secondary generalization and
specifically in the secondary generalization subgroup.
MATERIALS AND METHODS: A systematic literature review of all RCTs of PER and
selected AEDs in EMBASE, Medline, and the Cochrane Central from 1998 to January
2011 with an update in PubMed in March 2013 was performed. A network
meta-analysis was conducted for 50% responder rate for overall seizures;
withdrawal due to adverse events; seizure freedom; and 50% responder rate for
secondary generalized seizures.
RESULTS: Twelve RCTs (three PER, three LCS, three RTG and three ESL) were
included. PER performed significantly better than placebo for 'responder rate'
(OR 2.151, 95% CrI 1.348-3.472) and 'seizure freedom' (OR 2.507, 95% CrI
1.067-7.429). When compared to other agents, PER was found to be equally
effective. For 'withdrawal due to adverse events', PER had the lowest odds ratio
vs. placebo compared with other AEDs. In the analysis for the subgroup of
patients with secondary generalization, only four RCTs (three PER and one LCS)
met the inclusion criteria for one outcome (responder rate) for LCS. In this
subgroup, PER was statistically significantly better than placebo (OR 2.448, 95%
CrI 1.088-5.828).
CONCLUSION: PER was statistically significantly superior to placebo in responder
rate, seizure freedom, and responder rate in the secondary generalization
population. Though PER had statistically significant greater withdrawal compared
to placebo, it had the lowest ORs vs. placebo, suggesting a superior safety
profile among the comparators included in this analysis. In patients with partial
onset seizure with secondary generalization, PER had a statistically significant
effect on responder rate compared to placebo.

PMID: 23659562  [PubMed - indexed for MEDLINE]


123. Eur J Prev Cardiol. 2013 Aug;20(4):658-70. doi: 10.1177/2047487313483600. Epub
2013 Mar 25.

Dose-comparative effects of different statins on serum lipid levels: a network
meta-analysis of 256,827 individuals in 181 randomized controlled trials.

Naci H(1), Brugts JJ, Fleurence R, Ades AE.

Author information:
(1)Department of Social Policy, London School of Economics & Political Science,
London, UK. h.naci@lse.ac.uk

AIMS: The extent to which individual statins vary in terms of their impact on
serum lipid levels has been studied mainly on the basis of placebo-controlled
trials. Our objective was to review and quantify the dose-comparative effects of
different statins on serum lipid levels using both placebo- and active-comparator
trials.
METHODS: We systematically reviewed randomized trials evaluating different
statins in participants with, or at risk of developing, cardiovascular disease.
We performed random-effects Bayesian network meta-analyses to quantify the the
relative potency of individual statins across all possible dose combinations
using both direct and indirect evidence. Dose-comparative effects were determined
by estimating the mean change from baseline in serum lipids as compared to
control treatment. (systematic review registration: PROSPERO
2011:CRD42011001470).
RESULTS: We included 181 placebo-controlled and active-comparator trials
including 256,827 individuals. There were 83 two-armed placebo-controlled trials
and the remaining 98 were two- or multi-armed active-comparator trials. All
statins reduced serum LDL and total cholesterol levels: higher doses resulted in
higher reductions in pretreatment LDL and total cholesterol concentrations. In
absolute terms, all statins significantly reduced LDL cholesterol levels as
compared to control treatment from average baseline levels of approximately
150 mg/dl, except for fluvastatin at ≤20 mg/day and lovastatin at ≤10 mg/day.
Atorvastatin, rosuvastatin, and simvastatin were broadly equivalent in terms of
their LDL cholesterol-lowering effects. Dose-comparative effects of indivudual
statins were not different between those with and without coronary heart disease
at baseline. According to meta-regression analyses, LDL cholesterol-lowering
effects of individual statins were not impacted by differences across trials in
terms of baseline mean age and proportion of women as trial participants.
Pretreatment LDL cholesterol concentrations had a marginally statistically
significant effect on LDL cholesterol change from baseline. Mean differences from
baseline in HDL cholesterol as compared to control treatment was not significant
for any statin-dose combination.
CONCLUSIONS: The findings of this comprehensive review provide supporting
evidence for the dose-response relationship of statins in reducing LDL and total
cholesterol. The LDL cholesterol-reducing effects of some statins appear less
pronounced than the findings of previous meta-analyses, which is particularly the
case for the high-dose formulations of atorvastatin and rosuvastatin. The most
consistent evidence for a combined reduction in both LDL and total cholesterol
was achieved with atorvastatin at >40 mg/day, rosuvastatin at >10 mg/day, and
simvastatin at >40 mg/day, which appear equivalent in terms of their LDL and
total cholesterol-reducing effects.

PMID: 23529608  [PubMed - indexed for MEDLINE]


124. Diabetologia. 2013 Jul;56(7):1489-93. doi: 10.1007/s00125-013-2902-4. Epub 2013
Apr 13.

Progression rates from HbA1c 6.0-6.4% and other prediabetes definitions to type 2
diabetes: a meta-analysis.

Morris DH(1), Khunti K, Achana F, Srinivasan B, Gray LJ, Davies MJ, Webb D.

Author information:
(1)Diabetes Research Unit, Leicester Diabetes Centre, University of Leicester,
Leicester General Hospital, Gwendolen Road, Leicester, LE5 4PW, UK. dhm6@le.ac.uk

AIMS/HYPOTHESIS: Precise estimates of progression rates from 'prediabetes' to
type 2 diabetes are needed to optimise prevention strategies for high-risk
individuals. There is acceptance of prediabetes defined by impaired fasting
glucose (IFG) and impaired glucose tolerance (IGT), but there is some controversy
surrounding HbA1c-defined prediabetes ranges, with some favouring 6.0-6.4%
(42-46 mmol/mol). Comparing progression rates between groups might aid this
issue, thus we aimed to accurately estimate progression rates to diabetes from
different prediabetes categories.
METHODS: Meta-analysis of prospective observational studies in which participants
had prediabetes at baseline (ADA-defined IFG [5.6-6.9 mmol/l], WHO-defined IFG
[6.1-6.9 mmol/l], IGT (7.8-11.0 mmol/l) or raised HbA1c
[6.0-6.4%/42-46 mmol/mol]) and were followed up for incident diabetes. Incidence
rates were combined using Bayesian random effects models.
RESULTS: Overall, 70 studies met the inclusion criteria. In the six studies that
used raised HbA1c, the pooled incidence rate (95% credible interval) of diabetes
was 35.6 (15.1, 83.0) per 1,000 person-years. This rate was most similar to that
for ADA-defined IFG (11 studies; 35.5 [26.6, 48.0]) and was non-significantly
lower than WHO-defined IFG (34 studies; 47.4 [37.4, 59.8]), IGT (46 studies, 45.5
[37.8, 54.5]) and IFG plus IGT (15 studies, 70.4 [53.8, 89.7]). Similar results
were seen when the data were analysed by the criteria used to diagnose diabetes.
CONCLUSIONS/INTERPRETATION: This study provides evidence that progression rates
differ by prediabetes definition, which has implications for the planning and
implementation of diabetes prevention programmes. HbA1c 6.0-6.4% might identify
people at a lower diabetes risk than other prediabetes definitions, but further
research is needed.

PMID: 23584433  [PubMed - indexed for MEDLINE]


125. Eur J Med Res. 2013 Jun 21;18:17. doi: 10.1186/2047-783X-18-17.

Use of mixed-treatment-comparison methods in estimating efficacy of treatments
for heavy menstrual bleeding.

Hoaglin DC(1), Filonenko A, Glickman ME, Wasiak R, Gidwani R.

Author information:
(1)United BioSource Corporation, 26-28 Hammersmith Grove, London W6 7HA, UK.

BACKGROUND: A variety of pharmacological and surgical treatments have been
developed for heavy menstrual bleeding (HMB), which can have negative physical,
social, psychological, and economic consequences. We conducted a systematic
literature review and mixed-treatment-comparison (MTC) meta-analysis of available
data from randomized controlled trials (RCTs) to derive estimates of efficacy for
8 classes of treatments for HMB, to inform health-economic analysis and future
studies.
METHODS: A systematic review identified RCTs that reported data on menstrual
blood loss (MBL) at baseline and one or more follow-up times. Eight treatment
classes were considered: COCs, danazol, endometrial ablation, LNG-IUS, placebo,
progestogens given for less than 2 weeks out of 4 during the menstrual cycle,
progestogens given for close to 3 weeks out of 4, and TXA. The primary measure of
efficacy was the proportion of women who achieved MBL < 80 mL per cycle (month),
as measured by the alkaline hematin method. A score less than 100 on an
established pictorial blood-loss assessment chart (PBAC) was considered an
acceptable substitute for MBL < 80 mL. Estimates of efficacy by treatment class
and time were obtained from a Bayesian MTC model. The model also included effects
for treatment class, study, and the combination of treatment class and study and
an adjustment for baseline mean MBL. Several methodological challenges
complicated the analysis. Some trials reported various summary statistics for MBL
or PBAC, requiring estimation (with less precision) of % MBL < 80 mL or % PBAC <
100. Also, reported follow-up times varied substantially.
RESULTS: The evidence network involved 34 RCTs, with follow-up times from 1 to 36
months. Efficacy at 3 months of follow-up (estimated as the posterior median)
ranged from 87.5% for the levonorgestrel-releasing intrauterine system (LNG-IUS)
to 14.2% for progestogens administered for less than 2 weeks out of 4 in the
menstrual cycle. The 95% credible intervals for most estimates were quite wide,
mainly because of the limited evidence for many combinations of treatment class
and follow-up time and the uncertainty from estimating % MBL < 80 mL or % PBAC <
100 from summary statistics.
CONCLUSIONS: LNG-IUS and endometrial ablation are very efficacious in treating
HMB. The study yielded useful insights on using MTC in sparse evidence networks.
Diversity of outcome measures and follow-up times in the HMB literature presented
considerable challenges. The Bayesian credible intervals reflected the various
sources of uncertainty.

PMCID: PMC3698104
PMID: 23786677  [PubMed - indexed for MEDLINE]


126. Int J Cardiol. 2013 Jun 20;166(2):431-9. doi: 10.1016/j.ijcard.2011.10.128. Epub
2011 Dec 20.

Impact of statin dose on major cardiovascular events: a mixed treatment
comparison meta-analysis involving more than 175,000 patients.

Ribeiro RA(1), Ziegelmann PK, Duncan BB, Stella SF, da Costa Vieira JL,
Restelatto LM, Moriguchi EH, Polanczyk CA.

Author information:
(1)Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
rodrigo.ribeiro@htanalyze.com

BACKGROUND: The benefit of statins in the reduction of cardiovascular events was
demonstrated in several placebo-controlled trials. More intensive therapy seems
to be associated with greater benefit. Our objective was to compare different
statin doses in the reduction of cardiovascular events and deaths, combining
direct and indirect evidence, through mixed treatment comparisons (MTC).
METHODS: We conducted a systematic review in MEDLINE and Cochrane CENTRAL. A
random-effects Bayesian MTC model was used to combine placebo-controlled and
direct statin comparison trials. Intensity of statin doses was classified
according to expected LDL-cholesterol reduction effect: ≤30% as low; 30-40%,
intermediate, and ≥40%, high. Outcomes evaluated were non-fatal myocardial
infarction (MI), stroke, coronary revascularization and coronary, cardiovascular
and all-cause death. Inconsistency was assessed with split-node methodology.
RESULTS: 47 trials (11 with direct statin comparisons) were included. High doses
reduced non-fatal MI by 28% (95% CI: 18%-36%) and by 14% (7%-21%) when compared
to low and intermediate doses, respectively. High doses also diminished
revascularization [RR versus low and intermediate doses of 0.81 (0.69-0.95) and
0.88 (0.77-0.99), respectively] and stroke [RR of 0.83 (0.68-0.99) against low
doses]. Regimen intensity did not change death rates (e.g., for all-cause
mortality, RRs of 0.93 (0.80-1.06) and 0.98 (0.87-1.08) for high vs. low and
intermediate doses, respectively). No statistical inconsistencies were found in
the analyses.
CONCLUSIONS: In this study, in which all available evidence from statin trials
was simultaneously analyzed, the benefit of more intensive therapy was restricted
to non-fatal events.

Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

PMID: 22192281  [PubMed - indexed for MEDLINE]


127. Cochrane Database Syst Rev. 2013 Jun 6;6:CD008933. doi:
10.1002/14651858.CD008933.pub2.

Immunomodulators and immunosuppressants for multiple sclerosis: a network
meta-analysis.

Filippini G(1), Del Giovane C, Vacchi L, D'Amico R, Di Pietrantonj C, Beecher D,
Salanti G.

Author information:
(1)Neuroepidemiology Unit, Fondazione I.R.C.C.S. Istituto Neurologico Carlo
Besta, Milano, Italy. gfilippini@istituto-besta.it

Comment in
    Eur J Neurol. 2013 Dec;20(12):e131.

BACKGROUND: Different therapeutic strategies are available for treatment of
multiple sclerosis (MS) including immunosuppressants, immunomodulators, and
monoclonal antibodies. Their relative effectiveness in the prevention of relapse
or disability progression is unclear due to the limited number of direct
comparison trials. A summary of the results, including both direct and indirect
comparisons of treatment effects, may help to clarify the above uncertainty.
OBJECTIVES: To estimate the relative efficacy and acceptability of interferon
ß-1b (IFNß-1b) (Betaseron), interferon ß-1a (IFNß-1a) (Rebif and Avonex),
glatiramer acetate, natalizumab, mitoxantrone, methotrexate, cyclophosphamide,
azathioprine, intravenous immunoglobulins, and long-term corticosteroids versus
placebo or another active agent in participants with MS and to provide a ranking
of the treatments according to their effectiveness and risk-benefit balance.
SEARCH METHODS: We searched the Cochrane Database of Systematic Reviews, the
Cochrane MS Group Trials Register, and the Food and Drug Administration (FDA)
reports. The most recent search was run in February 2012.
SELECTION CRITERIA: Randomized controlled trials (RCTs) that studied one of the
11 treatments for use in adults with MS and that reported our pre-speciﬁed
efficacy outcomes were considered for inclusion.
DATA COLLECTION AND ANALYSIS: Identifying search results and data extraction were
performed independently by two authors. Data synthesis was performed by pairwise
meta-analysis and network meta-analysis that was performed within a Bayesian
framework. The body of evidence for outcomes within the pairwise meta-analysis
was assessed according to GRADE, as very low, low, moderate, or high quality.
MAIN RESULTS: Forty-four trials were included in this review, in which 17,401
participants had been randomised. Twenty-three trials included
relapsing-remitting MS (RRMS) (9096 participants, 52%), 18 trials included
progressive MS (7726, 44%), and three trials included both RRMS and progressive
MS (579, 3%). The majority of the included trials were short-term studies, with
the median duration being 24 months. The results originated mostly from 33 trials
on IFNß, glatiramer acetate, and natalizumab that overall contributed outcome
data for 9881 participants (66%).From the pairwise meta-analysis, there was high
quality evidence that natalizumab and IFNß-1a (Rebif) were effective against
recurrence of relapses in RRMS during the first 24 months of treatment compared
to placebo (odds ratio (OR) 0.32, 95% confidence interval (CI) 0.24 to 0.43; OR
0.45, 95% CI 0.28 to 0.71, respectively); they were more effective than IFNß-1a
(Avonex) (OR 0.28, 95% CI 0.22 to 0.36; OR 0.19, 95% CI 0.06 to 0.60,
respectively). IFNß-1b (Betaseron) and mitoxantrone probably decreased the odds
of the participants with RRMS having clinical relapses compared to placebo (OR
0.55, 95% CI 0.31 to 0.99; OR 0.15, 95% CI 0.04 to 0.54, respectively) but the
quality of evidence for these treatments was graded as moderate. From the network
meta-analysis, the most effective drug appeared to be natalizumab (median OR
versus placebo 0.29, 95% credible intervals (CrI) 0.17 to 0.51), followed by
IFNß-1a (Rebif) (median OR versus placebo 0.44, 95% CrI 0.24 to 0.70),
mitoxantrone (median OR versus placebo 0.43, 95% CrI 0.20 to 0.87), glatiramer
acetate (median OR versus placebo 0.48, 95% CrI 0.38 to 0.75), IFNß-1b
(Betaseron) (median OR versus placebo 0.48, 95% CrI 0.29 to 0.78). However, our
confidence was moderate for direct comparison of mitoxantrone and IFNB-1b vs
placebo and very low for direct comparison of glatiramer vs placebo. The relapse
outcome for RRMS at three years' follow-up was not reported by any of the
included trials.Disability progression was based on surrogate markers in the
majority of included studies and was unavailable for RRMS beyond two to three
years. The pairwise meta-analysis suggested, with moderate quality evidence, that
natalizumab and IFNß-1a (Rebif) probably decreased the odds of the participants
with RRMS having disability progression at two years' follow-up, with an absolute
reduction of 14% and 10%, respectively, compared to placebo. Natalizumab and
IFNß-1b (Betaseron) were significantly more effective (OR 0.62, 95% CI 0.49 to
0.78; OR 0.35, 95% CI 0.17 to 0.70, respectively) than IFNß-1a (Avonex) in
reducing the number of the participants with RRMS who had progression at two
years' follow-up, and confidence in this result was graded as moderate. From the
network meta-analyses, mitoxantrone appeared to be the most effective agent in
decreasing the odds of the participants with RRMS having progression at two
years' follow-up, but our confidence was very low for direct comparison of
mitoxantrone vs placebo. Both pairwise and network meta-analysis revealed that
none of the individual agents included in this review were effective in
preventing disability progression over two or three years in patients with
progressive MS.There was not a dose-effect relationship for any of the included
treatments with the exception of mitoxantrone.
AUTHORS' CONCLUSIONS: Our review should provide some guidance to clinicians and
patients. On the basis of high quality evidence, natalizumab and IFNß-1a (Rebif)
are superior to all other treatments for preventing clinical relapses in RRMS in
the short-term (24 months) compared to placebo. Moderate quality evidence
supports a protective effect of natalizumab and IFNß-1a (Rebif) against
disability progression in RRMS in the short-term compared to placebo. These
treatments are associated with long-term serious adverse events and their
benefit-risk balance might be unfavourable. IFNß-1b (Betaseron) and mitoxantrone
probably decreased the odds of the participants with RRMS having relapses,
compared with placebo (moderate quality of evidence). The benefit-risk balance
with azathioprine is uncertain, however this agent might be effective in
decreasing the odds of the participants with RRMS having relapses and disability
progression over 24 to 36 months, compared with placebo. The lack of convincing
efficacy data shows that IFNß-1a (Avonex), intravenous immunoglobulins,
cyclophosphamide and long-term steroids have an unfavourable benefit-risk balance
in RRMS. None of the included treatments are effective in decreasing disability
progression in patients with progressive MS. It is important to consider that the
clinical effects of all these treatments beyond two years are uncertain, a
relevant point for a disease of 30 to 40 years duration. Direct head-to-head
comparison(s) between natalizumab and IFNß-1a (Rebif) or between azathioprine and
IFNß-1a (Rebif) should be top priority on the research agenda and follow-up of
the trial cohorts should be mandatory.

PMID: 23744561  [PubMed - indexed for MEDLINE]


128. Circulation. 2013 Jun 4;127(22):2177-85. doi: 10.1161/CIRCULATIONAHA.112.000646.
Epub 2013 May 14.

Bayesian methods affirm the use of percutaneous coronary intervention to improve
survival in patients with unprotected left main coronary artery disease.

Bittl JA(1), He Y, Jacobs AK, Yancy CW, Normand SL; American College of
Cardiology Foundation/American Heart Association Task Force on Practice
Guidelines.

Author information:
(1)Ocala Heart Institute, Munroe Regional Medical Center, 1221 SE 5th St, Ocala,
FL 34471, USA. jabittl@mac.com

Comment in
    Circulation. 2014 Jan 28;129(4):e307.
    Circulation. 2014 Jan 28;129(4):e309.
    Circulation. 2013 Jun 18;127(24):2367-9.
    Circulation. 2014 Jan 28;129(4):e308.

BACKGROUND: Several randomized clinical trials support the use of coronary artery
bypass grafting (CABG) for patients with unprotected left main coronary artery
disease. Studies suggesting the equivalence of percutaneous coronary intervention
(PCI) with CABG for this indication indirectly support the 2011 American College
of Cardiology Foundation/American Heart Association Class IIa recommendation for
PCI to improve survival in patients with unprotected left main coronary artery
disease. We tested whether bayesian approaches uphold the new recommendation.
METHODS AND RESULTS: We performed a bayesian cross-design and network
meta-analysis of 12 studies (4 randomized clinical trials and 8 observational
studies) comparing CABG with PCI (n=4574 patients) and of 7 studies (2 randomized
clinical trials and 5 observational studies) comparing CABG with medical therapy
(n=3224 patients). The odds ratios of 1-year mortality after PCI compared with
CABG using bayesian cross-design meta-analysis were not different among
randomized clinical trials (odds ratio, 0.99; 95% bayesian credible interval,
0.67-1.43), matched cohort studies (odds ratio, 1.10; 95% bayesian credible
interval, 0.76-1.73), and other types of cohort studies (odds ratio, 0.93; 95%
bayesian credible interval, 0.58-1.35). A network meta-analysis suggested that
medical therapy is associated with higher 1-year mortality than the use of PCI
for patients with unprotected left main coronary artery disease (odds ratio,
3.22; 95% bayesian credible interval, 1.96-5.30).
CONCLUSIONS: Bayesian methods support the current guidelines, which were based on
traditional statistical methods and have proposed that PCI, like CABG, improves
survival for patients with unprotected left main coronary artery disease compared
with medical therapy. An integrated approach using both direct and indirect
evidence may yield new insights to enhance the translation of clinical trial data
into practice.

PMID: 23674397  [PubMed - indexed for MEDLINE]


129. Arch Gynecol Obstet. 2013 Jun;287(6):1059-66. doi: 10.1007/s00404-013-2789-9.
Epub 2013 Mar 27.

Progestogens for preterm birth prevention: a systematic review and meta-analysis
by drug route.

Velez Edwards DR(1), Likis FE, Andrews JC, Woodworth AL, Jerome RN, Fonnesbeck
CJ, Nikki McKoy J, Hartmann KE.

Author information:
(1)Vanderbilt Epidemiology Center, Institute for Medicine and Public Health, 2525
West End Ave., Suite 600 6th Floor, Nashville, TN 37203, USA.
digna.r.velez.edwards@vanderbilt.edu

PURPOSE: Progestogen has been investigated as a preventive intervention among
women with increased preterm birth risk. Our objective was to systematically
review the effectiveness of intramuscular (IM), vaginal, and oral progestogens
for preterm birth and neonatal death prevention.
METHODS: We included articles published from January 1966 to January 2013 and
found 27 randomized trials with data for Bayesian meta-analysis.
RESULTS: Across all studies, only vaginal and oral routes were effective at
reducing preterm births (IM risk ratio [RR] 0.95, 95 % Bayesian credible interval
[BCI]: 0.88-1.03; vaginal RR 0.87, 95 % BCI: 0.80-0.94; oral RR 0.64, 95 % BCI:
0.49-0.85). However, when analyses were limited to only single births all routes
were effective at reducing preterm birth (IM RR 0.77, 95 % BCI: 0.69-0.87;
vaginal RR 0.80, 95 % BCI: 0.69-0.91; oral RR 0.66, 95 % BCI: 0.47-0.84). Only IM
progestogen was effective at reducing neonatal deaths (IM RR 0.78, 95 % BCI:
0.56-0.99; vaginal RR 0.75, 95 % BCI: 0.45-1.09; oral RR 0.72, 95 % BCI:
0.09-1.74). Vaginal progestogen was effective in reducing neonatal deaths when
limited to singletons births.
CONCLUSIONS: All progestogen routes reduce preterm births but not neonatal
deaths. Future studies are needed that directly compare progestogen delivery
routes.

PMID: 23532387  [PubMed - indexed for MEDLINE]




131. Lancet Infect Dis. 2013 Jun;13(6):507-18. doi: 10.1016/S1473-3099(13)70071-9.
Epub 2013 Apr 4.

Soil-transmitted helminth infection in South America: a systematic review and
geostatistical meta-analysis.

Chammartin F(1), Scholte RG, Guimarães LH, Tanner M, Utzinger J, Vounatsou P.

Author information:
(1)Department of Epidemiology and Public Health, Swiss Tropical and Public Health
Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.

Comment in
    Lancet Infect Dis. 2014 Mar;14(3):184.
    Lancet Infect Dis. 2013 Jun;13(6):469-70.
    Lancet Infect Dis. 2014 Mar;14(3):183.

BACKGROUND: The four common soil-transmitted helminth species-Ascaris
lumbricoides, Trichuris trichiura, and the two hookworm species Ancylostoma
duodenale and Necator americanus-are endemic in South America, but their
distribution, infection prevalence, and regional burden are poorly understood. We
aimed to estimate the risk and number of people infected with A lumbricoides, T
trichiura, and hookworm across South America.
METHODS: We did a systematic review of reports on the prevalence of
soil-transmitted helminth infection in South America published up to May 14,
2012. We extracted and georeferenced relevant survey data and did a meta-analysis
of the data to assess the geographical distribution of the infection risk with
Bayesian geostatistical models. We used advanced Bayesian variable selection to
identify environmental determinants that govern the distribution of
soil-transmitted helminth infections.
FINDINGS: We screened 4085 scientific papers and identified 174 articles
containing relevant survey prevalence data. We georeferenced 6948 survey
locations and entered the data into the open-access Global Neglected Tropical
Diseases database. Survey data were sparse for the south of the continent and for
the western coast, and we identified no relevant information for Uruguay and
little data for smaller countries such as Suriname, Guyana, French Guiana, and
Ecuador. Population-adjusted prevalence of infection with A lumbricoides was
15·6%, with T trichiura was 12·5%, and with hookworm was 11·9% from 2005 onwards.
Risks of contracting soil-transmitted helminth infection have substantially
reduced since 2005 (odds ratio 0·47 [95% Bayesian credible interval 0·46-0·47]
for A lumbricoides, 0·54 [0·54-0·55] for T trichiura, and 0·58 [0·58-0·59] for
hookworm infection).
INTERPRETATION: Our findings offer important baseline support for spatial
targeting of soil-transmitted helminthiasis control, and suggest that more
information about the prevalence of soil-transmitted helminth infection is
needed, especially in countries in which we estimate prevalence of infection to
be high but for which current data are scarce.
FUNDING: UBS Optimus Foundation and Brazilian Swiss Joint Research Programme
(BSJRP 011008).

Copyright © 2013 Elsevier Ltd. All rights reserved.

PMID: 23562238  [PubMed - indexed for MEDLINE]


132. Pediatrics. 2013 Jun;131(6):e1908-16. doi: 10.1542/peds.2013-0073. Epub 2013 May
20.

Magnetic resonance imaging for locating nonpalpable undescended testicles: a
meta-analysis.

Krishnaswami S(1), Fonnesbeck C, Penson D, McPheeters ML.

Author information:
(1)Department of Biostatistics, Vanderbilt University Medical Center, Nashville,
TN 37232, USA.

BACKGROUND AND OBJECTIVE: Preoperative imaging techniques may guide management of
nonpalpable, cryptorchid testicles. We evaluated conventional MRI for identifying
and locating nonpalpable testicles in prepubescent boys via meta-analysis.
METHODS: Databases including Medline were searched from 1980 to February 2012.
Eligible studies included ≥10 boys with cryptorchidism/suspected cryptorchidism
and reported data on testicular presence/absence and position (abdominal,
inguinal, or scrotal) as determined by imaging and surgery. Two investigators
independently reviewed studies against inclusion criteria. We captured the number
of testicles that were correctly and incorrectly identified and located, relative
to surgically verified status, and estimated sensitivity and specificity by using
a random-effects model.
RESULTS: Eight unique prospective case series included 171 boys with 193
nonpalpable testicles (22 with bilateral testicles). Surgery identified 158
testicles (81.9%) present and 35 absent. MRI correctly identified testicles with
an estimated median sensitivity of 0.62 (95% Bayesian credible interval [BCI]:
0.47-0.77) and a specificity of 1.0 (95% BCI: 0.99-1.0). MRI located
intraabdominal testicles with a sensitivity of 0.55 (95% BCI: 0.09-1.0) and
inguino-scrotal testicles with a sensitivity of 0.86 (95% BCI: 0.67-1.0). We were
not able to obtain estimates for MRI sensitivity or specificity for locating
atrophied testicles. The estimated specificity for location-specific testicles
reached almost 100%.
CONCLUSIONS: Conventional MRI has low sensitivity for estimating the population
sensitivity for identifying the presence of nonpalpable cryptorchid testicles.
When testicles are identified, MRI is poor at locating both atrophied and
intraabdominal testicles but performs modestly well in locating those in the
inguino-scrotal regions.

PMCID: PMC4074662
PMID: 23690512  [PubMed - indexed for MEDLINE]


133. Value Health. 2013 Jun;16(4):619-28. doi: 10.1016/j.jval.2013.02.007. Epub 2013
May 10.

Meta-analysis of the accuracy of two diagnostic tests used in combination:
application to the ddimer test and the wells score for the diagnosis of deep vein
thrombosis.

Novielli N(1), Sutton AJ, Cooper NJ.

Author information:
(1)Department of Health Sciences, University of Leicester, Leicester, UK.

OBJECTIVES: It is standard practice for diagnostic tests to be evaluated against
gold standards in isolation. In routine clinical practice, however, it is
commonplace for multiple tests to be used before making definitive diagnoses.
This article describes a meta-analytic modeling framework developed to estimate
the accuracy of the combination of two diagnostic tests, accounting for the
likely nonindependence of the tests.
METHODS: A novel multicomponent framework was developed to synthesize information
available on different parameters in the model. This allows data to be included
from studies evaluating single tests or both tests. Different likelihoods were
specified for the different sources of data and linked by means of common
parameters. The framework was applied to evaluate the diagnostic accuracy of the
Ddimer test and the Wells score for deep vein thrombosis, and the results were
compared with those of a model in which independence of tests was assumed. All
models were evaluated by using Bayesian Markov chain Monte Carlo simulation
methods.
RESULTS: The results showed the importance of allowing for the (likely)
nonindependence of tests in the meta-analysis model when evaluating a combination
of diagnostic tests. The analysis also highlighted the relatively limited impact
of those studies that evaluated only one of the two tests of interest.
CONCLUSIONS: The models developed allowed the assumption of independence between
diagnostic tests to be relaxed while combining a broad array of relevant
information from disparate studies. The framework also raises questions regarding
the utility of studies limited to the evaluation of single diagnostic tests.

Copyright © 2013 International Society for Pharmacoeconomics and Outcomes
Research (ISPOR). Published by Elsevier Inc. All rights reserved.

PMID: 23796297  [PubMed - indexed for MEDLINE]


134. Epidemiol Infect. 2013 May;141(5):893-904. doi: 10.1017/S0950268812002154. Epub
2012 Sep 27.

Three polymorphisms in the IL-10 gene and the risk of HCV infection: a
meta-analysis plus a Chinese Association Study involving 1140 subjects.

Li J(1), Liu Y, Xu F, Chen J, Chen Y.

Author information:
(1)Department of Infectious Diseases, the First Affiliated Hospital of Nanjing
Medical University, Nanjing, China.

The influence of an immunosuppressive cytokine, interleukin-10 (IL-10), on the
outcome of hepatitis C virus (HCV) infection has been increasingly reported
recently. A number of polymorphisms appear to control the level of IL-10
production. Among them, -592C/A, -819C/T and -1082G/A in the IL-10 gene are three
most studied single nucleotide polymorphisms. To provide a more definitive
conclusion about their association with the risk of HCV infection, a
meta-analysis was performed by combining and summarizing a total of 17 studies. A
biological justification for the choice of genetic model was provided. The
results indicated no significant association between these IL-10 polymorphisms
and the susceptibility to HCV infection [-592C/A: odds ratio (OR) 0.99, 95%
confidence interval (CI) 0.78-1.25; -819C/T: OR 0.90, 95% CI 0.69-1.18; -1082G/A:
OR 1.34, 95% CI 0.90-2.00]. However, this analysis did not account for the
possible risk modifications by other factors, such as ethnicity and virus
persistence. Therefore, the effects of ethnicity and virus persistence were
investigated using Bayesian meta-regression and subgroup analysis. Finally, an
extended case-control association study was conducted in a Chinese population
involving 1140 subjects. Both serum level and genotype data of IL-10 -1082G/A
were determined. As a result, a low prevalence of G allele was observed.
Significantly higher IL-10 production was observed in HCV patients, especially
patients with the GG genotype.

PMID: 23013641  [PubMed - indexed for MEDLINE]


135. Heart. 2013 May;99(9):601-13. doi: 10.1136/heartjnl-2012-301968. Epub 2012 Aug
21.

Blood pressure targets in patients with coronary artery disease: observations
from traditional and Bayesian random effects meta-analysis of randomised trials.

Bangalore S(1), Kumar S, Volodarskiy A, Messerli FH.

Author information:
(1)Division of Cardiology, New York University School of Medicine, New York, NY
10016, USA. sripalbangalore@gmail.com

CONTEXT: Most guidelines for treatment of hypertension including the Joint
National Committee-7 recommend a blood pressure (BP) goal of <140/90 mm Hg for
hypertensive patients and a more aggressive goal of <130/80 mm Hg for patients
with coronary artery disease (CAD), based largely on expert consensus.
OBJECTIVE: To evaluate the BP targets in patients with CAD DATA SOURCES: PUBMED,
EMBASE and CENTRAL Study Selection: Randomised clinical trials (RCTs) of
antihypertensive therapy in patients with CAD, enrolling at least 100 patients,
with achieved systolic pressure of <=135 mm Hg in the 'intensive BP' group and
<=140 mm Hg in the 'standard BP' group with follow-up for at least 1 year and
evaluating cardiovascular outcomes.
DATA EXTRACTION: The following efficacy outcomes were extracted- all-cause
mortality, cardiovascular mortality, myocardial infarction, stroke, angina
pectoris, heart failure and revascularisation.
RESULTS: We identified 15 RCTs enrolling 66,504 participants with 276,328
patient-years of follow-up. Intensive BP group (≤ 135 mm Hg) was associated with
a 15% decrease in heart failure rate and 10% decrease in stroke rate, driven
largely by trials with a more intensive BP group (≤ 130 mm Hg), with similar
outcomes for death and cardiovascular death and was associated with a 105%
increase in the risk of hypotension. More intensive BP group (≤ 130 mm Hg) was
also associated with a reduction in myocardial infarction and angina pectoris.
The results were similar in a Bayesian random effects model. In addition, lower
seemed to be better (based on regression analysis) for the outcomes of myocardial
infarction, stroke, heart failure and perhaps angina.
CONCLUSIONS: The present body of evidence suggests that in patients with CAD,
intensive systolic BP control to ≤ 135 mm Hg and possibly to ≤ 130 mm Hg is
associated with a modest reduction in stroke and heart failure but at the expense
of hypotension. Lower was better, although not consistently so for myocardial
infarction, stroke, heart failure and perhaps angina. Further trials are needed
to prove these findings.

PMID: 22914531  [PubMed - indexed for MEDLINE]


136. PLoS Genet. 2013 May;9(5):e1003509. doi: 10.1371/journal.pgen.1003509. Epub 2013
May 23.

Imputation-based meta-analysis of severe malaria in three African populations.

Band G(1), Le QS, Jostins L, Pirinen M, Kivinen K, Jallow M, Sisay-Joof F, Bojang
K, Pinder M, Sirugo G, Conway DJ, Nyirongo V, Kachala D, Molyneux M, Taylor T,
Ndila C, Peshu N, Marsh K, Williams TN, Alcock D, Andrews R, Edkins S, Gray E,
Hubbart C, Jeffreys A, Rowlands K, Schuldt K, Clark TG, Small KS, Teo YY,
Kwiatkowski DP, Rockett KA, Barrett JC, Spencer CC; Malaria Genomic Epidemiology
Network.

Author information:
(1)Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom.

Erratum in
    PLoS Genet. 2013 Jun;9(6).
doi:10.1371/annotation/adc2beaf-4bee-4e22-925b-6788d62fe029. Malaria Genomic
Epidemiological Network [corrected to Malaria Genomic Epidemiology Network].

Combining data from genome-wide association studies (GWAS) conducted at different
locations, using genotype imputation and fixed-effects meta-analysis, has been a
powerful approach for dissecting complex disease genetics in populations of
European ancestry. Here we investigate the feasibility of applying the same
approach in Africa, where genetic diversity, both within and between populations,
is far more extensive. We analyse genome-wide data from approximately 5,000
individuals with severe malaria and 7,000 population controls from three
different locations in Africa. Our results show that the standard approach is
well powered to detect known malaria susceptibility loci when sample sizes are
large, and that modern methods for association analysis can control the potential
confounding effects of population structure. We show that pattern of association
around the haemoglobin S allele differs substantially across populations due to
differences in haplotype structure. Motivated by these observations we consider
new approaches to association analysis that might prove valuable for multicentre
GWAS in Africa: we relax the assumptions of SNP-based fixed effect analysis; we
apply Bayesian approaches to allow for heterogeneity in the effect of an allele
on risk across studies; and we introduce a region-based test to allow for
heterogeneity in the location of causal alleles.

PMCID: PMC3662650
PMID: 23717212  [PubMed - indexed for MEDLINE]


137. Emerg Med J. 2013 Apr;30(4):280-6. doi: 10.1136/emermed-2012-201174. Epub 2012
May 16.

Heart-type fatty acid binding protein as an early marker for myocardial
infarction: systematic review and meta-analysis.

Carroll C(1), Al Khalaf M, Stevens JW, Leaviss J, Goodacre S, Collinson PO, Wang
J.

Author information:
(1)School of Health and Related Research, University of Sheffield, Sheffield, UK.

BACKGROUND: Heart-type fatty acid binding protein (H-FABP) has been proposed as
an early biomarker of myocardial infarction (MI). The authors aimed to undertake
a systematic review and meta-analysis to estimate the early sensitivity and
specificity of quantitative and qualitative H-FABP assays.
METHODS: The authors undertook a systematic search using electronic databases,
citation lists and expert contacts to identify all diagnostic cohort studies of
patients presenting with suspected acute coronary syndrome that compared H-FABP
at presentation to a reference standard based on the Universal definition of MI.
Study quality was assessed using the Quality Assessment of Diagnostic Accuracy
Studies tool. Meta-analysis was conducted using Bayesian Markov chain Monte Carlo
simulation.
RESULTS: The authors included eight studies of quantitative H-FABP and nine
studies of qualitative H-FABP. The summary estimates of sensitivity and
specificity were 81% (95% prediction interval 50% to 95%) and 80% (26% to 98%)
respectively for the quantitative assays and 68% (11% to 97%) and 92% (20% to
100%) respectively for the qualitative assays. Four studies reported the
sensitivity of troponin and H-FABP at presentation in which the combination was
considered positive if either test was positive. The addition of H-FABP to
troponin increased sensitivity from 42-75% to 76-97% but decreased specificity
from 94-100% to 65-93%.
CONCLUSION: H-FABP has modest sensitivity and specificity for MI at presentation
but estimates are subject to substantial uncertainty and primary data are subject
to substantial heterogeneity. H-FABP may have a role alongside troponin in
improving early sensitivity but comparison with high sensitivity troponin assays
is required.

PMID: 22593266  [PubMed - indexed for MEDLINE]


138. Int J Epidemiol. 2013 Apr;42(2):475-92. doi: 10.1093/ije/dyt034.

Apolipoprotein E genotype, cardiovascular biomarkers and risk of stroke:
systematic review and meta-analysis of 14,015 stroke cases and pooled analysis of
primary biomarker data from up to 60,883 individuals.

Khan TA(1), Shah T, Prieto D, Zhang W, Price J, Fowkes GR, Cooper J, Talmud PJ,
Humphries SE, Sundstrom J, Hubacek JA, Ebrahim S, Lawlor DA, Ben-Shlomo Y,
Abdollahi MR, Slooter AJ, Szolnoki Z, Sandhu M, Wareham N, Frikke-Schmidt R,
Tybjærg-Hansen A, Fillenbaum G, Heijmans BT, Katsuya T, Gromadzka G, Singleton A,
Ferrucci L, Hardy J, Worrall B, Rich SS, Matarin M, Whittaker J, Gaunt TR,
Whincup P, Morris R, Deanfield J, Donald A, Davey Smith G, Kivimaki M, Kumari M,
Smeeth L, Khaw KT, Nalls M, Meschia J, Sun K, Hui R, Day I, Hingorani AD, Casas
JP.

Author information:
(1)Faculty of Epidemiology and Population Health, London School of Hygiene and
Tropical Medicine, London, UK.

BACKGROUND: At the APOE gene, encoding apolipoprotein E, genotypes of the
ε2/ε3/ε4 alleles associated with higher LDL-cholesterol (LDL-C) levels are also
associated with higher coronary risk. However, the association of APOE genotype
with other cardiovascular biomarkers and risk of ischaemic stroke is less clear.
We evaluated the association of APOE genotype with risk of ischaemic stroke and
assessed whether the observed effect was consistent with the effects of APOE
genotype on LDL-C or other lipids and biomarkers of cardiovascular risk.
METHODS: We conducted a systematic review of published and unpublished studies
reporting on APOE genotype and ischaemic stroke. We pooled 41 studies (with a
total of 9027 cases and 61,730 controls) using a Bayesian meta-analysis to
calculate the odds ratios (ORs) for ischaemic stroke with APOE genotype. To
better evaluate potential mechanisms for any observed effect, we also conducted a
pooled analysis of primary data using 16 studies (up to 60,883 individuals) of
European ancestry. We evaluated the association of APOE genotype with lipids,
other circulating biomarkers of cardiovascular risk and carotid intima-media
thickness (C-IMT).
RESULTS: The ORs for association of APOE genotypes with ischaemic stroke were:
1.09 (95% credible intervals (CrI): 0.84-1.43) for ε2/ε2; 0.85 (95% CrI:
0.78-0.92) for ε2/ε3; 1.05 (95% CrI: 0.89-1.24) for ε2/ε4; 1.05 (95% CrI:
0.99-1.12) for ε3/ε4; and 1.12 (95% CrI: 0.94-1.33) for ε4/ε4 using the ε3/ε3
genotype as the reference group. A regression analysis that investigated the
effect of LDL-C (using APOE as the instrument) on ischaemic stroke showed a
positive dose-response association with an OR of 1.33 (95% CrI: 1.17, 1.52) per 1
mmol/l increase in LDL-C. In the separate pooled analysis, APOE genotype was
linearly and positively associated with levels of LDL-C (P-trend: 2 × 10(-152)),
apolipoprotein B (P-trend: 8.7 × 10(-06)) and C-IMT (P-trend: 0.001), and
negatively and linearly associated with apolipoprotein E (P-trend: 6 × 10(-26))
and HDL-C (P-trend: 1.6 × 10(-12)). Associations with lipoprotein(a), C-reactive
protein and triglycerides were non-linear.
CONCLUSIONS: In people of European ancestry, APOE genotype showed a positive
dose-response association with LDL-C, C-IMT and ischaemic stroke. However, the
association of APOE ε2/ε2 genotype with ischaemic stroke requires further
investigation. This cross-domain concordance supports a causal role of LDL-C on
ischaemic stroke.

PMCID: PMC3619955
PMID: 23569189  [PubMed - indexed for MEDLINE]


139. J Clin Periodontol. 2013 Apr;40(4):372-86. doi: 10.1111/jcpe.12028. Epub 2013 Jan
24.

Bayesian network meta-analysis of root coverage procedures: ranking efficacy and
identification of best treatment.

Buti J(1), Baccini M, Nieri M, La Marca M, Pini-Prato GP.

Author information:
(1)Department of Public Health, University of Florence, Florence, Italy.
ruijack@libero.it

Comment in
    J Evid Based Dent Pract. 2013 Dec;13(4):157-9.

AIMS: The aim of this work was to conduct a Bayesian network meta-analysis (NM)
of randomized controlled trials (RCTs) to establish a ranking in efficacy and the
best technique for coronally advanced flap (CAF)-based root coverage procedures.
MATERIAL AND METHODS: A literature search on PubMed, Cochrane libraries, EMBASE,
and hand-searched journals until June 2012 was conducted to identify RCTs on
treatments of Miller Class I and II gingival recessions with at least 6 months of
follow-up. The treatment outcomes were recession reduction (RecRed), clinical
attachment gain (CALgain), keratinized tissue gain (KTgain), and complete root
coverage (CRC).
RESULTS: Twenty-nine studies met the inclusion criteria, 20 of which were
classified as at high risk of bias. The CAF+connective tissue graft (CTG)
combination ranked highest in effectiveness for RecRed (Probability of being the
best = 40%) and CALgain (Pr = 33%); CAF+enamel matrix derivative (EMD) was
slightly better for CRC; CAF+Collagen Matrix (CM) appeared effective for KTgain
(Pr = 69%). Network inconsistency was low for all outcomes excluding CALgain.
CONCLUSION: CAF+CTG might be considered the gold standard in root coverage
procedures. The low amount of inconsistency gives support to the reliability of
the present findings.

© 2012 John Wiley & Sons A/S.

PMID: 23346965  [PubMed - indexed for MEDLINE]


140. Syst Rev. 2013 Mar 13;2:18. doi: 10.1186/2046-4053-2-18.

Systematic review and network meta-analysis of interventions for fibromyalgia: a
protocol.

Busse JW(1), Ebrahim S, Connell G, Coomes EA, Bruno P, Malik K, Torrance D, Ngo
T, Kirmayr K, Avrahami D, Riva JJ, Struijs P, Brunarski D, Burnie SJ, LeBlanc F,
Steenstra IA, Mahood Q, Thorlund K, Montori VM, Sivarajah V, Alexander P,
Jankowski M, Lesniak W, Faulhaber M, Bała MM, Schandelmaier S, Guyatt GH.

Author information:
(1)Department of Anesthesia, McMaster University, 1200 Main Street West,
Hamilton, Ontario, L8S 4K1, Canada. bussejw@mcmaster.ca

BACKGROUND: Fibromyalgia is associated with substantial socioeconomic loss and,
despite considerable research including numerous randomized controlled trials
(RCTs) and systematic reviews, there exists uncertainty regarding what treatments
are effective. No review has evaluated all interventional studies for
fibromyalgia, which limits attempts to make inferences regarding the relative
effectiveness of treatments.
METHODS/DESIGN: We will conduct a network meta-analysis of all RCTs evaluating
therapies for fibromyalgia to determine which therapies show evidence of
effectiveness, and the relative effectiveness of these treatments. We will
acquire eligible studies through a systematic search of CINAHL, EMBASE, MEDLINE,
AMED, HealthSTAR, PsychINFO, PapersFirst, ProceedingsFirst, and the Cochrane
Central Registry of Controlled Trials. Eligible studies will randomly allocate
patients presenting with fibromyalgia or a related condition to an intervention
or a control. Teams of reviewers will, independently and in duplicate, screen
titles and abstracts and complete full text reviews to determine eligibility, and
subsequently perform data abstraction and assess risk of bias of eligible trials.
We will conduct meta-analyses to establish the effect of all reported therapies
on patient-important outcomes when possible. To assess relative effects of
treatments, we will construct a random effects model within the Bayesian
framework using Markov chain Monte Carlo methods.
DISCUSSION: Our review will be the first to evaluate all treatments for
fibromyalgia, provide relative effectiveness of treatments, and prioritize
patient-important outcomes with a focus on functional gains. Our review will
facilitate evidence-based management of patients with fibromyalgia, identify key
areas for future research, and provide a framework for conducting large
systematic reviews involving indirect comparisons.

PMCID: PMC3610251
PMID: 23497523  [PubMed - indexed for MEDLINE]


141. Eur Rev Med Pharmacol Sci. 2013 Mar;17(5):658-67.

Ranking antireabsorptive agents to prevent vertebral fractures in postmenopausal
osteoporosis by mixed treatment comparison meta-analysis.

Migliore A(1), Broccoli S, Massafra U, Cassol M, Frediani B.

Author information:
(1)S. Pietro Fatebenefratelli Hospital, Rome, Italy. albertomigliore@terra.es

INTRODUCTION: Bisphosphonates are considered as a first-line therapy for the
prevention and treatment of osteoporosis, showing in double-blind, randomized,
controlled trials a significant reduction of incidence of new vertebral fractures
compared to placebo. Recently also, Denosumab has been shown to reduce the
appearance of new vertebral fractures by blocking RANK. There are not head to
head comparative studies between the above mentioned drugs. Mixed treatment
comparison, an extension of traditional meta-analysis, is able to compare
simultaneously several drugs across a range producing a synthetic evidence of
efficacy and a range of probability as to the best treatment.
OBJECTIVES: The aim of this study is to simultaneously compare alendronate,
risedronate, ibandronate, zolendronate and denosumab in the prevention of OP
vertebral fractures in a Bayesian meta-analysis for assessing indirect
comparisons.
MATERIALS AND METHODS: A search for randomized controlled trials involving
alendronate, risedronate, ibandronate, zolendronate and denosumab was conducted
using several databases. Randomized controlled trials (RCTs) with a double blind
treatment period of at least 3 years were included. Men and Glucorticoid Induced
osteoporosis, RCTs having as primary or secondary endpoints continuous values as
body mineral density (BMD) and studies comparing different dosing regimens of the
same agent, which are not used in clinical practice, were excluded. Only fully
published reports were considered.
RESULTS: A total of 9 RCTs were identiﬁed providing data on 31,393 participants.
Zolendronate had the highest probability (52%) of being the most effective
treatment towards placebo, followed by denosumab (46% probability), ibandronate
and then alendronate and risedronate against placebo.
CONCLUSIONS: Although the mixed treatment comparisons among alendronate,
risedronate, ibandronate, zolendronate and denosumab did not show a statistically
significant difference, this analysis suggests that zolendronate, compared to
placebo, is expected to provide the highest rate of reduction in vertebral
fractures affecting osteoporosis affected patients.

PMID: 23543450  [PubMed - indexed for MEDLINE]




143. JAMA Dermatol. 2013 Mar;149(3):341-9. doi: 10.1001/jamadermatol.2013.1721.

Efficacy of topical antifungals in the treatment of dermatophytosis: a
mixed-treatment comparison meta-analysis involving 14 treatments.

Rotta I(1), Ziegelmann PK, Otuki MF, Riveros BS, Bernardo NL, Correr CJ.

Author information:
(1)Pharmaceutical Sciences Postgraduate Program.

Comment in
    JAMA Dermatol. 2013 Oct;149(10):1243-4.
    JAMA Dermatol. 2013 Oct;149(10):1244.

IMPORTANCE: Considering that most randomized controlled trials compare
antifungals with placebo instead of other antifungals, conventional meta-analysis
is insufficient to define superiority between the evaluated strategies. To our
knowledge, this is the first mixed-treatment comparison meta-analysis on
antifungal treatments in the literature and shows all the evidence available at
the time of the study.
OBJECTIVE: To evaluate and compare the efficacy of topical antifungals used in
dermatophytosis treatment, using mixed-treatment comparisons.
EVIDENCE ACQUISITION: We performed a comprehensive search (up to July 31, 2012)
for all entries in MEDLINE, Cochrane Central Register of Controlled Trials,
EMBASE, Literatura Latino Americana e do Caribe em Ciências da Saúde, and
International Pharmaceutical Abstracts. Randomized controlled trials that
compared topical antifungals with one another or with placebo in dermatophytosis
treatment were selected for analysis. Methodologic quality of the trials was
assessed using the Jadad scale. We excluded studies that scored less than 3
points. The outcomes evaluated were mycologic cure at the end of treatment and
sustained cure. A random-effects Bayesian mixed-treatment comparisons model was
applied to combine placebo-controlled and direct topical antifungals comparison
trials. RESULTS Pooled data of the 65 trials identified did not show any
statistically significant differences among the antifungals concerning the
outcome of mycologic cure at the end of treatment. Regarding the sustained cure
outcome, butenafine hydrochloride and terbinafine hydrochloride were
significantly more efficacious than were clotrimazole, oxiconazole nitrate, and
sertaconazole nitrate. Terbinafine also demonstrated statistical superiority when
compared with ciclopirox (ciclopiroxolamine), and naftifine hydrochloride showed
better response compared with oxiconazole. No inconsistency was detected in the
network of evidence for both outcomes, sustaining the validity of the
mixed-treatment comparisons results.
CONCLUSIONS AND RELEVANCE: With the outcome mycologic cure at the end of
treatment, there was no significant difference among the antifungals. Butenafine,
naftifine, and terbinafine might be the best strategies for maintaining cured
status. Because of the different costs of the antifungals, pharmacoeconomic
analysis is required to identify the most efficient strategy for dermatophytosis
management.

PMID: 23553036  [PubMed - indexed for MEDLINE]


144. Value Health. 2013 Mar-Apr;16(2):403-17. doi: 10.1016/j.jval.2012.10.019. Epub
2013 Jan 26.

Progression-free survival with fulvestrant 500 mg and alternative endocrine
therapies as second-line treatment for advanced breast cancer: a network
meta-analysis with parametric survival models.

Cope S(1), Ouwens MJ, Jansen JP, Schmid P.

Author information:
(1)MAPI Consultancy, Boston, MA 02114, USA.

BACKGROUND: Ouwens et al. and Jansen have presented methods for (network)
meta-analysis of survival data by using a multidimensional treatment effect as an
alternative to the synthesis of constant hazards ratios, which allow for a better
fit to the data and the expected survival of competing interventions for
cost-effectiveness analysis. However, results may be sensitive to the assumed
underlying survival function.
OBJECTIVE: To estimate the expected progression-free survival (PFS) for
fulvestrant 500 mg versus alternative hormonal therapies for postmenopausal women
with advanced breast cancer who relapsed previously by means of a network
meta-analysis of currently available randomized controlled trials using
alternative underlying survival functions.
METHODS: Eleven randomized controlled trials were included that evaluated
fulvestrant 500 mg (n = 3), fulvestrant 250 mg (n = 5), fulvestrant 250 mg
loading dose (n = 3), anastrozole 1 mg (n = 3), megestrol acetate (n = 4),
letrozole 2.5 mg (n = 3), letrozole 0.5 mg (n = 3), and exemestane (n = 2). PFS
percentages and numbers at risk were derived from Kaplan-Meier curves and
combined by means of Bayesian network meta-analysis on the basis of the
difference in the shape and scale parameters of the Weibull, log-normal, and
log-logistic parametric survival functions.
RESULTS: The log-normal distribution provided the best fit, suggesting that the
proportional hazard assumption was not valid. Based on the difference in expected
PFS, it was found that fulvestrant 500 mg is more efficacious than fulvestrant
250 mg, megestrol acetate, and anastrozole (-5.73 months; 95% credible interval
[CrI]-10.67,-1.67). Expected PFS for fulvestrant 500 mg ranged from 10.87 (95%
CrI 9.21, 13.07) to 17.02 (95% CrI 13.33, 22.02) months for the Weibull versus
log-logistic distribution.
CONCLUSIONS: Fulvestrant 500 mg is expected to be more efficacious than
fulvestrant 250 mg, megestrol acetate, and anastrozole 1 mg and at least as
efficacious as exemestane and letrozole 2.5 mg in terms of PFS among
postmenopausal women with advanced breast cancer after failure on endocrine
therapy. The findings were not sensitive to the distribution, although the
expected PFS varied substantially, emphasizing the importance of performing
sensitivity analyses.

Copyright © 2013 International Society for Pharmacoeconomics and Outcomes
Research (ISPOR). Published by Elsevier Inc. All rights reserved.

PMID: 23538193  [PubMed - indexed for MEDLINE]


145. Clin Nutr. 2013 Feb;32(1):8-15. doi: 10.1016/j.clnu.2012.07.002. Epub 2012 Jul
31.

Effect of gastric versus post-pyloric feeding on the incidence of pneumonia in
critically ill patients: observations from traditional and Bayesian
random-effects meta-analysis.

Jiyong J(1), Tiancha H, Huiqin W, Jingfen J.

Author information:
(1)Neurological Intensive Care Unit, The Second Affiliated Hospital, School of
Medicine, Zhejiang University, Jiefang Road 88#, Hangzhou 310009, Zhejiang
Province, China. Jiyong_jing@hotmail.com

BACKGROUND & AIMS: Administration of enteral feeding is associated with a higher
risk of nosocomial pneumonia. Herein, we systematically review the impact of
gastric versus post-pyloric feeding on the incidence of pneumonia.
METHODS: We searched the MEDLINE, EMBASE, Web of Science, and CCTRD (1966 to
August 2011) for studies comparing gastric and post-pyloric feeding in critically
ill patients. Two reviewers reviewed the quality of the studies and performed
data extraction independently. Main outcome measures were the incidence of
nosocomial pneumonia, aspiration, and vomiting. The meta-analysis was performed
using traditional and Bayesian random-effects model.
RESULTS: Our initial searches yielded 563 studies. Of these, we identified 15
randomized clinical trials enrolling 966 participants. Post-pyloric feeding was
associated with reduction in pneumonia compared with gastric feeding (relative
risk [RR] 0.63, 95% confidence interval [CI] 0.48-0.83, p = 0.001; I² = 0%). The
risk of aspiration (RR, 1.11; 95% CI, 0.80-1.53, p = 0.55; I² = 0%) and vomiting
(RR, 0.80; 95% CI, 0.38-1.67, p = 0.56; I² = 65.3%) were not significantly
different between patients treated with gastric and post-pyloric feeding.
CONCLUSIONS: Comparing with gastric feeding, post-pyloric route can reduce
incidence of pneumonia in critically ill patients.

Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

PMID: 22853861  [PubMed - indexed for MEDLINE]


146. QJM. 2013 Feb;106(2):153-63. doi: 10.1093/qjmed/hcs214. Epub 2012 Nov 17.

Direct-acting antiviral therapies for hepatitis C genotype 1 infection: a
multiple treatment comparison meta-analysis.

Cooper C(1), Lester R, Thorlund K, Druyts E, El Khoury AC, Yaya S, Mills EJ.

Author information:
(1)Division of Infectious Diseases, Department of Medicine, The Ottawa Hospital,
University of Ottawa, 501 Smyth Road, Ottawa, ON, Canada K1H 8L6.

BACKGROUND: New direct-acting antiviral agents for hepatitis C genotype 1
infection, boceprevir and telaprevir, offer enhanced sustained virologic response
(SVR) among both treatment-naïve and treatment-experienced patients.
AIM: To determine the relative efficacy of the new direct-acting antiviral agents
by applying a multiple treatment comparison meta-analysis.
DESIGN: We included published Phase II and III randomized controlled trials
evaluating head-to-head comparisons between boceprevir, telaprevir,
peg-interferon alpha-2a with ribavirin and peg-interferon alpha-2b with ribavirin
in hepatitis C genotype 1 patients. We applied Bayesian multiple treatment
comparison meta-analysis.
RESULTS: We included data from four boceprevir, three telaprevir and six
peg-interferon alpha-2a plus ribavirin vs. peg-interferon alpha-2b plus ribavirin
randomized controlled trials. Both boceprevir and telaprevir offer statistically
superior outcomes for SVR, relapse and discontinuation due to adverse events than
either peg-interferons among both treatment-naïve and treatment-experienced
patients. Among treatment-naïve patients, clinical outcomes were similar for
boceprevir and telaprevir, for SVR [odds ratio (OR) 0.90, 95% credible interval
(95% CrI) 0.41-1.91] and for relapse (OR 1.09, 95% CrI 0.19-4.84). Similarly,
among treatment-experienced patients, clinical outcomes were similar for
boceprevir and telaprevir and for SVR (OR 1.45, 95% CrI 0.70-3.08) and for
relapse (OR 0.35, 95% CrI 0.13-1.02). For treatment-naïve patients receiving
standard-duration therapy, telaprevir yielded lower rates of anemia and
neutropenia, but higher rates of rash and pruritus. For treatment-experience
patients, all adverse event rates were higher with telaprevir.
DISCUSSION: Boceprevir and telaprevir exhibit similar effects among hepatitis C
genotype 1 treatment-naïve and treatment-experienced patients.

PMCID: PMC3550598
PMID: 23159839  [PubMed - indexed for MEDLINE]


147. BMJ. 2013 Jan 16;346:f55. doi: 10.1136/bmj.f55.

Benefits of β blockers in patients with heart failure and reduced ejection
fraction: network meta-analysis.

Chatterjee S(1), Biondi-Zoccai G, Abbate A, D'Ascenzo F, Castagno D, Van Tassell
B, Mukherjee D, Lichstein E.

Author information:
(1)Division of Internal Medicine, Maimonides Medical Center, New York, NY, USA.
sauravchatterjeemd@gmail.com

Erratum in
    BMJ. 2013;346:f596.

Comment in
    Ann Intern Med. 2013 May 21;158(10):JC2-3.
    BMJ. 2013;346:f480.

OBJECTIVE: To clarify whether any particular β blocker is superior in patients
with heart failure and reduced ejection fraction or whether the benefits of these
agents are mainly due to a class effect.
DESIGN: Systematic review and network meta-analysis of efficacy of different β
blockers in heart failure.
DATA SOURCES: CINAHL(1982-2011), Cochrane Collaboration Central Register of
Controlled Trials (-2011), Embase (1980-2011), Medline/PubMed (1966-2011), and
Web of Science (1965-2011).
STUDY SELECTION: Randomized trials comparing β blockers with other β blockers or
other treatments.
DATA EXTRACTION: The primary endpoint was all cause death at the longest
available follow-up, assessed with odds ratios and Bayesian random effect 95%
credible intervals, with independent extraction by observers.
RESULTS: 21 trials were included, focusing on atenolol, bisoprolol, bucindolol,
carvedilol, metoprolol, and nebivolol. As expected, in the overall analysis, β
blockers provided credible mortality benefits in comparison with placebo or
standard treatment after a median of 12 months (odds ratio 0.69, 0.56 to 0.80).
However, no obvious differences were found when comparing the different β
blockers head to head for the risk of death, sudden cardiac death, death due to
pump failure, or drug discontinuation. Accordingly, improvements in left
ventricular ejection fraction were also similar irrespective of the individual
study drug.
CONCLUSION: The benefits of β blockers in patients with heart failure with
reduced ejection fraction seem to be mainly due to a class effect, as no
statistical evidence from current trials supports the superiority of any single
agent over the others.

PMCID: PMC3546627
PMID: 23325883  [PubMed - indexed for MEDLINE]


148. Br J Anaesth. 2013 Jan;110(1):21-7. doi: 10.1093/bja/aes344. Epub 2012 Sep 21.

Efficacy of adding clonidine to intrathecal morphine in acute postoperative pain:
meta-analysis.

Engelman E(1), Marsala C.

Author information:
(1)Department of Anaesthesia, CUB Hopital Erasme, Route de Lennik 808, 1070
Brussels, Belgium. eengelma@ulb.ac.be

BACKGROUND: Clonidine may be used along with intrathecal morphine for single-dose
postoperative analgesia in adults. The efficacy of this is not clear.
METHODS: A meta-analysis was performed for two endpoints of efficacy: the time to
first postoperative analgesia request and the amount of systemic morphine used
during the first 24 h after operation. A Bayesian inference supporting direct
statements about the probability of the magnitude of an effect was also used. The
frequency of the five adverse events (postoperative nausea or vomiting, sedation,
respiratory depression, pruritus, and hypotension) was analysed.
RESULTS: Clonidine increased the duration of analgesia by 1.63 h [95% confidence
interval (CI): 0.93-2.33]. There is a 90% probability that clonidine increases
the duration of postoperative analgesia by more than 75 min compared with
morphine alone. Clonidine reduced the amount of postoperative morphine by a mean
of 4.45 mg (95% CI: 1.40-7.49 mg). There is a probability of 90% to obtain a
decrease >2.3 mg but only 35% to obtain a decrease >5 mg. The incidence of
hypotension was the only adverse event increased by clonidine (odds ratio 1.78;
95% CI: 1.02-3.12).
CONCLUSIONS: The addition of clonidine to intrathecal morphine extends the time
to first analgesia and decreases the amount of morphine used. However, as the
effects are small, and the results heavily influenced by a study in which
intrathecal fentanyl was also given, this must be balanced with the increased
frequency of hypotension.

PMID: 23002167  [PubMed - indexed for MEDLINE]


149. Expert Opin Pharmacother. 2013 Jan;14(1):27-39. doi:
10.1517/14656566.2013.758713. Epub 2012 Dec 21.

Second-line treatments for the management of advanced renal cell carcinoma:
systematic review and meta-analysis.

Larkin J(1), Paine A, Tumur I, Cappelleri JC, Healey PJ Sr, Foley G, Mitchell S,
Kroes M, Chen C.

Author information:
(1)Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK.

OBJECTIVES: A systematic review/meta-analysis was conducted to assess the
effectiveness and safety of second-line treatments for advanced renal cell
carcinoma (RCC), which includes the vascular endothelial growth factor inhibitor
axitinib.
METHODS: Database searches were conducted to identify randomised controlled
trials (RCTs). Indirect comparisons using a fixed-effect Bayesian model were used
to assess the relative effectiveness of treatments and reported as hazard ratio
(HR) and 95% credible intervals (CrI).
RESULTS: Although 24 RCTs met eligibility criteria, only three studies were
included in the fixed-effect Bayesian meta-analysis, due to differences in
patient inclusion criteria/reported outcomes in the wider dataset. Robust
meta-analysis was restricted to the subgroup pretreated with cytokines. In terms
of progression-free survival (PFS), axitinib was superior compared with placebo
(HR = 0.25, 95% CrI: 0.17 - 0.38), sorafenib (HR = 0.46, 95% CrI: 0.32 - 0.68)
and pazopanib (HR = 0.47, 95% CrI: 0.26 - 0.85). An analysis including all
patients, regardless of previous first-line treatment, reported similar results.
There was no significant difference in PFS between sorafenib and pazopanib.
CONCLUSION: Results from the present study suggest that axitinib will be an
important treatment option to extend PFS in the management of advanced RCC in the
second-line setting. Ongoing research will define the optimal treatment algorithm
leading to a patient-focused treatment strategy.

PMID: 23256638  [PubMed - indexed for MEDLINE]


150. Health Technol Assess. 2013;17(1):v-vi, 1-188. doi: 10.3310/hta17010.

Systematic review, meta-analysis and economic modelling of diagnostic strategies
for suspected acute coronary syndrome.

Goodacre S(1), Thokala P, Carroll C, Stevens JW, Leaviss J, Al Khalaf M,
Collinson P, Morris F, Evans P, Wang J.

Author information:
(1)School of Health and Related Research (ScHARR), University of Sheffield,
Sheffield, UK.

BACKGROUND: Current practice for suspected acute coronary syndrome (ACS) involves
troponin testing 10-12 hours after symptom onset to diagnose myocardial
infarction (MI). Patients with a negative troponin can be investigated further
with computed tomographic coronary angiography (CTCA) or exercise
electrocardiography (ECG).
OBJECTIVES: We aimed to estimate the diagnostic accuracy of early biomarkers for
MI, the prognostic accuracy of biomarkers for major adverse cardiac adverse
events (MACEs) in troponin-negative patients, the diagnostic accuracy of CTCA and
exercise ECG for coronary artery disease (CAD) and the prognostic accuracy of
CTCA and exercise ECG for MACEs in patients with suspected ACS. We then aimed to
estimate the cost-effectiveness of using alternative biomarker strategies to
diagnose MI, and using biomarkers, CTCA and exercise ECG to risk-stratify
troponin-negative patients.
DATA SOURCES: We searched MEDLINE, MEDLINE In-Process & Other Non-Indexed
Citations; Cumulative Index of Nursing and Allied Health Literature (CINAHL),
EMBASE, Web of Science, Cochrane Central Database of Controlled Trials (CENTRAL),
Cochrane Database of Systematic Reviews (CDSR), NHS Database of Abstracts of
Reviews of Effects (DARE) and the Health Technology Assessment database from 1985
(CTCA review) or 1995 (biomarkers review) to November 2010, reviewed citation
lists and contacted experts to identify relevant studies.
REVIEW METHODS: Diagnostic studies were assessed using the Quality Assessment of
Diagnostic Accuracy Studies (QUADAS) tool and prognostic studies using a
framework adapted for the project. Meta-analysis was conducted using bayesian
Markov chain Monte Carlo simulation. We developed a decision-analysis model to
evaluate the cost-effectiveness of alternative biomarker strategies to diagnose
MI, and the cost-effectiveness of biomarkers, CTCA or exercise ECG to
risk-stratify patients with a negative troponin. Strategies were applied to a
theoretical cohort of patients with suspected ACS. Cost-effectiveness was
estimated as the incremental cost per quality-adjusted life-year (QALY) of each
strategy compared with the next most effective, taking a health-service
perspective and a lifetime horizon.
RESULTS: Sensitivity and specificity (95% predictive interval) were 77% (29-96%)
and 93% (46-100%) for troponin I, 80% (33-97%) and 91% (53-99%) for troponin T
(99th percentile threshold), 81% (50-95%) and 80% (26-98%) for quantitative
heart-type fatty acid-binding protein (H-FABP), 68% (11-97%) and 92% (20-100%)
for qualitative H-FABP, 77% (19-98%) and 39% (2-95%) for ischaemia-modified
albumin and 62% (35-83%) and 83% (35-98%) for myoglobin. CTCA had 94% (61-99%)
sensitivity and 87% (16-100%) specificity for CAD. Positive CTCA and
positive-exercise ECG had relative risks of 5.8 (0.6-24.5) and 8.0 (2.3-22.7) for
MACEs. In most scenarios in the economic analysis presentation, high-sensitivity
troponin measurement was the most effective strategy with an incremental
cost-effectiveness ratio (ICER) of less than the £20,000-30,000/QALY threshold
(ICER £7487-17,191/QALY). CTCA appeared to be the most cost-effective strategy
for patients with a negative troponin, with an ICER of £11,041/QALY. However,
when a lower MACE rate was assumed, CTCA had a high ICER (£262,061/QALY) and the
no-testing strategy was optimal.
LIMITATIONS: There was substantial variation between the primary studies and
heterogeneity in their results. Findings of the economic model were dependent on
assumptions regarding the value of detecting and treating positive cases.
CONCLUSIONS: Although presentation troponin has suboptimal sensitivity,
measurement of a 10-hour troponin level is unlikely to be cost-effective in most
scenarios compared with a high-sensitivity presentation troponin. CTCA may be a
cost-effective strategy for troponin-negative patients, but further research is
required to estimate the effect of CTCA on event rates and health-care costs.
FUNDING: The National Institute for Health Research Health Technology Assessment
programme.

PMID: 23331845  [PubMed - indexed for MEDLINE]


151. Int J Chron Obstruct Pulmon Dis. 2013;8:405-23. doi: 10.2147/COPD.S48967. Epub
2013 Sep 9.

Comparative efficacy of aclidinium versus glycopyrronium and tiotropium, as
maintenance treatment of moderate to severe COPD patients: a systematic review
and network meta-analysis.

Karabis A(1), Lindner L, Mocarski M, Huisman E, Greening A.

Author information:
(1)MAPI Consultancy, AX Houten, The Netherlands. akarabis@mapigroup.com

BACKGROUND: Aclidinium bromide is a new long-acting muscarinic antagonist (LAMA)
indicated for maintenance bronchodilator treatment of chronic obstructive
pulmonary disease (COPD). The efficacy of aclidinium was compared with tiotropium
and glycopyrronium, using a network meta-analysis (NMA) of randomized controlled
trials (RCTs) in moderate-to-severe COPD patients.
METHODS: A systematic review was performed to identify RCTs evaluating aclidinium
400 μg twice daily (BID), glycopyrronium 50 μg once daily (OD), tiotropium 18 μg
OD, or tiotropium 5 μg OD in adults with moderate-to-severe COPD. The outcomes of
interest were: trough forced expiratory volume in 1 second (FEV1); St George's
Respiratory Questionnaire (SGRQ) total score and proportion of patients achieving
≥4 unit change; Transition Dyspnea Index (TDI) focal score and proportion of
patients achieving ≥1 point change. The results were synthesized by means of a
Bayesian NMA.
RESULTS: Twenty-one studies (22,542 patients) were included: aclidinium 400 μg
BID (three studies); tiotropium 5 μg OD (three studies); tiotropium 18 μg OD (13
studies); and glycopyrronium 50 μg OD (two studies). Regarding trough FEV1 at 24
weeks, aclidinium demonstrated comparable efficacy to tiotropium 5 μg (difference
in change from baseline [CFB]), (0.02 L [95% credible interval CrI -0.05, 0.09]);
tiotropium 18 μg (0.02 L [95% CrI -0.05, 0.08]); and glycopyrronium (0.00 L [95%
CrI -0.07, 0.07]). Aclidinium resulted in higher improvement in SGRQ score at 24
weeks, compared to tiotropium 5 μg (difference in CFB, -2.44 [95% CrI -4.82,
-0.05]); and comparable results to tiotropium 18 μg (-1.80 [95% CrI -4.52, 0.14])
and glycopyrronium (-1.52 [95% CrI -4.08, 1.03]). Improvements in TDI score were
comparable for all treatments.
CONCLUSION: Maintenance treatment with aclidinium 400 μg BID is expected to
produce similar improvements in lung function, health-related quality of life,
and dyspnea compared to tiotropium 5 μg OD; tiotropium 18 μg OD; and
glycopyrronium 50 μg OD.

PMCID: PMC3772873
PMID: 24043936  [PubMed - indexed for MEDLINE]


152. Int J Vitam Nutr Res. 2013;83(2):101-11. doi: 10.1024/0300-9831/a000149.

Protective effects of vitamin E on chemotherapy-induced peripheral neuropathy: a
meta-analysis of randomized controlled trials.

Eum S(1), Choi HD(1), Chang MJ(2), Choi HC(3), Ko YJ(3), Ahn JS(3), Shin WG(1),
Lee JY(4).

Author information:
(1)Department of Clinical Pharmacy, College of Pharmacy, Seoul National
University, South Korea. (2)College of Pharmacy, Yonsei University, Gyeonggi-do,
South Korea. (3)Department of Family Medicine, Seoul National University
Hospital, South Korea. (4)College of Pharmacy, Institute of Pharmaceutical
Science and Technology, Hanyang University, Gyeonggi-do, South Korea.

PURPOSE: This study aimed to investigate the neuroprotective effects of vitamin E
for preventing chemotherapy-induced peripheral neuropathy (CIPN).
METHODS: A comprehensive search from 1973 through July 2011 identified randomized
controlled trials (RCTs) that reported the preventive effects of vitamin E on
CIPN. The relative risk (RR) of CIPN with vitamin E supplementation, compared
with placebo, was assessed with the Bayesian random effect model and expressed as
RR with a 95 % credible-interval (CrI). Bayesian outcome probabilities were
calculated as the probability (P) of RR < 1.
RESULTS: Five RCTs, involving 319 patients, were identified. Upon pooling these
RCTs, vitamin E supplementation (300 - 600 mg/day) had a significant effect on
CIPN prevention (RR 0.43; 95 % CrI 0.10 - 1.00, P = 97.5 %). Subgroup analysis by
chemotherapeutic agent type was only available for cisplatin and showed that
vitamin E supplementation significantly reduced the incidence of CIPN (RR 0.26;
95 % CrI 0.06 - 0.89, P = 98.1 %). Furthermore, there were no adverse effects
caused by vitamin E supplementation in any of the RCTs.
CONCLUSION: Available data included in this meta-analysis show that vitamin E
supplementation might significantly prevent CIPN. Currently, however, the data
are insufficient to confidently conclude the true value. Large-scale, rigorously
designed RCTs are needed to confirm the role of vitamin E supplementation in CIPN
prevention.

PMID: 24491883  [PubMed - indexed for MEDLINE]


153. J Clin Periodontol. 2013 Jan;40(1):53-64. doi: 10.1111/jcpe.12011. Epub 2012 Oct
11.

In-office treatment for dentin hypersensitivity: a systematic review and network
meta-analysis.

Lin PY(1), Cheng YW, Chu CY, Chien KL, Lin CP, Tu YK.

Author information:
(1)Department of Dentistry, School of Dentistry, National Taiwan University and
National Taiwan University Hospital, Taipei, Taiwan.

AIM: Dentin hypersensitivity, caused by the exposure and patency of dentinal
tubules, can affect patients' quality of life. The aim of this study was to
undertake a systematic review and a network meta-analysis, comparing the
effectiveness in resolving dentin hypersensitivity among different in-office
desensitizing treatments.
MATERIALS AND METHODS: A literature search was performed with electronic
databases and by hand until December 2011. The included trials were divided into
six treatment groups as placebo, physical occlusion, chemical occlusion, nerve
desensitization, laser therapy and combined treatments. The treatment effects
between groups were estimated with standardized mean differences by using a
Bayesian network meta-analysis.
RESULTS: Forty studies were included. The standardized mean difference between
placebo and physical occlusion was -2.57 [95% credible interval (CI): -4.24 to
-0.94]; placebo versus chemical occlusion was -2.33 (95% CI: -3.65 to -1.04);
placebo versus nerve desensitization was -1.72 (95% CI: -4.00 to 0.52); placebo
versus laser therapy was -2.81 (95% CI: -4.41 to -1.24); placebo versus combined
treatment was -3.47 (95% CI: -5.99 to -0.96). The comparisons of the five active
treatments showed no significant differences.
CONCLUSIONS: The results from network meta-analysis showed that most active
treatment options had significantly better treatment outcome than placebo.

© 2012 John Wiley & Sons A/S.

PMID: 23057701  [PubMed - indexed for MEDLINE]


154. PLoS One. 2013 Dec 17;8(12):e82853. doi: 10.1371/journal.pone.0082853.
eCollection 2013.

Impact of different training modalities on anthropometric and metabolic
characteristics in overweight/obese subjects: a systematic review and network
meta-analysis.

Schwingshackl L(1), Dias S(2), Strasser B(3), Hoffmann G(1).

Author information:
(1)Department of Nutritional Sciences, Faculty of Life Sciences, University of
Vienna, Vienna, Austria. (2)School of Social and Community Medicine, University
of Bristol, Bristol, United Kingdom. (3)Institute of Nutritional Sciences and
Physiology, University for Health Sciences, Medical Informatics and Technology,
Hall in Tirol, Austria.

BACKGROUND: The aim of this systematic review of randomized controlled trials was
to compare the effects of aerobic training (AET), resistance training (RT), and
combined aerobic and resistance training (CT) on anthropometric parameters, blood
lipids, and cardiorespiratory fitness in overweight and obese subjects.
METHODS: Electronic searches for randomized controlled trials were performed in
MEDLINE, EMBASE and the Cochrane Trial Register. Inclusion criteria were: Body
Mass Index: ≥25 kg/m(2), 19+ years of age, supervised exercise training, and a
minimum intervention period of 8 weeks. Anthropometric outcomes, blood lipids,
and cardiorespiratory fitness parameters were included. Pooled effects were
calculated by inverse-variance random effect pairwise meta-analyses and Bayesian
random effects network meta-analyses.
FINDINGS: 15 trials enrolling 741 participants were included in the
meta-analysis. Compared to RT, AET resulted in a significantly more pronounced
reduction of body weight [mean differences (MD): -1.15 kg, p = 0.04], waist
circumference [MD: -1.10 cm, p = 0.004], and fat mass [MD: -1.15 kg, p = 0.001]
respectively. RT was more effective than AET in improving lean body mass [MD:
1.26 kg, p<0.00001]. When comparing CT with RT, MD in change of body weight [MD:
-2.03 kg, p<0.0001], waist circumference [MD: -1.57 cm, p = 0.0002], and fat mass
[MD: -1.88 kg, p<0.00001] were all in favor of CT. Results from the network
meta-analyses confirmed these findings.
CONCLUSION: Evidence from both pairwise and network meta-analyses suggests that
CT is the most efficacious means to reduce anthropometric outcomes and should be
recommended in the prevention and treatment of overweight, and obesity whenever
possible.

PMCID: PMC3866267
PMID: 24358230  [PubMed - indexed for MEDLINE]


155. PLoS One. 2013 Nov 13;8(11):e79203. doi: 10.1371/journal.pone.0079203.
eCollection 2013.

A Bayesian meta-analysis on prevalence of hepatitis B virus infection among
Chinese volunteer blood donors.

Liu GC(1), Sui GY, Liu GY, Zheng Y, Deng Y, Gao YY, Wang L.

Author information:
(1)School of Public Health, China Medical University, Shenyang, Liaoning, PR
China.

Erratum in
    PLoS One. 2014;9(8):e105458.

BACKGROUND: Although transfusion-transmitted infection of hepatitis B virus (HBV)
threatens the blood safety of China, the nationwide circumstance of HBV infection
among blood donors is still unclear.
OBJECTIVES: To comprehensively estimate the prevalence of HBsAg positive and HBV
occult infection (OBI) among Chinese volunteer blood donors through bayesian
meta-analysis.
METHODS: We performed an electronic search in Pub-Med, Web of Knowledge, Medline,
Wanfang Data and CNKI, complemented by a hand search of relevant reference lists.
Two authors independently extracted data from the eligible studies. Then two
bayesian random-effect meta-analyses were performed, followed by bayesian
meta-regressions.
RESULTS: 5957412 and 571227 donors were identified in HBsAg group and OBI group,
respectively. The pooled prevalence of HBsAg group and OBI group among donors is
1.085% (95% credible interval [CI] 0.859%~1.398%) and 0.094% (95% CI
0.0578%~0.1655%). For HBsAg group, subgroup analysis shows the more developed
area has a lower prevalence than the less developed area; meta-regression
indicates there is a significant decreasing trend in HBsAg positive prevalence
with sampling year (beta = -0.1202, 95% -0.2081~-0.0312).
CONCLUSION: Blood safety against HBV infection in China is suffering serious
threats and the government should take effective measures to improve this
situation.

PMCID: PMC3827339
PMID: 24236110  [PubMed - indexed for MEDLINE]


156. PLoS One. 2013 Oct 24;8(10):e76635. doi: 10.1371/journal.pone.0076635.
eCollection 2013.

The global epidemiology and contribution of cannabis use and dependence to the
global burden of disease: results from the GBD 2010 study.

Degenhardt L(1), Ferrari AJ, Calabria B, Hall WD, Norman RE, McGrath J, Flaxman
AD, Engell RE, Freedman GD, Whiteford HA, Vos T.

Author information:
(1)National Drug and Alcohol Research Centre, University of New South Wales,
Sydney, New South Wales, Australia ; Melbourne School of Population and Global
Health, University of Melbourne, Melbourne, Victoria, Australia.

AIMS: Estimate the prevalence of cannabis dependence and its contribution to the
global burden of disease.
METHODS: Systematic reviews of epidemiological data on cannabis dependence
(1990-2008) were conducted in line with PRISMA and meta-analysis of Observational
Studies in Epidemiology (MOOSE) guidelines. Culling and data extraction followed
protocols, with cross-checking and consistency checks. DisMod-MR, the latest
version of generic disease modelling system, redesigned as a Bayesian
meta-regression tool, imputed prevalence by age, year and sex for 187 countries
and 21 regions. The disability weight associated with cannabis dependence was
estimated through population surveys and multiplied by prevalence data to
calculate the years of life lived with disability (YLDs) and disability-adjusted
life years (DALYs). YLDs and DALYs attributed to regular cannabis use as a risk
factor for schizophrenia were also estimated.
RESULTS: There were an estimated 13.1 million cannabis dependent people globally
in 2010 (point prevalence0.19% (95% uncertainty: 0.17-0.21%)). Prevalence peaked
between 20-24 yrs, was higher in males (0.23% (0.2-0.27%)) than females (0.14%
(0.12-0.16%)) and in high income regions. Cannabis dependence accounted for 2
million DALYs globally (0.08%; 0.05-0.12%) in 2010; a 22% increase in crude DALYs
since 1990 largely due to population growth. Countries with statistically higher
age-standardised DALY rates included the United States, Canada, Australia, New
Zealand and Western European countries such as the United Kingdom; those with
lower DALY rates were from Sub-Saharan Africa-West and Latin America. Regular
cannabis use as a risk factor for schizophrenia accounted for an estimated 7,000
DALYs globally.
CONCLUSION: Cannabis dependence is a disorder primarily experienced by young
adults, especially in higher income countries. It has not been shown to increase
mortality as opioid and other forms of illicit drug dependence do. Our estimates
suggest that cannabis use as a risk factor for schizophrenia is not a major
contributor to population-level disease burden.

PMCID: PMC3811989
PMID: 24204649  [PubMed - indexed for MEDLINE]


157. PLoS One. 2013 Sep 18;8(9):e75357. doi: 10.1371/journal.pone.0075357. eCollection
2013.

Long-term survival of dental implants placed in the grafted maxillary sinus:
systematic review and meta-analysis of treatment modalities.

Duttenhoefer F(1), Souren C, Menne D, Emmerich D, Schön R, Sauerbier S.

Author information:
(1)Department of Oral and Craniomaxillofacial Surgery, University Hospital
Freiburg, Freiburg, Germany.

BACKGROUND: A prevalent modality to increase the amount of available bone prior
to implantation is grafting of the maxillary sinus. Multiple factors such as the
surgical technique, moment of implant placement as well as grafting materials and
membranes are known to affect implant survival. However, the role of different
factor combinations and associated reciprocal effects remain unclear.
Conventional statistical methods do not consider inconsistency of study designs
and do not take covariables into account. Hence, a systematic research and
meta-analysis was conducted to investigate the influence of various treatment
modalities on implant survival in the grafted maxillary sinus.
MATERIALS AND METHODS: A meta-analysis was conducted according to the PRISMA
guidelines. Articles published from 1980 through January 2013 were electronically
and manually searched in MEDLINE (Ovid), the Cochrane Register of Controlled
Trials, the Database of Abstracts of Effects, and the Cochrane Database of
Systematic Reviews. Clinical reports on single intervention sinus augmentation
with root-form implants, a minimum of 10 patients and 6 months of loading were
eligible for inclusion if implant survival was stated or calculable. Results were
calculated by non-parametric univariate Kaplan-Meier analysis and Bayesian
multivariate interval-censored Cox regression.
RESULTS: A total of 122 publications on 16268 endosseous implants placed in
grafted maxillary sinus were included. The treatment parameters surgical
approach, grafting material and implant type showed no selective preference.
However, application of membranes showed a significantly reduced hazard-ratio,
independent of other co-factors.
CONCLUSIONS: The use of membranes is the most significant factor to achieve
long-term implant survival in sinus augmentation procedures. More data exceeding
3 years follow-up are needed to address prospective confounding and improve
clinical evidence.

PMCID: PMC3776785
PMID: 24058679  [PubMed - indexed for MEDLINE]


158. PLoS One. 2013 Sep 5;8(9):e72697. doi: 10.1371/journal.pone.0072697. eCollection
2013.

Antiplatelets versus anticoagulants for the treatment of cervical artery
dissection: Bayesian meta-analysis.

Sarikaya H(1), da Costa BR, Baumgartner RW, Duclos K, Touzé E, de Bray JM, Metso
A, Metso T, Arnold M, Arauz A, Zwahlen M, Jüni P.

Author information:
(1)Department of Neurology, University Hospital of Zurich, Zurich, Switzerland ;
Department of Neurology, University Hospital of Bern, Bern, Switzerland.

OBJECTIVE: To compare the effects of antiplatelets and anticoagulants on stroke
and death in patients with acute cervical artery dissection.
DESIGN: Systematic review with Bayesian meta-analysis.
DATA SOURCES: The reviewers searched MEDLINE and EMBASE from inception to
November 2012, checked reference lists, and contacted authors.
STUDY SELECTION: Studies were eligible if they were randomised, quasi-randomised
or observational comparisons of antiplatelets and anticoagulants in patients with
cervical artery dissection.
DATA EXTRACTION: Data were extracted by one reviewer and checked by another.
Bayesian techniques were used to appropriately account for studies with scarce
event data and imbalances in the size of comparison groups.
DATA SYNTHESIS: Thirty-seven studies (1991 patients) were included. We found no
randomised trial. The primary analysis revealed a large treatment effect in
favour of antiplatelets for preventing the primary composite outcome of ischaemic
stroke, intracranial haemorrhage or death within the first 3 months after
treatment initiation (relative risk 0.32, 95% credibility interval 0.12 to 0.63),
while the degree of between-study heterogeneity was moderate (τ(2) = 0.18). In an
analysis restricted to studies of higher methodological quality, the possible
advantage of antiplatelets over anticoagulants was less obvious than in the main
analysis (relative risk 0.73, 95% credibility interval 0.17 to 2.30).
CONCLUSION: In view of these results and the safety advantages, easier usage and
lower cost of antiplatelets, we conclude that antiplatelets should be given
precedence over anticoagulants as a first line treatment in patients with
cervical artery dissection unless results of an adequately powered randomised
trial suggest the opposite.

PMCID: PMC3764185
PMID: 24039795  [PubMed - indexed for MEDLINE]


159. PLoS One. 2013;8(2):e54695. doi: 10.1371/journal.pone.0054695. Epub 2013 Feb 26.

Are Treponema pallidum specific rapid and point-of-care tests for syphilis
accurate enough for screening in resource limited settings? Evidence from a
meta-analysis.

Jafari Y(1), Peeling RW, Shivkumar S, Claessens C, Joseph L, Pai NP.

Author information:
(1)Department of Epidemiology, Biostatistics and Occupational Health, McGill
University, Montréal, Canada.

BACKGROUND: Rapid and point-of-care (POC) tests for syphilis are an invaluable
screening tool, yet inadequate evaluation of their diagnostic accuracy against
best reference standards limits their widespread global uptake. To fill this gap,
a systematic review and meta-analysis was conducted to evaluate the sensitivity
and specificity of rapid and POC tests in blood and serum samples against
Treponema pallidum (TP) specific reference standards.
METHODS: Five electronic databases (1980-2012) were searched, data was extracted
from 33 articles, and Bayesian hierarchical models were fit.
RESULTS: In serum samples, against a TP specific reference standard point
estimates with 95% credible intervals (CrI) for the sensitivities of popular
tests were: i) Determine, 90.04% (80.45, 95.21), ii) SD Bioline, 87.06% (75.67,
94.50), iii) VisiTect, 85.13% (72.83, 92.57), and iv) Syphicheck, 74.48% (56.85,
88.44), while specificities were: i) Syphicheck, 99.14% (96.37, 100), ii)
Visitect, 96.45% (91.92, 99.29), iii) SD Bioline, 95.85% (89.89, 99.53), and iv)
Determine, 94.15% (89.26, 97.66). In whole blood samples, sensitivities were: i)
Determine, 86.32% (77.26, 91.70), ii) SD Bioline, 84.50% (78.81, 92.61), iii)
Syphicheck, 74.47% (63.94, 82.13), and iv) VisiTect, 74.26% (53.62, 83.68), while
specificities were: i) Syphicheck, 99.58% (98.91, 99.96), ii) VisiTect, 99.43%
(98.22, 99.98), iii) SD Bioline, 97.95%(92.54, 99.33), and iv) Determine, 95.85%
(92.42, 97.74).
CONCLUSIONS: Rapid and POC treponemal tests reported sensitivity and specificity
estimates comparable to laboratory-based treponemal tests. In resource limited
settings, where access to screening is limited and where risk of patients lost to
follow up is high, the introduction of these tests has already been shown to
improve access to screening and treatment to prevent stillbirths and neonatal
mortality due to congenital syphilis. Based on the evidence, it is concluded that
rapid and POC tests are useful in resource limited settings with poor access to
laboratories or screening for syphilis.

PMCID: PMC3582640
PMID: 23468842  [PubMed - indexed for MEDLINE]


160. Ann Surg. 2012 Dec;256(6):894-901. doi: 10.1097/SLA.0b013e31826cc8da.

Should perioperative supplemental oxygen be routinely recommended for surgery
patients? A Bayesian meta-analysis.

Kao LS(1), Millas SG, Pedroza C, Tyson JE, Lally KP.

Author information:
(1)Center for Clinical Research and Evidence-Based Medicine, The University of
Texas Health Science Center at Houston, TX 77026, USA. Lillian.S.Kao@uth.tmc.edu

OBJECTIVE: The purpose of this study is to use updated data and Bayesian methods
to evaluate the effectiveness of hyperoxia to reduce surgical site infections
(SSIs) and/or mortality in both colorectal and all surgery patients. Because few
trials assessed potential harms of hyperoxia, hazards were not included.
BACKGROUND: Use of hyperoxia to reduce SSIs is controversial. Three recent
meta-analyses have had conflicting conclusions.
METHODS: A systematic literature search and review were performed. Traditional
fixed-effect and random-effect meta-analyses and Bayesian meta-analysis were
performed to evaluate SSIs and mortality.
RESULTS: Traditional meta-analysis yielded a relative risk of an SSI with
hyperoxia among all surgery patients of 0.84 [95% confidence interval (CI):
0.73-0.97] and 0.84 (95% CI: 0.61-1.16) for the fixed-effect and random-effect
models, respectively. The probabilities of any risk reduction in SSIs among all
surgery patients were 77%, 81%, and 83% for skeptical, neutral, and enthusiastic
priors. The subset analysis of colorectal surgery patients increased the
probabilities to 86%, 89%, and 92%. The probabilities of at least a 10% reduction
were 57%, 62%, and 68% for all surgery patients and 71%, 75%, and 80% among the
colorectal surgery subset.
CONCLUSIONS: There is a moderately high probability of a benefit to hyperoxia in
reducing SSIs in colorectal surgery patients; however, the magnitude of benefit
is relatively small and might not exceed treatment hazards. Further studies
should focus on generalizability to other patient populations or on treatment
hazards and other outcomes.

PMCID: PMC3504355
PMID: 23160100  [PubMed - indexed for MEDLINE]


161. Int J Antimicrob Agents. 2012 Dec;40(6):479-95. doi:
10.1016/j.ijantimicag.2012.08.004. Epub 2012 Oct 25.

A network meta-analysis of antibiotics for treatment of hospitalised patients
with suspected or proven meticillin-resistant Staphylococcus aureus infection.

Bally M(1), Dendukuri N, Sinclair A, Ahern SP, Poisson M, Brophy J.

Author information:
(1)Department of Epidemiology, Biostatistics and Occupational Health, Faculty of
Medicine, McGill University, 1020 Pine Avenue West, Montreal, QC H3A 1A2, Canada.
michele.bally.chum@ssss.gouv.qc.ca

Infections due to meticillin-resistant Staphylococcus aureus (MRSA) pose a
serious health risk. Novel methods for assessing comparative effectiveness and
safety may provide valuable insights into therapeutic choices. We did a
systematic review searching electronic databases including the archives of
FDA/CDER and performed a Bayesian network meta-analysis to compare parenteral
antibiotics used for treating hospitalised adults with complicated skin and
soft-tissue infections (cSSTIs) or hospital-acquired or ventilator-associated
pneumonia (HAP/VAP). Models were adjusted for clinical heterogeneity due to
between-arm differences in the proportion of patients with diabetes (for cSSTI)
and in those requiring mechanical ventilation (for pneumonia). Treatments were
ranked on efficacy, defined as clinical success in the modified
intention-to-treat population (MITT) and in the MITT population with MRSA at
baseline (MRSA m-MITT), on all-cause mortality (in pneumonia only), and on
serious adverse events and withdrawals due to adverse events. We identified 24
randomised controlled trials (17 for cSSTI and 10 for HAP/VAP) comparing one of
six antibiotics with vancomycin. The network meta-analysis indicated that
vancomycin ranked third (of six antibiotics) in cSSTI and second (of four) in
pneumonia on both efficacy and safety. However, direct pairwise meta-analyses
remained inconclusive as evidenced by the adjusted median odds ratios (ORs) and
their 95% credible intervals. In cSSTI, linezolid and ceftaroline were
non-significantly more effective than vancomycin. Linezolid ORs were 1.15
(0.74-1.71) and 1.01 (0.42-2.14) and ceftaroline ORs were 1.12 (0.78-1.64) and
1.59 (0.68-3.74) in the MITT and MRSA m-MITT populations, respectively. For
HAP/VAP, linezolid was non-significantly better than vancomycin, with ORs of 1.05
(0.72-1.57) and 1.32 (0.71-2.48) in the MITT and MRSA m-MITT populations,
respectively. We suspect performance and detection bias in cSSTI trials involving
linezolid, but regression methods could not adjust for this potential bias. In
these clinical trials, the preferred agents for treating serious MRSA infections
were ceftaroline (for cSSTI, not studied in HAP/VAP) and linezolid. However,
translation of these findings into practice should consider the small size of the
evidence networks and the consequent uncertainty associated with the parameter
estimates, the lack of evidence for ceftaroline in patients with severe renal
impairment, and the lower internal validity of some of the linezolid trials.

Copyright © 2012 Elsevier B.V. and the International Society of Chemotherapy. All
rights reserved.

PMID: 23102749  [PubMed - indexed for MEDLINE]


162. Am J Cardiol. 2012 Nov 15;110(10):1468-76. doi: 10.1016/j.amjcard.2012.07.007.
Epub 2012 Aug 17.

Meta-analysis of comparison of effectiveness of lowering apolipoprotein B versus
low-density lipoprotein cholesterol and nonhigh-density lipoprotein cholesterol
for cardiovascular risk reduction in randomized trials.

Robinson JG(1), Wang S, Jacobson TA.

Author information:
(1)University of Iowa, Iowa City, IA, USA. jennifer-g-robinson@uiowa.edu

This study evaluated the relation between apolipoprotein B (apoB) decrease and
coronary heart disease, stroke, and cardiovascular disease risk. Bayesian
random-effects meta-analysis was used to evaluate the association of mean
absolute apoB decrease (milligrams per deciliter) with relative risk of coronary
heart disease (nonfatal myocardial infarction and coronary heart disease death),
stroke (nonfatal stroke and fatal stroke), or cardiovascular disease (coronary
heart disease, stroke, and coronary revascularization). Analysis included 25
trials (n = 131,134): 12 on statin, 4 on fibrate, 5 on niacin, 2 on
simvastatin-ezetimibe, 1 on ileal bypass surgery, and 1 on aggressive versus
standard low-density lipoprotein (LDL) cholesterol and blood pressure targets.
Combining the 25 trials, each 10-mg/dl decrease in apoB was associated with a 9%
decrease in coronary heart disease, no decrease in stroke, and a 6% decrease in
major cardiovascular disease risk. Non-high-density lipoprotein (non-HDL)
cholesterol decrease modestly outperformed apoB decrease for prediction of
coronary heart disease (Bayes factor [BF] 1.45) and cardiovascular disease (BF
2.07) risk decrease; apoB decrease added to non-HDL cholesterol plus LDL
cholesterol decrease slightly improved cardiovascular disease risk prediction
(1.13) but did not improve coronary heart disease risk prediction (BF 1.03) and
worsened stroke risk prediction (BF 0.83). In the 12 statin trials, apoB and
non-HDL cholesterol decreases similarly predicted cardiovascular disease risk;
apoB improved coronary heart disease prediction when added to non-HDL
cholesterol/LDL cholesterol decrease (BF 3.33) but did not improve stroke risk
prediction when added to non-HDL cholesterol/LDL cholesterol decrease (BF 1.06).
In conclusion, across all drug classes, apoB decreases did not consistently
improve risk prediction over LDL cholesterol and non-HDL cholesterol decreases.
For statins, apoB decreases added information to LDL cholesterol and non-HDL
cholesterol decreases for predicting coronary heart disease but not stroke or
overall cardiovascular disease risk decrease.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID: 22906895  [PubMed - indexed for MEDLINE]


163. Am J Hum Genet. 2012 Nov 2;91(5):778-93. doi: 10.1016/j.ajhg.2012.08.026. Epub
2012 Oct 18.

Unraveling multiple MHC gene associations with systemic lupus erythematosus:
model choice indicates a role for HLA alleles and non-HLA genes in Europeans.

Morris DL(1), Taylor KE, Fernando MM, Nititham J, Alarcón-Riquelme ME, Barcellos
LF, Behrens TW, Cotsapas C, Gaffney PM, Graham RR, Pons-Estel BA, Gregersen PK,
Harley JB, Hauser SL, Hom G; International MHC and Autoimmunity Genetics Network,
Langefeld CD, Noble JA, Rioux JD, Seldin MF; Systemic Lupus Erythematosus
Genetics Consortium, Criswell LA, Vyse TJ.

Collaborators: Rioux JD, Goyette P, Vyse TJ, Hammarström L, Fernando MM, Green T,
De Jager PL, Foisy S, Wang J, de Bakker PI, Leslie S, McVean G, Padyukov L,
Alfredsson L, Annese V, Hafler DA, Pan-Hammarström Q, Matell R, Sawcer SJ,
Compston AD, Cree BA, Mirel DB, Daly MJ, Behrens TW, Klareskog L, Gregersen PK,
Oksenberg JR, Hauser SL, Harley JB, Alarcón-Riquelme ME, Criswell LA, Jacob CO,
Kimberly RP, Moser KL, Tsao BP, Vyse TJ, Langefeld CD.

Author information:
(1)Divisions of Genetics and Molecular Medicine and Immunology, Infection and
Inflammatory Disease, King's College London, London, UK.

We have performed a meta-analysis of the major-histocompatibility-complex (MHC)
region in systemic lupus erythematosus (SLE) to determine the association with
both SNPs and classical human-leukocyte-antigen (HLA) alleles. More specifically,
we combined results from six studies and well-known out-of-study control data
sets, providing us with 3,701 independent SLE cases and 12,110 independent
controls of European ancestry. This study used genotypes for 7,199 SNPs within
the MHC region and for classical HLA alleles (typed and imputed). Our results
from conditional analysis and model choice with the use of the Bayesian
information criterion show that the best model for SLE association includes both
classical loci (HLA-DRB1(∗)03:01, HLA-DRB1(∗)08:01, and HLA-DQA1(∗)01:02) and two
SNPs, rs8192591 (in class III and upstream of NOTCH4) and rs2246618 (MICB in
class I). Our approach was to perform a stepwise search from multiple baseline
models deduced from a priori evidence on HLA-DRB1 lupus-associated alleles, a
stepwise regression on SNPs alone, and a stepwise regression on HLA alleles. With
this approach, we were able to identify a model that was an overwhelmingly better
fit to the data than one identified by simple stepwise regression either on SNPs
alone (Bayes factor [BF] > 50) or on classical HLA alleles alone (BF > 1,000).

Copyright © 2012 The American Society of Human Genetics. Published by Elsevier
Inc. All rights reserved.

PMCID: PMC3487133
PMID: 23084292  [PubMed - indexed for MEDLINE]


164. Bone. 2012 Nov;51(5):969-74. doi: 10.1016/j.bone.2012.07.013. Epub 2012 Jul 26.

Association between beta-blockers and fracture risk: a Bayesian meta-analysis.

Yang S(1), Nguyen ND, Eisman JA, Nguyen TV.

Author information:
(1)Division of Musculoskeletal Diseases, Garvan Institute of Medical Research,
Australia.

BACKGROUND: The association between beta-blockers (BB) and fracture risk is
controversial, due largely to conflicting findings from previous studies. The
present study sought to evaluate the effect of BB on fracture risk by using a
Bayesian meta-analysis approach.
METHODS AND RESULTS: We systematically retrieved 13 observational studies on the
association between BB use and fracture risk. This meta-analysis involved more
than 907,000 men and women with mean/median age of individual studies ranging
from 43 to 81 years. We used a hierarchical Bayesian random effects model to
synthesize the results. BB use was associated with an average 17% reduction in
the risk of any fracture (risk ratio [RR] 0.83; 95% credible interval [CrI]:
0.71-0.93), hip fracture (RR 0.83; 95% CrI: 0.70-0.92) and vertebral fracture (RR
0.81; 95% CrI: 0.61-0.99). The probability that BB use reduces fracture risk by
at least 10% was 0.91.
CONCLUSIONS: Beta-blockers are associated with reduced risk of fracture in older
adults, but the effect size is likely to be modest.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID: 22842220  [PubMed - indexed for MEDLINE]


165. Curr Med Res Opin. 2012 Nov;28(11):1841-56. doi: 10.1185/03007995.2012.734798.
Epub 2012 Oct 31.

Efficacy of telaprevir and boceprevir in treatment-naïve and
treatment-experienced genotype 1 chronic hepatitis C patients: an indirect
comparison using Bayesian network meta-analysis.

Cure S(1), Diels J, Gavart S, Bianic F, Jones E.

Author information:
(1)OptumInsight, Uxbridge, UK. Sandrine.cure@optum.com

BACKGROUND AND AIMS: To indirectly compare the efficacy of telaprevir (TVR) and
boceprevir (BOC) combined with peginterferon/ribavirin α-2a/2b (PR) in achieving
sustained viral response (SVR) in treatment-naïve and treatment-experienced
patients with genotype 1 chronic hepatitis C virus (HCV) infection.
METHODS: A systematic literature review was conducted to identify randomized
controlled trials reporting the efficacy of PR-based treatment in genotype 1
chronic HCV patients. A Bayesian network meta-analysis was performed on the
endpoint of SVR, assuming fixed study effects. For treatment-experienced
patients, only previous relapsers and partial responders were included, as no
results in prior null responders were available for boceprevir.
RESULTS: Eleven publications were included. In treatment-naïve patients, the odds
ratios (OR) (posterior median [95% credible interval]) for telaprevir (12
weeks + response guided treatment [RGT] 24/48 weeks PR) and boceprevir (24
weeks + RGT 28/48 weeks PR) versus PR were respectively 3.80 (2.78-5.22) and 2.99
(2.23-4.01). The OR for telaprevir versus boceprevir was 1.42 (0.89-2.25), with a
probability for telaprevir being more effective (P[OR > 1]) of 0.93. In
treatment-experienced patients, the OR of telaprevir (12 weeks + 48 weeks PR) and
boceprevir (32 weeks + RGT 36/48 weeks PR) versus PR were respectively 13.11
(7.30-24.43) and 5.36 (2.90-10.30). The OR for telaprevir versus boceprevir was
2.45 (1.02-5.80), with telaprevir having a probability of 0.98 of being more
effective.
LIMITATIONS: The main limitation of this study is the low number of trials
included in the analysis, especially for the treatment-experienced patient
population, which only allowed random-effect models to be explored. We tried to
identify potential biases due to study heterogeneity.
CONCLUSIONS: In the absence of direct comparative head-to-head studies between
telaprevir and boceprevir for the treatment of chronic HCV genotype 1 patients,
an indirect comparison based on Bayesian network meta-analysis suggests better
efficacy for telaprevir than boceprevir in both treatment-naïve and
treatment-experienced patients.

PMID: 23016967  [PubMed - indexed for MEDLINE]


166. Diabetes Metab. 2012 Nov;38(5):420-7. doi: 10.1016/j.diabet.2012.04.002. Epub
2012 Jun 7.

Mortality in diabetes compared with previous cardiovascular disease: a
gender-specific meta-analysis.

Lee C(1), Joseph L, Colosimo A, Dasgupta K.

Author information:
(1)Department of Medicine, McGill University, Montreal, Quebec, Canada.

AIMS: Diabetes has been described as a cardiovascular disease (CVD) risk
equivalent. There is evidence, however, that its impact may differ between women
and men. For this reason, our study aimed to obtain gender-specific hazard ratios
(HRs) comparing diabetes and CVD patients in terms of all-cause, CVD and coronary
heart disease (CHD) mortality.
METHODS: Individuals with diabetes (without CVD) and those with CVD (without
diabetes) were examined through a systematic review of articles that provided
gender-specific HRs for mortality. Searches included Medline, Embase and the
Cochrane Library database (from January 1998 to December 2009) and exploded MeSH
headings [cardiovascular diseases, risk, epidemiologic studies, case-control
studies, cohort studies, mortality, outcome assessment (health care), sex
factors, survival analysis and diabetes mellitus, type 2]. Two observers selected
and reviewed the studies and hierarchical Bayesian random-effects models were
used to combine HRs, thereby accommodating any between-study differences through
inclusion of a between-study variance in HRs.
RESULTS: Out of 5425 studies, nine were relevant (0.17%). CVD and CHD mortality
in men was lower for diabetes alone (CVD mortality HR: 0.82, 95% CrI: 0.69-0.98;
CHD mortality HR: 0.73, 95% CrI: 0.65-0.83). In contrast, rates appeared to be
higher in women with diabetes alone (CVD mortality HR: 1.29, 95% CrI: 0.79-2.26;
CHD mortality HR: 1.28, 95% CrI: 0.75-2.22), although wide credible intervals
precluded any definitive conclusions. All-cause mortality in men was similar for
diabetes and previous CVD (HR: 1.02, 95% CrI: 0.93-1.12) whereas, among women, it
was at least as high and possibly higher for diabetes alone (HR: 1.25, 95% CrI:
0.89-1.76).
CONCLUSION: Compared with previous CVD, diabetes alone leads to lower CVD and CHD
mortality risk in men, and similar all-cause mortality. In contrast, although
further studies are needed, it is possible that diabetes leads to higher CVD, CHD
and all-cause mortality in women.

Copyright © 2012 Elsevier Masson SAS. All rights reserved.

PMID: 22682738  [PubMed - indexed for MEDLINE]


167. Diabetologia. 2012 Nov;55(11):2895-905. doi: 10.1007/s00125-012-2677-z. Epub 2012
Aug 14.

Sedentary time in adults and the association with diabetes, cardiovascular
disease and death: systematic review and meta-analysis.

Wilmot EG(1), Edwardson CL, Achana FA, Davies MJ, Gorely T, Gray LJ, Khunti K,
Yates T, Biddle SJ.

Author information:
(1)Department of Cardiovascular Sciences, University of Leicester, Leicester
Diabetes Centre, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW,
UK.

Erratum in
    Diabetologia. 2013 Apr;56(4):942-3.

AIMS/HYPOTHESIS: Sedentary (sitting) behaviours are ubiquitous in modern society.
We conducted a systematic review and meta-analysis to examine the association of
sedentary time with diabetes, cardiovascular disease and cardiovascular and
all-cause mortality.
METHODS: Medline, Embase and the Cochrane Library databases were searched for
terms related to sedentary time and health outcomes. Cross-sectional and
prospective studies were included. RR/HR and 95% CIs were extracted by two
independent reviewers. Data were adjusted for baseline event rate and pooled
using a random-effects model. Bayesian predictive effects and intervals were
calculated to indicate the variance in outcomes that would be expected if new
studies were conducted in the future.
RESULTS: Eighteen studies (16 prospective, two cross-sectional) were included,
with 794,577 participants. Fifteen of these studies were moderate to high
quality. The greatest sedentary time compared with the lowest was associated with
a 112% increase in the RR of diabetes (RR 2.12; 95% credible interval [CrI] 1.61,
2.78), a 147% increase in the RR of cardiovascular events (RR 2.47; 95% CI 1.44,
4.24), a 90% increase in the risk of cardiovascular mortality (HR 1.90; 95% CrI
1.36, 2.66) and a 49% increase in the risk of all-cause mortality (HR 1.49; 95%
CrI 1.14, 2.03). The predictive effects and intervals were only significant for
diabetes.
CONCLUSIONS/INTERPRETATION: Sedentary time is associated with an increased risk
of diabetes, cardiovascular disease and cardiovascular and all-cause mortality;
the strength of the association is most consistent for diabetes.

PMID: 22890825  [PubMed - indexed for MEDLINE]




169. AJR Am J Roentgenol. 2012 Oct;199(4):822-9.

Diffusion-weighted MRI in the detection of prostate cancer: meta-analysis.

Tan CH(1), Wei W, Johnson V, Kundra V.

Author information:
(1)Department of Diagnostic Radiology, Division of Diagnostic Imaging, The
University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
cherhengtan@gmail.com

OBJECTIVE: The objective of our study was to estimate and compare the performance
of diffusion-weighted imaging (DWI) with other MRI techniques including
T2-weighted MRI for the detection of prostate cancer.
MATERIALS AND METHODS: Searches of the PubMed and Scopus electronic databases for
the terms "prostate," "cancer," "diffusion-weighted imaging," and "magnetic
resonance imaging" using an end date of December 2010 were completed. All
included studies had histopathologic correlation; 2×2 contingency data were
constructed for each study. A Bayesian receiver operating characteristic (ROC)
model was used across studies to determine sensitivity, specificity, and area
under the full or partial ROC curve.
RESULTS: Nineteen articles consisting of a total of 5892 lesions were analyzed.
Based on a 95% credible interval, DWI alone yielded a significantly better area
under the ROC curve, sensitivity, and specificity (0.85, 0.69, 0.89,
respectively) than T2-weighted imaging alone (0.75, 0.60, 0.76). Combined DWI and
T2-weighted imaging (0.73, 0.70, 0.83) showed a similar area under the ROC curve
but significantly better sensitivity and specificity than T2-weighted imaging
alone. DWI and combined DWI and T2-weighted imaging yielded similar overall
sensitivity, but DWI alone showed better overall specificity than combined DWI
and T2-weighted imaging. At specificities of greater than 80%, combined DWI and
T2-weighted imaging yielded a partial area under the ROC curve (0.138) similar to
that of DWI alone (0.129) and was significantly better than the partial area
under the ROC curve of T2-weighted imaging alone (0.070). DWI alone and combined
DWI and T2-weighted imaging appear to be superior to dynamic contrast-enhanced
imaging alone (area under the ROC curve, 0.79; sensitivity, 0.58; specificity,
0.82).
CONCLUSION: DWI appears to improve diagnostic performance and can be a useful
adjunct to conventional anatomic imaging for identifying tumor foci in prostate
cancer.

PMCID: PMC3888871
PMID: 22997374  [PubMed - indexed for MEDLINE]


170. Am J Surg. 2012 Oct;204(4):428-33. doi: 10.1016/j.amjsurg.2011.12.019. Epub 2012
May 11.

The role of sentinel lymph node biopsy in select sarcoma patients: a
meta-analysis.

Wright S(1), Armeson K, Hill EG, Streck C, Leddy L, Cole D, Esnaola N, Camp ER.

Author information:
(1)Department of Surgery, Division of Surgical Oncology, Medical University of
South Carolina and Ralph H. Johnson VA Medical Center, Charleston, SC, USA.

BACKGROUND: Sentinel lymph node (SLN) biopsy is a staging technique for occult
lymph node disease. SLN biopsy has been applied to select patients with sarcoma,
although the clinical utility remains uncertain.
METHODS: A PubMed/MEDLINE literature search was performed, and SLN biopsy
outcomes were analyzed using a Bayesian meta-analytic approach to obtain point
and interval estimates of rates of interest.
RESULTS: Sixteen studies involving SLN biopsy in patients with sarcoma were
identified. Of 114 patients reported, 14 patients had positive SLNs (crude
estimate, 12%; meta-analysis estimate, 17%). The meta-analysis false-negative
rate was 29% (95% credible interval, 5%-59%). Recurrence and death rates in the
SLN-positive group were higher than in the SLN-negative group.
CONCLUSIONS: This investigation highlights the current role of SLN biopsy in
select patients with sarcoma for tumor staging. Questions regarding the high
false-negative rate and management of micrometastatic lymphatic disease in
patients with sarcoma still exist.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID: 22578407  [PubMed - indexed for MEDLINE]


171. Clin Gastroenterol Hepatol. 2012 Oct;10(10):1101-9. doi:
10.1016/j.cgh.2012.05.017. Epub 2012 May 27.

Balloon dilation with adequate duration is safer than sphincterotomy for
extracting bile duct stones: a systematic review and meta-analyses.

Liao WC(1), Tu YK, Wu MS, Wang HP, Lin JT, Leung JW, Chien KL.

Author information:
(1)Department of Internal Medicine, National Taiwan University Hospital, National
Taiwan University College of Medicine, Taipei, Taiwan.

BACKGROUND & AIMS: Endoscopic sphincterotomy (EST) is the standard treatment for
choledocholithiasis. Endoscopic papillary balloon dilation (EPBD) has a lower
risk for bleeding than EST, but EPBD is reserved for patients with bleeding
diathesis because some studies reported that it increases the risk for
pancreatitis. A short dilation time (≤1 minute) is therefore recommended to
reduce pancreatitis. However, there is evidence for an inverse relationship
between EPBD duration and pancreatitis, prompting reevaluation of the optimal
duration and relative safety of EPBD vs EST.
METHODS: We systematically reviewed randomized controlled trials to compare long
EPBD (>1 minute), short EPBD (≤1 minute), and EST regarding pancreatitis and
overall complications. In addition to pairwise meta-analyses, Bayesian network
meta-analysis was undertaken to compare the 3 procedures together. Relation
between duration and outcome was also analyzed by meta-regression.
RESULTS: Compared with EST, short EPBD had a higher risk for pancreatitis (odds
ratio [OR] by traditional analysis, 3.87; 95% confidence interval, 1.08-13.84 and
OR by network meta-analysis, 4.14; 95% credible interval, 1.58-12.56), but long
EPBD did not pose a higher risk than EST (1.14, 0.56-2.35 and 1.07, 0.38-2.76).
Long EPBD had a lower overall rate of complications than EST (0.61, 0.36-1.04 and
0.54, 0.20-1.36). In network meta-analysis, probabilities of being the safest
treatment for long EPBD/short EPBD/EST regarding pancreatitis and overall
complications were 43.9%/0.2%/55.9% and 90.3%/1.3%/8.4%, respectively.
CONCLUSIONS: Duration of EPBD is inversely associated with pancreatitis risk.
Currently recommended ≤1-minute dilation actually increases pancreatitis. EPBD
with adequate duration may be preferred over EST because of comparable
pancreatitis but lower overall complication rates.

Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

PMID: 22642953  [PubMed - indexed for MEDLINE]


172. J Neurosurg Anesthesiol. 2012 Oct;24(4):376-81. doi:
10.1097/ANA.0b013e31826a038d.

Pediatric anesthesia and neurodevelopmental impairments: a Bayesian
meta-analysis.

DiMaggio C(1), Sun LS, Ing C, Li G.

Author information:
(1)Department of Anesthesiology, Columbia University, New York, NY 10032, USA.
cjd11@columbia.edu

Experimental evidence of anesthesia-induced neurotoxicity has caused serious
concern about the long-term effect of commonly used volatile anesthetic agents on
young children. Several observational studies based on existing data have been
conducted to address this concern with inconsistent results. We conducted a
meta-analysis to synthesize the epidemiologic evidence on the association of
anesthesia/surgery with neurodevelopmental outcomes in children. Using Bayesian
meta-analytic approaches, we estimated the synthesized odds ratios (OR) and 95%
credible interval (CrI) as well as the predictive distribution of a future study
given the synthesized evidence. Data on 7 unadjusted and 6 adjusted measures of
association were abstracted from 7 studies. The synthesized OR based on the 7
unadjusted measures for the association of anesthesia/surgery with an adverse
behavioral or developmental outcome was 1.9 (95% CrI, 1.2-3.0). The most likely
unadjusted OR from a future study was estimated to be 2.2 (95% CrI, 0.6-6.1). The
synthesized OR based on the 6 adjusted measures for the association of
anesthesia/surgery with an adverse behavioral or developmental outcome was 1.4
(95% CrI, 0.9-2.2). The most likely adjusted OR from a future study was estimated
to be 1.5 (95% CrI, 0.5-4.0). We conclude that existent epidemiologic evidence
suggests a modestly elevated risk of adverse behavioral or developmental outcomes
in children who were exposed to anesthesia/surgery during early childhood. The
evidence, however, is considerably uncertain.

PMCID: PMC3475986
PMID: 23076225  [PubMed - indexed for MEDLINE]


173. Obstet Gynecol. 2012 Oct;120(4):897-907.

Progestogens for preterm birth prevention: a systematic review and meta-analysis.

Likis FE(1), Edwards DR, Andrews JC, Woodworth AL, Jerome RN, Fonnesbeck CJ,
McKoy JN, Hartmann KE.

Author information:
(1)Vanderbilt Evidence-based Practice Center, Institute for Medicine and Public
Health, and the Department of Medicine, Vanderbilt University Medical Center,
Nashville, Tennessee 37203-1738, USA. frances.likis@vanderbilt.edu

OBJECTIVE: We systematically reviewed the effectiveness of progestogens for
prevention of preterm birth among women with prior spontaneous preterm birth,
multiple gestations, preterm labor, short cervix, or other indications.
DATA SOURCES: We searched MEDLINE and EMBASE databases for English language
articles published from January 1966 to October 2011.
METHODS OF STUDY SELECTION: We excluded publications that were not randomized
controlled trials or had fewer than 20 participants, identifying 34 publications,
of which 19 contained data for Bayesian meta-analysis.
TABULATION, INTEGRATION, AND RESULTS: Two reviewers independently extracted data
and assigned overall quality ratings based on predetermined criteria. Among women
with prior preterm birth and a singleton pregnancy (five randomized controlled
trials), progestogen treatment decreased the median risk of preterm birth by 22%
(relative risk [RR] 0.78, 95% Bayesian credible interval 0.68-0.88) and neonatal
death by 42% (RR 0.58, 95% Bayesian credible interval 0.27-0.98). The evidence
suggests progestogen treatment does not prevent prematurity (RR 1.02, 95%
Bayesian credible interval 0.87-1.17) or neonatal death (RR 1.44, 95% Bayesian
credible interval 0.46-3.18) in multiple gestations. Limited evidence suggests
progestogen treatment may prevent prematurity in women with preterm labor (RR
0.62, 95% Bayesian credible interval 0.47-0.79) and short cervix (RR 0.52, 95%
Bayesian credible interval 0.36-0.70). Across indications, evidence about
maternal, fetal, or neonatal health outcomes, other than reducing preterm birth
and neonatal mortality, is inconsistent, insufficient, or absent.
CONCLUSION: Progestogens prevent preterm birth when used in singleton pregnancies
for women with a prior preterm birth. In contrast, evidence suggests lack of
effectiveness for multiple gestations. Evidence supporting all other uses is
insufficient to guide clinical care. Overall, clinicians and patients lack
longer-term information to understand whether intervention has the ultimately
desired outcome of preventing morbidity and promoting normal childhood
development.

PMID: 22955308  [PubMed - indexed for MEDLINE]


174. Am J Gastroenterol. 2012 Sep;107(9):1306-13. doi: 10.1038/ajg.2012.141. Epub 2012
May 29.

Rapid point-of-care first-line screening tests for hepatitis B infection: a
meta-analysis of diagnostic accuracy (1980-2010).

Shivkumar S(1), Peeling R, Jafari Y, Joseph L, Pai NP.

Author information:
(1)Division of Clinical Epidemiology, McGill University and Health Center,
Montreal, Quebec, Canada.

OBJECTIVES: Three-hundred fifty million people worldwide are chronically infected
with Hepatitis B, with four million acute infections annually. With infection
concentrated in hard-to-reach populations and low resource settings, rapid
point-of-care (POC) tests offer an efficient screening alternative to laboratory
tests. We conducted a meta-analysis to evaluate accuracy of rapid POC tests
screening for Hepatitis B.
METHODS: Two reviewers searched four databases, critiqued quality. A hierarchical
Bayesian meta-analysis correcting for imperfect reference standards was used.
Based on components of the antigen-antibody response, 17 studies were stratified
into three subgroups: (i) Hepatitis B surface antigen (HBsAg) tests; (ii)
anti-HBsAg tests, and (iii) HBs+eAg tests. Further, we pooled estimates on
individual tests with sufficient data.
RESULTS: In subgroup 1, the pooled sensitivity (Sn) was 94.76% (95% credible
interval (CrI): 90.08-98.23%) and specificity (Sp) was 99.54% (95% CrI:
99.03-99.95%). The Determine test reported a pooled Sn 98.2% (95% CrI: 94.7,
99.9) and Sp 99.9% (95% CrI: 99.3, 100); in subgroup 2, Sn 93.2% (95% CrI: 85.1,
98.5), Sp 93.1% (95% CrI: 81.9, 99.9); and in subgroup 3, the Binax test showed
Sn 95.5% (95% CrI: 88.9, 99.4), Sp 99.8% (95% CrI: 99.3, 100).
CONCLUSIONS: HBsAg tests, including Determine, and the HBs+eAg test, Binax showed
high accuracy. Improvements in sensitivity of antibody-based tests will enhance
their potential for global first-line screening.

PMID: 22641308  [PubMed - indexed for MEDLINE]


175. Ann Med. 2012 Sep;44(6):588-97. doi: 10.3109/07853890.2012.705016. Epub 2012 Aug
6.

Comparisons of high-dose and combination nicotine replacement therapy,
varenicline, and bupropion for smoking cessation: a systematic review and
multiple treatment meta-analysis.

Mills EJ(1), Wu P, Lockhart I, Thorlund K, Puhan M, Ebbert JO.

Author information:
(1)Department of Clinical Epidemiology & Biostatistics, McMaster University,
Hamilton, Ontario, Canada. Edward.mills@uottawa.ca

Erratum in
    Ann Med. 2012 Sep;44(6):597.

AIM: This review compared the effect of high-dose nicotine replacement therapy
(NRT) and combinations of NRT for increasing smoking abstinence rates compared to
standard-dose NRT patch, varenicline, and bupropion on smoking abstinence.
METHODS: Ten electronic databases were searched (up to January 2012) for
randomized controlled trials (RCT) of standard-dose (≤ 22 mg) or high-dose
nicotine patch therapy (> 22 mg), combination NRT (e.g. nicotine patch + nicotine
inhaler), bupropion, and varenicline. Analysis consisted of random-effects
pairwise meta-analysis and a Bayesian multiple treatment comparison (MTC).
RESULTS: We identified 146 RCTs (65 standard-doses of the nicotine patch (≤ 22
mg); 6 high-dose NRT patch (> 22 mg); 5 high versus standard-dose NRT patch; 5
combination NRT versus inert controls; 6 combination versus single NRT patch; 48
bupropion; and 11 varenicline). The MTC found that all therapies offered
treatment benefits at most time points over controls. Combination NRT and
higher-dose NRT did not demonstrate consistent effects over other interventions.
With the exception of varenicline, the benefits of treatments over standard-dose
NRT were not retained in the long term.
CONCLUSIONS: All pharmacologic treatments were significantly more effective than
inert controls. Varenicline was the only treatment demonstrating effects over
other options. These results should be considered in the development of clinical
practice guidelines.

PMID: 22860882  [PubMed - indexed for MEDLINE]


176. Diabetes Obes Metab. 2012 Sep;14(9):810-20. doi:
10.1111/j.1463-1326.2012.01606.x. Epub 2012 Apr 29.

Effect of antidiabetic agents added to metformin on glycaemic control,
hypoglycaemia and weight change in patients with type 2 diabetes: a network
meta-analysis.

Liu SC(1), Tu YK, Chien MN, Chien KL.

Author information:
(1)Division of Endocrinology and Metabolism, Department of Internal Medicine,
Mackay Memorial Hospital, Taipei, Taiwan.

AIM: Most guidelines recommend metformin as first-line therapy in patients with
type 2 diabetes. However, the choice of a second-line drug lacks consistent
consensus. We aimed to assess available information of antidiabetic drugs added
to metformin on the change in glycated haemoglobin A1c (A1C), risk of
hypoglycaemia and change in body weight.
METHODS: PubMed and Cochrane Central Register of Controlled Trials were searched
for randomized controlled trials (RCTs) written in English through December 2011.
We analysed direct and indirect comparisons of different treatments using
Bayesian network meta-analysis.
RESULTS: Thirty-nine RCTs involving 17 860 individuals were included.
Glucagon-like peptide-1 (GLP-1) analogues resulted in greater decrease in A1C
compared with sulfonylureas, glinides, thiazolidinediones, α-glucosidase
inhibitors and DPP-4 inhibitors [-0.20% (95% CI -0.34 to -0.04%), -0.31% (95% CI
-0.61 to -0.02%), -0.20% (95% CI -0.38 to -0.00), -0.36% (95% CI -0.64 to
-0.07%), -0.32% (95% CI -0.47 to -0.17%), respectively] and was comparable with
basal insulin and biphasic insulin. A1C decrease was greater for sulfonylureas
compared with DPP-4 inhibitors [-0.12% (-0.23 to -0.03%)], and for biphasic
insulin compared with glinides (-0.36%; 95% CI -0.82 to -0.11%). Compared with
placebo, the risk of hypoglycaemia was increased in the sulfonylureas, glinides,
basal insulin and biphasic insulin. Weight increase was seen with sulfonylureas,
glinides, thiazolidinediones, basal insulin and biphasic insulin, and weight loss
was seen with α-glucosidase inhibitors and GLP-1 analogues.
CONCLUSIONS: Biphasic insulin, GLP-1 analogues and basal insulin were ranked the
top three drugs in terms of A1C reduction. GLP-1 analogues did not increase the
risk of hypoglycaemia and resulted in a significant decrease in body weight. Most
oral antidiabetic drugs had similar effects on A1C, but some agents had a lower
risk of hypoglycaemia and body weight gain.

© 2012 Blackwell Publishing Ltd.

PMID: 22486990  [PubMed - indexed for MEDLINE]


177. Acta Anaesthesiol Scand. 2012 Aug;56(7):817-32. doi:
10.1111/j.1399-6576.2012.02651.x. Epub 2012 Feb 7.

Bayesian enhanced meta-analysis of post-operative analgesic efficacy of additives
for caudal analgesia in children.

Engelman E(1), Marsala C.

Author information:
(1)Department of Anaesthesia, CUB Hopital Erasme, Brussels, Belgium.
eengelma@ulb.ac.be

BACKGROUND: The authors calculated the effect size for post-operative analgesia
of three additives, clonidine, neostigmine, and tramadol to bupivacaine,
ropivacaine, or levobupivacaine used for single-dose caudal extradural blockade
in children.
METHODS: A meta-analysis was performed for three end points of efficacy: the
increase of time until administration of analgesic drugs, the proportion of
patients requiring analgesic drugs during the initial 24 post-operative hours,
and the amounts of post-operative analgesic drugs. A Bayesian inference
supporting direct statements about the probability of the magnitude of an effect
was used to compare the effects size.
RESULTS: Neostigmine increased the duration of analgesia by 9.96 h (95%
confidence interval: 7.75 to 12.16), as compared with 3.68 h (2.65 to 4.7) with
clonidine and 4.45 (2.84 to 6.07) with tramadol. There is a 95% probability that
neostigmine increases the duration of post-operative analgesia by more than 8 h,
clonidine by more than 2.8 h, and tramadol by more than 3.25 h, as compared with
local anesthetics alone. The odds ratios for the proportion of patients requiring
analgesic drugs were 0.22 [0.13 to 0.37] for clonidine and 0.28 [0.10 to 0.75]
for neostigmine. With tramadol, there was no statistically significant
difference. All three additives reduced the amounts of post-operative analgesic
drugs. Neostigmine and tramadol increase the probability for post-operative
nausea or vomiting (PONV).
CONCLUSIONS: Neostigmine provides the longest post-operative analgesia. With
clonidine, the duration of analgesia is shorter and sedation is increased, but
the probability for PONV could be decreased.

© 2012 The Authors. Acta Anaesthesiologica Scandinavica © 2012 The Acta
Anaesthesiologica Scandinavica Foundation.

PMID: 22313028  [PubMed - indexed for MEDLINE]


178. Surgery. 2012 Aug;152(2):202-11. doi: 10.1016/j.surg.2012.05.005.

Revisiting the effectiveness of interventions to decrease surgical site
infections in colorectal surgery: A Bayesian perspective.

Phatak UR(1), Pedroza C, Millas SG, Chang GJ, Lally KP, Kao LS.

Author information:
(1)Department of Surgery, University of Texas Health Science Center at Houston,
Houston, TX, USA.

OBJECTIVE: To evaluate the evidence for interventions to decrease surgical site
infections (SSIs) in colorectal operations using Bayesian meta-analysis.
BACKGROUND: Interventions other than appropriate administration of prophylactic
antibiotics to prevent SSIs have not been adopted widely, in part because of lack
of recommendations for these interventions based on traditional meta-analyses.
Bayesian methods can provide probabilities of specific thresholds of benefit,
which may be more useful in guiding clinical decision making. We hypothesized
that Bayesian meta-analytic methods would complement the interpretation of
traditional analyses regarding the effectiveness of interventions to decrease
SSIs.
METHODS: We conducted a systematic search of the Cochrane database for reviews of
interventions to decrease SSIs after colorectal surgery other than prophylactic
antibiotics. Traditional and Bayesian meta-analyses were performed using RevMan
(Nordic Cochrane Center, Copenhagen, Denmark) and WinBUGS (MRC Biostatistics
Unit, Cambridge, UK). Bayesian posterior probabilities of any benefit, defined as
a relative risk of <1, were calculated using skeptical, neutral, and enthusiastic
prior probabilities. Probabilities were also calculated that interventions
decreased SSIs by ≥10%, and ≥20% using neutral prior probability distributions.
RESULTS: A total of 9 Cochrane reviews met the search criteria. Using traditional
meta-analysis methods, only laparoscopic colorectal surgery resulted in a
significant reduction in SSIs and a recommendation for use of the intervention.
Using Bayesian analysis, several interventions that did not result in
"significant" decreases in SSIs using traditional analytic methods had a >85%
probability of benefit. Also, nonuse of 2 interventions (mechanical bowel
preparation and adhesive drapes) had a high probability of decreasing SSIs
compared with their use.
CONCLUSION: Bayesian probabilities and traditional point estimates of treatment
effect yield similar information in terms of potential effectiveness. Bayesian
meta-analysis, however, provides complementary information on the probability of
a large magnitude of effect. The clinical impact of using Bayesian methods to
inform decisions about which interventions to institute first or which
interventions to combine requires further study.

Copyright © 2012 Mosby, Inc. All rights reserved.

PMID: 22828141  [PubMed - indexed for MEDLINE]


179. Thromb Haemost. 2012 Aug;108(2):318-27. doi: 10.1160/TH11-08-0586. Epub 2012 May
25.

Network meta-analysis of prasugrel, ticagrelor, high- and standard-dose
clopidogrel in patients scheduled for percutaneous coronary interventions.

Steiner S(1), Moertl D, Chen L, Coyle D, Wells GA.

Author information:
(1)Department of Internal Medicine II, Division of Angiology, Medical University
Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
sabine.m.steiner@meduniwien.ac.at

Comment in
    Thromb Haemost. 2012 Aug;108(2):203-5.

Since novel antiplatelet treatments (prasugrel, ticagrelor, high-dose
clopidogrel) have been predominantly tested against standard-dose clopidogrel,
data on direct comparisons between these therapies are scarce. We therefore
indirectly compared their efficacy and safety in patients undergoing percutaneous
coronary intervention. Electronic databases were searched systematically to
identify head-to-head randomised controlled trials (RCTs). Network meta-analysis
was performed using generalised linear mixed models with adjustment for length of
follow-up. Findings were corroborated by mixed treatment comparison through
Bayesian methods. Fourteen RCTs were identified and included in the analysis
(high- vs. standard-dose clopidogrel: 9 trials, prasugrel vs. high-dose
clopidogrel: 2 trials, prasugrel vs. standard-dose clopidogrel: 2 trials,
ticagrelor vs. standard-dose clopidogrel: 1 trial). No significant differences
were found for efficacy outcomes except for stent thrombosis favouring prasugrel
(vs. ticagrelor: odds ratio [OR] 0.63, 95% confidence interval [CI]: 0.42, 0.94;
vs. high-dose clopidogrel: OR 0.70, 95%CI: 0.48, 1.01). Prasugrel exhibited a
similar bleeding risk as high-dose clopidogrel, but more major (OR 1.43, 95%CI
1.07, 1.90) and major or minor bleeding (OR 1.36, 95%CI 1.09, 1.69) compared to
ticagrelor. Ticagrelor was also associated with less major or minor bleeding
compared to high-dose clopidogrel (OR 0.81, 95%CI 0.69, 0.96). No differences
were seen for non CABG-related major bleeding between the three strategies.
Results were corroborated in a subgroup analysis comprising only patients with
acute coronary syndromes. In the absence of head-to-head clinical trials, network
meta-analysis suggests potentially relevant differences in efficacy and bleeding
risk among novel antiplatelet treatments and may thereby advance understanding of
their differential therapeutic properties.

PMID: 22627948  [PubMed - indexed for MEDLINE]


180. J Clin Oncol. 2012 Jul 10;30(20):2559-65. doi: 10.1200/JCO.2011.38.4818. Epub
2012 Apr 23.

Impact of intraoperative stimulation brain mapping on glioma surgery outcome: a
meta-analysis.

De Witt Hamer PC(1), Robles SG, Zwinderman AH, Duffau H, Berger MS.

Author information:
(1)Neurosurgical Center Amsterdam, VU University Medical Center, Amsterdam, the
Netherlands. p.dewitthamer@vumc.nl

Comment in
    J Clin Oncol. 2012 Jul 10;30(20):2437-40.

PURPOSE: Surgery for infiltrative gliomas aims to balance tumor removal with
preservation of functional integrity. The usefulness of intraoperative
stimulation mapping (ISM) has not been addressed in randomized trials. This study
addresses glioma surgery outcome on the basis of a meta-analysis of observational
studies.
METHODS: A systematic search retrieved 90 reports published between 1990 and 2010
with 8,091 adult patients who had resective surgery for supratentorial
infiltrative glioma, with or without ISM. Quality criteria consisted of
postoperative neurologic examination details and follow-up timing. New
postoperative neurologic deficits were categorized on the basis of timing and
severity. Meta-analysis with a Bayesian random effects model determined summary
event rates of deficits as well as gross total resection rate and eloquent
locations. Meta-regression analysis explored heterogeneity among studies.
RESULTS: Late severe neurologic deficits were observed in 3.4% (95% CI, 2.3% to
4.8%) of patients after resections with ISM, and in 8.2% (95% CI, 5.7% to 11.4%)
of patients after resections without ISM (adjusted odds ratio, 0.39; 95% CI, 0.23
to 0.64). The percentages of radiologically confirmed gross total resections were
75% (95% CI, 66% to 82%) with ISM and 58% (95% CI, 48% to 69%) without ISM.
Eloquent locations were involved in 99.9% (95% CI, 99.9% to 100%) of resections
with ISM and in 95.8% (95% CI, 73.1% to 99.8%) of resections without ISM.
Relevant sources of heterogeneity among studies were ISM, continent, and academic
setting.
CONCLUSION: Glioma resections using ISM are associated with fewer late severe
neurologic deficits and more extensive resection, and they involve eloquent
locations more frequently. This indicates that ISM should be universally
implemented as standard of care for glioma surgery.

PMID: 22529254  [PubMed - indexed for MEDLINE]


181. Catheter Cardiovasc Interv. 2012 Jul 1;80(1):128-38. doi: 10.1002/ccd.23368. Epub
2012 Mar 13.

Meta-analysis of complications in aortic valve replacement: comparison of
Medtronic-Corevalve, Edwards-Sapien and surgical aortic valve replacement in
8,536 patients.

Jilaihawi H(1), Chakravarty T, Weiss RE, Fontana GP, Forrester J, Makkar RR.

Author information:
(1)Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.

BACKGROUND: We sought to establish the complication rates following transcatheter
aortic valve replacement (TAVR) in the context of high risk and octogenarian
surgical aortic valve replacement (SAVR) in the contemporary literature, and to
critically analyze population characteristics and outcomes.
METHODS: TAVR studies were selected from nonoverlapping series and SAVR studies
for comparison if they met similar entry criteria. Bayesian meta-analytic methods
were employed.
RESULTS: For the 5024 TAVR and 3512 SAVR patients included in the study, TAVR
subjects had greater baseline renal impairment (P < 0.001), a higher incidence of
prior myocardial infarction (P = 0.032) and respiratory disease (P = 0.005) and a
higher logistic EuroSCORE (P = 0.039). There were no significant differences
observed in complications studied in SAVR and TAVR: 30 day mortality (9% vs 8.5%,
P = 0.31), 1 year mortality (18.4% vs 22.8%, P = 0.65), 30 day stroke (2.4% vs
2.6%, P = 0.72), new permanent pacemaker (5.9% vs 12.1%, P = 0.055) and dialysis
inception (2.4% vs 4.1%, P = 0.70). We also compared demographics and outcomes
between the two types of transcatheter valves. Apart from some variation in
functional status, there were no significant differences at baseline with
different TAVR designs. The only difference in complications was the need for
pacemaker insertion, higher with the Medtronic-Corevalve than with the
Edwards-Sapien design (24.5% vs 5.9% P < 0.0001).
CONCLUSIONS: Complications for elderly and high risk aortic stenosis patients
being treated by TAVR appear comparable to those selected for SAVR in the
real-world.

Copyright © 2012 Wiley Periodicals, Inc.

PMID: 22415849  [PubMed - indexed for MEDLINE]


182. Diabetes Obes Metab. 2012 Jul;14(7):616-25. doi:
10.1111/j.1463-1326.2012.01571.x. Epub 2012 Feb 21.

Effectiveness of interventions for reducing diabetes and cardiovascular disease
risk in people with metabolic syndrome: systematic review and mixed treatment
comparison meta-analysis.

Dunkley AJ(1), Charles K, Gray LJ, Camosso-Stefinovic J, Davies MJ, Khunti K.

Author information:
(1)Department of Health Sciences, University of Leicester, Leicester, UK.

AIMS: To review the evidence on interventions for reversing metabolic syndrome or
preventing development of type 2 diabetes and cardiovascular disease in people
with metabolic syndrome.
METHODS: A systematic review and Bayesian mixed treatment comparison
meta-analysis was conducted. Relevant electronic bibliographic databases were
searched up to January 2010. Included studies were randomized controlled trials
with a follow-up of ≥24 weeks and outcomes comparing incidence of diabetes and/or
cardiovascular disease, or reversal of metabolic syndrome.
RESULTS: A total of 16 studies met the inclusion criteria. Thirteen studies with
outcome data for reversal of metabolic syndrome, involving 3907 participants,
were included in the meta-analysis. Insufficient trials reported cardiovascular
events/mortality, or incidence of type 2 diabetes, to conduct a meta-analysis for
these outcomes. Interventions, alone or in combination, included lifestyle (diet
and/or exercise) and pharmacological therapy. Using random-effect models, both
lifestyle (odds ratio, OR 3.81; 95% confidence interval, CI 2.47-5.88) and
pharmacological interventions (OR 1.59; 95% CI 1.04-2.45) were statistically
superior compared with control for reversing metabolic syndrome. Using mixed
treatment comparison methods, the probability that lifestyle interventions were
the most clinically effective was 87%.
CONCLUSIONS: Evidence suggests that both lifestyle and pharmacological
interventions can reverse metabolic syndrome. However, there is a lack of data on
whether these benefits are sustained and translate into longer term prevention of
diabetes and/or cardiovascular disease.

© 2012 Blackwell Publishing Ltd.

PMID: 22284386  [PubMed - indexed for MEDLINE]


183. Epidemiology. 2012 Jul;23(4):594-606. doi: 10.1097/EDE.0b013e3182572795.

Ambient temperature and cardiorespiratory morbidity: a systematic review and
meta-analysis.

Turner LR(1), Barnett AG, Connell D, Tong S.

Author information:
(1)School of Public Health and Social Work, Institute of Health and Biomedical
Innovation, Queensland University of Technology, Brisbane, Australia.

BACKGROUND: The effect of extreme temperature has become an increasing public
health concern. Evaluating the impact of ambient temperature on morbidity has
received less attention than its impact on mortality.
METHODS: We performed a systematic literature review and extracted quantitative
estimates of the effects of hot temperatures on cardiorespiratory morbidity.
There were too few studies on effects of cold temperatures to warrant a summary.
Pooled estimates of effects of heat were calculated using a Bayesian hierarchical
approach that allowed multiple results to be included from the same study,
particularly results at different latitudes and with varying lagged effects.
RESULTS: Twenty-one studies were included in the final meta-analysis. The pooled
results suggest an increase of 3.2% (95% posterior interval = -3.2% to 10.1%) in
respiratory morbidity with 1°C increase on hot days. No apparent association was
observed for cardiovascular morbidity (-0.5% [-3.0% to 2.1%]). The length of lags
had inconsistent effects on the risk of respiratory and cardiovascular morbidity,
whereas latitude had little effect on either.
CONCLUSIONS: The effects of temperature on cardiorespiratory morbidity seemed to
be smaller and more variable than previous findings related to mortality.

PMID: 22531668  [PubMed - indexed for MEDLINE]


184. Int J Biometeorol. 2012 Jul;56(4):569-81. doi: 10.1007/s00484-011-0497-3.

Daily average temperature and mortality among the elderly: a meta-analysis and
systematic review of epidemiological evidence.

Yu W(1), Mengersen K, Wang X, Ye X, Guo Y, Pan X, Tong S.

Author information:
(1)School of Public Health and Institute of Health and Biomedical Innovation,
Queensland University of Technology, Kelvin Grove, QLD 4059, Brisbane, Australia.
weiwei.yu@qut.edu.au

The impact of climate change on the health of vulnerable groups such as the
elderly has been of increasing concern. However, to date there has been no
meta-analysis of current literature relating to the effects of temperature
fluctuations upon mortality amongst the elderly. We synthesised risk estimates of
the overall impact of daily mean temperature on elderly mortality across
different continents. A comprehensive literature search was conducted using
MEDLINE and PubMed to identify papers published up to December 2010. Selection
criteria including suitable temperature indicators, endpoints, study-designs and
identification of threshold were used. A two-stage Bayesian hierarchical model
was performed to summarise the percent increase in mortality with a 1°C
temperature increase (or decrease) with 95% confidence intervals in hot (or cold)
days, with lagged effects also measured. Fifteen studies met the eligibility
criteria and almost 13 million elderly deaths were included in this
meta-analysis. In total, there was a 2-5% increase for a 1°C increment during hot
temperature intervals, and a 1-2 % increase in all-cause mortality for a 1°C
decrease during cold temperature intervals. Lags of up to 9 days in exposure to
cold temperature intervals were substantially associated with all-cause
mortality, but no substantial lagged effects were observed for hot intervals.
Thus, both hot and cold temperatures substantially increased mortality among the
elderly, but the magnitude of heat-related effects seemed to be larger than that
of cold effects within a global context.

PMID: 21975970  [PubMed - indexed for MEDLINE]




186. BMC Pulm Med. 2012 Jun 25;12:29. doi: 10.1186/1471-2466-12-29.

Efficacy of once-daily indacaterol 75 μg relative to alternative bronchodilators
in COPD: a study level and a patient level network meta-analysis.

Cope S(1), Zhang J, Williams J, Jansen JP.

Author information:
(1)Mapi Consultancy, Boston, MA, USA.

BACKGROUND: The objective of this study was to evaluate the comparative efficacy
of indacaterol 75 μg once daily (OD), tiotropium 18 μg OD, salmeterol 50 μg twice
daily (BID), formoterol 12 μg BID, and placebo for the treatment of chronic
obstructive pulmonary disease (COPD) based on individual patient data (IPD) from
randomized controlled trials (RCTs) from the indacaterol trial program and
aggregate data (AD) identified from a systematic review of RCTs.
METHODS: 22 RCTs were included in the AD analysis that evaluated: indacaterol 75
μg (n = 2 studies), indacaterol 150 μg n = 5 (i.e. salmeterol 50 μg) (n = 5),
indacaterol 300 μg (n = 2), tiotropium 18 μg (n = 10), salmeterol 50 μg (n = 7),
and formoterol 12 μg (n = 4). All of the studies except for one head-to-head
comparison (tiotropium vs. salmeterol) were placebo controlled. Outcomes of
interest were trough forced expiratory volume in 1 second (FEV1) and St. George's
Respiratory Questionnaire (SGRQ) total score at week 12. The AD from all trials
was analysed simultaneously using a Bayesian network meta-analysis (NMA) and
relative treatment effects between all regimens were obtained. In a separate
analysis, the IPD available from the 6 indacaterol RCTs was analysed in a NMA.
Treatment-by-covariate interactions were included in both analyses to improve
similarity of the trials.
RESULTS: All interventions compared were more efficacious than placebo regarding
FEV1 at 12 weeks. Indacaterol 75 μg is expected to result in a comparable FEV1 at
12 weeks to tiotropium and salmeterol based on both IPD and AD analyses. In
comparison to formoterol, the IPD and AD results indicate indacaterol 75 μg is
more efficacious (IPD = 0.07 L difference; 95%Credible Interval (CrI) 0.02 to
0.11; AD = 0.05 L difference; 95%CrI 0.01; 0.09). In terms of SGRQ total score at
12 weeks, indacaterol 75 μg and formoterol were more efficacious than placebo,
whereas for tiotropium and salmeterol the credible intervals included zero for
the AD results only (tiotropium: -2.99 points improvement versus placebo; 95%CrI
-6.48 to 0.43; salmeterol:-2.52; 95%CrI: -5.34; 0.44). Both IPD and AD results
suggest that indacaterol 75 μg is expected to be comparable to all active
treatments.
CONCLUSIONS: Based on a synthesis of currently available AD RCT evidence as well
as an IPD network meta-analysis of six RCTs, indacaterol 75 μg is expected to be
at least as efficacious as formoterol and comparable to tiotropium and salmeterol
regarding FEV1. Furthermore, indacaterol 75 μg shows comparable level of
improvement in health-related quality of life to tiotropium, salmeterol, and
formoterol, as measured by the SGRQ.

PMCID: PMC3512498
PMID: 22732017  [PubMed - indexed for MEDLINE]


187. BMC Cancer. 2012 Jun 12;12:236. doi: 10.1186/1471-2407-12-236.

Detection of cervical lymph node metastasis in head and neck cancer patients with
clinically N0 neck-a meta-analysis comparing different imaging modalities.

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

Author information:
(1)Graduate Institute of Epidemiology and Preventive Medicine, College of Public
Health, National Taiwan University, Taipei, Taiwan.

BACKGROUND: How to properly manage clinically negative neck of head and neck
cancer patients is a controversial topic. Research is now directed toward finding
a method sensitive enough to bring the risk of occult metastases below 20%. The
aim of this review was to compare the diagnostic accuracy of different imaging
modalities, including CT, MRI, PET and US, in clinically N0 head and neck cancer
patients.
METHODS: For this systematic review and meta-analysis, PubMed and the Cochrane
Database were searched for relevant original articles published up to May 2011.
Inclusion criteria were as follows: articles were reported in English; CT, MRI,
PET or US were performed to identify cervical metastases in clinically N0 head
and neck squamous cell carcinoma; and data were sufficient for the calculation of
true-positive or false-negative values. A bivariate random effect model was used
to obtain pooled sensitivity and specificity. The positive and negative test
probability of neck metastasis was generated based on Bayesian theory and
collected data for different pre-test possibilities.
RESULTS: Of the 168 identified relevant articles, 7 studies fulfilled all
inclusion criteria for CT, 6 studies for MRI, 11 studies for PET and 8 studies
for US. There was no difference in sensitivity and specificity among these
imaging modalities, except CT was superior to US in specificity. The pooled
estimates for sensitivity were 52% (95% confidence interval [CI], 39% ~ 65%), 65%
(34 ~ 87%) 66% (47 ~ 80%), and 66% (45 ~ 77%), on a per-neck basis for CT, MRI,
PET and US, respectively. The pooled estimates for specificity were 93%
(87% ~ 97%), 81% (64 ~ 91%), 87% (77 ~ 93%), and 78% (71 ~ 83%) for CT, MRI, PET
and US, respectively. With pre-examination nodal metastasis probabilities set at
10%, 20% and 30%, the post-exam probabilities of positive nodal metastasis rates
were 47%, 66% and 77% for CT; 27%, 46% and 59% for MRI; 36%, 56% and 69% for PET;
and 25%, 42% and 56% for US, respectively. Negative nodal metastasis
probabilities were 95%, 89% and 82% for CT; 95%, 90% and 84% for MRI; 96%, 91%
and 86% for PET; and 95%, 90% and 84% for US, respectively.
CONCLUSIONS: Modern imaging modalities offer similar diagnostic accuracy to
define and diagnose clinically N0 neck. Minimizing morbidity and avoiding
elective neck dissection is acceptable in some select cases.

PMCID: PMC3476985
PMID: 22691269  [PubMed - indexed for MEDLINE]


188. J Clin Psychopharmacol. 2012 Jun;32(3):309-16. doi: 10.1097/JCP.0b013e3182549259.

Adverse effects of second-generation antipsychotics in children and adolescents:
a Bayesian meta-analysis.

Cohen D(1), Bonnot O, Bodeau N, Consoli A, Laurent C.

Author information:
(1)Department of Child and Adolescent Psychiatry, Université Pierre et Marie
Curie, GH Pitié-Salpétrière, Paris, France. david.cohen@psl.aphp.fr

Comment in
    Evid Based Ment Health. 2012 Nov;15(4):100.

In adults, second-generation antipsychotics (SGAs) have a low frequency of
extrapyramidal syndrome (EPS) and a moderate frequency of metabolic adverse
effects. Here we aimed to assess short-term adverse effects of SGAs in children
and adolescents. We searched for relevant studies in MEDLINE and EMBASE
(1996-2010), Food and Drug Administration and European Medicines Agency clinical
trial registries, and reference lists of review articles. We found 41 were
short-term (3-12 weeks) controlled studies that evaluated SGA adverse effects in
youths. Using Bayesian meta-analysis, we analyzed odds ratios (ORs) or mean
average effects. Numbers of arms (subjects) in the 41 trials were aripiprazole,
10 (n = 671); olanzapine, 14 (n = 413); quetiapine, 10 (n = 446); risperidone, 25
(n = 1040); ziprasidone, 4 (n = 228); clozapine, 5 (n = 79); and
placebo/untreated, 23 (n = 1138), totaling 93 arms (4015 patients). Clozapine was
assessed only for weight gain and somnolence. Compared with placebo, significant
treatment-related increases were observed for weight gain with olanzapine (mean ±
SD = 3.99 ± 0.42 kg; 95% credible interval, 3.17-4.84 kg), clozapine (2.38 ± 1.13
kg; 95% credible interval, 0.19-4.62 kg), risperidone (2.02 ± 0.32 kg; 95%
credible interval, 1.39-2.66 kg), quetiapine (1.74 ± 0.38 kg; 95% credible
interval, 0.99-2.5 kg), and aripiprazole (0.89 ± 0.32 kg; 95% credible interval,
0.26-1.51 kg); glucose levels with risperidone (3.7 ± 1.36 mg/dL; 95% credible
interval, 1.08-6.42 mg/dL) and olanzapine (2.09 ± 1.08 mg/dL; 95% credible
interval, 0.13-4.32 mg/dL); cholesterol levels with quetiapine (10.77 ± 2.14
mg/dL; 95% credible interval, 6.6-14.95 mg/dL) and olanzapine (4.46 ± 1.65 mg/dL;
95% credible interval, 1.24-7.73 mg/dL); triglyceride levels with olanzapine
(20.18 ± 5.26 mg/dL; 95% credible interval, 9.85-30.53 mg/dL) and quetiapine
(19.5 ± 3.92 mg/dL; 95% credible interval, 11.84-27.17 mg/dL); hyperprolactinemia
with risperidone (OR, 38.63; 95% credible interval, 8.62-125.6), olanzapine (OR,
15.6; 95% credible interval, 4.39-41.1), and ziprasidone (OR, 9.35; 95% credible
interval, 1.24-37.03); and EPS with ziprasidone (OR, 20.56; 95% credible
interval, 3.53-68.94), olanzapine (OR, 6.36; 95% credible interval, 2.43-13.84),
aripiprazole (OR, 3.79; 95% credible interval, 2.17-6.17), and risperidone (OR,
3.71; 95% credible interval, 2.18-6.02). All SGAs increased the risk of
somnolence/sedation. We conclude that short-term metabolic effects and EPS are
frequent in children treated with SGAs. Second-generation antipsychotics have
distinct profiles of secondary effects, which should be considered in making
treatment decisions.

PMID: 22544019  [PubMed - indexed for MEDLINE]


189. Spine (Phila Pa 1976). 2012 May 15;37(11):943-52. doi:
10.1097/BRS.0b013e31823da169.

A meta-analysis of comparative outcomes following cervical arthroplasty or
anterior cervical fusion: results from 4 prospective multicenter randomized
clinical trials and up to 1226 patients.

McAfee PC(1), Reah C, Gilder K, Eisermann L, Cunningham B.

Author information:
(1)Spine and Scoliosis Center, St. Joseph's Hospital, Baltimore, MD, USA.
mack8132@gmail.com

Comment in
    Spine (Phila Pa 1976). 2012 Sep 1;37(19):1720; author reply 1721-2.

STUDY DESIGN: Meta-analysis of 4 prospective randomized controlled Food and Drug
Administration (FDA) Investigational Device Exemption (IDE) clinical trials.
OBJECTIVE: To maximize the information available from 4 IDE studies by analyzing
the combined outcomes of cervical arthroplasty versus fusion at 24-month
follow-up.
SUMMARY OF BACKGROUND DATA: To date, 4 randomized clinical trials have been
completed in the United States under FDA IDE protocols to study cervical
arthroplasty. Each trial reported arthroplasty to be at least as successful as
fusion controls based on noninferiority trial designs. However, sample sizes in
any given trial may not be sufficient to demonstrate superiority of treatment
effect. Meta-analysis enables pooling of results from comparable trials, which
may lead to more precise and statistically significant estimates of treatment
effect.
METHODS: Four cervical arthroplasty randomized clinical trials with comparable
enrollment criteria and outcome measures were conducted independently by 3
separate sponsors to study the following devices: Bryan, Prestige, ProDisc-C, and
PCM cervical disc replacements. A total of 1608 patients were treated across 98
investigative sites. Data were available for 1352 treated patients, of which 1226
were evaluable at 24 months. Assessments included clinical success definitions
based on neck disability index, maintenance or improvement of neurological
status, subsequent surgery or intervention at the index level (survivorship), and
a composite score comprising these as well as serious device-related adverse
events. Trial endpoint comparisons were made at 24 months postoperatively. For
each endpoint, a random-effects meta-analysis was performed to compare the
success rates of cervical arthroplasty with anterior cervical discectomy and
fusion (ACDF). Also, supportive frequentist and bayesian analyses were performed.
RESULTS: The pooled primary overall success results indicated a statistically
significant treatment effect favoring arthroplasty compared with ACDF. Overall
success was achieved by 77.6% of the arthroplasty patients and by 70.8% of the
ACDF patients (pooled odds ratio [OR]: 0.699, 95% confidence interval [CI]:
0.539-0.908, P = 0.007). The results of the individual subcomponent
meta-analyses, all of which favored arthroplasty, were neck disability index
success (OR: 0.786, 95% CI: 0.589-1.050, P = 0.103), neurological status (OR:
0.552, 95% CI: 0.364-0.835, P = 0.005), and survivorship (OR: 0.510, 95% CI:
0.275-0.946, P = 0.033). Only the survivorship endpoint suggested low
heterogeneity.
CONCLUSION: These findings suggest that cervical arthroplasty is superior to ACDF
in overall success, neurological success, and survivorship outcomes at 24 months
postoperatively.

PMID: 22037535  [PubMed - indexed for MEDLINE]


190. Malar J. 2012 May 3;11:147. doi: 10.1186/1475-2875-11-147.

Multiple treatment comparisons in a series of anti-malarial trials with an
ordinal primary outcome and repeated treatment evaluations.

Whegang Youdom S(1), Samson A, Basco LK, Thalabard JC.

Author information:
(1)Ecole Nationale Supérieure Polytechnique, Université de Yaoundé 1, B. P. 8390
Yaoundé, Cameroon. solange.whegang@math-info.univ-paris5.fr

BACKGROUND: Artemisinin-based combination therapies (ACT) are widely used in
African countries, including Cameroon. Between 2005 and 2007, five randomized
studies comparing different treatment arms among artesunate-amodiaquine and other
ACT were conducted in Cameroonian children aged two to 60 months who had
uncomplicated Plasmodium falciparum malaria. In these studies, the categorical
criterion proposed by the World Health Organization (WHO) to assess the relative
effectiveness of anti-malarial drugs was repeatedly evaluated on Days 14, 21 and
28 after treatment initiation. The aim of the present study was to compare the
effects of different treatments on this repeated ordinal outcome, hence using the
fully available information.
METHODS: The quantitative synthesis was based on individual patient data. Due to
the incomplete block design concerning treatment arms between different trials, a
mixed treatment comparison (MTC) meta-analysis approach was adopted. The repeated
ordinal outcome was modelled through a latent variable, as a proportional odds
mixed model with trial, period and treatment arms as covariates. The model was
further complexified to account for the variance heterogeneity, and the
individual log-residual variance was modelled as a linear mixed model, as well.
The effects of individual covariates at inclusion, such as parasitaemia, fever,
gender and weight, were also tested. Model parameters were estimated using a
Bayesian approach via the WinBUGS software. After selecting the best model using
Deviance Information Criterion (DIC), mixed treatment comparisons were based on
the estimated treatment effects.
RESULTS: Modeling the residual variance improved the model ability to adjust the
data. The results showed that, compared to artesunate-amodiaquine (ASAQ),
dihydroartemisinin-piperaquine (DHPP) was significantly more efficacious.
Artesunate-chlorproguanil-dapsone (ASCD) was less efficacious than
artesunate-sulphadoxine-pyrimethamine (ASSP), artemether-lumefantrine (AMLM) and
DHPP, the difference with the latter being significant. No difference in efficacy
was found between ASAQ and AMLM.
CONCLUSIONS: Bayesian mixed treatment comparisons of a network of connected
randomized trials with repeated measurements of the primary categorical outcome
allowed to take into account both the individual- and between- studies sources of
heterogeneity. The results of the present study complete the previous
quantitative review based on a binary outcome at a fixed time point, suggesting
that DHPP represents an alternative for the treatment of uncomplicated P.
falciparum malaria in Cameroonian children.

PMCID: PMC3496581
PMID: 22554024  [PubMed - indexed for MEDLINE]


191. Am J Epidemiol. 2012 May 1;175(9):867-77. doi: 10.1093/aje/kwr408. Epub 2012 Apr
10.

Growth hormone receptor polymorphism and growth hormone therapy response in
children: a Bayesian meta-analysis.

Renehan AG(1), Solomon M, Zwahlen M, Morjaria R, Whatmore A, Audí L, Binder G,
Blum W, Bougnères P, Santos CD, Carrascosa A, Hokken-Koelega A, Jorge A, Mullis
PE, Tauber M, Patel L, Clayton PE.

Author information:
(1)School of Cancer andEnabling Sciences, University of Manchester, United
Kingdom. arenehan@picr.man.ac.uk

Recombinant human growth hormone (rhGH) therapy is used in the long-term
treatment of children with growth disorders, but there is considerable treatment
response variability. The exon 3-deleted growth hormone receptor polymorphism
(GHR(d3)) may account for some of this variability. The authors performed a
systematic review (to April 2011), including investigator-only data, to quantify
the effects of the GHR(fl-d3) and GHR(d3-d3) genotypes on rhGH therapy response
and used a recently established Bayesian inheritance model-free approach to
meta-analyze the data. The primary outcome was the 1-year change-in-height
standard-deviation score for the 2 genotypes. Eighteen data sets from 12 studies
(1,527 children) were included. After several prior assumptions were tested, the
most appropriate inheritance model was codominant (posterior probability = 0.93).
Compared with noncarriers, carriers had median differences in 1-year
change-in-height standard-deviation score of 0.09 (95% credible interval (CrI):
0.01, 0.17) for GHR(fl-d3) and of 0.14 (95% CrI: 0.02, 0.26) for GHR(d3-d3).
However, the between-study standard deviation of 0.18 (95% CrI: 0.10, 0.33) was
considerable. The authors tested by meta-regression for potential modifiers and
found no substantial influence. They conclude that 1) the GHR(d3) polymorphism
inheritance is codominant, contrasting with previous reports; 2) GHR(d3)
genotypes account for modest increases in rhGH effects in children; and 3)
considerable unexplained variability in responsiveness remains.

PMID: 22494952  [PubMed - indexed for MEDLINE]




193. J Vasc Surg. 2012 May;55(5):1463-73. doi: 10.1016/j.jvs.2011.12.082. Epub 2012
Mar 21.

Treatment of acute iliofemoral deep vein thrombosis.

Casey ET(1), Murad MH, Zumaeta-Garcia M, Elamin MB, Shi Q, Erwin PJ, Montori VM,
Gloviczki P, Meissner M.

Author information:
(1)Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN 55905, USA.

OBJECTIVE: The objective of this systematic review and meta-analysis was to
compare the efficacy of three available treatments for acute iliofemoral deep
vein thrombosis (DVT): systemic anticoagulation, surgical thrombectomy, and
catheter-directed thrombolysis.
METHODS: We searched electronic databases (MEDLINE, EMBASE, Cochrane CENTRAL, Web
of Science, and Scopus) and sought additional references from experts. Eligible
studies enrolled participants with acute iliofemoral DVT and measured the
outcomes of interest. Reviewers working independently in duplicate extracted
study characteristics, quality, and outcome data (death, pulmonary embolism,
local complications, hemorrhagic complications, postthrombotic syndrome, pain,
quality of life, and surrogate markers of venous function such as valve
competence and patency). We pooled relative risks (RRs) from each study using the
random effects model and estimated the 95% confidence intervals (CIs). Bayesian
indirect comparison techniques were used to compare thrombectomy to
catheter-directed thrombolysis.
RESULTS: We found 15 unique studies that fulfilled eligibility criteria. When
compared to systemic anticoagulation, thrombectomy was associated with a
statistically significant reduction in the risk of developing postthrombotic
syndrome (RR, 0.67; 95% CI, 0.52-0.87), venous reflux (RR, 0.68; 95% CI,
0.46-0.99), and a trend for reduction in the risk of venous obstruction (RR,
0.84; 95% CI, 0.60-1.19). When compared to systemic anticoagulation,
pharmacologic catheter-directed thrombolysis was associated with statistically
significant reduction in the risk of postthrombotic syndrome (RR, 0.19; 95% CI,
0.07-0.48), venous obstruction (RR, 0.38; 95% CI, 0.18-0.37), and a trend for
reduction in the risk of venous reflux (RR, 0.39; 95% CI, 0.16-1.00). Overall,
the quality of evidence was low; downgraded due to the observational nature of
the majority of studies, lack of comparability of study cohorts at baseline, loss
to follow-up, imprecision, and indirectness of outcomes (surrogacy). There were
insufficient data to compare the outcomes of thrombectomy to catheter-directed
thrombolysis.
CONCLUSIONS: Low-quality evidence suggests that surgical thrombectomy decreases
the incidence of postthrombotic syndrome and venous reflux. Catheter-directed
pharmacologic thrombolysis decreases the incidence of postthrombotic syndrome and
venous obstruction.

Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All
rights reserved.

PMID: 22440631  [PubMed - indexed for MEDLINE]


194. Lancet Infect Dis. 2012 May;12(5):373-80. doi: 10.1016/S1473-3099(11)70368-1.
Epub 2012 Jan 24.

Head-to-head comparison of accuracy of a rapid point-of-care HIV test with oral
versus whole-blood specimens: a systematic review and meta-analysis.

Pant Pai N(1), Balram B, Shivkumar S, Martinez-Cajas JL, Claessens C, Lambert G,
Peeling RW, Joseph L.

Author information:
(1)Department of Medicine, Division of Clinical Epidemiology and Infectious
Diseases, McGill University Health Center, Montreal, QC, Canada.

Comment in
    Praxis (Bern 1994). 2012 Nov 14;101(23):1505-6.
    Lancet Infect Dis. 2012 May;12(5):356-7.

BACKGROUND: The focus on prevention strategies aimed at curbing the HIV epidemic
is growing, and therefore screening for HIV has again taken centre stage. Our aim
was to establish whether a convenient, non-invasive, HIV test that uses oral
fluid was accurate by comparison with the same test with blood-based specimens.
METHODS: We did a systematic review and meta-analysis to compare the diagnostic
accuracy of a rapid HIV-antibody-based point-of-care test (Oraquick advance rapid
HIV-1/2, OraSure Technologies Inc, PA, USA) when used with oral versus
blood-based specimens in adults. We searched five databases of published work and
databases of five key HIV conferences. Studies we deemed eligible were those
focused on adults at risk of HIV; we excluded studies in children, in co-infected
populations, with self-reported inferior reference standards, and with incomplete
reporting of key data items. We assessed the diagnostic accuracy of testing with
oral and blood-based specimens with bivariate regression analysis. We computed
positive predictive values (PPVs) in high-prevalence and low-prevalence settings
with Bayesian methods.
FINDINGS: In a direct head-to-head comparison of studies, we identified a pooled
sensitivity about 2% lower in oral (98·03%, 95% CI 95·85-99·08) than in
blood-based specimens (99·68%, 97·31-99·96), but similar specificity (oral
99·74%, 99·47-99·88; blood 99·91%, 99·84-99·95). Negative likelihood ratios were
small and similar (oral 0·019, 0.009-0·040; blood 0·003, 0·001-0·034), but
positive likelihood ratios differed (oral 383·37, 183·87-799·31; blood 1105·16,
633·14-2004·37). Although in high-prevalence settings PPVs were similar (oral
98·65%, 95% credible interval 85·71-99·94; blood 98·50, 93·10-99·79), in
low-prevalence settings PPVs were lower for oral (88·55%, 77·31-95·87) than blood
(97·65%, 95·48-99·09) specimens.
INTERPRETATION: Although Oraquick had a high PPV in high-prevalence settings in
oral specimens, the slightly lower sensitivity and PPV in low-prevalence settings
in oral specimens should be carefully reviewed when planning worldwide expanded
initiatives with this popular test.

Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID: 22277215  [PubMed - indexed for MEDLINE]


195. J Natl Cancer Inst. 2012 Apr 4;104(7):507-16. doi: 10.1093/jnci/djs142. Epub 2012
Mar 22.

Network meta-analysis of margin threshold for women with ductal carcinoma in
situ.

Wang SY(1), Chu H, Shamliyan T, Jalal H, Kuntz KM, Kane RL, Virnig BA.

Author information:
(1)Division of Health Policy and Management, University of Minnesota School of
Public Health, 420 Delaware St S.E., MMC 729, Minneapolis, MN 55455, USA.
wang1018@umn.edu

Comment in
    J Natl Cancer Inst. 2012 Apr 4;104(7):494-5.

BACKGROUND: Negative margins are associated with reduced risk of ipsilateral
breast tumor recurrence (IBTR) for women with ductal carcinoma in situ (DCIS)
treated with breast-conserving surgery (BCS). However, there is no consensus
about the best minimum margin width.
METHODS: We searched the PubMed database for studies of DCIS published in English
between January 1970 and July 2010 and examined the relationship between IBTR and
margin status after BCS for DCIS. Women with DCIS were stratified into two
groups, BCS with or without radiotherapy. We used frequentist and Bayesian
approaches to estimate the odds ratios (OR) of IBTR for groups with negative
margins and positive margins. We further examined specific margin thresholds
using mixed treatment comparisons and meta-regression techniques. All statistical
tests were two-sided.
RESULTS: We identified 21 studies published in 24 articles. A total of 1066 IBTR
events occurred in 7564 patients, including BCS alone (565 IBTR events in 3098
patients) and BCS with radiotherapy (501 IBTR events in 4466 patients). Compared
with positive margins, negative margins were associated with reduced risk of IBTR
in patients with radiotherapy (OR = 0.46, 95% credible interval [CrI] = 0.35 to
0.59), and in patients without radiotherapy (OR = 0.34, 95% CrI = 0.24 to 0.47).
Compared with patients with positive margins, the risk of IBTR for patients with
negative margins was smaller (negative margin >0 mm, OR = 0.45, 95% CrI = 0.38 to
0.53; >2 mm, OR = 0.38, 95% CrI = 0.28 to 0.51; >5 mm, OR = 0.55, 95% CrI = 0.15
to 1.30; and >10 mm, OR = 0.17, 95% CrI = 0.12 to 0.24). Compared with a negative
margin greater than 2 mm, a negative margin of at least 10 mm was associated with
a lower risk of IBTR (OR = 0.46, 95% CrI = 0.29 to 0.69). We found a probability
of .96 that a negative margin threshold greater than 10 mm is the best option
compared with other margin thresholds.
CONCLUSIONS: Negative surgical margins should be obtained for DCIS patients after
BCS regardless of radiotherapy. Within cosmetic constraint, surgeons should
attempt to achieve negative margins as wide as possible in their first attempt.
More studies are needed to understand whether margin thresholds greater than 10
mm are warranted.

PMCID: PMC3916966
PMID: 22440677  [PubMed - indexed for MEDLINE]


196. Am Heart J. 2012 Apr;163(4):632-48. doi: 10.1016/j.ahj.2012.01.015.

Comparison of transradial and femoral approaches for percutaneous coronary
interventions: a systematic review and hierarchical Bayesian meta-analysis.

Bertrand OF(1), Bélisle P, Joyal D, Costerousse O, Rao SV, Jolly SS, Meerkin D,
Joseph L.

Author information:
(1)Quebec Heart and Lung Institute, Quebec City, Quebec, Canada.
olivier.bertrand@criucpq.ulaval.ca

BACKGROUND: Despite lower risks of access site-related complications with
transradial approach (TRA), its clinical benefit for percutaneous coronary
intervention (PCI) is uncertain. We conducted a systematic review and
meta-analysis of clinical studies comparing TRA and transfemoral approach (TFA)
for PCI.
METHODS: Randomized trials and observational studies (1993-2011) comparing TRA
with TFA for PCI with reports of ischemic and bleeding outcomes were included.
Crude and adjusted (for age and sex) odds ratios (OR) were estimated by a
hierarchical Bayesian random-effects model with prespecified stratification for
observational and randomized designs. The primary outcomes were rates of death,
combined incidence of death or myocardial infarction, bleeding, and transfusions,
early (≤ 30 days) and late after PCI.
RESULTS: We collected data from 76 studies (15 randomized, 61 observational)
involving a total of 761,919 patients. Compared with TFA, TRA was associated with
a 78% reduction in bleeding (OR 0.22, 95% credible interval [CrI] 0.16-0.29) and
80% in transfusions (OR 0.20, 95% CrI 0.11-0.32). These findings were consistent
in both randomized and observational studies. Early after PCI, there was a 44%
reduction of mortality with TRA (OR 0.56, 95% CrI 0.45-0.67), although the effect
was mainly due to observational studies (OR 0.52, 95% CrI 0.40-0.63, adjusted OR
0.49 [95% CrI 0.37-0.60]), with an OR of 0.80 (95% CrI 0.49-1.23) in randomized
trials.
CONCLUSION: Our results combining observational and randomized studies show that
PCI performed by TRA is associated with substantially less risks of bleeding and
transfusions compared with TFA. Benefit on the incidence of death or combined
death or myocardial infarction is found in observational studies but remains
inconclusive in randomized trials.

Copyright © 2012 Mosby, Inc. All rights reserved.

PMID: 22520530  [PubMed - indexed for MEDLINE]


197. Cardiovasc Drugs Ther. 2012 Apr;26(2):167-79. doi: 10.1007/s10557-012-6374-4.

Systematic review and meta-analysis of the efficacy of cardioversion by
vernakalant and comparators in patients with atrial fibrillation.

Bash LD(1), Buono JL, Davies GM, Martin A, Fahrbach K, Phatak H, Avetisyan R,
Mwamburi M.

Author information:
(1)Merck & Co., Inc, Whitehouse Station, NJ, USA. lori_bash@merck.com

PURPOSE: Rate and rhythm control are two well established treatment objectives
for atrial fibrillation (AF) patients. While symptom reduction is a primary
treatment goal, therapeutic practice related to cardioversion varies by region
and patient, with several precautions associated with the use of current
therapies. No comprehensive literature review on the relative efficacy of
existing cardioversion approaches compared to newly available therapies has been
conducted.
METHODS AND RESULTS: A systematic literature review and meta-analysis were
undertaken to evaluate the efficacy of pharmacologic therapies in eliciting
cardioversion within 2 and 8-24 h among patients with recent-onset, short
duration AF. Eligible studies included randomized controlled trials in which
cardioversion rates were evaluated in at least 2 treatment groups. Bayesian
mixed-treatment comparisons estimated odds ratios (95% credible intervals) for
successful cardioversion. Results within 2 h showed vernakalant IV, propafenone
IV and flecainide (IV and oral) were more efficacious in pair-wise comparisons to
placebo. Results were mixed in analyses comparing efficacy rates between 8 and 24
h. Few adverse events were reported, with the most common being bradycardia and
hypotension.
CONCLUSIONS: In pair-wise comparisons of active treatment arms to one another,
results suggest vernakalant IV, propafenone IV and flecainide appear to be
effective in achieving rapid cardioversion in patients with short duration AF
compared to other agents. Application of these findings to clinical practice need
to account for the variable comorbidity profiles of patients, important
determinants in the selection of appropriate therapy for individual patients.
Though best practice methods were used, further research comparing treatments
through direct head-to-head comparisons may be warranted to confirm these
findings and further inform clinical practice.

PMID: 22418856  [PubMed - indexed for MEDLINE]


198. Int J Technol Assess Health Care. 2012 Apr;28(2):115-24. doi:
10.1017/S0266462312000037.

Bayesian meta-analysis on medical devices: application to implantable
cardioverter defibrillators.

Youn JH(1), Lord J, Hemming K, Girling A, Buxton M.

Author information:
(1)Health Economics Research Group, Brunel University, Uxbridge, United Kingdom.
cmp11jy@sheffield.ac.uk

OBJECTIVES: The aim of this study is to describe and illustrate a method to
obtain early estimates of the effectiveness of a new version of a medical device.
METHODS: In the absence of empirical data, expert opinion may be elicited on the
expected difference between the conventional and modified devices. Bayesian Mixed
Treatment Comparison (MTC) meta-analysis can then be used to combine this expert
opinion with existing trial data on earlier versions of the device. We illustrate
this approach for a new four-pole implantable cardioverter defibrillator (ICD)
compared with conventional ICDs, Class III anti-arrhythmic drugs, and
conventional drug therapy for the prevention of sudden cardiac death in high risk
patients. Existing RCTs were identified from a published systematic review, and
we elicited opinion on the difference between four-pole and conventional ICDs
from experts recruited at a cardiology conference.
RESULTS: Twelve randomized controlled trials were identified. Seven experts
provided valid probability distributions for the new ICDs compared with current
devices. The MTC model resulted in estimated relative risks of mortality of 0.74
(0.60-0.89) (predictive relative risk [RR] = 0.77 [0.41-1.26]) and 0.83
(0.70-0.97) (predictive RR = 0.84 [0.55-1.22]) with the new ICD therapy compared
to Class III anti-arrhythmic drug therapy and conventional drug therapy,
respectively. These results showed negligible differences from the preliminary
results for the existing ICDs.
CONCLUSIONS: The proposed method incorporating expert opinion to adjust for a
modification made to an existing device may play a useful role in assisting
decision makers to make early informed judgments on the effectiveness of
frequently modified healthcare technologies.

PMCID: PMC3339879
PMID: 22559753  [PubMed - indexed for MEDLINE]


199. Dent Mater. 2012 Mar;28(3):298-303. doi: 10.1016/j.dental.2011.11.002. Epub 2011
Dec 3.

Longevity of materials for pit and fissure sealing--results from a meta-analysis.

Kühnisch J(1), Mansmann U, Heinrich-Weltzien R, Hickel R.

Author information:
(1)Department of Conservative Dentistry and Periodontology, School of Dentistry,
Ludwig-Maximilians-University of Munich, Munich, Germany.
jkuehn@dent.med.uni-muenchen.de

Comment in
    Dent Mater. 2012 Jul;28(7):e75.
    Tex Dent J. 2013 Jul;130(7):618.
    Evid Based Dent. 2012 Mar;13(1):9-10.

OBJECTIVE: This meta-analysis investigates the clinical retention of pit and
fissure sealants in relation to observation time and material type.
DATA, SOURCES AND STUDY SELECTION: A search in the MEDLINE, EMBASE and CENTRAL
databases identified 2944 abstracts (published prior to 9/30/2011), of which 485
clinical publications were analyzed in detail. A total of 146 articles included
information about sealant retention, with a minimum observation time of 2 years.
These publications were analyzed to determine the retention rates of the various
materials studied (UV-light-, light- and auto-polymerizing resin-based sealants,
fluoride-releasing materials, compomers, flowable composites and
glass-ionomer-cement-based sealants). The meta-analysis used random effects
models for longitudinal logistic regression and Bayesian statistics.
RESULTS: As part of the systematic review, 98 clinical reports and 12 field trial
reports were identified. Auto-polymerizing sealants had the longest observation
time (up to 20 years) and were found to have a 5-year retention rate of 64.7%
(95%CI=57.1-73.1%), which was estimated from the meta-analysis model. Resin-based
light-polymerizing sealants and fluoride-releasing products showed similar 5-year
retention rates (83.8%, 95%CI=54.9-94.7% and 69.9%, 95%CI=51.5-86.5%,
respectively) for completely retained sealants. In contrast to these high
retention rates, poor retention rates were documented for UV-light-polymerizing
materials, compomers and glass-ionomer-cement-based sealants (5-year retention
rates were <19.3%). Retention rates for UV-light-polymerizing materials,
compomers and glass-ionomer-cement-based sealants were classified as inferior.
CONCLUSIONS VERSUS SIGNIFICANCE: The results of this meta-analysis suggested that
resin-based sealants can be recommended for clinical use. The faster and less
error-prone clinical application of light-polymerizing materials, however, makes
them the preferred choice for daily dental practice.

Copyright © 2011 Academy of Dental Materials. Published by Elsevier Ltd. All
rights reserved.

PMID: 22137936  [PubMed - indexed for MEDLINE]


200. Eur Arch Otorhinolaryngol. 2012 Mar;269(3):721-9. doi: 10.1007/s00405-011-1744-2.
Epub 2011 Oct 9.

Traditional endonasal and microscopic sinus surgery complications versus
endoscopic sinus surgery complications: a meta-analysis.

Re M(1), Massegur H, Magliulo G, Ferrante L, Sciarretta V, Farneti G, Macrì G,
Mallardi V, Pasquini E.

Author information:
(1)Department of Otorhinolaryngology, Polytechnic University of Marche, Via
Tronto 10/A, 60126, Ancona, Italy. remassimo@hotmail.com

The aim of this study was to compare the incidence of complications of endoscopic
sinus surgery (ESS) to the incidence of complications of traditional and
microscopic sinus surgery. A meta-analysis was carried out on 28 series of
patients (a total of 13,405) who had undergone ESS, 8 series of patients (3,887
in total) who had undergone traditional endonasal sinus surgery and 7 series of
patients (1,630 in total) who had undergone microscopic sinus surgery. The
authors used the Bayesian inference package WinBUGS operating from within the
statistical computer program R (version 2.7.1). Major complications had a higher
incidence after traditional sinus surgery than ESS but this fact did not cause a
significant statistical difference, whereas microscopic surgery had significantly
more complications than ESS (p < 0.05). Carrying out our meta-analytic study,
comparing major and minor complications of endonasal surgical approaches, was
very difficult due to several methodological biases of data extraction and
evaluation from studies concerning a broad timespan. Regarding major
complications, we only found a significant statistical difference (p < 0.05)
between the endoscopic (1%) and the microscopic methods (2.0%), but, if we had
analyzed the data considering the natural learning curve of the latest ESS
surgical approach, and if we had not considered the results produced in the first
10 years (1988-1998) concerning ESS in our meta-analysis, we would have found a
statistically significant difference (p < 0.05) between the endoscopic (0.4%) and
the traditional (1.1%) approach as well.

PMID: 21984058  [PubMed - indexed for MEDLINE]


201. J Clin Periodontol. 2012 Mar;39(3):303-14.

A Bayesian network meta-analysis on comparisons of enamel matrix derivatives,
guided tissue regeneration and their combination therapies.

Tu YK(1), Needleman I, Chambrone L, Lu HK, Faggion CM Jr.

Author information:
(1)Department of Periodontology, Leeds Dental Institute, University of Leeds, UK.
y.k.tu@leeds.ac.uk

AIMS: Guided tissue regeneration (GTR) and enamel matrix derivatives (EMD) are
two popular regenerative treatments for periodontal infrabony lesions. Both have
been used in conjunction with other regenerative materials. We conducted a
Bayesian network meta-analysis of randomized controlled trials on treatment
effects of GTR, EMD and their combination therapies.
MATERIAL AND METHODS: A systematic literature search was conducted using the
Medline, EMBASE, LILACS and CENTRAL databases up to and including June 2011.
Treatment outcomes were changes in probing pocket depth (PPD), clinical
attachment level (CAL) and infrabony defect depth. Different types of bone grafts
were treated as one group and so were barrier membranes.
RESULTS: A total of 53 studies were included in this review, and we found small
differences between regenerative therapies which were non-significant
statistically and clinically. GTR and GTR-related combination therapies achieved
greater PPD reduction than EMD and EMD-related combination therapies. Combination
therapies achieved slightly greater CAL gain than the use of EMD or GTR alone.
GTR with BG achieved greatest defect fill.
CONCLUSION: Combination therapies performed better than single therapies, but the
additional benefits were small. Bayesian network meta-analysis is a promising
technique to compare multiple treatments. Further analysis of methodological
characteristics will be required prior to clinical recommendations.

© 2012 John Wiley & Sons A/S

PMID: 22393565  [PubMed - indexed for MEDLINE]


202. Nutr Metab Cardiovasc Dis. 2012 Mar;22(3):182-91. doi:
10.1016/j.numecd.2010.05.007. Epub 2010 Aug 14.

Exposure to isoflavone-containing soy products and endothelial function: a
Bayesian meta-analysis of randomized controlled trials.

Beavers DP(1), Beavers KM, Miller M, Stamey J, Messina MJ.

Author information:
(1)Department of Biostatistical Sciences, Wake Forest University School of
Medicine, Winston-Salem, NC, USA.

BACKGROUND AND AIMS: To determine whether and to what degree exposure to
isoflavone-containing soy products affects EF. Endothelial dysfunction has been
identified as an independent coronary heart disease risk factor and a strong
predictor of long-term cardiovascular morbidity and mortality. Data on the
effects of exposure to isoflavone-containing soy products on EF are conflicting.
METHODS AND RESULTS: A comprehensive literature search was conducted using the
PUBMED database (National Library of Medicine, Bethesda, MD) inclusively through
August 21, 2009 on RCTs using the keywords: soy, isoflavone, phytoestrogen, EF,
flow mediated vasodilation, and FMD. A Bayesian meta-analysis was conducted to
provide a comprehensive account of the effect of isoflavone-containing soy
products on EF, as measured by FMD. A total of 17 RCTs were selected as having
sufficient data for study inclusion. The overall mean absolute change in FMD (95%
Bayesian CI) for isoflavone-containing soy product interventions was 1.15%
(-0.52, 2.75). When the effects of separate interventions were considered, the
treatment effect for isolated isoflavones was 1.98% (0.07, 3.97) compared to
0.72% (-1.39, 2.90) for isoflavone-containing soy protein. The models were not
improved when considering study-specific effects such as cuff measurement
location, prescribed dietary modification, and impaired baseline FMD.
CONCLUSIONS: Cumulative evidence from the RCTs included in this meta-analysis
indicates that exposure to soy isoflavones can modestly, but significantly,
improve EF as measured by FMD. Therefore, exposure to isoflavone supplements may
beneficially influence vascular health.

Copyright Â© 2010 Elsevier B.V. All rights reserved.

PMID: 20709515  [PubMed - indexed for MEDLINE]


203. Ophthalmology. 2012 Mar;119(3):571-80. doi: 10.1016/j.ophtha.2011.09.027. Epub
2011 Dec 15.

Age and gender variations in age-related macular degeneration prevalence in
populations of European ancestry: a meta-analysis.

Rudnicka AR(1), Jarrar Z, Wormald R, Cook DG, Fletcher A, Owen CG.

Author information:
(1)Division of Population Health Sciences and Education, St. George's, University
of London, London, UK.

OBJECTIVE: To obtain prevalence estimates of age-related macular degeneration
(AMD; late, geographic atrophy, neovascular) by age and gender amongst
populations of European ancestry taking into account study design and time
trends.
DESIGN: Systematic review of population-based studies published by September 2010
with quantitative estimates of geographic atrophy (GA), neovascular (NV), and
late AMD prevalence. Studies were identified by a literature search of MEDLINE
(from 1950), EMBASE (from 1980), and Web of Science (from 1980) databases.
PARTICIPANTS: Data from 25 published studies (57 173 subjects: 455 with GA, 464
with NVAMD, and 1571 with late AMD).
METHODS: Bayesian meta-regression of the log odds of AMD with age, gender, and
year of study allowing for differences in study design characteristics, to
estimate prevalences of AMD (late, GA, NVAMD) along with 95% credible intervals
(CrI).
MAIN OUTCOME MEASURES: Log odds and prevalence of AMD.
RESULTS: There was considerable heterogeneity in prevalence rates between
studies; for late AMD, 20% of the variability in prevalence rates was explained
by differences in age and 50% by study characteristics. The prevalence of AMD
increased exponentially with age (odds ratio [OR], 4.2 per decade; 95% CrI,
3.8-4.6), which did not differ by gender. There was some evidence to suggest
higher risk of NVAMD in women compared with men (OR, 1.2; 95% CrI, 1.0-1.5).
Compared with studies using fundus imaging and international classification
systems, studies using fundus imaging with alternative classifications were more
likely (OR, 2.7; 95% CrI, 1.1-2.8), and studies using alternative classifications
without fundus imaging most likely to diagnose late AMD (OR, 2.9; 95% CrI,
1.3-7.8). There was no good evidence of trends in AMD prevalence over time.
Estimated prevalence of late AMD is 1.4% (95% CrI, 1.0%-2.0%) at 70 years of age,
rising to 5.6% (95% CrI, 3.9%-7.7%) at age 80 and 20% (95% CrI, 14%-27%) at age
90.
CONCLUSIONS: Studies using recognized classifications systems with fundus
photography reported the lowest prevalences of AMD taking account of age and
gender, and were stable over time, with a potentially higher risk of NVAMD for
women. These prevalence estimates can be used to guide health service provision
in populations of European ancestry.

Copyright Â© 2012 American Academy of Ophthalmology. Published by Elsevier Inc.
All rights reserved.

PMID: 22176800  [PubMed - indexed for MEDLINE]


204. Clin Ther. 2012 Feb;34(2):282-94. doi: 10.1016/j.clinthera.2012.01.007. Epub 2012
Jan 31.

A network meta-analysis on the efficacy of serotonin type 3 receptor antagonists
used in adults during the first 24 hours for postoperative nausea and vomiting
prophylaxis.

Tang DH(1), Malone DC.

Author information:
(1)The University of Arizona College of Pharmacy, Tucson, Arizona 85721, USA.
dtang@pharmacy.arizona.edu

Comment in
    Clin Ther. 2012 May;34(5):1204-6; author reply 1206-8.

BACKGROUND: The serotonin type 3 receptor antagonists (5-HT(3) antagonists)
ondansetron, granisetron, tropisetron, and dolasetron are potential prophylactic
agents for patients with mild to moderate risk of postoperative nausea and
vomiting (PONV). A few trials have been conducted to compare the efficacy among 2
to 3 of these 4 agents. However, the comparative efficacy of all four 5-HT(3)
antagonists has not yet been quantitatively investigated.
OBJECTIVE: The goal of this study was to investigate whether the 5-HT(3)
antagonists--ondansetron, granisetron, tropisetron, and dolasetron-differ in
efficacy when used for the prevention of PONV.
METHODS: PubMed and the Cochrane Library were searched for randomized controlled,
double-blind studies measuring efficacy in terms of PONV prophylaxis. A Bayesian
meta-analysis was conducted using published studies of 5-HT(3) antagonists for
PONV prophylaxis. The odds of patients with no PONV and postoperative vomiting
(POV) within each study arm 24 hours after surgery were the primary indices of
drug efficacy. Data were extracted and analyzed via indirect comparisons using
random effects Bayesian models in WinBUGS version 1.4.3.
RESULTS: A total of 85 studies were identified, representing 15,269 patients. The
results indicate that granisetron was significantly better than ondansetron (odds
ratio [OR] = 1.53 [95% credible interval (CI), 1.15-2.00]) and dolasetron (OR =
1.67 [95% CI, 1.12-2.38]) in preventing PONV. Four antiemetic drugs had
comparable efficacy in terms of preventing POV: granisetron showed similar
efficacy compared with ondansetron (OR = 1.49 [95% CI, 0.90-2.43]), tropisetron
(OR = 1.69 [95% CI, 0.92-3.13]), and dolasetron (OR = 1.32 [95% CI, 0.71-2.38]).
Ondansetron exhibited comparable efficacy compared with tropisetron (OR = 1.14
[95% CI, 0.66-1.96]) and dolasetron (OR = 0.88 [95% CI, 0.51-1.47]). Tropisetron
and dolasetron were also similar in efficacy (OR = 0.78 [95% CI, 0.40-1.45]). All
5-HT(3) antagonists were statistically significantly better at preventing PONV or
POV than placebo.
CONCLUSIONS: With respect to PONV prophylaxis, granisetron was significantly
better than ondansetron and dolasetron; ondansetron, tropisetron, and dolasetron
exhibited similar efficacy. With respect to POV prophylaxis, ondansetron,
granisetron, tropisetron, and dolasetron seemed to have comparable efficacy.

Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

PMID: 22296947  [PubMed - indexed for MEDLINE]


205. Int J Biostat. 2012 Jan 6;8(2). pii:
/j/ijb.2012.8.issue-2/1557-4679.1350/1557-4679.1350.xml. doi:
10.2202/1557-4679.1350.

Meta-analysis of observational studies with unmeasured confounders.

McCandless LC(1).

Author information:
(1)Simon Fraser University.

Meta-analysis of observational studies is an exciting new area of innovation in
statistical science. Unlike randomized controlled trials, which are the gold
standard for proving causation, observational studies are prone to biases
including confounding. In this article, we describe a novel Bayesian procedure to
control for a confounder that is missing across the sequence of studies in a
meta-analysis. We motivate the discussion with the example of a meta-analysis of
cohort, case-control and cross-sectional studies examining the relationship
between oral contraceptives and endometriosis. An important unmeasured confounder
is dysmennoreah, which is an indication for oral contraceptive use. To adjust for
unmeasured confounding, we combine random effects models with probabilistic
sensitivity analysis techniques. Information about the unmeasured confounder is
incorporated into the analysis via prior distributions, and we use MCMC to sample
from posterior.

PMID: 22499731  [PubMed - indexed for MEDLINE]


206. Br J Dermatol. 2012 Jan;166(1):179-88. doi: 10.1111/j.1365-2133.2011.10583.x.
Epub 2011 Nov 11.

Efficacy of biologics in the treatment of moderate to severe psoriasis: a network
meta-analysis of randomized controlled trials.

Reich K(1), Burden AD, Eaton JN, Hawkins NS.

Author information:
(1)Dermatologikum Hamburg, Drehbahn 1-3, 20354 Hamburg, Germany.

BACKGROUND: Ustekinumab, a novel monoclonal antibody for the treatment of
moderate to severe plaque-type psoriasis, has recently received regulatory
approval in Europe, bringing the total number of biologic agents licensed in this
indication to five. To assist treatment selection in daily practice it is
essential to understand the benefit/risk profile of these agents and in the
absence of a clinical trial comparing all available biologics a number of reviews
have used statistical techniques to generate estimates of the comparative
effectiveness of these therapies through the available network of randomized
clinical trials. These estimates have previously been published for a limited
range of psoriasis biologic treatments, although, to date no review has compared
all the currently available agents in Europe.
OBJECTIVES: To estimate the comparative effectiveness of all biologic agents
indicated in the treatment of moderate to severe psoriasis currently available in
Europe based on the primary trial endpoints.
METHODS: A number of databases were searched for details of randomized controlled
trials of available biologics in the treatment of plaque-type psoriasis in
adults. Comparative effectiveness was estimated based on the reported Psoriasis
Area and Severity Index (PASI) 50, 75 and 90 response rates. A network
meta-analysis conducted on the ordered probit scale and implemented as a Bayesian
hierarchical model provided estimates for the probability of response and
relative risk vs. placebo, based on all observed comparisons.
RESULTS: Twenty trials were included in the meta-analysis including patients with
a mean disease duration of 18-22years. Based on the indirect comparison and given
a placebo PASI 50 response of 13%, infliximab had the highest predicted mean
probability of response at PASI levels 50 (93%), 75 (80%) and 90 (54%), followed
by ustekinumab 90 mg at 90%, 74% and 46%, respectively, and then ustekinumab
45mg, adalimumab, etanercept and efalizumab.
CONCLUSIONS: The ordered probit model allowed a quantitative comparison of all
currently licensed biologics, providing estimates on comparative effectiveness
and a suggested ranking of treatments that is of potential use to
decision-makers. However, the analysis is based on indirect comparisons of the
primary endpoint reported from short-term randomized trials.

© 2011 The Authors. BJD © 2011 British Association of Dermatologists.

PMID: 21910698  [PubMed - indexed for MEDLINE]


207. Epidemiol Rev. 2012;34:46-56. doi: 10.1093/epirev/mxr021. Epub 2011 Nov 14.

Roadway characteristics and pediatric pedestrian injury.

DiMaggio C(1), Li G.

Author information:
(1)Department of Anesthesiology, College of Physicians and Surgeons, Columbia
University, 622 West 168 Street, Room PH5-531, New York, NY 10032, USA.
cjd11@columbia.edu

Changing the built environment is a sound, but often underutilized approach to
injury control. The authors reviewed the literature and conducted a meta-analysis
to synthesize the evidence on the association of roadway characteristics with
risk of pediatric pedestrian injury. To synthesize the data, they converted
results to odds ratios based on direct results or abstracted outcomes and used
Bayesian meta-analytic approaches by modeling outcomes as the logit of a normally
distributed set of outcomes with vague prior distributions for the central
measure of effect and its variance. On the basis of 10 studies of roadway
features restricted exclusively to pediatric populations, the synthesized effect
estimate for the association of roadway characteristics with pedestrian injury
risk was 2.5 (95% credible interval: 1.8, 3.2). The probability of a new study
showing an association between the built roadway and pediatric pedestrian injury
was nearly 100%. The authors concluded that the built environment is directly
related to the risk of pedestrian injury. This review and meta-analysis suggests
that even modest interventions to the built roadway environment may result in
meaningful reductions in the risk of pediatric pedestrian injury.

PMID: 22084212  [PubMed - indexed for MEDLINE]


208. Health Technol Assess. 2012;16(38):1-205, iii-v. doi: 10.3310/hta16380.

Effectiveness and cost-effectiveness of computer and other electronic aids for
smoking cessation: a systematic review and network meta-analysis.

Chen YF(1), Madan J, Welton N, Yahaya I, Aveyard P, Bauld L, Wang D, Fry-Smith A,
Munafò MR.

Author information:
(1)School of Health and Population Sciences, University of Birmingham,
Birmingham, UK.

BACKGROUND: Smoking is harmful to health. On average, lifelong smokers lose 10
years of life, and about half of all lifelong smokers have their lives shortened
by smoking. Stopping smoking reverses or prevents many of these harms. However,
cessation services in the NHS achieve variable success rates with smokers who
want to quit. Approaches to behaviour change can be supplemented with electronic
aids, and this may significantly increase quit rates and prevent a proportion of
cases that relapse.
OBJECTIVE: The primary research question we sought to answer was: What is the
effectiveness and cost-effectiveness of internet, pc and other electronic aids to
help people stop smoking? We addressed the following three questions: (1) What is
the effectiveness of internet sites, computer programs, mobile telephone text
messages and other electronic aids for smoking cessation and/or reducing relapse?
(2) What is the cost-effectiveness of incorporating internet sites, computer
programs, mobile telephone text messages and other electronic aids into current
nhs smoking cessation programmes? and (3) What are the current gaps in research
into the effectiveness of internet sites, computer programs, mobile telephone
text messages and other electronic aids to help people stop smoking?
DATA SOURCES: For the effectiveness review, relevant primary studies were sought
from The Cochrane Library [Cochrane Central Register of Controlled Trials
(CENTRAL)] 2009, Issue 4, and MEDLINE (Ovid), EMBASE (Ovid), PsycINFO (Ovid),
Health Management Information Consortium (HMIC) (Ovid) and Cumulative Index to
Nursing and Allied Health Literature (CINAHL) (EBSCOhost) from 1980 to December
2009. In addition, NHS Economic Evaluation Database (NHS EED) and Database of
Abstracts of Reviews of Effects (DARE) were searched for information on
cost-effectiveness and modelling for the same period. Reference lists of included
studies and of relevant systematic reviews were examined to identify further
potentially relevant studies. Research registries of ongoing studies including
National Institute for Health Research (NIHR) Clinical Research Network Portfolio
Database, Current Controlled Trials and ClinicalTrials.gov were also searched,
and further information was sought from contacts with experts.
REVIEW METHODS: Randomised controlled trials (RCTs) and quasi-RCTs evaluating
smoking cessation programmes that utilise computer, internet, mobile telephone or
other electronic aids in adult smokers were included in the effectiveness review.
Relevant studies of other design were included in the cost-effectiveness review
and supplementary review. Pair-wise meta-analyses using both random- and
fixed-effects models were carried out. Bayesian mixed-treatment comparisons
(MTCs) were also performed. A de novo decision-analytical model was constructed
for estimating the cost-effectiveness of interventions. Expected value of perfect
information (EVPI) was calculated. Narrative synthesis of key themes and issues
that may influence the acceptability and usability of electronic aids was
provided in the supplementary review.
RESULTS: This effectiveness review included 60 RCTs/quasi-RCTs reported in 77
publications. Pooled estimate for prolonged abstinence [relative risk (RR) =
1.32, 95% confidence interval (CI) 1.21 to 1.45] and point prevalence abstinence
(RR = 1.14, 95% CI 1.07 to 1.22) suggested that computer and other electronic
aids increase the likelihood of cessation compared with no intervention or
generic self-help materials. There was no significant difference in effect sizes
between aid to cessation studies (which provide support to smokers who are ready
to quit) and cessation induction studies (which attempt to encourage a cessation
attempt in smokers who are not yet ready to quit). Results from MTC also showed
small but significant intervention effect (time to relapse, mean hazard ratio
0.87, 95% credible interval 0.83 to 0.92). Cost-threshold analyses indicated some
form of electronic intervention is likely to be cost-effective when added to
non-electronic behavioural support, but there is substantial uncertainty with
regard to what the most effective (thus most cost-effective) type of electronic
intervention is, which warrants further research. EVPI calculations suggested the
upper limit for the benefit of this research is around £ 2000-3000 per person.
LIMITATIONS: The review focuses on smoking cessation programmes in the adult
population, but does not cover smoking cessation in adolescents. Most available
evidence relates to interventions with a single tailored component, while
evidence for different modes of delivery (e.g. e-mail, text messaging) is
limited. Therefore, the findings of lack of sufficient evidence for proving or
refuting effectiveness should not be regarded as evidence of ineffectiveness. We
have examined only a small number of factors that could potentially influence the
effectiveness of the interventions. A comprehensive evaluation of potential
effect modifiers at study level in a systematic review of complex interventions
remains challenging. Information presented in published papers is often
insufficient to allow accurate coding of each intervention or comparator. A
limitation of the cost-effectiveness analysis, shared with several previous
cost-effectiveness analyses of smoking cessation interventions, is that
intervention benefit is restricted to the first quit attempt. Exploring the
impact of interventions on subsequent attempts requires more detailed information
on patient event histories than is available from current evidence.
CONCLUSIONS: Our effectiveness review concluded that computer and other
electronic aids increase the likelihood of cessation compared with no
intervention or generic self-help materials, but the effect is small. The
effectiveness does not appear to vary with respect to mode of delivery and
concurrent non-electronic co-interventions. Our cost-effectiveness review
suggests that making some form of electronic support available to smokers
actively seeking to quit is highly likely to be cost-effective. This is true
whether the electronic intervention is delivered alongside brief advice or more
intensive counselling. The key source of uncertainty is that around the
comparative effectiveness of different types of electronic interventions. Our
review suggests that further research is needed on the relative benefits of
different forms of delivery for electronic aids, the content of delivery, and the
acceptability of these technologies for smoking cessation with subpopulations of
smokers, particularly disadvantaged groups. More evidence is also required on the
relationship between involving users in the design of interventions and the
impact this has on effectiveness, and finally on how electronic aids developed
and tested in research settings are applied in routine practice and in the
community.

PMID: 23046909  [PubMed - indexed for MEDLINE]


209. Int J Chron Obstruct Pulmon Dis. 2012;7:415-20. doi: 10.2147/COPD.S31526. Epub
2012 Jul 5.

Efficacy of indacaterol 75 μg versus fixed-dose combinations of
formoterol-budesonide or salmeterol-fluticasone for COPD: a network
meta-analysis.

Cope S(1), Kraemer M, Zhang J, Capkun-Niggli G, Jansen JP.

Author information:
(1)MAPI Consultancy, Boston, MA 02114, USA.

BACKGROUND: The purpose of this study was to update our network meta-analysis in
order to compare the efficacy of indacaterol 75 μg with that of a fixed-dose
combination of formoterol and budesonide (FOR/BUD) and a fixed-dose combination
salmeterol and fluticasone (SAL/FP) for the treatment of chronic obstructive
pulmonary disease (COPD) based on evidence identified previously in addition to
two new randomized clinical trials.
METHODS: Fifteen randomized, placebo-controlled clinical trials including COPD
patients were evaluated: indacaterol 75 μg once daily (n = 2 studies),
indacaterol 150 μg once daily (n = 5), indacaterol 300 μg once daily (n = 4),
FOR/BUD 9/160 μg twice daily (n = 2), FOR/BUD 9/320 μg twice daily (n = 2),
SAL/FP 50/500 μg twice daily (n = 4), and SAL/FP 50/250 μg twice daily (n = 1).
All trials were analyzed simultaneously using a Bayesian network meta-analysis
and relative treatment effects between all regimens were obtained.
Treatment-by-covariate interactions were included where possible to improve the
similarity of the trials. Outcomes of interest were trough forced expiratory
volume in 1 second (FEV(1)) and transitional dyspnea index at 12 weeks.
RESULTS: Based on the results without adjustment for covariates, indacaterol 75
μg resulted in a greater improvement in FEV(1) at 12 weeks compared with FOR/BUD
9/160 μg (difference in change from baseline 0.09 L [95% credible interval
0.04-0.13]) and FOR/BUD 9/320 μg (0.07 L [0.03-0.11]) and was comparable with
SAL/FP 50/250 μg (0.00 L [-0.07-0.07]) and SAL/FP 50/500 μg (0.01 L
[-0.04-0.05]). For transitional dyspnea index, data was available only for
indacaterol 75 μg versus SAL/FP 50/500 μg (-0.49 points [-1.87-0.89]).
CONCLUSION: Based on results of a network meta-analysis with and without
covariates, indacaterol 75 μg is expected to be at least as efficacious as
FOR/BUD (9/320 μg and 9/160 μg) and comparable with SAL/FP (50/250 μg and 50/500
μg) in terms of lung function. In terms of breathlessness (transitional dyspnea
index) at 12 weeks, the results are inconclusive given the limited data.

PMCID: PMC3402062
PMID: 22848154  [PubMed - indexed for MEDLINE]


210. Oncologist. 2012;17(11):1376-85. doi: 10.1634/theoncologist.2011-0427. Epub 2012
Sep 28.

Systematic review and network meta-analysis of overall survival comparing 3 mg/kg
ipilimumab with alternative therapies in the management of pretreated patients
with unresectable stage III or IV melanoma.

Dequen P(1), Lorigan P, Jansen JP, van Baardewijk M, Ouwens MJ, Kotapati S.

Author information:
(1)MAPI Group, Houten, The Netherlands.

OBJECTIVE: To compare the overall survival (OS) of patients treated with 3 mg/kg
ipilimumab versus alternative systemic therapies in pretreated unresectable stage
III or IV melanoma patients.
METHODS: A systematic literature search was performed to identify relevant
randomized clinical trials. From these trials, Kaplan-Meier survival curves for
each intervention were digitized and combined by means of a Bayesian network
meta-analysis (NMA) to compare different drug classes.
RESULTS: Of 38 trials identified, 15 formed one interlinked network by drug class
to allow for an NMA. Ipilimumab, at a dose of 3 mg/kg, was associated with a
greater mean OS time (18.8 months; 95% credible interval [CrI], 15.5-23.0 months)
than single-agent chemotherapy (12.3 months; 95% CrI, 6.3-28.0 months),
chemotherapy combinations (12.2 months; 95% CrI, 7.1-23.3 months),
biochemotherapies (11.9 months; 95% CrI, 7.0-22.0 months), single-agent
immunotherapy (11.1 months; 95% CrI, 8.5-16.2 months), and immunotherapy
combinations (14.1 months; 95% CrI, 9.0-23.8 months).
CONCLUSION: Results of this NMA were in line with previous findings and suggest
that OS with ipilimumab is expected to be greater than with alternative systemic
therapies, alone or in combination, for the management of pretreated patients
with unresectable stage III or IV melanoma.

PMCID: PMC3500357
PMID: 23024154  [PubMed - indexed for MEDLINE]


211. PLoS One. 2012;7(10):e46175. doi: 10.1371/journal.pone.0046175. Epub 2012 Oct 3.

Timing matters in hip fracture surgery: patients operated within 48 hours have
better outcomes. A meta-analysis and meta-regression of over 190,000 patients.

Moja L(1), Piatti A, Pecoraro V, Ricci C, Virgili G, Salanti G, Germagnoli L,
Liberati A, Banfi G.

Author information:
(1)Department of Biomedical Sciences for Health, University of Milan, Milan,
Italy. moja@marionegri.it

BACKGROUND: To assess the relationship between surgical delay and mortality in
elderly patients with hip fracture. Systematic review and meta-analysis of
retrospective and prospective studies published from 1948 to 2011. Medline (from
1948), Embase (from 1974) and CINAHL (from 1982), and the Cochrane Library. Odds
ratios (OR) and 95% confidence intervals for each study were extracted and pooled
with a random effects model. Heterogeneity, publication bias, bayesian analysis,
and meta-regression analyses were done. Criteria for inclusion were retro- and
prospective elderly population studies, patients with operated hip fractures,
indication of timing of surgery and survival status.
METHODOLOGY/PRINCIPAL FINDINGS: There were 35 independent studies, with 191,873
participants and 34,448 deaths. The majority considered a cut-off between 24 and
48 hours. Early hip surgery was associated with a lower risk of death (pooled
odds ratio (OR) 0.74, 95% confidence interval (CI) 0.67 to 0.81; P<0.000) and
pressure sores (0.48, 95% CI 0.38 to 0.60; P<0.000). Meta-analysis of the
adjusted prospective studies gave similar results. The bayesian probability
predicted that about 20% of future studies might find that early surgery is not
beneficial for decreasing mortality. None of the confounders (e.g. age, sex, data
source, baseline risk, cut-off points, study location, quality and year)
explained the differences between studies.
CONCLUSIONS/SIGNIFICANCE: Surgical delay is associated with a significant
increase in the risk of death and pressure sores. Conservative timing strategies
should be avoided. Orthopaedic surgery services should ensure the majority of
patients are operated within one or two days.

PMCID: PMC3463569
PMID: 23056256  [PubMed - indexed for MEDLINE]


212. J Clin Psychopharmacol. 2011 Dec;31(6):698-704. doi:
10.1097/JCP.0b013e31823657d9.

A review and Bayesian meta-analysis of clinical efficacy and adverse effects of 4
atypical neuroleptic drugs compared with haloperidol and placebo.

Klemp M(1), Tvete IF, Skomedal T, Gaasemyr J, Natvig B, Aursnes I.

Author information:
(1)Department of Pharmacology, University of Oslo, Oslo, Norway.
Marianne.Klemp@kunnskapssenteret.no

AIMS: The objective of the study was to examine the efficacy and the degree of
adverse effects connected with atypical neuroleptic drugs and haloperidol by
using a previously described Bayesian statistical method that includes both
direct and indirect comparisons simultaneously.
METHODS: The authors used the results of 30 double-blind, randomized studies
including comparisons of 4 atypical neuroleptics and haloperidol, head-to-head or
against placebo. We calculated the response ratios for drugs against placebo and
thereafter the relative response ratios for one drug against another. With
uniform priors, we calculated and ranked the posterior estimates of response
ratios for antipsychotic effect, weight gain, and occurrence of extrapyramidal
symptoms.
RESULTS: All second-generation neuroleptics analyzed are fairly effective with
response ratios against placebo ranging between 1.55 (credibility interval,
1.36-1.76) and 1.99 (1.76-2.26), with clozapine being the most effective and
aripiprazole the least effective among them. The risk of inducing weight gain is
clearly very high for all 5 neuroleptic drugs compared with placebo with response
ratios of 12.21 (10.22-15.05) for olanzapine and 11.28 (6.89-17.77) for
clozapine. There is a clear increased risk of extrapyramidal adverse effects for
haloperidol compared with placebo as the response ratio is 2.33 (2.03-2.49). The
other drugs all have considerably less risk of extrapyramidal adverse effects.
CONCLUSIONS: The 4 second-generation neuroleptics included in our meta-analysis
show only small differences in overall efficacy, with clozapine being the most
effective and aripiprazole the least effective among them. When the risk of
adverse effects is analyzed, olanzapine and clozapine are afflicted with the
highest risk of inducing weight gain and haloperidol with extrapyramidal
symptoms. Even aripiprazole and risperidone, however, induce considerable weight
gain compared with placebo but may be acceptable alternatives when tailoring drug
treatment to the individual patient.

PMID: 22020356  [PubMed - indexed for MEDLINE]


213. BMC Med. 2011 Nov 17;9:123. doi: 10.1186/1741-7015-9-123.

A systematic review on the effect of sweeteners on glycemic response and
clinically relevant outcomes.

Wiebe N(1), Padwal R, Field C, Marks S, Jacobs R, Tonelli M.

Author information:
(1)Department of Medicine, 13-103 Clinical Sciences Building, University of
Alberta, Edmonton, Alberta, T6G 2G3 Canada.

BACKGROUND: The major metabolic complications of obesity and type 2 diabetes may
be prevented and managed with dietary modification. The use of sweeteners that
provide little or no calories may help to achieve this objective.
METHODS: We did a systematic review and network meta-analysis of the comparative
effectiveness of sweetener additives using Bayesian techniques. MEDLINE, EMBASE,
CENTRAL and CAB Global were searched to January 2011. Randomized trials comparing
sweeteners in obese, diabetic, and healthy populations were selected. Outcomes of
interest included weight change, energy intake, lipids, glycated hemoglobin,
markers of insulin resistance and glycemic response. Evidence-based items
potentially indicating risk of bias were assessed.
RESULTS: Of 3,666 citations, we identified 53 eligible randomized controlled
trials with 1,126 participants. In diabetic participants, fructose reduced 2-hour
blood glucose concentrations by 4.81 mmol/L (95% CI 3.29, 6.34) compared to
glucose. Two-hour blood glucose concentration data comparing hypocaloric
sweeteners to sucrose or high fructose corn syrup were inconclusive. Based on two
≤10-week trials, we found that non-caloric sweeteners reduced energy intake
compared to the sucrose groups by approximately 250-500 kcal/day (95% CI 153,
806). One trial found that participants in the non-caloric sweetener group had a
decrease in body mass index compared to an increase in body mass index in the
sucrose group (-0.40 vs 0.50 kg/m2, and -1.00 vs 1.60 kg/m2, respectively). No
randomized controlled trials showed that high fructose corn syrup or fructose
increased levels of cholesterol relative to other sweeteners.
CONCLUSIONS: Considering the public health importance of obesity and its
consequences; the clearly relevant role of diet in the pathogenesis and
maintenance of obesity; and the billions of dollars spent on non-caloric
sweeteners, little high-quality clinical research has been done. Studies are
needed to determine the role of hypocaloric sweeteners in a wider population
health strategy to prevent, reduce and manage obesity and its consequences.

© 2011 Wiebe et al; licensee BioMed Central Ltd.

PMCID: PMC3286380
PMID: 22093544  [PubMed - indexed for MEDLINE]


214. Can J Cardiol. 2011 Nov-Dec;27(6):843-50. doi: 10.1016/j.cjca.2011.04.014. Epub
2011 Aug 20.

Coronary artery perforation during percutaneous coronary intervention: a
systematic review and meta-analysis.

Shimony A(1), Joseph L, Mottillo S, Eisenberg MJ.

Author information:
(1)Divisions of Cardiology and Clinical Epidemiology, Jewish General Hospital,
Lady Davis Institute for Medical Research, McGill University, Montreal, Québec,
Canada. avidorit@gmail.com

Numerous studies have examined the incidence, predictors, outcomes, and
management strategies of coronary artery perforation (CAP). Individually, these
studies have been inconclusive because of their limited sample sizes and/or
single-centre designs. We conducted a systematic review and meta-analysis of
studies pertaining to CAP in order to estimate its incidence and outcomes and to
critically review its risk factors and treatment. We systematically searched the
literature to identify all registry studies investigating CAP. Data were pooled
by means of the random-effects model. In 16 studies involving 197,061
percutaneous coronary interventions, the pooled incidence of CAP was 0.43% (95%
confidence interval, 0.35%-0.52%). The most reproducible risk factors were
treatment of complex lesions and use of atheroablative devices. A variety of
major management strategies for CAP were used, in particular, observation,
heparin reversal, prolonged balloon inflation, covered stent implantation,
pericardiocentesis, and surgery. In a hierarchical Bayesian random-effects model,
the pooled tamponade rates were 0.4% (95% credible interval [CrI], 0.0%-5.7%),
3.3% (95% CrI, 0.0%-11.4%), and 45.7% (95% CrI, 34.9%-57.5%) for patients with
Ellis class I, II, and III CAP, respectively. Pooled mortality rates were 0.3%
(95% CrI, 0.0%-4.4%), 0.4% (95% CrI, 0.0%-2.8%), and 21.2% (95% CrI, 12.0%-31.4%)
for patients with Ellis class I, II, and III CAP respectively. CAP complicating
percutaneous coronary intervention is rare, and its morbidity and mortality vary
directly with Ellis classification. Management discrepancies highlight the need
to establish a uniform treatment paradigm for CAP.

Copyright © 2011 Canadian Cardiovascular Society. Published by Elsevier Inc. All
rights reserved.

PMID: 21862280  [PubMed - indexed for MEDLINE]


215. Chest. 2011 Aug;140(2):374-81. doi: 10.1378/chest.10-3084. Epub 2011 Feb 24.

Dosing frequency of unfractionated heparin thromboprophylaxis: a meta-analysis.

Phung OJ(1), Kahn SR, Cook DJ, Murad MH.

Author information:
(1)College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766,
USA. ophung@westernu.edu

BACKGROUND: In medical patients, it is unclear whether thromboprophylaxis with
low-dose unfractionated heparin (UFH) should be administered bid or tid.
METHODS: This study was a mixed-treatment comparison meta-analysis of randomized
control trials that enrolled hospitalized nonsurgical patients at risk for VTE
and compared UFH bid, UFH tid, or low-molecular-weight heparin (LMWH) to one
another or to an inactive control subject. DVT, pulmonary embolism (PE), major
bleeding, and death were measured. A Bayesian framework using a random-effects
model was applied.
RESULTS: Sixteen trials with moderate methodologic quality enrolling 27,667
patients contributed to this analysis. The relative risk and 95% credible
intervals comparing UFH tid to UFH bid for DVT, PE, death, and major bleeding
were 1.56 (0.64-4.33), 1.67 (0.49-208.09), 1.17 (0.72-1.95), and 0.89
(0.08-7.05), respectively. When compared with either dose of UFH, the use of LMWH
has an effect similar to UFH on all four outcomes.
CONCLUSIONS: Moderate-quality evidence suggests that subcutaneous UFH bid and UFH
tid do not differ in effect on DVT, PE, major bleeding, and mortality. Either of
the two dosing regimens of UFH or LMWH appears to be a reasonable strategy for
thromboprophylaxis in medical patients. A future randomized trial comparing the
two doses of UFH is very unlikely, considering the very large sample size that
would be required to demonstrate a significant difference, which, if it exists,
is undoubtedly small.

PMID: 21349929  [PubMed - indexed for MEDLINE]


216. Obes Rev. 2011 Aug;12(8):602-21. doi: 10.1111/j.1467-789X.2011.00866.x. Epub 2011
Mar 28.

Bariatric surgery: a systematic review and network meta-analysis of randomized
trials.

Padwal R(1), Klarenbach S, Wiebe N, Birch D, Karmali S, Manns B, Hazel M, Sharma
AM, Tonelli M.

Author information:
(1)Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.

The clinical efficacy and safety of bariatric surgery trials were systematically
reviewed. MEDLINE, EMBASE, CENTRAL were searched to February 2009. A basic
PubCrawler alert was run until March 2010. Trial registries, HTA websites and
systematic reviews were searched. Manufacturers were contacted. Randomized trials
comparing bariatric surgeries and/or standard care were selected. Evidence-based
items potentially indicating risk of bias were assessed. Network meta-analysis
was performed using Bayesian techniques. Of 1838 citations, 31 RCTs involving
2619 patients (mean age 30-48 y; mean BMI levels 42-58 kg/m(2) ) met eligibility
criteria. As compared with standard care, differences in BMI levels from baseline
at year 1 (15 trials; 1103 participants) were as follows: jejunoileal bypass [MD:
-11.4 kg/m(2) ], mini-gastric bypass [-11.3 kg/m(2) ], biliopancreatic diversion
[-11.2 kg/m(2) ], sleeve gastrectomy [-10.1 kg/m(2) ], Roux-en-Y gastric bypass
[-9.0 kg/m(2) ], horizontal gastroplasty [-5.0 kg/m(2) ], vertical banded
gastroplasty [-6.4 kg/m(2) ], and adjustable gastric banding [-2.4 kg/m(2) ].
Bariatric surgery appears efficacious compared to standard care in reducing BMI.
Weight losses are greatest with diversionary procedures, intermediate with
diversionary/restrictive procedures, and lowest with those that are purely
restrictive. Compared with Roux-en-Y gastric bypass, adjustable gastric banding
has lower weight loss efficacy, but also leads to fewer serious adverse effects.

© 2011 The Authors. obesity reviews © 2011 International Association for the
Study of Obesity.

PMID: 21438991  [PubMed - indexed for MEDLINE]


217. HIV Clin Trials. 2011 Jul-Aug;12(4):175-89. doi: 10.1310/HCT1204-175.

Comparative effectiveness of efavirenz, protease inhibitors, and
raltegravir-based regimens as first-line treatment for HIV-infected adults: a
mixed treatment comparison.

Vieira MC(1), Kumar RN, Jansen JP.

Author information:
(1)Mapi Values, Boston, MA, USA.

OBJECTIVE: Compare the efficacy of 2 NRTIs combined with raltegravir (RAL),
efavirenz (EFV), or protease inhibitors (PI) in the management of
antiretroviral-naïve HIV adult patients.
METHODS: By means of a systematic literature view, 7 randomized controlled trials
were identified: 2 RAL vs EFV trials; 1 ritonavir-boosted lopinavir (LPV/RTV) vs
EFV trial; 1 ritonavir-boosted atazanavir (ATV/RTV) vs LPV/RTV trial; 1
ritonavir-boosted darunavir (DRV/RTV) vs LPV/RTV trial; 1 ritonavir-boosted
fosamprenavir (FPV/RTV) vs LPV/RTV trial; and 1 FPV/RTV vs ATV/RTV trial.
Endpoints concerned virological suppression and immunologic efficacy. Trials were
analyzed with Bayesian mixed treatment comparison meta-analysis.
RESULTS: For up to 24 weeks of treatment, a PI-based regimen resulted in a lower
proportion of patients with virological response than an EFV-based regimen,
whereas RAL seems more efficacious than EFV up to at least 12 weeks. After 48
weeks, the odds ratio (OR) of virological suppression with RAL relative to EFV
was 1.34 (95% credible interval [CrI], 0.87-2.07). ORs for PIs relative to EFV
varied from 0.68 (0.41-1.07) with LPV/RTV to 0.99 (0.52-1.84) with DRV/RTV. RAL
demonstrated a greater improvement in CD4+ T cell counts than EFV at 48 weeks.
The PI regimens showed all similar improvements relative to EFV.
CONCLUSION: Based on available RCTs, the fastest virological suppression is
expected with RAL followed by EFV and PIs. Over time, RAL appears to be at least
as good as PI and EFV regimens. CD4+ cell recovery seems the greatest with
LPV/RTV, DRV/RTV, and RAL. Given the limited number of RCTs, additional studies
are recommended.

PMID: 22044854  [PubMed - indexed for MEDLINE]


218. Risk Anal. 2011 Jul;31(7):1141-55. doi: 10.1111/j.1539-6924.2010.01572.x. Epub
2011 Jan 13.

A Bayesian evidence synthesis for estimating campylobacteriosis prevalence.

Albert I(1), Espié E, de Valk H, Denis JB.

Author information:
(1)INRA-Unité Met@risk, Paris France. isabelle.albert@paris.inra.fr

Stakeholders making decisions in public health and world trade need improved
estimations of the burden-of-illness of foodborne infectious diseases. In this
article, we propose a Bayesian meta-analysis or more precisely a Bayesian
evidence synthesis to assess the burden-of-illness of campylobacteriosis in
France. Using this case study, we investigate campylobacteriosis prevalence, as
well as the probabilities of different events that guide the disease pathway, by
(i) employing a Bayesian approach on French and foreign human studies (from
active surveillance systems, laboratory surveys, physician surveys,
epidemiological surveys, and so on) through the chain of events that occur during
an episode of illness and (ii) including expert knowledge about this chain of
events. We split the target population using an exhaustive and exclusive
partition based on health status and the level of disease investigation. We
assume an approximate multinomial model over this population partition. Thereby,
each observed data set related to the partition brings information on the
parameters of the multinomial model, improving burden-of-illness parameter
estimates that can be deduced from the parameters of the basic multinomial model.
This multinomial model serves as a core model to perform a Bayesian evidence
synthesis. Expert knowledge is introduced by way of pseudo-data. The result is a
global estimation of the burden-of-illness parameters with their accompanying
uncertainty.

© 2011 Society for Risk Analysis.

PMID: 21231950  [PubMed - indexed for MEDLINE]


219. Gastrointest Endosc. 2011 Jun;73(6):1122-34. doi: 10.1016/j.gie.2011.01.030. Epub
2011 Mar 27.

EUS for the staging of gastric cancer: a meta-analysis.

Mocellin S(1), Marchet A, Nitti D.

Author information:
(1)Meta-Analysis Unit, Department of Oncological and Surgical Sciences,
University of Padova, Padova, Italy. simone.mocellin@unipd.it

BACKGROUND: The role of EUS in the locoregional staging of gastric carcinoma is
undefined.
OBJECTIVE: We aimed to comprehensively review and quantitatively summarize the
available evidence on the staging performance of EUS.
DESIGN: We systematically searched the MEDLINE, Cochrane, CANCERLIT, and EMBASE
databases for relevant studies published until July 2010.
SETTING: Formal meta-analysis of diagnostic accuracy parameters was performed by
using a bivariate random-effects model.
PATIENTS: Fifty-four studies enrolling 5601 patients with gastric cancer
undergoing disease staging with EUS were eligible for the meta-analysis.
MAIN OUTCOME MEASUREMENTS: EUS staging accuracy across eligible studies was
measured by computing overall sensitivity, specificity, positive likelihood ratio
(PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR).
RESULTS: EUS can differentiate T1-2 from T3-4 gastric cancer with high accuracy,
with overall sensitivity, specificity, PLR, NLR, and DOR of 0.86 (95% CI,
0.81-0.90), 0.91 (95% CI, 0.89-0.93), 9.8 (95% CI, 7.5-12.8), 0.15 (95% CI,
0.11-0.21), and 65 (95% CI, 41-105), respectively. In contrast, the diagnostic
performance of EUS for lymph node status is less reliable, with overall
sensitivity, specificity, PLR, NLR, and DOR of 0.69 (95% CI, 0.63-0.74), 0.84
(95% CI, 0.81-0.88), 4.4 (95% CI, 3.6-5.4), 0.37 (95% CI, 0.32-0.44), and 12 (95%
CI, 9-16), respectively. Results regarding single T categories (including T1
substages) and Bayesian nomograms to calculate posttest probabilities for any
target condition prevalence are also provided.
LIMITATIONS: Statistical heterogeneity was generally high; unfortunately,
subgroup analysis did not identify a consistent source of the heterogeneity.
CONCLUSIONS: Our results support the use of EUS for the locoregional staging of
gastric cancer, which can affect the therapeutic management of these patients.
However, clinicians must be aware of the performance limits of this staging tool.

Copyright © 2011 American Society for Gastrointestinal Endoscopy. Published by
Mosby, Inc. All rights reserved.

PMID: 21444080  [PubMed - indexed for MEDLINE]


220. Osteoarthritis Cartilage. 2011 Jun;19(6):611-9. doi: 10.1016/j.joca.2010.09.014.
Epub 2011 Apr 9.

Therapeutic trajectory following intra-articular hyaluronic acid injection in
knee osteoarthritis--meta-analysis.

Bannuru RR(1), Natov NS, Dasi UR, Schmid CH, McAlindon TE.

Author information:
(1)Tufts Medical Center, Boston, MA, USA.

OBJECTIVE: To evaluate the therapeutic trajectory of intra-articular hyaluronic
acid (IAHA) vs placebo for knee osteoarthritis (OA).
DESIGN: Our data sources include Medline, EMBASE, CINAHL, BIOSIS, Web of Science,
Google Scholar, Cochrane database; hand searched reviews, manuscripts, and,
supplements; author contacts for unpublished data. Randomized trials that
reported effects of IAHA vs placebo on knee OA were selected based on inclusion
criteria. We computed effect sizes for change from baseline at 4, 8, 12, 16, 20
and 24 weeks, using Bayesian random effects model. We performed multivariate
analyses adjusting for correlation between time points. Meta-regressions were
performed adjusting for potential confounders.
RESULTS: The 54 eligible trials included 7545 participants. The conduct and
quality of these trials varied in number of aspects. The effect size (ES) favored
IAHA by week 4 (0.31; 95% CI 0.17, 0.45), reaching peak at week 8 (0.46; 0.28,
0.65), and then trending downwards, with a residual detectable effect at week 24
(0.21; 0.10, 0.31). This therapeutic trajectory was consistent among the subset
of high quality trials and on multivariate analysis adjusting for correlation
between time points.
CONCLUSIONS: Our meta-analysis highlights a therapeutic trajectory of IAHA for
knee OA pain over 6 months post-intervention. With this additional perspective,
we are able to infer that IAHA is efficacious by 4 weeks, reaches its peak
effectiveness at 8 weeks and exerts a residual detectable at 24 weeks. On the
other hand, the peak effect size (0.46; 0.28, 0.65), is greater than published
effects from other OA analgesics [acetaminophen (ES=0.13; 0.04, 0.22); NSAIDs
(ES=0.29; 0.22, 0.35); COX-2 inhibitors (ES=0.44; 0.33, 0.55)]. An effect size
above 0.20 is considered to be clinically relevant on an individual patient basis
in chronic pain conditions such as knee OA. Thus, its properties could have
utility for certain clinical situations, or in combination with other therapies.

Copyright © 2011 Osteoarthritis Research Society International. Published by
Elsevier Ltd. All rights reserved.

PMID: 21443958  [PubMed - indexed for MEDLINE]


221. Surgery. 2011 Jun;149(6):830-40. doi: 10.1016/j.surg.2010.11.003. Epub 2011 Jan
14.

Enhanced recovery pathways optimize health outcomes and resource utilization: a
meta-analysis of randomized controlled trials in colorectal surgery.

Adamina M(1), Kehlet H, Tomlinson GA, Senagore AJ, Delaney CP.

Author information:
(1)University Hospitals Case Medical Center, Cleveland, OH 44106-5047, USA.

Comment in
    Surgery. 2012 Apr;151(4):632-3.

BACKGROUND: Health care systems provide care to increasingly complex and elderly
patients. Colorectal surgery is a prime example, with high volumes of major
procedures, significant morbidity, prolonged hospital stays, and unplanned
readmissions. This situation is exacerbated by an exponential rise in costs that
threatens the stability of health care systems. Enhanced recovery pathways (ERP)
have been proposed as a means to reduce morbidity and improve effectiveness of
care. We have reviewed the evidence supporting the implementation of ERP in
clinical practice.
METHODS: Medline, Embase, and the Cochrane library were searched for randomized,
controlled trials comparing ERP with traditional care in colorectal surgery.
Systematic reviews and papers on ERP based on data published in major surgical
and anesthesiology journals were critically reviewed by international
contributors, experienced in the development and implementation of ERP.
RESULTS: A random-effect Bayesian meta-analysis was performed, including 6
randomized, controlled trials totalizing 452 patients. For patients adhering to
ERP, length of stay decreased by 2.5 days (95% credible interval [CrI] -3.92 to
-1.11), whereas 30-day morbidity was halved (relative risk, 0.52; 95% CrI,
0.36-0.73) and readmission was not increased (relative risk, 0.59; 95% CrI,
0.14-1.43) when compared with patients undergoing traditional care.
CONCLUSION: Adherence to ERP achieves a reproducible improvement in the quality
of care by enabling standardization of health care processes. Thus, while
accelerating recovery and safely reducing hospital stay, ERPs optimize
utilization of health care resources. ERPs can and should be routinely used in
care after colorectal and other major gastrointestinal procedures.

Copyright © 2011 Mosby, Inc. All rights reserved.

PMID: 21236454  [PubMed - indexed for MEDLINE]


222. Anesth Analg. 2011 May;112(5):1019-33. doi: 10.1213/ANE.0b013e31820f286f. Epub
2011 Mar 3.

The predictive value of preoperative natriuretic peptide concentrations in adults
undergoing surgery: a systematic review and meta-analysis.

Lurati Buse GA(1), Koller MT, Burkhart C, Seeberger MD, Filipovic M.

Author information:
(1)Department of Anesthesia and Intensive Care Medicine, University Hospital
Basel, Spitalstrasse 21CH-4031, Basel, Switzerland. glurati@uhbs.ch

Comment in
    Anesth Analg. 2011 May;112(5):1005-7.

BACKGROUND: Several studies have evaluated preoperative B-type natriuretic
peptides (NPs) for predicting mortality after surgery; however, the number of
deaths in each study was small, limiting the power of these studies. We conducted
a systematic review and meta-analysis of studies addressing preoperative NP
levels to predict mortality after cardiac and noncardiac surgery.
METHODS: We searched MEDLINE and EMBASE using the terms "natriuretic peptides,"
"surgery or surgical procedures," and a validated combination of prognostic and
diagnostic terms. Two investigators independently assessed studies for
eligibility and extracted data. The end points were all-cause mortality at ≥6
months and at ≤90 days. We used a bivariate model to derive measures of
prognostic accuracy and their heterogeneity. We calculated the pooled positive
predictive value (PPV) and negative predictive value (NPV) by Bayesian Markov
chain Monte Carlo methods.
RESULTS: Of the 1558 retrieved articles, 23 studies satisfied the predefined
eligibility criteria. After cardiac surgery, the diagnostic odds ratio of NP was
4.11 (95% confidence interval, 2.22-7.60) for ≥6-month mortality, the PPV 0.17
(95% Bayesian confidence interval, 0.07-0.36), and the NPV 0.96 (0.90-0.98).
After noncardiac surgery, the diagnostic odds ratio of NP was 4.97 (3.06-8.07)
for ≥6-month mortality. The corresponding PPV was 0.24 (0.14-0.38) and the NPV
0.94 (0.88-0.97). Results were similar for ≤90-day mortality.
CONCLUSIONS: Preoperative NP concentrations were associated with mortality after
cardiac and noncardiac surgery. NP had high NPVs for both types of surgery
suggesting that preoperative NP concentrations may be helpful in preoperative
risk stratification.

© 2011 International Anesthesia Research Society

PMID: 21372274  [PubMed - indexed for MEDLINE]


223. Cancer Invest. 2011 May;29(4):293-9. doi: 10.3109/07357907.2011.568563.

Addressing the incremental benefit of histamine dihydrochloride when added to
interleukin-2 in treating acute myeloid leukemia: a Bayesian meta-analysis.

Berry SM(1), Broglio KR, Berry DA.

Author information:
(1)Berry Consultants, LLC, College Station, Texas, USA.
scott@berryconsultants.com

IL-2 has been investigated as maintenance therapy for patients with AML in five
randomized trials. None has shown a statistically significant benefit. A
randomized trial of HDC + IL-2 showed a statistically significant benefit for
leukemia-free survival (LFS) in comparison with standard of care. Because HDC +
IL-2 has not been randomized against IL-2 alone, the question remains as to
whether and to what extent HDC + IL-2 is an improvement compared to IL-2 alone.
This is a literature-based meta-analysis. We employ two versions of a Bayesian
hierarchical model to compare HDC + IL-2 versus IL-2 alone on the basis of LFS in
patients in remission from AML.

PMID: 21469978  [PubMed - indexed for MEDLINE]


224. BMJ. 2011 Apr 6;342:d1714. doi: 10.1136/bmj.d1714.

Steroids and bronchodilators for acute bronchiolitis in the first two years of
life: systematic review and meta-analysis.

Hartling L(1), Fernandes RM, Bialy L, Milne A, Johnson D, Plint A, Klassen TP,
Vandermeer B.

Author information:
(1)Alberta Research Centre for Health Evidence, Department of Pediatrics,
University of Alberta, 11402 University Avenue, Edmonton, AB, Canada T6G 2J3.
hartling@ualberta.ca

Comment in
    BMJ. 2011;342:d3348.
    Evid Based Med. 2012 Feb;17(1):12-3.
    BMJ. 2011;342:d1658.

OBJECTIVE: To evaluate and compare the efficacy and safety of bronchodilators and
steroids, alone or combined, for the acute management of bronchiolitis in
children aged less than 2 years.
DESIGN: Systematic review and meta-analysis.
DATA SOURCES: Medline, Embase, Central, Scopus, PubMed, LILACS, IranMedEx,
conference proceedings, and trial registers. Inclusion criteria Randomised
controlled trials of children aged 24 months or less with a first episode of
bronchiolitis with wheezing comparing any bronchodilator or steroid, alone or
combined, with placebo or another intervention (other bronchodilator, other
steroid, standard care).
REVIEW METHODS: Two reviewers assessed studies for inclusion and risk of bias and
extracted data. Primary outcomes were selected by clinicians a priori based on
clinical relevance: rate of admission for outpatients (day 1 and up to day 7) and
length of stay for inpatients. Direct meta-analyses were carried out using random
effects models. A mixed treatment comparison using a Bayesian network model was
used to compare all interventions simultaneously.
RESULTS: 48 trials (4897 patients, 13 comparisons) were included. Risk of bias
was low in 17% (n = 8), unclear in 52% (n = 25), and high in 31% (n = 15). Only
adrenaline (epinephrine) reduced admissions on day 1 (compared with placebo:
pooled risk ratio 0.67, 95% confidence interval 0.50 to 0.89; number needed to
treat 15, 95% confidence interval 10 to 45 for a baseline risk of 20%; 920
patients). Unadjusted results from a single large trial with low risk of bias
showed that combined dexamethasone and adrenaline reduced admissions on day 7
(risk ratio 0.65, 0.44 to 0.95; number needed to treat 11, 7 to 76 for a baseline
risk of 26%; 400 patients). A mixed treatment comparison supported adrenaline
alone or combined with steroids as the preferred treatments for outpatients
(probability of being the best treatment based on admissions at day 1 were 45%
and 39%, respectively). The incidence of reported harms did not differ. None of
the interventions examined showed clear efficacy for length of stay among
inpatients.
CONCLUSIONS: Evidence shows the effectiveness and superiority of adrenaline for
outcomes of most clinical relevance among outpatients with acute bronchiolitis,
and evidence from a single precise trial for combined adrenaline and
dexamethasone.

PMCID: PMC3071611
PMID: 21471175  [PubMed - indexed for MEDLINE]


225. Arch Intern Med. 2011 Mar 14;171(5):384-94. doi: 10.1001/archinternmed.2010.427.
Epub 2010 Nov 8.

Antihypertensive treatment and development of heart failure in hypertension: a
Bayesian network meta-analysis of studies in patients with hypertension and high
cardiovascular risk.

Sciarretta S(1), Palano F, Tocci G, Baldini R, Volpe M.

Author information:
(1)Department of Cardiology, Second Faculty of Medicine, University of Rome La
Sapienza, S. Andrea Hospital, Rome, Italy.

Comment in
    Arch Intern Med. 2011 Mar 14;171(5):471-2; author reply 472-3.
    Arch Intern Med. 2011 Mar 14;171(5):394-5.
    Arch Intern Med. 2011 Mar 14;171(5):472; author reply 472-3.

BACKGROUND: It is still debated whether there are differences among the various
antihypertensive strategies in heart failure prevention. We performed a network
meta-analysis of recent trials in hypertension aimed at investigating this issue.
METHODS: Randomized, controlled trials published from 1997 through 2009 in
peer-reviewed journals indexed in the PubMed and EMBASE databases were selected.
Selected trials included patients with hypertension or a high-risk population
with a predominance of patients with hypertension.
RESULTS: A total of 223,313 patients were enrolled in the selected studies.
Network meta-analysis showed that diuretics (odds ratio [OR], 0.59; 95%
credibility interval [CrI], 0.47-0.73), angiotensin-converting enzyme (ACE)
inhibitors (OR, 0.71; 95% CrI, 0.59-0.85) and angiotensin II receptor blockers
(ARBs) (OR, 0.76; 95% CrI, 0.62-0.90) represented the most efficient classes of
drugs to reduce the heart failure onset compared with placebo. On the one hand, a
diuretic-based therapy represented the best treatment because it was
significantly more efficient than that based on ACE inhibitors (OR, 0.83; 95%
CrI, 0.69-0.99) and ARBs (OR, 0.78; 95% CrI, 0.63-0.97). On the other hand,
diuretics (OR, 0.71; 95% CrI, 0.60-0.86), ARBs (OR, 0.91; 95% CrI, 0.78-1.07),
and ACE inhibitors (OR, 0.86; 95% CrI, 0.75-1.00) were superior to calcium
channel blockers, which were among the least effective first-line agents in heart
failure prevention, together with β-blockers and α-blockers.
CONCLUSIONS: Diuretics represented the most effective class of drugs in
preventing heart failure, followed by renin-angiotensin system inhibitors. Thus,
our findings support the use of these agents as first-line antihypertensive
strategy to prevent heart failure in patients with hypertension at risk to
develop heart failure. Calcium channel blockers and β-blockers were found to be
less effective in heart failure prevention.

©2011 American Medical Association. All rights reserved.

PMID: 21059964  [PubMed - indexed for MEDLINE]


226. BMJ. 2011 Mar 11;342:d1199. doi: 10.1136/bmj.d1199.

Efficacy of drug treatments for generalised anxiety disorder: systematic review
and meta-analysis.

Baldwin D(1), Woods R, Lawson R, Taylor D.

Author information:
(1)Faculty of Medicine, University Department of Psychiatry, University of
Southampton Academic Centre, Southampton SO14 3DT, UK. D.S.Baldwin@soton.ac.uk

Comment in
    BMJ. 2011;342:d1216.

OBJECTIVE: To appraise the evidence for comparative efficacy and tolerability of
drug treatments in patients with generalised anxiety disorder.
DESIGN: Systematic review of randomised controlled trials. Primary Bayesian
probabilistic mixed treatment meta-analyses allowed pharmacological treatments to
be ranked for effectiveness for each outcome measure, given as percentage
probability of being the most effective treatment. Secondary frequentist mixed
treatment meta-analyses conducted with random effects model; effect size reported
as odds ratio and 95% confidence interval.
DATA SOURCES: Medline, Embase, BIOSIS, PsycINFO, Health Economic Evaluations
Database, National Health Service Economic Evaluation Database, and Database of
Abstracts of Reviews of Effects via DataStar, and Cochrane Database of Systematic
Reviews via Cochrane Library (January 1980 to February 2009). Eligibility
criteria Double blind placebo controlled randomised controlled trials; published
systematic reviews and meta-analyses of randomised controlled trials. Randomised
controlled trials including adult participants (aged ≥ 18) receiving any
pharmacological treatment for generalised anxiety disorder. Data abstraction
methods Titles or abstracts reviewed initially, followed by review of full text
publications for citations remaining after first pass. A three person team
conducted screening; an independent reviewer checked a random selection (10%) of
articles screened. Data extracted for meta-analysis were also independently
reviewed.
MAIN OUTCOME MEASURES: Proportion of participants experiencing ≥ 50% reduction
from baseline score on Hamilton anxiety scale (HAM-A) (response), proportion with
final HAM-A score ≤ 7 (remission), proportion withdrawing from trial because of
adverse events (tolerability).
RESULTS: The review identified 3249 citations, and 46 randomised controlled
trials met inclusion criteria; 27 trials contained sufficient or appropriate data
for inclusion in the analysis. Analyses compared nine drugs (duloxetine,
escitalopram, fluoxetine, lorazepam, paroxetine, pregabalin, sertraline,
tiagabine, and venlafaxine). In the primary probabilistic mixed treatment
meta-analyses, fluoxetine was ranked first for response and remission
(probability of 62.9% and 60.6%, respectively) and sertraline was ranked first
for tolerability (49.3%). In a subanalysis ranking treatments for generalised
anxiety disorder currently licensed in the United Kingdom, duloxetine was ranked
first for response (third across all treatments; 2.7%), escitalopram was ranked
first for remission (second across all treatments; 26.7%), and pregabalin was
ranked first for tolerability (second across all treatments; 7.7%).
CONCLUSIONS: Though the frequentist analysis was inconclusive because of a high
level of uncertainty in effect sizes (based on the relatively small number of
comparative trials), the probabilistic analysis, which did not rely on
significant outcomes, showed that fluoxetine (in terms of response and remission)
and sertraline (in terms of tolerability) seem to have some advantages over other
treatments. Among five UK licensed treatments, duloxetine, escitalopram, and
pregabalin might offer some advantages over venlafaxine and paroxetine.

PMID: 21398351  [PubMed - indexed for MEDLINE]


227. Int Orthop. 2011 Mar;35(3):331-9. doi: 10.1007/s00264-010-1008-6. Epub 2010 Apr
8.

Imageless computer assisted versus conventional total knee replacement. A
Bayesian meta-analysis of 23 comparative studies.

Brin YS(1), Nikolaou VS, Joseph L, Zukor DJ, Antoniou J.

Author information:
(1)Department of Orthopaedic Surgery, Jewish General Hospital, McGill University,
Montreal, Quebec, Canada.

We have undertaken a meta-analysis of the English literature, to assess the
component alignment outcomes after imageless computer assisted (CAOS) total knee
arthroplasty (TKA) versus conventional TKA. We reviewed 23 publications that met
the inclusion criteria. Results were summarised via a Bayesian hierarchical
random effects meta-analysis model. Separate analyses were conducted for
prospective randomised trials alone, as well as for all randomised and
observational studies. In 20 papers (4,199 TKAs) we found a reduction in outliers
rate of approximately 80% in limb mechanical axis when operated with the CAOS.
For the coronal femoral and tibial implants positions, the analysis included
3,058 TKAs. The analysis for the femoral implant showed a reduction in outliers
rate of approximately 87% and for the tibial implant a reduction in outliers rate
of approximately 80%. Imageless navigation when performing TKA improves component
orientation and postoperative limb alignment. The clinical significance of these
findings though has to be proven in the future.

PMCID: PMC3047658
PMID: 20376440  [PubMed - indexed for MEDLINE]


228. QJM. 2011 Mar;104(3):193-200. doi: 10.1093/qjmed/hcq258. Epub 2011 Jan 23.

Early vs. delayed invasive strategy in patients with acute coronary syndromes
without ST-segment elevation: a meta-analysis of randomized studies.

Navarese EP(1), De Servi S, Gibson CM, Buffon A, Castriota F, Kubica J, Petronio
AS, Andreotti F, De Luca G.

Author information:
(1)Institute of Cardiology, Catholic University of the Sacred Heart, Rome.
eliano.navarese@alice.it

Although early percutaneous coronary intervention has been demonstrated to reduce
the risk of mortality in patients with non-ST-segment elevation acute coronary
syndromes (NSTE-ACS), there are emerging conflicting data as to whether the
catheterization needs to be done very early or whether it could be delayed while
the patient receives medical therapy. The aim of the current study was to perform
a meta-analysis of randomized controlled trials (RCTs) comparing early vs.
delayed invasive strategies for NSTE-ACS patients. Medline/CENTRAL and the Web
were searched for RCTs comparing early vs. delayed invasive strategies for
NSTE-ACS patients. The primary endpoint was all cause mortality, whereas
myocardial infarction (MI), coronary revascularizations and 30-day major bleeding
complications were secondary end points. Fixed or random effects models were used
based on statistical heterogeneity. As a sensitivity analysis, Bayesian random
effects meta-analysis was performed in addition to the classical random effects
meta-analysis. A total of 5 RCTs were finally included, enrolling 4155 patients.
As compared with a delayed strategy, an early invasive approach did not
significantly reduce the rates of death [odds ratio (OR) 95% confidence interval
(95% CI) = 0.81 (95% CI 0.60-1.09), P = 0.17], MI [OR = 1.18 (95% CI 0.68-2.05),
P = 0.55] or revascularizations [OR = 0.97 (0.77-1.24), P = 0.82]. There was a
not significant trend toward fewer major bleeding complications for the early
invasive approach [OR (95% CI) = 0.76 (0.55-1.04), P = 0.08]. The present
meta-analysis shows that for NSTE-ACS patients a routine early invasive strategy
does not significantly improve survival nor reduce MI and revascularization rates
as compared with a delayed approach.

PMID: 21262739  [PubMed - indexed for MEDLINE]




230. Curr Drug Targets. 2011 Feb;12(2):212-20.

Pharmacological treatments for neovascular age-related macular degeneration: can
mixed treatment comparison meta-analysis be useful?

Virgili G(1), Novielli N, Menchini F, Murro V, Giacomelli G.

Author information:
(1)Department of Ophthalmology, University of Florence, Florence, Italy.
gianni.virgili@unifi.it

OBJECTIVE: To investigated the use of mixed treatment comparison (MTC)
meta-analysis models to summarize results from randomized clinical trials (RCTs)
on approved pharmacological treatments for neovascular age-related macular
degeneration (AMD).
METHODS: The number of patients with visual loss or visual gain of 3 or more
lines of visual acuity (15 ETDRS letters) at 1 year was extracted from 10 RCTs
including patients with neovascular AMD and comparing at least one of the
following drugs to sham treatment (1080 control patients, 8 studies) or to each
other: verteporfin photodynamic therapy (PDT, 1124 patients, 4 studies),
pegaptanib (904 patients, 2 twin studies), ranibizumab (984 patients, 4 studies).
Both frequentist and Bayesian methods were used to conduct MTCs.
RESULTS: Direct and indirect evidence was available and found to be overall in
good agreement for the comparisons: PDT vs. control, ranibizumab vs. control,
ranibizumab vs. PDT. Bayesian model fit was better for a model including a
covariate coding for the PIER study ranibizumab regimen, i.e. quarterly
injections after three initial monthly doses. In the MTC model, monthly
ranibizumab was superior to PDT and pegaptanib, and could not be shown to be
better than PIER ranibizumab regarding visual loss, being estimates imprecise.
Ranibizumab PIER retreatment regimen was better than PDT and pegaptanib regarding
visual loss, whereas an advantage over them regarding visual gain was suggested
by a frequentist MTC approach, but not by a Bayesian approach, which was more
conservative. A limitation of our MTC model was that only two twin studies
connected pegaptanib to the treatment network, and only one study was available
for the PIER ranibizumab regimen.
CONCLUSION: The clinically heterogeneous and sparse typology of the evidence is a
limitation to carry out MTC meta-analyses of approved pharmacological treatments
for neovascular AMD. Ranibizumab was found to be the most effective treatment
compared to PDT and pegaptanib, although this superiority cannot be demonstrated
regarding visual gain for the PIER ranibizumab regimen in a Bayesian analytic
setting. We did not find RCTs which investigated the current ranibizumab as
needed retreatment regimen approved in Europe.

PMID: 20887240  [PubMed - indexed for MEDLINE]


231. Pharmacoepidemiol Drug Saf. 2011 Feb;20(2):119-30. doi: 10.1002/pds.2046. Epub
2010 Dec 7.

Cancer risk with tumor necrosis factor alpha (TNF) inhibitors: meta-analysis of
randomized controlled trials of adalimumab, etanercept, and infliximab using
patient level data.

Askling J(1), Fahrbach K, Nordstrom B, Ross S, Schmid CH, Symmons D.

Author information:
(1)Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
johan.askling@ki.se

PURPOSE: Uncertain short- and long-term cancer risks with anti-TNF therapies is a
concern, and led to a recent black box warning. This meta-analysis, requested by
the European Medicines Agency, aimed at better assessing short-term risks by
using meta-analytic techniques based on individual patient data from all
corporate-sponsored randomized controlled trials (RCTs) of adalimumab,
etanercept, and infliximab.
METHODS: All 74 RCTs of TNF inhibitors of at least 4 weeks duration were provided
to independent investigators, including case narratives for events occurring
between trial start until 30 days after planned end of treatment and indicating a
possible cancer. Relative risks were estimated using Bayesian piecewise
exponential models.
RESULTS: One hundred thirty (0.84%) of 15,418 individuals randomized to anti-TNF
therapy were diagnosed with cancer, compared to 48 (0.64%) of 7486 individuals
randomized to comparators. The relative risks associated with all anti-TNF were
0.99 (95%CI 0.61-1.68) for cancers excluding non-melanoma skin cancer (NMSC), and
2.02 (95%CI 1.11-3.95) for NMSC. There were indications of differences in the
relative risks for the three anti-TNF drugs, but also of differences across the
cancer rates in the three comparator arms for adalimumab, etanercept, and
infliximab.
CONCLUSIONS: Despite a reassuring overall short-term risk, we could neither
refute nor verify that individual anti-TNF therapies affect the short-term
clinical emergence of cancer. Despite representing the best available evidence,
statistical precision, and differences in baseline cancer risk and reporting
detail between trials of adilumumab, etanercept, and infliximab hampered
distinction of drug-specific from trial effects, illustrating the challenges in
safety-assessments using RCT meta-analyses. Long-term risk assessment requires
observational studies.

Copyright © 2010 John Wiley & Sons, Ltd.

PMID: 21254282  [PubMed - indexed for MEDLINE]


232. QJM. 2011 Feb;104(2):109-24. doi: 10.1093/qjmed/hcq165. Epub 2010 Oct 7.

Efficacy and safety of statin treatment for cardiovascular disease: a network
meta-analysis of 170,255 patients from 76 randomized trials.

Mills EJ(1), Wu P, Chong G, Ghement I, Singh S, Akl EA, Eyawo O, Guyatt G,
Berwanger O, Briel M.

Author information:
(1)Faculty of Health Sciences, University of Ottawa, Ottawa, Canada.
Edward.mills@uottawa.ca

Comment in
    QJM. 2011 Feb;104(2):174-8.

BACKGROUND: Statins represent the largest selling class of cardiovascular drug in
the world. Previous randomized trials (RCTs) have demonstrated important clinical
benefits with statin therapy.
AIM: We combined evidence from all RCTs comparing a statin with placebo or usual
care among patients with and without prior coronary heart disease (CHD) to
determine clinical outcomes.
DESIGN: We searched independently, in duplicate, 12 electronic databases (from
inception to August 2010), including full text journal content databases, to
identify all statin versus inert control RCTs. We included RCTs of any statin
versus any non-drug control in any populations. We abstracted data in duplicate
on reported major clinical events and adverse events. We performed a
random-effects meta-analysis and meta-regression. We performed a mixed treatment
comparison using Bayesian methods.
RESULTS: We included a total of 76 RCTs involving 170,255 participants. There
were a total of 14,878 deaths. Statin therapy reduced all-cause mortality,
Relative Risk (RR) 0.90 [95% confidence interval (CI) 0.86-0.94, P ≤ 0.0001,
I(2)=17%]; cardiovascular disease (CVD) mortality (RR 0.80, 95% CI 0.74-0.87,
P<0.0001, I(2)=27%); fatal myocardial infarction (MI) (RR 0.82, 95% CI 0.75-0.91,
P<0.0001, I(2)=21%); non-fatal MI (RR 0.74, 95% CI 0.67-0.81, P ≤ 0.001,
I(2)=45%); revascularization (RR 0.76, 95% CI 0.70-0.81, P ≤ 0.0001); and a
composite of fatal and non-fatal strokes (0.86, 95% CI 0.78-0.95, P=0.004,
I(2)=41%). Adverse events were generally mild, but 17 RCTs reported on increased
risk of development of incident diabetes [Odds Ratio (OR) 1.09; 95% CI 1.02-1.17,
P=0.001, I(2)=11%]. Studies did not yield important differences across
populations. We did not find any differing treatment effects between statins.
DISCUSSION: Statin therapies offer clear benefits across broad populations. As
generic formulations become more available efforts to expand access should be a
priority.

PMID: 20934984  [PubMed - indexed for MEDLINE]


233. Semin Arthritis Rheum. 2011 Feb;40(4):275-84.e1-2. doi:
10.1016/j.semarthrit.2010.06.001. Epub 2010 Sep 9.

The efficacy of bisphosphonates in the prevention of vertebral, hip, and
nonvertebral-nonhip fractures in osteoporosis: a network meta-analysis.

Jansen JP(1), Bergman GJ, Huels J, Olson M.

Author information:
(1)Mapi Values, Boston, MA 02114, USA. jeroen.jansen@mapivalues.com

OBJECTIVE: To evaluate the efficacy of available bisphosphonate therapies
regarding the prevention of vertebral, hip, and nonvertebral-nonhip fractures in
postmenopausal women with osteoporosis.
METHODS: Eight randomized placebo controlled trials investigating the effects of
zoledronic acid (1 study), alendronate (3), ibandronate (1), risedronate (2), and
etidronate (1) in terms of fractures with a follow-up of 3 years (or 2 years if
used for registration purposes) were identified with a systematic literature
search. The endpoints of interest were morphometric vertebral fractures, hip
fractures, and nonvertebral-nonhip fractures. Results of all trials were analyzed
simultaneously with a Bayesian network meta-analysis by which the relative
treatment effect of 1 intervention to another can be obtained in the absence of
head-to-head evidence. Given the estimated treatment effects and their
uncertainty, the Bayesian approach allowed for calculations of the probability of
which bisphosphonate is best in terms of overall fracture reductions by weighting
the impact of each by type of fracture on costs, quality of life, and incidence.
RESULTS: There is a 79% probability that zoledronic acid shows the greatest
reduction in vertebral fractures of all bisphophonates compared. Zoledronic acid
showed a relative risk (RR) of 0.30 (95% Credible Interval 0.23-0.37) relative to
placebo, an RR of 0.55 (0.41-0.76) relative to alendronate, an RR of 0.50
(0.36-0.70) relative to risedronate, and an RR of 0.58 (0.37-0.92) relative to
ibandronate. Regarding hip fractures, there is a 47% probability that zoledronic
acid shows the greatest risk reduction, followed by alendronate (36%) and
risedronate (11%). RRs of zoledronic acid relative to placebo, alendronate, and
risedronate were 0.58 (0.41-0.82), 0.95 (0.54-1.68), and 0.73 (0.37-1.44),
respectively. Risedronate showed the greatest reduction in nonvertebral-nonhip
fractures, followed by zoledronic acid. The RR of zoledronic acid relative to
risedronate was 1.28 (0.87-1.90). Overall, there was a 94% probability that
zoledronic acid showed the greatest reduction in any fracture. Weighting the
impact of the different type of fractures by incidence, cost, or quality of life
showed similar results.
CONCLUSION: Of the available bisphosphonates for osteoporosis, zoledronic acid
has the highest probability of offering the best overall fracture protection.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID: 20828791  [PubMed - indexed for MEDLINE]


234. J Natl Cancer Inst. 2011 Jan 19;103(2):129-42. doi: 10.1093/jnci/djq455. Epub
2010 Nov 16.

Contemporary diagnostic imaging modalities for the staging and surveillance of
melanoma patients: a meta-analysis.

Xing Y(1), Bronstein Y, Ross MI, Askew RL, Lee JE, Gershenwald JE, Royal R,
Cormier JN.

Author information:
(1)Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer
Center, Houston, TX 77030-4009, USA.

BACKGROUND: Meta-analyses were performed to examine the utility of
ultrasonography, computed tomography (CT), positron emission tomography (PET),
and a combination of both (PET-CT) for the staging and surveillance of melanoma
patients.
METHOD: Patient-level data from 74 studies containing 10,528 patients (between
January 1, 1990, and June, 30, 2009) were used to derive characteristics of the
diagnostic tests used. Meta-analyses were conducted by use of Bayesian bivariate
binomial models to estimate sensitivity and specificity. Diagnostic odds ratios
[ie, true-positive results/false-negative results)/(false-positive
results/true-negative results)] and their 95% credible intervals (CrIs) and
positive predictive values were used as indicators of test performance.
RESULTS: Among the four imaging methods examined for the staging of regional
lymph nodes, ultrasonography had the highest sensitivity (60%, 95% CrI = 33% to
83%), specificity (97%, 95% CrI = 88% to 99%), and diagnostic odds ratio (42, 95%
CrI = 8.08 to 249.8). For staging of distant metastases, PET-CT had the highest
sensitivity (80%, 95% CrI = 53% to 93%), specificity (87%, 95% CrI = 54% to 97%),
and diagnostic odds ratio (25, 95% CrI = 3.58 to 198.7). Similar trends were
observed for melanoma surveillance of lymph node involvement, with
ultrasonography having the highest sensitivity (96%, 95% CrI = 85% to 99%),
specificity (99%, 95% CrI = 95% to 100%), and diagnostic odds ratio (1675, 95%
CrI = 226.6 to 15,920). For distant metastases, PET-CT had the highest
sensitivity (86%, 95% CrI = 76% to 93%), specificity (91%, 95% CrI = 79% to 97%),
and diagnostic odds ratio (67, 95% CrI = 20.42 to 229.7). Positive predictive
values were likewise highest for ultrasonography in lymph node staging and for
PET-CT in detecting distant metastases.
CONCLUSION: Among the compared modalities, ultrasonography was superior for
detecting lymph node metastases, and PET-CT was superior for the detection of
distant metastases in both the staging and surveillance of melanoma patients.

PMCID: PMC3022618
PMID: 21081714  [PubMed - indexed for MEDLINE]


235. Breast Cancer Res Treat. 2011 Jan;125(2):495-504. doi: 10.1007/s10549-010-0978-9.
Epub 2010 Jun 22.

Possible risk modifications in the association between MnSOD Ala-9Val
polymorphism and breast cancer risk: subgroup analysis and evidence-based sample
size calculation for a future trial.

Chen Y(1), Pei J.

Author information:
(1)Department of Pharmacology, Nanjing Medical University, Nanjing, 210029,
China. ychen@njmu.edu.cn

Manganese superoxide dismutase (MnSOD) has been identified as an important
scavenger of reactive oxygen species (ROS), which can cause oxidative stress
followed by breast cancer. A number of subsequent population-based studies have
investigated the association between MnSOD Ala-9Val polymorphism and the risk of
breast cancer. However, these studies have yielded conflicting results. This fact
implies that the effect of MnSOD Ala-9Val polymorphism on the susceptibility to
breast cancer may be modified by other risk factors. To provide a more definitive
conclusion, a full meta-analysis combining and summarizing 16 studies was first
performed using both traditional and Bayesian approaches. During this step, a
recessive inheritance mode was determined after a biological justification. The
capability of the Bayesian method was highlighted in the estimation of a pooled
odds ratio and 95% confidence interval. As a result, no significant association
was observed (OR = 0.978, CI = 0.914-1.046). Bayesian meta-regression and
subgroup analysis were then conducted to find possible risk modifications by
other factors, including menopausal status, ethnicity effect, use of oral
contraceptives, use of hormone replacement therapy, fruits and vegetables intake,
vitamin supplement, and body mass index. While the power of most subgroups may be
insufficient to make a statistical statement, an evidence-based sample size
calculation based upon updated meta-analysis was performed to power a future
trial. For example, approximately 5,000 subjects are required for a new Asian
study (2,500 cases and 2,500 controls) to achieve 80% power.

PMID: 20567899  [PubMed - indexed for MEDLINE]


236. Cardiology. 2011;120(2):59-72. doi: 10.1159/000332369. Epub 2011 Nov 25.

Efficacy comparison of trimetazidine with therapeutic alternatives in stable
angina pectoris: a network meta-analysis.

Danchin N(1), Marzilli M, Parkhomenko A, Ribeiro JP.

Author information:
(1)Department of Coronary Artery Disease and Acute Cardiac Care, Hôpital Européen
Georges Pompidou, Paris, France. nicolas.danchin@egp.aphp.fr

AIMS: To compare the antianginal efficacy of trimetazidine with that of other
agents with no influence on heart rate.
METHODS AND RESULTS: Medline and Embase databases were searched for blinded,
randomized, controlled trials assessing the effects of non-heart-rate-lowering
antianginal treatments on exercise tolerance and/or clinical criteria in stable
angina patients. All relevant trimetazidine trials including the VASCO trial, the
results of which are published herein, were included. A Bayesian network
meta-analysis on the summary data was performed. Comparator antianginal agents
were considered as a group and in agent/class subgroups. Trials involving
β-blockers, non-dihydropyridine calcium channel blockers, and ivabradine were
excluded. 218 trials totaling 19,028 patients were included in at least 1 network
analysis. Effects of trimetazidine were statistically significant compared with
placebo for exercise tolerance and clinical criteria. Transposition of results
into seconds for clinical interpretation of exercise tolerance parameters showed
a mean improvement of +46 s (95% credibility interval: 28; 66) for total exercise
duration, +55 s (35; 77) for 1-mm ST segment depression (T1), and +54 s (24; 84)
for time to onset of angina, in favor of trimetazidine. Differences between
trimetazidine and active comparators were not significant when exercise tolerance
and clinical criteria were analyzed, with +7 s (-12; 28) for total exercise
duration, -1 s (-23; 22) for T1, +8 s (-22; 40) for time to onset of angina, and
-0.28 (-1.17; 0.64) attacks per week for trimetazidine compared with antianginal
agents as a group.
CONCLUSIONS: Trimetazidine efficacy was comparable to that of other
non-heart-rate-lowering antianginal treatments in patients with stable angina
pectoris.

Copyright © 2011 S. Karger AG, Basel.

PMID: 22122948  [PubMed - indexed for MEDLINE]


237. Curr Med Res Opin. 2011 Jan;27(1):225-38. doi: 10.1185/03007995.2010.541005. Epub
2010 Dec 13.

Mixed treatment comparison of a two-compound formulation (TCF) product containing
calcipotriol and betamethasone dipropionate with other topical treatments in
psoriasis vulgaris.

van de Kerkhof P(1), de Peuter R, Ryttov J, Jansen JP.

Author information:
(1)University Hospital Nijmegen, The Netherlands.

Comment in
    Curr Med Res Opin. 2011 Jan;27(1):197-203.

OBJECTIVE: The efficacy of the two-compound formulation (TCF) product containing
calcipotriol and betamethasone dipropionate applied once daily in psoriasis has
been demonstrated in phase III trials but no randomised clinical trial comparing
all commonly used topical treatments exists. The aim of the study was to compare
the efficacy of once-daily use of the TCF product relative to other commonly used
topical agents in plaque psoriasis.
RESEARCH DESIGN AND METHODS: Data on change in Psoriasis Area and Severity Index
(PASI) score from baseline and PASI 75 (percentage of patients achieving a 75%
reduction in PASI score), after 4 weeks of treatment were obtained by means of a
systematic literature review of randomised controlled trials and synthesised with
a Bayesian mixed treatment comparison meta-analysis.
RESULTS: Relative to all active interventions, except for the unlicensed
twice-daily application of the TCF product, the TCF once daily showed a greater
efficacy based on PASI 75 response (relative risk ranging from 1.22 to 3.18) and
improvement in PASI score from baseline (difference in % CFB PASI between TCF
once daily and other active interventions ranged from 4.01 to 49.68).
CONCLUSION: Among topical therapies evaluated, TCF once daily can be considered
the most efficacious treatment for plaque psoriasis.

PMID: 21142833  [PubMed - indexed for MEDLINE]


238. Int J Chron Obstruct Pulmon Dis. 2011;6:329-44. doi: 10.2147/COPD.S18759. Epub
2011 Jun 8.

Comparative efficacy of indacaterol 150 μg and 300 μg versus fixed-dose
combinations of formoterol + budesonide or salmeterol + fluticasone for the
treatment of chronic obstructive pulmonary disease--a network meta-analysis.

Cope S(1), Capkun-Niggli G, Gale R, Jardim JR, Jansen JP.

Author information:
(1)Mapi Values, Boston, MA, USA.

OBJECTIVE: To compare efficacy of indacaterol to that of fixed-dose combination
(FDC) formoterol and budesonide (FOR/BUD) and FDC salmeterol and fluticasone
(SAL/FP) for the treatment of chronic obstructive pulmonary disease (COPD) based
on the available randomized clinical trials (RCTs).
METHODS: Fifteen placebo-controlled RCTs were included that evaluated:
indacaterol 150 μg (n = 5 studies), indacaterol 300 μg (n = 4), FOR/BUD 9/160 μg
(n = 2), FOR/BUD 9/320 μg (n = 3), SAL/FP 50/500 μg (n = 5), and SAL/FP 50/250 μg
(n = 1). Outcomes of interest were trough forced expiratory volume in 1 second
(FEV(1)), total scores for St. George's Respiratory Questionnaire (SGRQ), and
transition dyspnea index (TDI). All trials were analyzed simultaneously using a
Bayesian network meta-analysis and relative treatment effects between all
regimens were obtained. Treatment-by-covariate interactions were included where
possible to improve the similarity of the trials.
RESULTS: Indacaterol 150 μg resulted in a higher change from baseline (CFB) in
FEV(1) at 12 weeks compared to FOR/BUD 9/160 μg (difference in CFB 0.11 L [95%
credible intervals: 0.08, 0.13]) and FOR/BUD 9/320 μg (0.09 L [0.06, 0.11]) and
was comparable to SAL/FP 50/250 μg (0.02 L [-0.04, 0.08]) and SAL/FP 50/500 μg
(0.03 L [0.00, 0.06]). Similar results were observed for indacaterol 300 μg at 12
weeks and indacaterol 150/300 μg at 6 months. Indacaterol 150 μg demonstrated
comparable improvement in SGRQ total score at 6 months versus FOR/BUD (both
doses), and SAL/FP 50/500 μg (-2.16 point improvement [-4.96, 0.95]). Indacaterol
150 and 300 μg demonstrated comparable TDI scores versus SAL/FP 50/250 μg (0.21
points (-0.57, 0.99); 0.39 [-0.39, 1.17], respectively) and SAL/FP 50/500 μg at 6
months.
CONCLUSION: Indacaterol monotherapy is expected to be at least as good as FOR/BUD
(9/320 and 9/160 μg) and comparable to SAL/FP (50/250 and 50/500 μg) in terms of
lung function. Indacaterol is also expected to be comparable to FOR/BUD (9/320
and 9/160 μg) and SAL/FP 50/500 μg in terms of health status and to SAL/FP
(50/250 and 50/500 μg) in terms of breathlessness.

PMCID: PMC3119108
PMID: 21697997  [PubMed - indexed for MEDLINE]


239. Value Health. 2011 Jan;14(1):80-9. doi: 10.1016/j.jval.2010.10.023.

Cost-effectiveness analysis of LHRH agonists in the treatment of metastatic
prostate cancer in Italy.

Iannazzo S(1), Pradelli L, Carsi M, Perachino M.

Author information:
(1)AdRes Health Economics & Outcomes Research, Torino, Italy.
s.iannazzo@adreshe.com

OBJECTIVES: Luteinizing hormone-releasing hormone (LHRH) agonists represent one
of the main cost factors in the management of patients with metastatic prostate
cancer. We compared the cost-effectiveness of the five different 3-month
formulations of LHRH agonists currently available for advanced prostate cancer in
Italy, because these differ both in their capacity to suppress testosterone and
in their acquisition costs.
METHODS: A probabilistic, patient-level simulation model was developed to compare
the cost-effectiveness, from the perspective of the Italian National Health
Service (INHS), of leuprorelin 11.25 mg and 22.5 mg, triptorelin 11.25 mg,
buserelin 9.9 mg, and goserelin 10.8 mg. The model incorporated
testosterone-dependent progression-free and cancer-specific survival functions,
LHRH agonist effectiveness data, and national costs and tariffs. Cox's
proportional hazard models were used to compute total and progression-free
survival functions based on clinical data from 129 patients with metastatic
prostate cancer treated in an Italian center. Bayesian random effects models were
employed to summarize evidence from published literature on testosterone
suppression obtained with the available LHRH agonists.
RESULTS: Estimated total survival was ≈5 years, with a maximum difference between
treatment options of ≈2 months. There was a mean difference of almost €2,500 in
lifetime total costs between the least costly option (leuprorelin 22.5 mg) and
the most expensive (goserelin). In the incremental cost-effectiveness analysis,
leuprorelin 22.5 mg dominated all alternatives except buserelin, which had an
incremental cost-effectiveness ratio versus leuprorelin 22.5 mg of ≈€12,000 per
life-month gained.
CONCLUSIONS: Based on modelling with meta-analysis of comparative survival data,
leuprorelin 22.5 mg was the most cost-effective treatment of the available depot
formulation LHRH agonists.

Copyright © 2011 International Society for Pharmacoeconomics and Outcomes
Research (ISPOR). Published by Elsevier Inc. All rights reserved.

PMID: 21211489  [PubMed - indexed for MEDLINE]




241. Circ Cardiovasc Interv. 2010 Dec;3(6):565-76. doi:
10.1161/CIRCINTERVENTIONS.110.949735. Epub 2010 Nov 23.

Drug-eluting or bare metal stents for the treatment of saphenous vein graft
disease: a Bayesian meta-analysis.

Paradis JM(1), Bélisle P, Joseph L, Bertrand OF, DeLarochellière R, Déry JP,
Larose E, Rodés-Cabau J, Rinfret S.

Author information:
(1)Institut Universitaire de Cardiologie et de Pneumologie de Québec (Quebec
Heart and Lung Institute), Quebec City, Canada.

Comment in
    Circ Cardiovasc Interv. 2011 Apr 1;4(2):e14; author reply e15.

BACKGROUND: Observational studies and randomized, controlled trials have yielded
uncertain results regarding the benefits of drug-eluting stents (DES) for the
treatment of saphenous vein graft (SVG) disease. The objective of this
meta-analysis was to assess the cumulative evidence regarding the efficacy and
effectiveness of DES to treat SVG compared with bare metal stent (BMS).
METHODS AND RESULTS: We conducted a bayesian hierarchical meta-analysis of all
randomized, controlled trials and observational studies that compared clinical
outcomes after DES or BMS placement in SVG disease. Our search resulted in 25
studies, cumulating 5755 patients. DES implantation was not associated with an
increased risk of death (odds ratio [OR], 0.85; 95% credible intervals (CrI)
[CrI], 0.62 to 1.21) or myocardial infarction (OR, 0.83; 95% CrI, 0.56 to 1.32),
but wide CrIs preclude definitive conclusions. Target vessel revascularization
(OR, 0.55; 95% CrI, 0.39 to 0.76) and target lesion revascularization (OR, 0.58;
95% CrI, 0.37 to 0.87) were both reduced by approximately 45% with DES. When
combining these outcomes, the OR for major adverse cardiac events was reduced in
patients treated with DES (OR, 0.62; 95% CrI, 0.46 to 0.81). Finally, the
relative risk of stent thrombosis appeared lower with DES, although again the
CrIs were very wide (OR, 0.54; 95% CrI, 0.13 to 1.39).
CONCLUSIONS: In this study-level meta-analysis, the largest ever reported and the
first using bayesian methods, the use of DES for the treatment of SVG disease
reduces target vessel revascularization and target lesion revascularization
procedures compared with BMS. Although there is no evidence to date to suggest
increased rates of mortality, myocardial infarction, or stent thrombosis, further
data are needed to address this safety issue.

PMID: 21098743  [PubMed - indexed for MEDLINE]


242. Eur Urol. 2010 Dec;58(6):865-74. doi: 10.1016/j.eururo.2010.09.024. Epub 2010 Oct
1.

Sacral neuromodulation for neurogenic lower urinary tract dysfunction: systematic
review and meta-analysis.

Kessler TM(1), La Framboise D, Trelle S, Fowler CJ, Kiss G, Pannek J, Schurch B,
Sievert KD, Engeler DS.

Author information:
(1)Department of Urology, University of Bern, Bern, Switzerland. tkessler@gmx.ch

CONTEXT: Treatment of neurogenic lower urinary tract dysfunction (LUTD) is a
challenge, because conventional therapies often fail. Sacral neuromodulation
(SNM) has become a well-established therapy for refractory non-neurogenic LUTD,
but its value in patients with a neurologic cause is unclear.
OBJECTIVE: To assess the efficacy and safety of SNM for neurogenic LUTD.
EVIDENCE ACQUISITION: Studies were identified by electronic search of PubMed,
EMBASE, and ScienceDirect (on 15 April 2010) and hand search of reference lists
and review articles. SNM articles were included if they reported on efficacy
and/or safety of tested and/or permanently implanted patients suffering from
neurogenic LUTD. Two reviewers independently selected studies and extracted data.
Study estimates were pooled using Bayesian random-effects meta-analysis.
EVIDENCE SYNTHESIS: Of the 26 independent studies (357 patients) included, the
evidence level ranged from 2b to 4 according to the Oxford Centre for
Evidence-Based Medicine. Half (n=13) of the included studies reported data on
both test phase and permanent SNM; the remaining studies were confined to test
phase (n=4) or permanent SNM (n=9). The pooled success rate was 68% for the test
phase (95% credibility interval [CrI], 50-87) and 92% (95% CrI, 81-98%) for
permanent SNM, with a mean follow-up of 26 mo. The pooled adverse event rate was
0% (95% CrI, 0-2%) for the test phase and 24% (95% CrI, 6-48%) for permanent SNM.
CONCLUSIONS: There is evidence indicating that SNM may be effective and safe for
the treatment of patients with neurogenic LUTD. However, the number of
investigated patients is low with high between-study heterogeneity, and there is
a lack of randomised, controlled trials. Thus, well-designed, adequately powered
studies are urgently needed before more widespread use of SNM for neurogenic LUTD
can be recommended.

Copyright © 2010 European Association of Urology. Published by Elsevier B.V. All
rights reserved.

PMID: 20934242  [PubMed - indexed for MEDLINE]


243. Value Health. 2010 Dec;13(8):934-45. doi: 10.1111/j.1524-4733.2010.00777.x. Epub
2010 Sep 3.

Mixed treatment comparison meta-analysis evaluating the relative efficacy of
nucleos(t)ides for treatment of nucleos(t)ide-naive patients with chronic
hepatitis B.

Dakin H(1), Fidler C, Harper C.

Author information:
(1)Abacus International, Bicester, Oxfordshire, UK. helen.dakin@abacusint.com

BACKGROUND/AIMS: Five nucleoside/nucleotide treatments are now available for
chronic hepatitis B (CHB). This meta-analysis aimed to assess the relative
efficacy of adefovir, entecavir, lamivudine, telbivudine, tenofovir disoproxil
fumarate (TDF), and nucleos(t)ide combinations in the treatment of CHB.
METHODS: A systematic review of MEDLINE and the Cochrane library was conducted to
identify all studies evaluating these nucleos(t)ides in adults with CHB.
Randomized controlled trials were included in the meta-analysis if they reported
the proportion of patients with undetectable hepatitis B virus (HBV) DNA or
hepatitis B e antigen (HBeAg) loss/seroconversion at 1 year. Bayesian mixed
treatment comparison meta-analyses were conducted in WinBUGS to assess relative
efficacy.
RESULTS: A random-effects meta-analysis of trials on treatment-naive patients
with HBeAg-positive CHB demonstrated that 94% of patients will achieve HBV DNA <
300 copies/ml after 1 year with TDF, compared with 73% for entecavir, 50% for
adefovir, and 38% for lamivudine. There was a 97.7% probability that TDF enabled
a greater proportion of patients to achieve HBV DNA < 300 copies/ml at 1 year
than all other treatments considered in the analysis. TDF was significantly
superior to all nucleos(t)ides for this outcome at the 0.05 level. There were no
statistically significant differences between nucleos(t)ides in HBeAg
seroconversion at 1 year, based on a fixed-effects meta-analysis in the same
population. More trials on HBeAg-negative and drug-resistant patients are
required to facilitate meta-analyses for these subgroups.
CONCLUSIONS: In nucleos(t)ide-naive patients with HBeAg-positive CHB, TDF is
associated with the highest probability of achieving undetectable HBV DNA at 1
year of all nucleos(t)ides considered.

© 2010, International Society for Pharmacoeconomics and Outcomes Research
(ISPOR).

PMID: 20825624  [PubMed - indexed for MEDLINE]


244. Cancer. 2010 Nov 15;116(22):5138-49. doi: 10.1002/cncr.25458.

Lymphedema beyond breast cancer: a systematic review and meta-analysis of
cancer-related secondary lymphedema.

Cormier JN(1), Askew RL, Mungovan KS, Xing Y, Ross MI, Armer JM.

Author information:
(1)Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer
Center, Houston, TX, USA. jcormier@mdanderson.org

BACKGROUND: Secondary lymphedema is a debilitating, chronic, progressive
condition that commonly occurs after the treatment of breast cancer. The purpose
of the current study was to perform a systematic review and meta-analysis of the
oncology-related literature excluding breast cancer to derive estimates of
lymphedema incidence and to identify potential risk factors among various
malignancies.
METHODS: The authors systematically reviewed 3 major medical indices (MEDLINE,
Cochrane Library databases, and Scopus) to identify studies (1972-2008) that
included a prospective assessment of lymphedema after cancer treatment. Studies
were categorized according to malignancy, and data included treatment,
complications, lymphedema measurement criteria, lymphedema incidence, and
follow-up interval. A quality assessment of individual studies was performed
using established criteria for systematic reviews. Bayesian meta-analytic
techniques were applied to derive summary estimates when sufficient data were
available.
RESULTS: A total of 47 studies (7779 cancer survivors) met inclusion criteria:
melanoma (n = 15), gynecologic malignancies (n = 22), genitourinary cancers (n =
8), head/neck cancers (n = 1), and sarcomas (n = 1). The overall incidence of
lymphedema was 15.5% and varied by malignancy (P < .001): melanoma, 16% (upper
extremity, 5%; lower extremity, 28%); gynecologic, 20%; genitourinary, 10%;
head/neck, 4%; and sarcoma, 30%. Increased lymphedema risk was also noted for
patients undergoing pelvic dissections (22%) and radiation therapy (31%).
Objective measurement methods and longer follow-up were both associated with
increased lymphedema incidence.
CONCLUSIONS: Lymphedema is a common condition affecting cancer survivors with
various malignancies. The incidence of lymphedema is related to the type and
extent of treatment, anatomic location, heterogeneity of assessment methods, and
length of follow-up.

Copyright © 2010 American Cancer Society.

PMID: 20665892  [PubMed - indexed for MEDLINE]


245. Am J Cardiol. 2010 Oct 15;106(8):1075-80. doi: 10.1016/j.amjcard.2010.06.010.

Meta-analysis of incidence, clinical characteristics and implications of stent
fracture.

Chakravarty T(1), White AJ, Buch M, Naik H, Doctor N, Schapira J, Kar S,
Forrester JS, Weiss RE, Makkar R.

Author information:
(1)Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles,
California, USA.

A meta-analysis of published studies was conducted to evaluate the incidence,
predictors, and clinical outcomes of stent fractures. Eight studies with 108
stent fractures in 5,321 patients were analyzed using the Bayesian method. Study
end points included in-stent restenosis (ISR) and target lesion revascularization
(TLR). The mean incidence of stent fracture per patient was 4.0% (95% confidence
interval 0.4% to 16.3%). All cases, except 1, were reported with
sirolimus-eluting stents. The incidence of stent fracture was 30.4% in the left
anterior descending coronary artery, 10.9% in the left circumflex coronary
artery, 56.4% in the right coronary artery, < 0.01% in the left main coronary
artery, and 1.7% in saphenous vein grafts. The probability of stent fracture was
significantly higher in the right coronary artery than in the left anterior
descending and left circumflex lesions (p < 0.01). Left main stents were less
likely to fracture compared to those in all other vessels (p < 0.01). The
probability of stent fracture was significantly increased in overlapping stents
(7.5% vs 2.1%, p = 0.01) and long stents (46 vs 32.5 mm, p < 0.01). Lesions with
stent fractures had higher rates of ISR (38% vs 8.2%, p < 0.01) and TLR (17% vs
5.6%, p < 0.01). Conversely, the probability of stent fractures was higher in
patients with ISR (12.8% vs 2.1%, p < 0.01) and TLR (8.8% vs 2.7%, p < 0.01). In
conclusion, although not always associated with clinical sequelae, the
probability of ISR and TLR is increased with stent fracture. Conversely, the
probability of stent fractures is increased in lesions with ISR or TLR, thus
raising the need for surveillance and management guidelines for at-risk patients.

Copyright © 2010 Elsevier Inc. All rights reserved.

PMID: 20920641  [PubMed - indexed for MEDLINE]


246. BMJ. 2010 Sep 16;341:c4675. doi: 10.1136/bmj.c4675.

Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis
of hip or knee: network meta-analysis.

Wandel S(1), Jüni P, Tendal B, Nüesch E, Villiger PM, Welton NJ, Reichenbach S,
Trelle S.

Author information:
(1)Institute of Social and Preventive Medicine, University of Bern, Switzerland.

Comment in
    J Fam Pract. 2011 Oct;60(10):610-2.
    Ann Intern Med. 2011 Mar 15;154(6):JC3-4.
    Evid Based Med. 2011 Apr;16(2):52-3.
    BMJ. 2010;341:c6328.
    BMJ. 2010;341:c6338.
    BMJ. 2010;341:c6335.

OBJECTIVE: To determine the effect of glucosamine, chondroitin, or the two in
combination on joint pain and on radiological progression of disease in
osteoarthritis of the hip or knee. Design Network meta-analysis. Direct
comparisons within trials were combined with indirect evidence from other trials
by using a Bayesian model that allowed the synthesis of multiple time points.
MAIN OUTCOME MEASURE: Pain intensity. Secondary outcome was change in minimal
width of joint space. The minimal clinically important difference between
preparations and placebo was prespecified at -0.9 cm on a 10 cm visual analogue
scale.
DATA SOURCES: Electronic databases and conference proceedings from inception to
June 2009, expert contact, relevant websites. Eligibility criteria for selecting
studies Large scale randomised controlled trials in more than 200 patients with
osteoarthritis of the knee or hip that compared glucosamine, chondroitin, or
their combination with placebo or head to head. Results 10 trials in 3803
patients were included. On a 10 cm visual analogue scale the overall difference
in pain intensity compared with placebo was -0.4 cm (95% credible interval -0.7
to -0.1 cm) for glucosamine, -0.3 cm (-0.7 to 0.0 cm) for chondroitin, and -0.5
cm (-0.9 to 0.0 cm) for the combination. For none of the estimates did the 95%
credible intervals cross the boundary of the minimal clinically important
difference. Industry independent trials showed smaller effects than commercially
funded trials (P=0.02 for interaction). The differences in changes in minimal
width of joint space were all minute, with 95% credible intervals overlapping
zero. Conclusions Compared with placebo, glucosamine, chondroitin, and their
combination do not reduce joint pain or have an impact on narrowing of joint
space. Health authorities and health insurers should not cover the costs of these
preparations, and new prescriptions to patients who have not received treatment
should be discouraged.

PMCID: PMC2941572
PMID: 20847017  [PubMed - indexed for MEDLINE]


247. J Hosp Infect. 2010 Sep;76(1):1-11. doi: 10.1016/j.jhin.2010.04.025. Epub 2010
Jul 16.

Effectiveness of different central venous catheters for catheter-related
infections: a network meta-analysis.

Wang H(1), Huang T, Jing J, Jin J, Wang P, Yang M, Cui W, Zheng Y, Shen H.

Author information:
(1)Intensive Care Unit, Second Affiliated Hospital, School of Medicine, Zhejiang
University, Hangzhou, Zhejiang Province, China.

We aimed to compare the effectiveness of various catheters for prevention of
catheter-related infection and to evaluate whether specific catheters are
superior to others for reducing catheter-related infections. We identified
randomised, controlled trials that compared different types of central venous
catheter (CVC), evaluating catheter-related infections in a systematic search of
articles published from January 1996 to November 2009 via Medline, Embase, Web of
Science, and the Cochrane Central Register of Controlled Trials. Network
meta-analysis with a mixed treatment comparison method using Bayesian Markov
Chain Monte Carlo simulation was used to combine direct within-trial,
between-treatment comparisons with indirect trial evidence. Forty-eight clinical
trials (12 828 CVCs) investigating 10 intervention catheters contributed to the
analyses. For prevention of CVC colonisation, adjusted silver iontophoretic
catheters (odds ratio: 0.58; 95% confidence interval: 0.33-0.95), chlorhexidine
and silver sulfadiazine catheters (0.49; 0.36-0.64), chlorhexidine and silver
sulfadiazine blue plus catheters (0.37; 0.17-0.69), minocycline-rifampicin
catheters (0.28; 0.17-0.43) and miconazole-rifampicin catheters (0.11; 0.02-0.33)
were associated with a significantly lower rate of catheter colonisation compared
with standard catheters. For prevention of CRBSI, adjusted heparin-bonded
catheters (0.20; 0.06-0.44) and minocycline-rifampicin catheters (0.18;
0.08-0.34) were associated with a significantly lower rate of CRBSI with standard
catheters. Rifampicin-based impregnated catheters seem to be better for
prevention of catheter-related infection compared with the other catheters.

Crown Copyright 2010. Published by Elsevier Ltd. All rights reserved.

PMID: 20638155  [PubMed - indexed for MEDLINE]


248. Int J Cardiol. 2010 Jul 23;142(3):218-23. doi: 10.1016/j.ijcard.2009.11.045. Epub
2010 Jan 12.

Antithrombotic treatment for the primary prevention of stroke in patients with
non valvular atrial fibrillation: a reappraisal of the evidence and network meta
analysis.

Owen A(1).

Author information:
(1)Princess of Wales Hospital, Coity Road, Bridgend, Mid Glamorgan, United
Kingdom.

The role of aspirin for the primary prevention of stroke in patients with non
valvular atrial fibrillation is critically reviewed. It is shown that the
currently held belief that aspirin (at doses of 75 to 325 mg daily) is an
effective treatment is based on a flawed interpretation of the data. A Bayesian
network meta analysis is presented that demonstrates that aspirin at 325 mg daily
is superior to control and similar to warfarin for the reduction of the risk of
both stroke and death. In contrast for lower daily doses of aspirin there is no
evidence of any efficacy over control for the reduction of the risk of stroke.
The data are inconclusive as to whether lower doses of aspirin may have some
benefit in reducing the risk of death.

Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

PMID: 20061035  [PubMed - indexed for MEDLINE]


249. Breast Cancer Res Treat. 2010 Jul;122(2):471-81. doi: 10.1007/s10549-009-0690-9.
Epub 2009 Dec 31.

Factors influencing the association between CYP17 T34C polymorphism and the risk
of breast cancer: meta-regression and subgroup analysis.

Chen Y(1), Pei J.

Author information:
(1)Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road,
Nanjing, 210029, China. ychen@njmu.edu.cn

A number of studies have been investigated the association between CYP17 T34C
polymorphism and the risk of breast cancer; the results of these studies are
inconsistent, however. This fact implies that the effect of CYP17 T34C
polymorphism on susceptibility to breast cancer may be modified by other risk
factors. In order to provide a more definitive conclusion, a full meta-analysis
combining and summarizing 24 studies was first performed. Both traditional method
and Bayesian approach were applied. Odds ratio was estimated using a dominant
mode of inheritance after a biological justification for the choice of genetic
model. The results of homogeneity analysis (H = 1.16, I (2) = 25.4%, and P =
0.127) suggested the presence of heterogeneity across the studies. Thus, random
effects models simulated by the DerSimonian-Laird method were employed. The
capability of a Bayesian approach was highlighted in the estimation of a pooled
odds ratio and 95% confidence interval. The results of meta-analysis (OR = 1.001,
CI = 0.832-1.208) suggest no significant association in the combined populations.
Furthermore, Bayesian meta-regression and subgroup analysis were conducted to
investigate the sources of heterogeneity. The risk factors evaluated in the study
were menopausal status, ethnicity, age at menarche, age at first birth, parity,
use of oral contraceptives, body mass index (BMI), and use of hormone repair
therapy (HRT). After these population stratifications, there was evidence
indicating that a possible impact of menopausal status, age at menarche, and BMI
on the association between CYP17 T34C polymorphism and the risk of breast cancer.

PMID: 20043206  [PubMed - indexed for MEDLINE]


250. Curr Med Res Opin. 2010 Jul;26(7):1565-78. doi: 10.1185/03007995.2010.481251.

Comparative effectiveness of antibiotics for the treatment of MRSA complicated
skin and soft tissue infections.

Logman JF(1), Stephens J, Heeg B, Haider S, Cappelleri J, Nathwani D, Tice A, van
Hout BA.

Author information:
(1)Pharmerit Europe, Rotterdam, The Netherlands.

OBJECTIVE: With a growing number of studies and comparators in MRSA skin
infections, a unified framework for comparing treatments is needed for health
technology assessment (HTA). The objective was to systematically assess the
success rates of common antimicrobial agents for the treatment of complicated
skin and soft tissue infections (cSSTIs) caused by MRSA.
METHODS: MEDLINE, EMBASE, and Cochrane databases were searched to identify
published clinical trials in which dalbavancin, daptomycin, linezolid,
telavancin, teicoplanin, tigecycline, and vancomycin were used to treat cSSTIs.
Pooled efficacy estimates were generated from clinical and microbiological
determinations of success for the MRSA-subgroups in cSSTI clinical trials using a
Bayesian meta-analytic approach. Success rates for each antibiotic were reported
with 95% Bayesian confidence intervals (called credible intervals [CrI]). In
sensitivity analyses the impact of different model parameters and article quality
were investigated.
RESULTS: Out of 36 identified studies, 14 studies on six antibiotics with 28
treatment arms (n = 1840) were included in the analysis. No MRSA data in cSSTI
were found for teicoplanin. The pooled success rate and CrI(95%) for each agent
was: vancomycin (74.7%; CrI(95%): 64.1%-83.5%), dalbavancin (87.7%; CrI(95%):
74.6%-95.4%), linezolid (84.4%; CrI(95%): 76.6%-90.6%), telavancin (83.5%;
CrI(95%): 73.6%-90.8%), daptomycin (78.1%; CrI(95%): 54.6%-93.2%) and tigecycline
(70.4%; CrI(95%): 48.0%-87.6%). Comparisons between antibiotics suggested
differences versus vancomycin for linezolid (+9.7%; CrI(95%): 4.4%-15.8%),
dalbavancin (+13.1%; CrI(95%): 1.0%-23.8%), and telavancin (+8.8%; CrI(95%):
1.5-16.7%). The finding of lower vancomycin efficacy in MRSA cSSTI did not change
in sensitivity analyses.
CONCLUSION: The results of this meta-analysis suggest higher success rates for
linezolid and the new glycopeptides (dalbavancin and telavancin) in
MRSA-confirmed cSSTIs. The uncertainty margins reflect the study limitations
including number of cases and indirect nature of the comparisons. This example of
Bayesian meta-analysis for MRSA cSSTI provides a potential framework for
comparisons that is useful for HTA and formulary decision-making.

PMID: 20429820  [PubMed - indexed for MEDLINE]


251. BMC Cardiovasc Disord. 2010 Jun 3;10:24. doi: 10.1186/1471-2261-10-24.

Omega-3 fatty acids in high-risk cardiovascular patients: a meta-analysis of
randomized controlled trials.

Filion KB(1), El Khoury F, Bielinski M, Schiller I, Dendukuri N, Brophy JM.

Author information:
(1)Department of Medicine, McGill University, Montreal, Quebec, Canada.

BACKGROUND: Multiple randomized controlled trials (RCTs) have examined the
cardiovascular effects of omega-3 fatty acids and have provided unexplained
conflicting results. A meta-analysis of these RCTs to estimate efficacy and
safety and potential sources of heterogeneity may be helpful.
METHODS: The Cochrane library, MEDLINE, and EMBASE were systematically searched
to identify all interventional trials of omega-3 fatty acids compared to placebo
or usual diet in high-risk cardiovascular patients. The primary outcome was
all-cause mortality and secondary outcomes were coronary restenosis following
percutaneous coronary intervention and safety. Meta-analyses were carried out
using Bayesian random-effects models, and heterogeneity was examined using
meta-regression.
RESULTS: A total of 29 RCTs (n = 35,144) met our inclusion criteria, with 25
reporting mortality and 14 reporting restenosis. Omega-3 fatty acids were not
associated with a statistically significant decreased mortality (relative risk
[RR] = 0.88, 95% Credible Interval [CrI] = 0.64, 1.03) or with restenosis
prevention (RR = 0.89, 95% CrI = 0.72, 1.06), though the probability of some
benefit remains high (0.93 and 0.90, respectively). However in meta-regressions,
there was a >90% probability that larger studies and those with longer follow-up
were associated with smaller benefits. No serious safety issues were identified.
CONCLUSIONS: Although not reaching conventional statistical significance, the
evidence to date suggests that omega-3 fatty acids may result in a modest
reduction in mortality and restenosis. However, caution must be exercised in
interpreting these benefits as results were attenuated in higher quality studies,
suggesting that bias may be at least partially responsible. Additional high
quality studies are required to clarify the role of omega-3 fatty acid
supplementation for the secondary prevention of cardiovascular disease.

PMCID: PMC2894745
PMID: 20525225  [PubMed - indexed for MEDLINE]


252. Curr Med Res Opin. 2010 May;26(5):1193-201. doi: 10.1185/03007991003659814.

Efficacy of vitamin D3 supplementation in preventing fractures in elderly women:
a meta-analysis.

Bergman GJ(1), Fan T, McFetridge JT, Sen SS.

Author information:
(1)Mapi Values, Houten, The Netherlands.

BACKGROUND: The efficacy of vitamin D(3) in preventing fractures and falls has
been explored in a number of clinical trials. However, recent evidence revealed
new questions about the adequate doses of vitamin D(3) supplementation and its
efficacy in fracture prevention independent of calcium supplements for various
types of fractures.
OBJECTIVE: To conduct a meta-analysis to estimate the effectiveness of 800 IU
daily vitamin D(3) supplementation for increasing bone mineral density (BMD) and
preventing fractures in postmenopausal women.
METHODS: Medline and EMBASE were searched for controlled trials comparing the
effectiveness of cholecalciferol (vitamin D(3)) against placebo with or without
background calcium supplementation in the treatment of postmenopausal women.
RESULTS: Eight controlled trials evaluating the effect of vitamin D(3)
supplementation with or without calcium were assessed. Of 12 658 women included
in a Bayesian meta-analysis, 6089 received vitamin D(3) (with or without calcium)
and 6569 received placebo (with or without calcium). Compared to placebo, vitamin
D(3) with calcium supplementation showed beneficial effects on the incidence of
non-vertebral (odds ratio [OR] 0.77, 95% credibility limit [CL] 0.6-0.93) and hip
(OR 0.70, 95% CL 0.53-0.90) fractures, while the effects on non-vertebral-non-hip
fractures (OR 0.84, 95% CL 0.67-1.04) % point increase) were associated with more
uncertainty. Vitamin D(3) supplementation showed a 70% probability of being a
better treatment than placebo for the prevention of non-vertebral fractures, hip
fractures, and non-vertebral, non-hip fractures. Compared to calcium
supplementation, vitamin D(3) plus calcium reduced non-vertebral fractures (OR
0.68, 95% CL 0.43-1.01) and non-vertebral, non-hip fractures (OR 0.64, 95% CL
0.38-0.99), but did not reduce hip fractures (OR 1.03, 95% CL 0.39-2.25). Key
limitations to this analysis include a small number of studies and heterogeneity
in the study populations.
CONCLUSIONS: This meta-analysis supports the use of vitamin D3 of 800 IU daily to
reduce the incidence of osteoporotic non-vertebral, hip, and
non-vertebral-non-hip fractures in elderly women. Vitamin D(3) with calcium
appears to achieve benefits above those attained with calcium supplementation
alone for non-vertebral and non-vertebral-non-hip fractures.

PMID: 20302551  [PubMed - indexed for MEDLINE]


253. J Gastrointest Surg. 2010 May;14(5):788-804. doi: 10.1007/s11605-010-1168-0. Epub
2010 Mar 13.

Effect of preoperative single-dose corticosteroid administration on postoperative
morbidity following esophagectomy.

Engelman E(1), Maeyens C.

Author information:
(1)Department of Anesthesiology, Post-anesthesia Care Unit and Acute Pain
Service, Erasme Hospital, Route de Lennik 808, 1070 Brussels, Belgium.
eengelma@ulb.ac.be

BACKGROUND: Eight clinical trials involving the administration of preoperative
i.v. methylprednisolone have been undertaken in order to decrease the
considerable inflammatory response to esophageal resection, in an effort to
decrease the supposedly associated morbidity and mortality
METHOD: A meta-analysis was performed for eight clinical end-points. Due to
quality problems in seven of the eight included studies, a Bayesian meta-analysis
using a skeptical prior derived from the results of the classical analysis was
also performed.
RESULTS: The end-points including any organ dysfunction (OR = 0.30), respiratory
complication (OR = 0.41), sepsis (OR = 0.37), liver dysfunction (OR = 18),
cardiovascular dysfunction (OR = 0.28), and surgical anastomotic leak (OR = 0.42)
were significantly decreased by methylprednisolone pretreatment. Following the
Bayesian analysis, despite the use of skeptical priors, there is a 95%
probability to obtain a relative risk reduction of at least 23% to 54%, depending
of the end-point, by methylprednisolone pretreatment.
CONCLUSION: We are in the presence of a potential benefit that cannot be accepted
at face value due to the quality problems of the included studies. But in the
presence of a remaining potential benefit after a Bayesian analysis starting from
a skeptical prior, the best option would be the planning of a large multicenter
prospective randomized study.

PMID: 20229072  [PubMed - indexed for MEDLINE]


254. Lancet Infect Dis. 2010 Apr;10(4):251-61. doi: 10.1016/S1473-3099(10)70026-8.

Immune reconstitution inflammatory syndrome in patients starting antiretroviral
therapy for HIV infection: a systematic review and meta-analysis.

Müller M(1), Wandel S, Colebunders R, Attia S, Furrer H, Egger M; IeDEA Southern
and Central Africa.

Author information:
(1)International epidemiological Databases to Evaluate AIDS, Southern African
region, Institute of Social and Preventive Medicine, University of Bern,
Switzerland.

Comment in
    Lancet Infect Dis. 2010 Dec;10(12):833-4.

In patients with HIV-1 infection who are starting combination antiretroviral
therapy (ART), the incidence of immune reconstitution inflammatory syndrome
(IRIS) is not well defined. We did a meta-analysis to establish the incidence and
lethality of the syndrome in patients with a range of previously diagnosed
opportunistic infections, and examined the relation between occurrence and the
degree of immunodeficiency. Systematic review identified 54 cohort studies of 13
103 patients starting ART, of whom 1699 developed IRIS. We calculated pooled
cumulative incidences with 95% credibility intervals (CrI) by Bayesian methods
and did a random-effects metaregression to analyse the relation between CD4 cell
count and incidence of IRIS. In patients with previously diagnosed AIDS-defining
illnesses, IRIS developed in 37.7% (95% CrI 26.6-49.4) of those with
cytomegalovirus retinitis, 19.5% (6.7-44.8) of those with cryptococcal
meningitis, 15.7% (9.7-24.5) of those with tuberculosis, 16.7% (2.3-50.7) of
those with progressive multifocal leukoencephalopathy, and 6.4% (1.2-24.7) of
those with Kaposi's sarcoma, and 12.2% (6.8-19.6) of those with herpes zoster.
16.1% (11.1-22.9) of unselected patients starting ART developed any type of IRIS.
4.5% (2.1-8.6) of patients with any type of IRIS died, 3.2% (0.7-9.2) of those
with tuberculosis-associated IRIS died, and 20.8% (5.0-52.7) of those with
cryptococcal meningitis died. Metaregression analyses showed that the risk of
IRIS is associated with CD4 cell count at the start of ART, with a high risk in
patients with fewer than 50 cells per microL. Occurrence of IRIS might therefore
be reduced by initiation of ART before immunodeficiency becomes advanced.

2010 Elsevier Ltd. All rights reserved.

PMCID: PMC4183458
PMID: 20334848  [PubMed - indexed for MEDLINE]


255. Anesth Analg. 2010 Feb 1;110(2):570-80. doi: 10.1213/ANE.0b013e3181b5dcb7. Epub
2009 Oct 9.

Statistical modeling of average and variability of time to extubation for
meta-analysis comparing desflurane to sevoflurane.

Dexter F(1), Bayman EO, Epstein RH.

Author information:
(1)Department of Anesthesia, University of Iowa, Iowa City, Iowa 52242, USA.
Franklin-Dexter@UIowa.ed

Comment in
    Anesth Analg. 2010 Feb 1;110(2):273-5.
    Anesth Analg. 2010 Feb 1;110(2):278-9.
    Anesth Analg. 2010 Feb 1;110(2):276-7.

BACKGROUND: The recovery profile of an ideal anesthetic or technique would be
fast (e.g., mean of 5 min from end of surgery to extubation) with little
variability (e.g., always 4-7 min). We used anesthesia information management
system (AIMS) data to learn how to model the time from end of surgery to
extubation. We applied that knowledge for meta-analyses of trials comparing
extubation times after use of desflurane and sevoflurane.
METHODS: AIMS data studied were 32,792 cases performed by 95 surgeons that
included tracheal intubation and extubation in the operating room (OR) and use of
volatile anesthetic(s). Meta-analysis included the 29 randomized controlled
trials through 2008 comparing extubation times with desflurane and sevoflurane.
Percentage differences in means and standard deviations were studied using random
effects meta-analysis and a Bayesian method.
RESULTS: Times to extubation were better fit by (skewed) Weibull distributions
than by (symmetric) normal distributions. Drug choice had nearly equally
proportional effects on the means and standard deviations of extubation times, as
shown by unchanged coefficients of variation (P > 0.10 for 26 of 29 studies) and
nonsignificant pooled difference in the coefficient of variation
(sevoflurane--desflurane = -1%, 95% confidence interval [CI] -3% to 1%, P =
0.22). Applying these findings, desflurane reduced the mean extubation time by
25% (95% CI 17%-32%, P < 0.0001) and standard deviation by 21% (95% CI 16%-26%).
To value the intangible costs (e.g., frustrated waiting surgeons) of prolonged
extubation times, we considered the 15% of AIMS cases with times >15 min. These
cases averaged 4.9 min longer times from out of the OR to the start of surgery of
the surgeon's next case (95% CI 2.7-7.1 min, P < 0.0001). Reduction in the means
and standard deviations by 20%-25% would likely reduce incidences of these
prolonged extubation times by 71%-82% (95% CI 68%-84%).
CONCLUSIONS: Desflurane reduces the average extubation time and the variability
of extubation time by 20%-25% relative to sevoflurane. The principal economic
value of these end points is their reductions of direct (labor) costs of OR time.
However, reductions in intangible costs of prolonged extubation are real, being
associated with subsequent delays. Reductions in the average and variance of
times to extubation can be interpreted and monitored in terms of corresponding
expected 75% reductions in the incidences of prolonged extubation times by using
desflurane relative to sevoflurane.

PMID: 19820242  [PubMed - indexed for MEDLINE]


256. Circ Cardiovasc Interv. 2010 Feb 1;3(1):6-16. doi:
10.1161/CIRCINTERVENTIONS.109.904037. Epub 2010 Jan 26.

Adjunctive thrombectomy for acute myocardial infarction: A bayesian
meta-analysis.

Mongeon FP(1), Bélisle P, Joseph L, Eisenberg MJ, Rinfret S.

Author information:
(1)Department of Medicine, Echocardiography, and Noninvasive Cardiology Service,
Montreal Heart Institute, Canada.

Comment in
    Circ Cardiovasc Interv. 2010 Jun 1;3(3):e8; author reply e9.
    Circ Cardiovasc Interv. 2010 Feb 1;3(1):1-2.

BACKGROUND: In available trials and meta-analyses, adjunctive thrombectomy in
acute myocardial infarction (MI) improves markers of myocardial reperfusion but
has limited effects on clinical outcomes. Thrombectomy devices simply aspirate
thrombus or mechanically fragment it before aspiration. Simple aspiration
thrombectomy may offer a distinct advantage.
METHODS AND RESULTS: We identified 21 eligible trials (16 that used a simple
aspiration thrombectomy device) involving 4299 patients with ST-segment elevation
MI randomized to reperfusion therapy by primary percutaneous coronary
intervention with or without thrombectomy. By using Bayesian meta-analysis
methods, we found that thrombectomy yielded substantially less no-reflow (odds
ratio [OR], 0.39; 95% credible interval [CrI], 0.18 to 0.69), more ST-segment
resolution > or =50% (OR, 2.22; 95% CrI, 1.60 to 3.23), and more thrombolysis in
myocardial infarction/myocardial perfusion grade 3 (OR, 2.50; 95% CrI, 1.48 to
4.41). There was no evidence for a decrease in death (OR, 0.94; 95% CrI, 0.47 to
1.80), death, recurrent MI, or stroke (OR, 1.07; 95% CrI, 0.63 to 1.92) with
thrombectomy. Restriction of the analysis to trials that used simple aspiration
thrombectomy devices did not yield substantially different results, except for a
positive effect on postprocedure thrombolysis in myocardial infarction grade 3
flow (OR, 1.49; 95% CrI, 1.14 to 1.99).
CONCLUSIONS: In this Bayesian meta-analysis, adjunctive thrombectomy improves
early markers of reperfusion but does not substantially effect 30-day post-MI
mortality, reinfarction, and stroke. The use of aspiration thrombectomy devices
is not associated with a reduction in post-MI clinical outcomes. Thrombectomy is
one of the rare effective preventive measures against no-reflow.

PMID: 20118149  [PubMed - indexed for MEDLINE]


257. Osteoarthritis Cartilage. 2010 Feb;18(2):200-7. doi: 10.1016/j.joca.2009.08.006.
Epub 2009 Sep 1.

Interleukin-1 region meta-analysis with osteoarthritis phenotypes.

Moxley G(1), Meulenbelt I, Chapman K, van Diujn CM, Slagboom PE, Neale MC, Smith
AJ, Carr AJ, Loughlin J.

Author information:
(1)Virginia Commonwealth University, Richmond, VA 23298-0263, USA.
gmoxley@vcu.edu

OBJECTIVE: Several research groups have examined osteoarthritis (OA) association
with Interleukin-1 (IL-1) region markers and haplotypes. The results have been
suggestive for hand OA, negative for knee OA, and conflicting for hip OA.
DESIGN: Our aim was to address conflicts employing meta-analytical methods on
data from 1238 European-descent cases with various OA phenotypes and 1269
European-descent controls from four study centers. We imputed some missing
genotype data and reconstructed IL-1 region extended haplotypes. A previously
reported 7-marker IL1A-IL1B-IL1RN extended risk haplotype was tested for
association with each specific index phenotype.
RESULTS: For hip OA, data from three centers showed heterogeneity of
extended-risk-haplotype effect, two panels showing trend toward risk and another
showing protection, with overall odds ratio (OR) 1.24 (95% Confidence interval
(CI) 0.45-3.41, P 0.67). The heterogeneity fell partly along control
ascertainment lines, chiefly between controls ascertained as spouses of
arthroplasty patients and controls identified through population radiographic
survey. For knee OA, the results showed no heterogeneity and no significant
extended-risk-haplotype effect. For hand OA, the results showed little
heterogeneity and a modest trend toward positive association (summary OR 1.34,
95% CI 0.83-2.17 P 0.23). Using a Bayesian partition modeling approach, the
7-marker extended haplotypes showed no significant effect on any OA phenotype
examined. A 3-single-nucleotide polymorphism (SNP) IL1B-IL1RN haplotype
rs1143627-rs16944-rs419598 showed a trend toward hand OA association (posterior
probability of association 0.72) with the most prominent feature being protection
from a specific haplotype representing a partial mirror image of the extended
risk haplotype (OR estimated at 0.46).
CONCLUSIONS: The meta-analysis data do not confirm but only suggest that some
hand and hip OA risk could be associated with the IL-1 region, particularly
centered in IL1B and possibly also IL1RN.

Copyright 2009. Published by Elsevier Ltd.

PMID: 19733643  [PubMed - indexed for MEDLINE]


258. Curr Med Res Opin. 2010 Jan;26(1):53-9. doi: 10.1185/03007990903416853.

Comparative efficacy and acceptability of pharmacotherapeutic agents for anxiety
disorders in children and adolescents: a mixed treatment comparison
meta-analysis.

Uthman OA(1), Abdulmalik J.

Author information:
(1)West Midlands Health Technology Assessment Collaboration, Department of Public
Health & Biostatistics, University of Birmingham, Birmingham, UK.
a.o.uthman@bham.ac.uk

OBJECTIVE: to compare efficacy and acceptability of different pharmacotherapeutic
agents for treating anxiety disorders in children and adolescents.
METHODS: A recently conducted Cochrane Review on pharmacotherapy for anxiety
disorders in children and adolescents was updated. A mixed treatment comparison
meta-analysis using Bayesian Markov Chain Monte Carlo simulation was used to
perform the indirect comparison. We calculated relative risk ratios (RR) with 95%
credible interval (CrI) using placebo as the common comparator.
RESULTS: Data were combined from 16 clinical trials that randomized children to
six different treatment strategies, including placebo. Fluoxetine, fluvoxamine,
paroxetine, sertraline, and venlafaxine were more efficacious than placebo.
Venlafaxine was significantly less efficacious than fluvoxamine (RR = 0.60; 95%
CrI 0.35-0.95) and paroxetine (RR = 0.65; 95% CrI 0.44-0.93). Fluoxetine,
fluvoxamine, paroxetine, and sertraline had higher acceptability profile than
placebo. Venlafaxine was less tolerated than fluvoxamine (RR = 0.16; 95% CrI
0.01-0.64), paroxetine (RR = 0.21; 95% CrI 0.05-0.59), and sertraline (RR = 0.31;
95% CrI 0.08-0.83). Fluvoxamine had a higher rate of clinical response and
acceptability compared to other treatments in the network, with probability of
47.5% and 50.6% of being the most efficacious and well-tolerated treatment,
respectively.
CONCLUSION: Clinically important differences exist between commonly prescribed
pharmacotherapeutic agents for treating anxiety among children in terms of both
efficacy and acceptability in favor of fluvoxamine. Fluvoxamine might be the best
choice when starting treatment for anxiety disorders among children and
adolescents because it has the most favorable balance between benefits and
acceptability.

PMID: 19905879  [PubMed - indexed for MEDLINE]


259. Psychother Psychosom. 2010;79(5):285-94. doi: 10.1159/000318295. Epub 2010 Jul 9.

Do primary care physicians have particular difficulty identifying late-life
depression? A meta-analysis stratified by age.

Mitchell AJ(1), Rao S, Vaze A.

Author information:
(1)Leicester General Hospital, Leicestershire Partnership Trust, Leicester Royal
Infirmary, Leicester, UK. ajm80@leicester.ac.uk

BACKGROUND: There is long-standing concern regarding poor recognition of
depression in primary care, especially in older people.
METHODS: Studies that examined the unassisted (clinical) ability of general
practitioners (GPs; primary care physicians) to identify depression were divided
into those of older adults, younger adults and mixed populations. Data were
extracted by 3 reviewers independently and pooled using a Bayesian meta-analysis.
RESULTS: We identified 31 valid studies that examined both sensitivity and
specificity (or rule-in and rule-out accuracy), involving 52,513 individuals.
Twelve studies recruited older individuals, 12 recruited younger adults and 7
recruited both younger and older adults (mixed populations). In the most robust
studies the point prevalence of depression in late life was 13.2% (95% CI =
7.9-19.6). GPs were able to correctly identify 47.3% of the late-life depressions
and 78.6% of the non-cases (71.0% overall accuracy). In younger adults GPs were
able to identify 39.7% of the mid-life depressions and 85.1% of the non-depressed
(77.8% overall accuracy). In mixed aged groups GPs we able to correctly identify
46.6% of the depressed individuals and 86.2% of the non-depressed (79.6% overall
accuracy). The overall fraction correctly identified was significantly lower in
older compared with younger adults. Correcting for differences in prevalence
showed a statistically lower rule-in performance for older compared with younger
adults. There was no difference in ability to identify non-depressed (healthy)
individuals by age.
CONCLUSIONS: In clinical practice GPs appear to be less successful in identifying
depression in older people than in younger adults, however there have been few
head-to-head studies stratified by age from one centre.

Copyright 2010 S. Karger AG, Basel.

PMID: 20616623  [PubMed - indexed for MEDLINE]


260. Infect Genet Evol. 2009 Dec;9(6):1356-63. doi: 10.1016/j.meegid.2009.09.010. Epub
2009 Sep 30.

An assessment of a TNF polymorphic marker for the risk of HCV infection:
meta-analysis and a new clinical study design.

Chen Y(1), Pei J.

Author information:
(1)Department of Pharmacology, Nanjing Medical University, Nanjing 210029, China.
ychen@njmu.edu.cn

A number of studies have investigated the association between TNF-alpha -308G/A
polymorphism and the risk of HCV infection; the results of these studies are
conflict, however. To provide a more definitive conclusion, a meta-analysis
combining and summarizing 12 studies was performed. The Mantel-Haenszel and
DerSimonian-Laird methods were employed in traditional fixed effects and random
effects meta-analysis, respectively. The capability of a Bayesian approach was
highlighted in the estimation of a pooled odds ratio and 95% confidence interval,
as well as in the calculation of a sample size for the new study design.
Heterogeneity and publication bias across the studies were also explored. The
results of the meta-analysis (OR=1.179, CI=0.833-1.649) suggest no significant
association between TNF-alpha -308G/A polymorphism and susceptibility to HCV
infection in the combined populations. However, there was evidence indicating a
possible impact of ethnicity (Asian vs. non-Asian populations) on the association
evaluated here (beta(ethnicity)=0.293+/-0.271). While the power of existing Asian
studies was insufficient to make a statistical statement, the sample size of a
new clinical study was estimated (500 subjects with 80% statistical power) for
further assessment of an association between TNF-alpha -308G/A polymorphism and
risk of HCV infection in Asians.

PMID: 19800032  [PubMed - indexed for MEDLINE]


261. Arch Intern Med. 2009 Nov 23;169(21):1952-60. doi:
10.1001/archinternmed.2009.357.

Meta-analysis of the impact of 9 medication classes on falls in elderly persons.

Woolcott JC(1), Richardson KJ, Wiens MO, Patel B, Marin J, Khan KM, Marra CA.

Author information:
(1)Faculty of Pharmaceutical Sciences, University of British Columbia, BC,
Canada.

Erratum in
    Arch Intern Med. 2010 Mar 8;170(5):477.

Comment in
    Arch Intern Med. 2010 May 10;170(9):834-5; author reply 835.
    Evid Based Med. 2010 Apr;15(2):59.

BACKGROUND: There is increasing recognition that the use of certain medications
contributes to falls in seniors. Our objective was to update a previously
completed meta-analysis looking at the association of medication use and falling
to include relevant drug classes and new studies that have been completed since a
previous meta-analysis.
METHODS: Studies were identified through a systematic search of English-language
articles published from 1996 to 2007. We identified studies that were completed
on patients older than 60 years, looking at the association between medication
use and falling. Bayesian methods allowed us to combine the results of a previous
meta-analysis with new information to estimate updated Bayesian odds ratios (ORs)
and 95% credible intervals (95% CrIs)
RESULTS: Of 11 118 identified articles, 22 met our inclusion criteria.
Meta-analyses were completed on 9 unique drug classes, including 79 081
participants, with the following Bayesian unadjusted OR estimates:
antihypertensive agents, OR, 1.24 (95% CrI, 1.01-1.50); diuretics, OR, 1.07 (95%
CrI, 1.01-1.14); beta-blockers, OR, 1.01 (95% CrI, 0.86-1.17); sedatives and
hypnotics, OR, 1.47 (95% CrI, 1.35-1.62); neuroleptics and antipsychotics, OR,
1.59 (95% CrI, 1.37-1.83); antidepressants, OR, 1.68 (95% CrI, 1.47-1.91);
benzodiazepines, OR, 1.57 (95% CrI, 1.43-1.72); narcotics, OR, 0.96 (95% CrI,
0.78-1.18); and nonsteroidal anti-inflammatory drugs, OR, 1.21 (95% CrI,
1.01-1.44). The updated Bayesian adjusted OR estimates for diuretics,
neuroleptics and antipsychotics, antidepressants, and benzodiazepines were 0.99
(95% CrI, 0.78-1.25), 1.39 (95% CrI, 0.94-2.00), 1.36 (95% CrI, 1.13-1.76), and
1.41 (95% CrI, 1.20-1.71), respectively. Stratification of studies had little
effect on Bayesian OR estimates, with only small differences in the stratified
ORs observed across population (for beta-blockers and neuroleptics and
antipsychotics) and study type (for sedatives and hypnotics, benzodiazepines, and
narcotics). An increased likelihood of falling was estimated for the use of
sedatives and hypnotics, neuroleptics and antipsychotics, antidepressants,
benzodiazepines, and nonsteroidal anti-inflammatory drugs in studies considered
to have "good" medication and falls ascertainment.
CONCLUSION: The use of sedatives and hypnotics, antidepressants, and
benzodiazepines demonstrated a significant association with falls in elderly
individuals.

PMID: 19933955  [PubMed - indexed for MEDLINE]


262. Am J Med. 2009 Nov;122(11):1016-1022.e1. doi: 10.1016/j.amjmed.2009.05.021.

Bayesian meta-analysis of hormone therapy and mortality in younger postmenopausal
women.

Salpeter SR(1), Cheng J, Thabane L, Buckley NS, Salpeter EE.

Author information:
(1)Santa Clara Valley Medical Center, 751 S. Bascom Ave, San Jose, CA 95128, USA.
salpeter@stanford.edu

Comment in
    Ann Intern Med. 2010 Apr 20;152(8):JC4-9.
    Am J Med. 2011 Sep;124(9):e17; author reply e19.

BACKGROUND: There is uncertainty over the risks and benefits of hormone therapy.
We performed a Bayesian meta-analysis to evaluate the effect of hormone therapy
on total mortality in younger postmenopausal women. This analysis synthesizes
evidence from different sources, taking into account varying views on the issue.
METHODS: A comprehensive search from 1966 through January 2008 identified
randomized controlled trials of at least 6 month's duration that evaluated
hormone therapy in women with mean age <60 years and reported at least one death,
and prospective observational cohort studies that evaluated the relative risk of
mortality associated with hormone therapy after adjustment for confounding
variables.
RESULTS: The results were synthesized using a hierarchical random-effects
Bayesian meta-analysis. The pooled results from 19 randomized trials, with 16,000
women (mean age 55 years) followed for 83,000 patient-years, showed a mortality
relative risk of 0.73 (95% credible interval 0.52-0.96). When data from 8
observational studies were added to the analysis, the resultant relative risk was
0.72 (credible interval 0.62-0.82). The posterior probability that hormone
therapy reduces total mortality in younger women is almost 1.
CONCLUSIONS: The synthesis of data using Bayesian meta-analysis indicates a
reduction in mortality in younger postmenopausal women taking hormone therapy
compared with no treatment. This finding should be interpreted taking into
account the potential benefits and harms of hormone therapy.

PMID: 19854329  [PubMed - indexed for MEDLINE]


263. Cancer Treat Rev. 2009 Nov;35(7):570-3. doi: 10.1016/j.ctrv.2009.05.005. Epub
2009 Jun 17.

Comparative survival with diverse chemotherapy regimens for cancer of unknown
primary site: multiple-treatments meta-analysis.

Golfinopoulos V(1), Pentheroudakis G, Salanti G, Nearchou AD, Ioannidis JP,
Pavlidis N.

Author information:
(1)Department of Medical Oncology/Digestive Oncology, Jules-Bordet Institute,
Brussels, Belgium.

OBJECTIVES: To synthesize the evidence from randomized controlled trials
concerning systemic treatment regimens for patients with cancer of unknown
primary site (CUP).
DATA SOURCES: PubMed and the Cochrane Library Central Registry of Controlled
Trials.
REVIEW METHODS: We retrieved all randomized controlled trials comparing at least
two arms of different systemic treatment regimens or a systemic regimen to no
treatment in patients with CUP, excluding data on favorable subset CUP, whenever
these could be separated. Treatments were categorized according to whether they
involved platinum, taxane, both, or neither; non-platinum/non-taxane regimens
were also categorized in monotherapy and combination regimens. We extracted or
estimated the logarithm of the hazard ratio and its variance for death for each
randomized comparison. Multiple-treatments meta-analysis with a hierarchical
Bayesian model obtained summary hazard ratios with 95% credibility intervals.
RESULTS: Ten articles were eligible for the meta-analysis. No trials compared
systemic treatment to best supportive care and all arms referred to chemotherapy
regimens. Overall 683 subjects were randomly assigned and eight randomized
comparisons were used for the multiple-treatments meta-analysis of survival (543
patients). Multiple-treatments meta-analysis showed no significant benefit for
any treatment group over others, with wide credibility intervals. Point estimates
of hazard ratios favored platinum, taxane, or both (hazard ratios 0.69, 0.66, and
0.81, respectively, as compared with monotherapy with an agent other than
platinum or taxane).
CONCLUSION: No type of chemotherapy has been solidly proven to prolong survival
in patients with CUP. Regimens using either platinum or taxanes or both need
further testing.

PMID: 19539430  [PubMed - indexed for MEDLINE]


264. Diabetes Obes Metab. 2009 Nov;11(11):1009-16. doi:
10.1111/j.1463-1326.2009.01084.x. Epub 2009 Jul 13.

Baseline differences in A1C explain apparent differences in efficacy of
sitagliptin, rosiglitazone and pioglitazone.

Chapell R(1), Gould AL, Alexander CM.

Author information:
(1)US Outcomes Research, Merck & Co., Inc., 351 North Sumneytown Pike, North
Wales, PA 19454, USA.

AIM: Published studies of patients treated with rosiglitazone or pioglitazone
have reported greater reductions in HbA1c (A1C) than studies of patients treated
with sitagliptin. However, studies of thiazolidinediones tended to enroll
patients with higher baseline A1C levels. This meta-analysis investigates the
relationship between baseline A1C and perceived efficacy of treatment.
METHODS: This report describes a Bayesian random effects analysis of 23 published
studies. We constructed a random effects model including a factor adjusting for
between-study differences in baseline A1C levels.
RESULTS: The random effects model correctly predicts post-treatment A1C levels
from baseline A1C within a 95% confidence interval (CI) for each of the 23
studies included in the meta-analysis. After applying the model to adjust for
differences in baseline A1C, we found that the difference in efficacy between
rosiglitazone and sitagliptin was not significantly different from zero (0.12;
95% CI -0.09 to 0.34). Similarly, no significant differences are observed between
the effects of pioglitazone and sitagliptin (0.01; 95% CI -0.21 to 0.22) or
between rosiglitazone and pioglitazone (0.11; 95% CI -0.37 to 0.146). When
baseline values are omitted from the Bayesian model, the findings suggest that
rosiglitazone is superior to pioglitazone or sitagliptin.
CONCLUSIONS: These results illustrate the necessity for careful application of
appropriate methodology when comparing results of different studies. When
between-study differences in treatment effects are adjusted for baseline
differences, then the findings suggest that none of the treatments has an effect
that is superior to any of the other treatments.

PMID: 19614948  [PubMed - indexed for MEDLINE]


265. Am J Clin Nutr. 2009 Oct;90(4):943-50. doi: 10.3945/ajcn.2009.27521. Epub 2009
Jul 1.

Effect of vegetarian diets on bone mineral density: a Bayesian meta-analysis.

Ho-Pham LT(1), Nguyen ND, Nguyen TV.

Author information:
(1)Department of Internal Medicine, Pham Ngoc Thach University of Medicine, Ho
Chi Minh City, Vietnam.

Comment in
    Am J Clin Nutr. 2009 Oct;90(4):910-1.

BACKGROUND: The association between vegetarian diets and bone mineral density
(BMD) is controversial because of conflicting findings from previous studies.
OBJECTIVE: The aim of this study was to estimate the effect of vegetarian diets
on BMD by using a meta-analytic approach.
DESIGN: A systematic electronic literature search was conducted to identify all
relevant articles on the association between vegetarian diet and BMD. Nine
studies of 2749 subjects (1880 women and 869 men) were included in the analysis.
Traditional and Bayesian methods of meta-analysis were applied to synthesize the
data.
RESULTS: Overall, BMD was approximately 4% lower in vegetarians than in omnivores
(95% CI: 2%, 7%) at both the femoral neck and the lumbar spine. Compared with
omnivores, vegans had a significantly lower lumbar spine BMD (6% lower; 95% CI:
2%, 9%), which was more pronounced than in lactoovovegetarians (2% lower; 95% CI:
1%, 4%). The probability that BMD was > or =5% lower in vegetarians than in
omnivores (or approximately 0.3 SD) was 42% for the femoral neck and 32% for the
lumbar spine. There was no evidence of publication bias. There was a moderate
degree of between-study heterogeneity; the coefficient of heterogeneity varied
between 46% and 51%.
CONCLUSION: The results suggest that vegetarian diets, particularly vegan diets,
are associated with lower BMD, but the magnitude of the association is clinically
insignificant.

PMID: 19571226  [PubMed - indexed for MEDLINE]


266. Circ Cardiovasc Interv. 2009 Oct;2(5):409-15. doi:
10.1161/CIRCINTERVENTIONS.109.868091. Epub 2009 Sep 22.

Double versus single stenting for coronary bifurcation lesions: a meta-analysis.

Katritsis DG(1), Siontis GC, Ioannidis JP.

Author information:
(1)Department of Cardiology, Athens Euroclinic, Athens, Greece.

BACKGROUND: Several trials have addressed whether bifurcation lesions require
stenting of both the main vessel and side branch, but uncertainty remains on the
benefits of such double versus single stenting of the main vessel only.
METHODS AND RESULTS: We have conducted a meta-analysis of randomized trials
including patients with coronary bifurcation lesions who were randomly selected
to undergo percutaneous coronary intervention by either double or single
stenting. Six studies (n=1642 patients) were eligible. There was increased risk
of myocardial infarction with double stenting (risk ratio, 1.78; P=0.001 by fixed
effects; risk ratio, 1.49 with Bayesian meta-analysis). The summary point
estimate suggested also an increased risk of stent thrombosis with double
stenting, but the difference was not nominally significant given the sparse data
(risk ratio, 1.85; P=0.19). No obvious difference was seen for death (risk ratio,
0.81; P=0.66) and target lesion revascularization (risk ratio, 1.09; P=0.67).
CONCLUSIONS: Stenting of both the main vessel and side branch in bifurcation
lesions may increase myocardial infarction and stent thrombosis risk compared
with stenting of the main vessel only.

PMID: 20031750  [PubMed - indexed for MEDLINE]


267. Eur Respir J. 2009 Oct;34(4):803-11. doi: 10.1183/09031936.00159708.

Risk of mortality associated with formoterol: a systematic review and
meta-analysis.

Wijesinghe M(1), Weatherall M, Perrin K, Harwood M, Beasley R.

Author information:
(1)Medical Research Institute of New Zealand, Wellington, New Zealand.

There is concern long-acting beta-agonist (LABA) drugs may increase the risk of
asthma mortality. We undertook a systematic review which included the AstraZeneca
Formoterol Clinical Trial Safety Database and Novartis Food and Drug
Administration Formoterol Briefing Document. Randomised controlled clinical
trials of duration > or = 4 weeks that compared formoterol with a non-LABA
comparator treatment in asthma were included in a meta-analysis of the risk of
all-cause mortality and asthma death. Simple contingency tables, Peto's one-step
method and a Bayesian analysis were used. There were 42 deaths (nine from asthma)
recorded in 62 studies with 49,327 subjects. The simple contingency table odds
ratio for risk of all-cause mortality with formoterol was 1.1 (95% CI 0.6-2.2)
and for asthma death was 2.7 (95% CI 0.5-26.7). Analyses by the other methods
using both "as randomised" and "as exposed" classifications of treatment gave
similar risk estimates with wide confidence and credible intervals. We conclude
that there was insufficient power to determine whether formoterol increases the
risk of mortality. However, the point estimates of a 2.0- to 3.2-fold increased
risk of asthma death are not reassuring and add weight to evidence that LABA use
in certain circumstances may increase the risk of asthma mortality.

PMID: 19797669  [PubMed - indexed for MEDLINE]


268. Med Care. 2009 Oct;47(10):1053-61. doi: 10.1097/MLR.0b013e31819e1ee9.

Modeling the value for money of changing clinical practice change: a stochastic
application in diabetes care.

Hoomans T(1), Abrams KR, Ament AJ, Evers SM, Severens JL.

Author information:
(1)Department of Health Organization, Policy, and Economics, Maastricht
University, Maastricht, The Netherlands, United Kingdom.
t.hoomans@beoz.unimaas.nl

BACKGROUND: Decision making about resource allocation for guideline
implementation to change clinical practice is inevitably undertaken in a context
of uncertainty surrounding the cost-effectiveness of both clinical guidelines and
implementation strategies. Adopting a total net benefit approach, a model was
recently developed to overcome problems with the use of combined ratio statistics
when analyzing decision uncertainty.
OBJECTIVE: To demonstrate the stochastic application of the model for informing
decision making about the adoption of an audit and feedback strategy for
implementing a guideline recommending intensive blood glucose control in type 2
diabetes in primary care in the Netherlands.
METHODS: An integrated Bayesian approach to decision modeling and evidence
synthesis is adopted, using Markov Chain Monte Carlo simulation in WinBUGs. Data
on model parameters is gathered from various sources, with effectiveness of
implementation being estimated using pooled, random-effects meta-analysis.
Decision uncertainty is illustrated using cost-effectiveness acceptability curves
and frontier.
RESULTS: Decisions about whether to adopt intensified glycemic control and
whether to adopt audit and feedback alter for the maximum values that decision
makers are willing to pay for health gain. Through simultaneously incorporating
uncertain economic evidence on both guidance and implementation strategy, the
cost-effectiveness acceptability curves and cost-effectiveness acceptability
frontier show an increase in decision uncertainty concerning guideline
implementation.
CONCLUSIONS: The stochastic application in diabetes care demonstrates that the
model provides a simple and useful tool for quantifying and exploring the
(combined) uncertainty associated with decision making about adopting guidelines
and implementation strategies and, therefore, for informing decisions about
efficient resource allocation to change clinical practice.

PMID: 19648827  [PubMed - indexed for MEDLINE]


269. BMC Musculoskelet Disord. 2009 Sep 21;10:113. doi: 10.1186/1471-2474-10-113.

Bisphosphonates and atrial fibrillation: Bayesian meta-analyses of randomized
controlled trials and observational studies.

Mak A(1), Cheung MW, Ho RC, Cheak AA, Lau CS.

Author information:
(1)Division of Rheumatology, Department of Medicine, Yong Loo Lin School of
Medicine, National University of Singapore, Singapore. mdcam@nus.edu.sg

BACKGROUND: Occurrence of atrial fibrillation (AF) amongst bisphosphonate users
has been increasingly reported but results are conflicting. We performed a
Bayesian meta-analysis to address the possible association between the occurrence
of AF and bisphosphonate use and estimated the posterior probability of
development of AF with bisphosphonate use.
METHODS: Randomized controlled trials (RCTs) evaluating the efficacy and safety
of bisphosphonates for treating and preventing osteoporosis, and observational
studies investigating the incidence of AF amongst bisphosphonate users, were
searched in electronic databases. We pooled the effect size with Bayesian
meta-analysis for odds ratio (OR) and calculated its posterior probability of
development of AF in bisphosphonate users for RCTs and observational studies,
reported with the 95% credible interval (CI).
RESULTS: Of 1751 potentially relevant citations initially retrieved, 4 RCTs and 2
reports of RCTs, and 3 observational studies were included for this
meta-analysis. On pooling the RCTs, there was a non-significantly higher risk of
overall (OR 1.184, 95% CI 0.837-1.656) and serious AF (OR 1.590, 95% CI
0.613-3.751) in bisphosphonate-treated patients. Combining data of observational
studies also revealed a non-significantly higher risk of AF in bisphosphonate
users (OR 1.251, 95% CI 0.980-1.732). Using Bayesian meta-analysis based on the
effect size of observational studies as the prior, the posterior probability of
OR>1.2 in the development of AF amongst bisphosphonate users in the RCTs was
0.484. Egger's regression demonstrated no notable publication bias in all the
analyses.
CONCLUSION: The current meta-analysis revealed no evidence of a higher risk of AF
associated with bisphosphonate use. Nevertheless, based on Bayesian meta-analysis
with the effect size of the observational studies as the prior, the posterior
probabilities of development of AF was found to be 0.484 if the risk of AF was
estimated to be more than 20%. The results of the current meta-analysis thus
offer clinicians the practical probability of development of AF in patients who
take bisphosphonates for the treatment of bone loss and corticosteroid induced
osteoporosis.

PMCID: PMC2758833
PMID: 19772579  [PubMed - indexed for MEDLINE]


270. Am J Epidemiol. 2009 Sep 1;170(5):537-45. doi: 10.1093/aje/kwp145. Epub 2009 Jul
14.

Underlying genetic models of inheritance in established type 2 diabetes
associations.

Salanti G(1), Southam L, Altshuler D, Ardlie K, Barroso I, Boehnke M, Cornelis
MC, Frayling TM, Grallert H, Grarup N, Groop L, Hansen T, Hattersley AT, Hu FB,
Hveem K, Illig T, Kuusisto J, Laakso M, Langenberg C, Lyssenko V, McCarthy MI,
Morris A, Morris AD, Palmer CN, Payne F, Platou CG, Scott LJ, Voight BF, Wareham
NJ, Zeggini E, Ioannidis JP.

Author information:
(1)Clinical and Molecular Epidemiology Unit and Clinical Trials and
Evidence-Based Medicine Unit, Department of Hygiene and Epidemiology, School of
Medicine, University of Ioannina, Ioannina, Greece.

Comment in
    Am J Epidemiol. 2010 May 15;171(10):1153-4; author reply 1154-5.

For most associations of common single nucleotide polymorphisms (SNPs) with
common diseases, the genetic model of inheritance is unknown. The authors
extended and applied a Bayesian meta-analysis approach to data from 19 studies on
17 replicated associations with type 2 diabetes. For 13 SNPs, the data fitted
very well to an additive model of inheritance for the diabetes risk allele; for 4
SNPs, the data were consistent with either an additive model or a dominant model;
and for 2 SNPs, the data were consistent with an additive or recessive model.
Results were robust to the use of different priors and after exclusion of data
for which index SNPs had been examined indirectly through proxy markers. The
Bayesian meta-analysis model yielded point estimates for the genetic effects that
were very similar to those previously reported based on fixed- or random-effects
models, but uncertainty about several of the effects was substantially larger.
The authors also examined the extent of between-study heterogeneity in the
genetic model and found generally small between-study deviation values for the
genetic model parameter. Heterosis could not be excluded for 4 SNPs. Information
on the genetic model of robustly replicated association signals derived from
genome-wide association studies may be useful for predictive modeling and for
designing biologic and functional experiments.

PMCID: PMC2732984
PMID: 19602701  [PubMed - indexed for MEDLINE]


271. Ann Clin Microbiol Antimicrob. 2009 Jun 26;8:23. doi: 10.1186/1476-0711-8-23.

Antifungal treatment for invasive Candida infections: a mixed treatment
comparison meta-analysis.

Mills EJ(1), Perri D, Cooper C, Nachega JB, Wu P, Tleyjeh I, Phillips P.

Author information:
(1)Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada.
emills@cfenet.ubc.ca

Erratum in
    Ann Clin Microbiol Antimicrob. 2009;8. doi: 10.1186/1476-0711-8-25.

OBJECTIVES: Invasive fungal infections are a major cause of mortality among
patients at risk. Treatment guidelines vary on optimal treatment strategies. We
aimed to determine the effects of different antifungal therapies on global
response rates, mortality and safety.
METHODS: We searched independently and in duplicate 10 electronic databases from
inception to May 2009. We selected any randomized trial assessing established
antifungal therapies for confirmed cases of invasive candidiasis among
predominantly adult populations. We performed a meta-analysis and then conducted
a Bayesian mixed treatment comparison to differentiate treatment effectiveness.
Sensitivity analyses included dosage forms of amphotericin B and fluconazole
compared to other azoles.
RESULTS: Our analysis included 11 studies enrolling a total of 965 patients. For
our primary analysis of global response rates, we pooled 7 trials comparing
azoles to amphotericin B, Relative Risk [RR] 0.87 (95% Confidence Interval [CI],
0.78-0.96, P = 0.007, I2 = 43%, P = 0.09. We also pooled 2 trials of
echinocandins versus amphotericin B and found a pooled RR of 1.10 (95% CI,
0.99-1.23, P = 0.08). One study compared anidulafungin to fluconazole and yielded
a RR of 1.26 (95% CI, 1.06-1.51) in favor of anidulafungin. We pooled 7 trials
assessing azoles versus amphotericin B for all-cause mortality, resulting in a
pooled RR of 0.88 (95% CI, 0.74-1.05, P = 0.17, I2 = 0%, P = 0.96). Echinocandins
versus amphotericin B (2 trials) for all-cause mortality resulted in a pooled RR
of 1.01 (95% CI, 0.84-1.20, P = 0.93). Anidulafungin versus fluconazole resulted
in a RR of 0.73 (95% CI, 0.48-1.10, P = 0.34). Our mixed treatment comparison
analysis found similar within-class effects across all interventions. Adverse
event profiles differed, with amphotericin B exhibiting larger adverse event
effects.
CONCLUSION: Treatment options appear to offer preferential effects on response
rates and mortality. When mycologic data are available, therapy should be
tailored.

PMCID: PMC2713200
PMID: 19558681  [PubMed - indexed for MEDLINE]


272. Addiction. 2009 Jun;104(6):894-904. doi: 10.1111/j.1360-0443.2009.02526.x.

Substance use and misuse in the aftermath of terrorism. A Bayesian meta-analysis.

DiMaggio C(1), Galea S, Li G.

Author information:
(1)Department of Epidemiology, Columbia University, Mailman School of Public
Health, New York, NY 10032, USA. cjd11@columbia.edu

Comment in
    Addiction. 2009 Jun;104(6):905-6.

AIM: To conduct a comprehensive analysis of the conflicting evidence on substance
use and misuse following mass traumas such as terrorist incidents.
METHODS: We reviewed and synthesized evidence from 31 population-based studies
using Bayesian meta-analysis and meta-regression.
RESULTS: The majority of the studied were conducted in the aftermath of the
terrorist attacks of 11 September 2001. Controlling for exposure, type of
incident and time since the event occurred, 7.3% [95% credible interval (CrI)
1.1-32.5%] of a population can be expected to report increased alcohol
consumption in the first 2 years following a terrorist event. There is, however,
a 20% probability that the prevalence will be as high as 14%. The unadjusted
prevalence of increased cigarette smoking following a terrorist event is 6.8%
(95% Cr I 2.6-16.5%). Unadjusted reports of mixed drug use (including narcotics
and prescription medications) was 16.3% (95% Cr I 1.3-72.5%).
CONCLUSIONS: These results underscore the potentially pervasive behavioral health
effects of mass terrorism, and suggest that public health interventions may
usefully consider substance use as an area of focus after such events.

PMID: 19392912  [PubMed - indexed for MEDLINE]


273. Hum Genet. 2009 Jun;125(5-6):627-31. doi: 10.1007/s00439-009-0660-7. Epub 2009
Apr 1.

ATG16L1 T300A polymorphism and Crohn's disease susceptibility: evidence from
13,022 cases and 17,532 controls.

Zhang HF(1), Qiu LX, Chen Y, Zhu WL, Mao C, Zhu LG, Zheng MH, Wang Y, Lei L, Shi
J.

Author information:
(1)Department of Cardiology, Institute of Cardiovascular Diseases, First
Affiliated Hospital, Guangxi Medical University, Nanning, China.

Many studies have reported the association between the autophagy-related 16-like
1 gene (ATG16L1) T300A polymorphism (rs2241880) and Crohn's disease (CD)
susceptibility, but the results were inconclusive. To derive a more precise
estimation of the relationship, a meta-analysis was performed. A total of 24
studies including 13,022 cases and 17,532 controls were included in this
meta-analysis. Logistic regression analysis indicated that the ATG16L1 T300A
polymorphism was associated with CD risk in Caucasians (P < 0.01). The pooled
estimations of OR(1) (GG vs. AA) and OR(2) (GA vs. AA) in Caucasian studies by
Bayesian meta-analysis method was [1.87, 95% confidence interval (CI) 1.69-2.05]
and (1.39, 95% CI 1.27-1.51), respectively. The mode of heritance of the G allele
was most likely to be co-dominant in Caucasians. However, no significant
association was found in Asians. This meta-analysis suggests that the G allele of
ATG16L1 T300A is a low-penetrant gene for developing CD in Caucasians.

PMID: 19337756  [PubMed - indexed for MEDLINE]


274. Am J Hum Genet. 2009 May;84(5):567-80. doi: 10.1016/j.ajhg.2009.04.001. Epub 2009
Apr 30.

Multilocus Bayesian meta-analysis of gene-disease associations.

Newcombe PJ(1), Verzilli C, Casas JP, Hingorani AD, Smeeth L, Whittaker JC.

Author information:
(1)Department of Epidemiology and Population Health, London School of Hygiene and
Tropical Medicine, WC1E 7HT London, UK.

Meta-analysis is a vital tool in genetic epidemiology. However, meta-analyses to
identify gene-disease associations are compromised when contributing studies have
typed partially overlapping sets of markers. Currently, only marginal analyses
are possible, and these are restricted to the subset of studies typing that
marker. This does not allow full use of available data and leads to the
confounding of marker effects by closely associated markers. We present a
Bayesian approach that exploits prior information on underlying haplotypes to
allow multi-marker analysis incorporating data from all relevant studies of a
gene or region, irrespective of the markers typed. We present results from
application of our approach to data on a possible association between PDE4D and
ischemic stroke.

PMCID: PMC2680997
PMID: 19409523  [PubMed - indexed for MEDLINE]


275. Heart. 2009 Apr;95(7):542-9. doi: 10.1136/hrt.2008.147165. Epub 2008 Dec 18.

Cost-effectiveness of radiofrequency catheter ablation for the treatment of
atrial fibrillation in the United Kingdom.

McKenna C(1), Palmer S, Rodgers M, Chambers D, Hawkins N, Golder S, Van Hout S,
Pepper C, Todd D, Woolacott N.

Author information:
(1)Centre for Health Economics, University of York, Heslington, UK.
cm535@york.ac.uk

OBJECTIVE: To assess the cost-effectiveness of radiofrequency catheter ablation
(RFCA) compared with anti-arrhythmic drug (AAD) therapy for the treatment of
atrial fibrillation (AF) from the perspective of the UK NHS.
DESIGN: Bayesian evidence synthesis and decision analytical model.
METHODS: A systematic review and meta-analysis was conducted and Bayesian
statistical methods used to synthesise the effectiveness evidence from randomised
control trials. A decision analytical model was developed to assess the costs and
consequences associated with the primary outcome of the trials over a lifetime
time horizon.
MAIN OUTCOME MEASURE: Costs from a health service perspective and outcomes
measured as quality-adjusted life years (QALYs).
RESULTS: The incremental cost-effectiveness ratio of RFCA varied between
pound7763 and pound7910 for each additional QALY according to baseline risk of
stroke, with a probability of being cost-effective from 0.98 to 0.99 for a
cost-effectiveness threshold of pound20 000. Results were sensitive to the
duration of quality of life benefits from treatment.
CONCLUSIONS: RFCA is potentially cost-effective for the treatment of paroxysmal
AF in patients' predominantly refractory to AAD therapy provided the
quality-of-life benefits from treatment are maintained for more than 5 years.
These findings remain subject to limitations in the existing evidence regarding
the nature of life benefits and the prognostic importance of restoring normal
sinus rhythm conferred using RFCA.

PMID: 19095714  [PubMed - indexed for MEDLINE]


276. Eur Heart J. 2009 Mar;30(6):718-30. doi: 10.1093/eurheartj/ehn552. Epub 2008 Dec
24.

Behavioural interventions for smoking cessation: a meta-analysis of randomized
controlled trials.

Mottillo S(1), Filion KB, Bélisle P, Joseph L, Gervais A, O'Loughlin J, Paradis
G, Pihl R, Pilote L, Rinfret S, Tremblay M, Eisenberg MJ.

Author information:
(1)Division of Cardiology and Clinical Epidemiology, Jewish General
Hospital/McGill University, 3755 Côte Ste-Catherine Road, Suite A-118, Montreal,
Quebec, Canada.

AIMS: Widely varying estimates of treatment effects have been reported in
randomized controlled trials (RCTs) investigating the efficacy of behavioural
interventions for smoking cessation. Previous meta-analyses investigating
behavioural interventions have important limitations and do not include recently
published RCTs. We undertook a meta-analysis of RCTs to synthesize the treatment
effects of four behavioural interventions, including minimal clinical
intervention (brief advice from a healthcare worker), and intensive
interventions, including individual, group, and telephone counselling.
METHODS AND RESULTS: We searched the CDC Tobacco Information and Prevention,
Cochrane Library, EMBASE, Medline, and PsycINFO databases. We included only RCTs
that reported biochemically validated smoking cessation outcomes at 6 and/or 12
months after the target quit date. Outcomes were aggregated using hierarchical
Bayesian random-effects models. We identified 50 RCTs, which randomized n = 26
927 patients (minimal clinical intervention: 9 RCTs, n = 6456; individual
counselling: 23 RCTs, n = 8646; group counselling: 12 RCTs, n = 3600; telephone
counselling: 10 RCTs, n = 8225). The estimated mean treatment effects were
minimal clinical intervention [odds ratio (OR) 1.50, 95% credible interval (CrI)
0.84-2.78], individual counselling (OR 1.49, 95% CrI 1.08-2.07), group
counselling (OR 1.76, 95% CrI 1.11-2.93), and telephone counselling (OR 1.58, 95%
CrI 1.15-2.29).
CONCLUSION: Intensive behavioural interventions result in substantial increases
in smoking abstinence compared with control. Although minimal clinical
intervention may increase smoking abstinence, there is insufficient evidence to
draw strong conclusions regarding its efficacy.

PMID: 19109354  [PubMed - indexed for MEDLINE]


277. Eur J Gastroenterol Hepatol. 2009 Mar;21(3):254-7. doi:
10.1097/MEG.0b013e328324b6a2.

Spontaneous regression of hepatocellular carcinoma: a systematic review.

Oquiñena S(1), Guillen-Grima F, Iñarrairaegui M, Zozaya JM, Sangro B.

Author information:
(1)Department of Gastroenterology, Hospital Virgen del Camino, Pamplona, Spain.

OBJECTIVE: To estimate the actual frequency of spontaneous regression of
hepatocellular carcinoma.
METHODS: A systematic review of the literature published during 1978-2007 has
been carried out to identify randomized clinical trials of hepatocellular
carcinoma that included a control arm receiving either placebo or best supportive
care, and in which patients were followed prospectively for tumor response using
predefined criteria. Data extraction was conducted independently by two
investigators. A meta-analysis to provide a global estimation of regressions in
the control arms was performed using an empiric Bayesian random-effects model.
RESULTS: We identified 16 cases of regression (including minor and partial
responses) in 10 phase III clinical trials. The rate of spontaneous objective
partial regression among patients with hepatocellular carcinoma was 0.406% [95%
confidence interval: 0.067-1.043%].
CONCLUSION: Although very infrequent, spontaneous regression is not an
extraordinary event among patients with hepatocellular carcinoma. Therefore,
individual responses to any given therapy should be assessed with caution and
this fact may be considered at the time of calculating sample size of pilot
clinical trials of new agents.

PMID: 19279469  [PubMed - indexed for MEDLINE]


278. Lancet Infect Dis. 2009 Mar;9(3):153-61. doi: 10.1016/S1473-3099(09)70041-6.

Treatment outcomes among patients with multidrug-resistant tuberculosis:
systematic review and meta-analysis.

Orenstein EW(1), Basu S, Shah NS, Andrews JR, Friedland GH, Moll AP, Gandhi NR,
Galvani AP.

Author information:
(1)Tugela Ferry Care and Research Collaboration, Tugela Ferry, KwaZulu-Natal,
South Africa. Orenstein.Evan@gmail.com

Comment in
    Lancet Infect Dis. 2010 Apr;10(4):215; author reply 215-6.

Multidrug-resistant (MDR) tuberculosis is a growing clinical and public-health
concern. To evaluate existing evidence regarding treatment regimens for MDR
tuberculosis, we used a Bayesian random-effects meta-analysis of the available
therapeutic studies to assess how the reported proportion of patients treated
successfully is influenced by differences in treatment regimen design, study
methodology, and patient population. Successful treatment outcome was defined as
cure or treatment completion. 34 clinical reports with a mean of 250 patients per
report met the inclusion criteria. Our analysis shows that the proportion of
patients treated successfully improved when treatment duration was at least 18
months, and if patients received directly observed therapy throughout treatment.
Studies that combined both factors had significantly higher pooled success
proportions (69%, 95% credible interval [CI] 64-73%) than other studies of
treatment outcomes (58%, 95% CI 52-64%). Individualised treatment regimens had
higher treatment success (64%, 95% CI 59-68%) than standardised regimens (54%,
95% CI 43-68%), although the difference was not significant. Treatment approaches
and study methodologies were heterogeneous across studies. Many important
variables, including patients' HIV status, were inconsistently reported between
studies. These results underscore the importance of strong patient support and
treatment follow-up systems to develop successful MDR tuberculosis treatment
programmes.

PMID: 19246019  [PubMed - indexed for MEDLINE]


279. BMC Med Genet. 2009 Feb 19;10:15. doi: 10.1186/1471-2350-10-15.

Association between TCF7L2 gene polymorphisms and susceptibility to type 2
diabetes mellitus: a large Human Genome Epidemiology (HuGE) review and
meta-analysis.

Tong Y(1), Lin Y, Zhang Y, Yang J, Zhang Y, Liu H, Zhang B.

Author information:
(1)Open laboratory, West China Second University Hospital, Sichuan University,
Chengdu, PR China. yuer.126@126.com

BACKGROUND: Transcription factor 7-like 2 (TCF7L2) has been shown to be
associated with type 2 diabetes mellitus (T2MD) in multiple ethnic groups in the
past two years, but, contradictory results were reported for Chinese and Pima
Indian populations. The authors then performed a large meta-analysis of 36
studies examining the association of type 2 diabetes mellitus (T2DM) with
polymorphisms in the TCF7L2 gene in various ethnicities, containing rs7903146
C-to-T (IVS3C>T), rs7901695 T-to-C (IVS3T>C), a rs12255372 G-to-T (IVS4G>T), and
rs11196205 G-to-C (IVS4G>C) polymorphisms and to evaluate the size of gene effect
and the possible genetic mode of action.
METHODS: Literature-based searching was conducted to collect data and three
methods, that is, fixed-effects, random-effects and Bayesian multivariate
mete-analysis, were performed to pool the odds ratio (OR). Publication bias and
study-between heterogeneity were also examined.
RESULTS: The studies included 35,843 cases of T2DM and 39,123 controls, using
mainly primary data. For T2DM and IVS3C>T polymorphism, the Bayesian OR for TT
homozygotes and TC heterozygotes versus CC homozygote was 1.968 (95% credible
interval (CrI): 1.790, 2.157), 1.406 (95% CrI: 1.341, 1.476), respectively, and
the population attributable risk (PAR) for the TT/TC genotypes of this variant is
16.9% for overall. For T2DM and IVS4G>T polymorphism, TT homozygotes and TG
heterozygotes versus GG homozygote was 1.885 (95%CrI: 1.698, 2.088), 1.360 (95%
CrI: 1.291, 1.433), respectively. Four ORs among these two polymorphisms all
yielded significant between-study heterogeneity (P < 0.05) and the main source of
heterogeneity was ethnic differences. Data also showed significant associations
between T2DM and the other two polymorphisms, but with low heterogeneity (P >
0.10). Pooled ORs fit a codominant, multiplicative genetic model for all the four
polymorphisms of TCF7L2 gene, and this model was also confirmed in different
ethnic populations when stratification of IVS3C>T and IVS4G>T polymorphisms
except for Africans, where a dominant, additive genetic mode is suggested for
IVS3C>T polymorphism.
CONCLUSION: This meta-analysis demonstrates that four variants of TCF7L2 gene are
all associated with T2DM, and indicates a multiplicative genetic model for all
the four polymorphisms, as well as suggests the TCF7L2 gene involved in near 1/5
of all T2MD. Potential gene-gene and gene-environmental interactions by which
common variants in the TCF7L2 gene influence the risk of T2MD need further
exploration.

PMCID: PMC2653476
PMID: 19228405  [PubMed - indexed for MEDLINE]


280. JAMA. 2009 Feb 18;301(7):753-62. doi: 10.1001/jama.2009.187.

Cancer survivors and unemployment: a meta-analysis and meta-regression.

de Boer AG(1), Taskila T, Ojajärvi A, van Dijk FJ, Verbeek JH.

Author information:
(1)Coronel Institute of Occupational Health, Academic Medical Center, PO Box
22700, 1100 DE Amsterdam, The Netherlands. a.g.deboer@amc.uva.nl

Comment in
    JAMA. 2009 Jul 1;302(1):33; author reply 34-5.
    JAMA. 2009 Jul 1;302(1):32-3; author reply 34-5.
    JAMA. 2009 Jul 1;302(1):33-4; author reply 34-5.

CONTEXT: Nearly half of adult cancer survivors are younger than 65 years, but the
association of cancer survivorship with employment status is unknown.
OBJECTIVE: To assess the association of cancer survivorship with unemployment
compared with healthy controls.
DATA SOURCES: A systematic search of studies published between 1966 and June 2008
was conducted using MEDLINE, CINAHL, EMBASE, PsycINFO, and OSH-ROM databases.
STUDY SELECTION: Eligible studies included adult cancer survivors and a control
group, and employment as an outcome.
DATA EXTRACTION: Pooled relative risks were calculated over all studies and
according to cancer type. A Bayesian meta-regression analysis was performed to
assess associations of unemployment with cancer type, country of origin, average
age at diagnosis, and background unemployment rate.
RESULTS: Twenty-six articles describing 36 studies met the inclusion criteria.
The analyses included 20,366 cancer survivors and 157,603 healthy control
participants. Studies included 16 from the United States, 15 from Europe, and 5
from other countries. Overall, cancer survivors were more likely to be unemployed
than healthy control participants (33.8% vs 15.2%; pooled relative risk [RR],
1.37; 95% confidence interval [CI], 1.21-1.55). Unemployment was higher in breast
cancer survivors compared with control participants (35.6% vs 31.7%; pooled RR,
1.28; 95% CI, 1.11-1.49), as well as in survivors of gastrointestinal cancers
(48.8% vs 33.4%; pooled RR, 1.44; 95% CI, 1.02-2.05), and cancers of the female
reproductive organs (49.1% vs 38.3%; pooled RR, 1.28; 95% CI, 1.17-1.40).
Unemployment rates were not higher for survivors of blood cancers compared with
controls (30.6% vs 23.7%; pooled RR, 1.41; 95% CI, 0.95-2.09), prostate cancers
(39.4% vs 27.1%; pooled RR, 1.11; 95% CI, 1.00-1.25), or testicular cancer (18.5%
vs 18.1%; pooled RR, 0.94; 95% CI, 0.74-1.20). For survivors in the United
States, the unemployment risk was 1.5 times higher compared with survivors in
Europe (meta-RR, 1.48; 95% credibility interval, 1.15-1.95). After adjustment for
diagnosis, age, and background unemployment rate, this risk disappeared (meta-RR,
1.24; 95% CI, 0.85-1.83).
CONCLUSION: Cancer survivorship is associated with unemployment.

PMID: 19224752  [PubMed - indexed for MEDLINE]


281. BMC Neurol. 2009 Feb 10;9:6. doi: 10.1186/1471-2377-9-6.

Meta-analysis of duloxetine vs. pregabalin and gabapentin in the treatment of
diabetic peripheral neuropathic pain.

Quilici S(1), Chancellor J, Löthgren M, Simon D, Said G, Le TK, Garcia-Cebrian A,
Monz B.

Author information:
(1)Health Economics & Outcomes Research, Uxbridge, UK. sibilia.quilici@gmail.com

BACKGROUND: Few direct head-to-head comparisons have been conducted between drugs
for the treatment of diabetic peripheral neuropathic pain (DPNP). Approved or
recommended drugs in this indication include duloxetine (DLX), pregabalin (PGB),
gabapentin (GBP) and amitriptyline (AMT). We conducted an indirect meta-analysis
to compare the efficacy and tolerability of DLX with PGB and GBP in DPNP, using
placebo as a common comparator.
METHODS: We searched PubMed, EMBASE, CENTRAL databases and regulatory websites
for randomized, double-blind, placebo-controlled, parallel group or crossover
clinical trials (RCTs) assessing DLX, PGB, GBP and AMT in DPNP. Study arms using
approved dosages with assessments after 5-13 weeks were eligible. Efficacy
criteria were: reduction in 24-hour pain severity (24 h PS) for all three drugs,
and response rate (>or= 50% pain reduction) and Patient Global Impression of
Improvement/Change (PGI-I/C) for DLX and PGB only. Tolerability criteria
included: discontinuation, diarrhoea, dizziness, headache, nausea and somnolence.
Direct comparisons versus placebo were conducted with pooled fixed - and
random-effects analyses on endpoints reported in at least two studies of each
drug. Indirect comparisons were performed between DLX and each of PGB and GBP
using Bayesian simulation.
RESULTS: Three studies of DLX, six of PGB, two of GBP and none of AMT met the
inclusion criteria. In random-effects and fixed-effects analyses of DLX, PGB and
GBP, all were superior to placebo for all efficacy parameters, with some
tolerability trade-offs. Indirect comparison of DLX with PGB found no differences
in 24 h PS, but significant differences in PGI-I/C, favouring PGB, and in
dizziness, favouring DLX were apparent. Comparing DLX and GBP, there were no
statistically significant differences.
CONCLUSION: From the few available studies suitable for indirect comparison, DLX
shows comparable efficacy and tolerability to GBP and PGB in DPNP. Duloxetine
provides an important treatment option for this disabling condition.

PMCID: PMC2663537
PMID: 19208243  [PubMed - indexed for MEDLINE]


282. BMC Cardiovasc Disord. 2009 Jan 28;9:5. doi: 10.1186/1471-2261-9-5.

Microvolt T-wave alternans as a predictor of mortality and severe arrhythmias in
patients with left-ventricular dysfunction: a systematic review and
meta-analysis.

van der Avoort CJ(1), Filion KB, Dendukuri N, Brophy JM.

Author information:
(1)Department of Medicine, McGill University Health Center, Montreal, Quebec,
Canada. charlotte.vanderavoort@gmail.com

BACKGROUND: Studies have demonstrated that the use of implantable cardioverter
defibrillators (ICDs) is effective for the primary prevention of arrhythmic
events but due to imposing costs, there remains a need to identify which patients
will derive the greatest benefit. Microvolt T-wave alternans (MTWA) has been
proposed to assist in this stratification.
METHODS: We systematically searched the literature using MEDLINE, EMBASE, Current
Contents, the Cochrane Library, INAHTA, and the Web of Science to identify all
primary prevention randomized controlled trials and prospective cohort studies
with at least 12 months of follow-up examining MTWA as a predictor of mortality
and severe arrhythmic events in patients with severe left-ventricular
dysfunction. The search was limited to full-text English publications between
January 1990 and May 2007. The primary outcome was a composite of mortality and
severe arrhythmias. Data were synthesized using Bayesian hierarchical models.
RESULTS: We identified no trials and 8 published cohort studies involving a total
of 1,946 patients, including 332 positive, 656 negative, 84 indeterminate, and
874 non-negative (which includes both positive and indeterminate tests) MTWA test
results. The risk of mortality or severe arrhythmic events was higher in patients
with a positive MTWA compared to a negative test (RR = 2.7, 95% credible interval
(CrI) = 1.4, 6.1). Similar results were obtained when comparing non-negative MTWA
to a negative test.
CONCLUSION: A positive MTWA test predicts mortality or severe arrhythmic events
in a population of individuals with severe left ventricular dysfunction. However,
the wide credible interval suggests the clinical utility of this test remains
incompletely defined, ranging from very modest to substantial. Additional high
quality studies are required to better refine the role of MTWA in the decision
making process for ICD implantation.

PMCID: PMC2653469
PMID: 19175926  [PubMed - indexed for MEDLINE]


283. J Am Coll Cardiol. 2009 Jan 27;53(4):316-22. doi: 10.1016/j.jacc.2008.10.024.

Meta-analysis of the relationship between non-high-density lipoprotein
cholesterol reduction and coronary heart disease risk.

Robinson JG(1), Wang S, Smith BJ, Jacobson TA.

Author information:
(1)Lipid Research Clinic, University of Iowa, Iowa City, IA 52242, USA.
jennifer-g-robinson@uiowa.edu

OBJECTIVES: To determine the relationship between non-high-density lipoprotein
cholesterol (HDL-C) lowering and coronary heart disease (CHD) risk reduction for
various lipid-modifying therapies.
BACKGROUND: Non-HDL-C is the second lipid target of therapy after low-density
lipoprotein cholesterol (LDL-C).
METHODS: Randomized placebo or active-controlled trials were evaluated. The
effect of mean non-HDL-C reduction on the relative risk of nonfatal myocardial
infarction and CHD death was estimated using Bayesian random-effects
meta-analysis models adjusted for study duration. Cochrane's Q was used to test
for heterogeneity.
RESULTS: Inclusion criteria were met by 14 statin (n = 100,827), 7 fibrate (n =
21,647), and 6 niacin (n = 4,445) trials, and 1 trial each of a bile acid
sequestrant (n = 3,806), diet (n = 458), and ileal bypass surgery (n = 838). For
statins, each 1% decrease in non-HDL-C resulted in an estimated 4.5-year CHD
relative risk of 0.99 (95% Bayesian confidence interval: 0.98 to 1.00). The
fibrate model did not differ from the statin model (Bayes factor K = 0.49) with
no evidence of heterogeneity. The niacin model was moderately different from the
statin model (K = 7.43), with heterogeneity among the trials (Q = 11.8, 5 df; p =
0.038). The only niacin monotherapy trial (n = 3,908) had a 1:1 relationship
between non-HDL-C and risk reduction. No consistent relationships were apparent
for the 5 small trials of niacin in combination. The 95% confidence intervals for
the single trials of diet, bile acid sequestrants, and surgery also included the
1:1 relationship.
CONCLUSIONS: Non-HDL-C is an important target of therapy for CHD prevention. Most
lipid-modifying drugs used as monotherapy have an approximately 1:1 relationship
between percent non-HDL-C lowering and CHD reduction.

PMID: 19161879  [PubMed - indexed for MEDLINE]


284. Anesthesiology. 2008 Dec;109(6):1023-35. doi: 10.1097/ALN.0b013e31818d6b26.

How much does pharmacologic prophylaxis reduce postoperative vomiting in
children? Calculation of prophylaxis effectiveness and expected incidence of
vomiting under treatment using Bayesian meta-analysis.

Engelman E(1), Salengros JC, Barvais L.

Author information:
(1)Department of Anesthesiology, Erasme Hospital, 808 Route de Lennik, 1070
Brussels, Belgium. eengelma@ulb.ac.be

BACKGROUND: The authors calculated the effect size for treatments recommended for
the pediatric population in the new Guidelines for the Management of
Postoperative Nausea and Vomiting that should be implemented with the help of a
new risk scale developed for children.
METHODS: Six single-drug therapies and five combination treatments were subjected
to a Bayesian analysis, with respect to the outcome reported, in a sequence that
parallels their dates of publication. Based on the Bayes theorem, a posterior
probability was calculated after inclusion of the data from the successive
studies, to update a prior probability existing before inclusion of that study.
The posterior for the preceding group of trials served as the prior for the
subsequent trial. The final odds ratio with its 95% credibility interval compared
with placebo is considered as the results for that treatment, and was transformed
into a relative risk whose 95% credibility interval allows the calculation of a
most pessimistic and a most optimistic incidence of postoperative vomiting.
RESULTS: The most pessimistic expectations with the 5-hydroxytryptamine receptor
antagonists and dexamethasone result in a 50-60% relative risk reduction. The
results with droperidol offer a decrease of only approximately 40%. With the
combinations of a 5-hydroxytryptamine receptor antagonist and dexamethasone, a
relative risk reduction of approximately 80% is expected.
CONCLUSIONS: The authors' tables list the expected incidence of postoperative
vomiting with each treatment for each risk category, and the expected relative
risks that can be used with baseline risk values from any source.

PMID: 19034099  [PubMed - indexed for MEDLINE]


285. J Interv Cardiol. 2008 Dec;21(6):459-82. doi: 10.1111/j.1540-8183.2008.00416.x.

A Bayesian meta-analysis comparing AngioJet thrombectomy to percutaneous coronary
intervention alone in acute myocardial infarction.

Grines CL(1), Nelson TR, Safian RD, Hanzel G, Goldstein JA, Dixon S.

Author information:
(1)Division of Cardiology, William Beaumont Hospital, Royal Oak, MI 48073, USA.
cgrines@beaumont.edu

OBJECTIVE: The purpose of this meta-analysis was to compare outcomes for AngioJet
thrombectomy versus percutaneous coronary intervention (PCI) without thrombectomy
in acute myocardial infarction (AMI) patients.
BACKGROUND: PCI is the preferred treatment for revascularizing the
infarct-related artery in patients with AMI. There is controversy about the
benefits of thrombectomy as an adjunct to PCI.
METHODS: AMI studies published between January 1, 1999, and March 1, 2007, were
used to compare AngioJet thrombectomy plus PCI to PCI alone. Bayesian
meta-analytic estimates were used to estimate the odds ratios (95% CI) for
short-term mortality, major adverse cardiac events (MACE), and final TIMI 3 flow.
RESULTS: The AngioJet data included 11 studies and 1,018 patients. The PCI data
included 81 studies and 24,076 patients. The AngioJet group included more
patients with large thrombus burden, rescue PCI after failed thrombolytic
therapy, and longer symptom duration compared to the PCI group. Despite the
higher risk profile of AngioJet patients, the groups had similar odds of
short-term mortality, 0.98 (0.53, 1.50), MACE, 1.25 (0.54, 2.40), and final TIMI
3 flow, 1.12 (0.70, 2.27).
CONCLUSION: AngioJet thrombectomy results in clinical and angiographic outcomes
that are similar to PCI in lower risk AMI patients. These observations suggest
that AngioJet thrombectomy may reduce the additional risk associated with visible
thrombus in the infarct-related lesion.

PMID: 19018943  [PubMed - indexed for MEDLINE]


286. Sleep Med. 2008 Oct;9(7):715-26. doi: 10.1016/j.sleep.2007.11.020. Epub 2008 Jan
28.

Meta-analysis of the efficacy and tolerability of pramipexole versus ropinirole
in the treatment of restless legs syndrome.

Quilici S(1), Abrams KR, Nicolas A, Martin M, Petit C, Lleu PL, Finnern HW.

Author information:
(1)i3 Innovus, 3rd floor, Beaufort House Cricket Field Road, Uxbridge UB8 1QG,
United Kingdom. sibilia.quilici@i3innovus.com

Comment in
    Sleep Med. 2008 Oct;9(7):709-11.

OBJECTIVE: In the absence of comparative trials a meta-analysis was performed to
compare the efficacy and tolerability of the non-ergot derived dopamine agonists,
pramipexole and ropinirole, in restless legs syndrome (RLS).
METHODS: Frequentist fixed and random-effects models were pre-specified for the
direct comparisons and a Bayesian approach for the indirect comparison. Efficacy
outcomes included the mean change from baseline in the International RLS Study
Group Rating Scale (IRLS) score and the percentage of responders on the clinical
global impressions - improvement scale (CGI-I). Safety outcomes included the
incidence of withdrawal and adverse events.
RESULTS: The direct meta-analysis confirmed superior efficacy for both treatments
versus placebo for the IRLS (pramipexole: -5.45; 95% CI: -7.70; -3.20;
ropinirole: -3.16; 95% CI: -4.26; -2.05) and the CGI-I (pramipexole: OR=2.98; 95%
CI: 2.08; 4.26; ropinirole: OR=1.99; 95% CI: 1.52; 2.60). Placebo comparisons
showed a significantly higher incidence of nausea for pramipexole (p<0.01),
whereas nausea, vomiting, dizziness, and somnolence were significantly higher for
ropinirole (all p<0.01). The indirect comparison showed with a probability of >
or = 95%, a superior reduction in the mean IRLS score (-2.33; 95% credibility
interval [CrI]: -4.23; -0.41), higher CGI-I response rate (OR=1.50; 95% CrI:
0.97; 2.32) and significantly lower incidence of nausea, vomiting, and dizziness
for pramipexole compared to ropinirole.
CONCLUSION: Differences in efficacy and tolerability favouring pramipexole over
ropinirole can be observed. These findings should be further confirmed in
head-to-head clinical trials.

PMID: 18226947  [PubMed - indexed for MEDLINE]


287. Ann Epidemiol. 2008 Aug;18(8):614-27. doi: 10.1016/j.annepidem.2008.04.006.

Sunburns and risk of cutaneous melanoma: does age matter? A comprehensive
meta-analysis.

Dennis LK(1), Vanbeek MJ, Beane Freeman LE, Smith BJ, Dawson DV, Coughlin JA.

Author information:
(1)Department of Epidemiology, College of Public Health, University of Iowa, Iowa
City, IA 52242, USA. leslie-dennis@uiowa.edu

PURPOSE: Sunburns are an important risk factor for melanoma and those occurring
in childhood are often cited as posing the greatest risk. We conducted a
meta-analysis to quantify the magnitude of association for melanoma and sunburns
during childhood, adolescence, adulthood and over a lifetime.
METHODS: After reviewing over 1300 article titles and evaluating 270 articles in
detail, we pooled odds ratios from 51 independent study populations for "ever"
sunburned and risk of cutaneous melanoma. Among these, 26 studies reported
results from dose-response analyses. Dose-response analyses were examined using
both fixed-effects models and Bayesian random-effects models.
RESULTS: An increased risk of melanoma was seen with increasing number of
sunburns for all time-periods (childhood, adolescence, adulthood, and lifetime).
In an attempt to understand how risk between life-periods compares, we also
report these same linear models on a scale of five sunburns per decade for each
life-period. The magnitude of risk for five sunburns per decade is highest for
adult and lifetime sunburns.
CONCLUSIONS: Overall, these results show an increased risk of melanoma with
increasing number of sunburns during all life-periods, not just childhood.
Prevention efforts should focus on reducing sunburns during all life-periods.

PMCID: PMC2873840
PMID: 18652979  [PubMed - indexed for MEDLINE]


288. CMAJ. 2008 Jul 15;179(2):135-44. doi: 10.1503/cmaj.070256.

Pharmacotherapies for smoking cessation: a meta-analysis of randomized controlled
trials.

Eisenberg MJ(1), Filion KB, Yavin D, Bélisle P, Mottillo S, Joseph L, Gervais A,
O'Loughlin J, Paradis G, Rinfret S, Pilote L.

Author information:
(1)Division of Cardiology and Clinical Epidemiology, Sir Mortimer B. Davis Jewish
General Hospital and McGill University, McGill University, Montréal, QC.
mark.eisenberg@mcgill.ca

Erratum in
    CMAJ. 2008 Oct 7;179(8):802.

Comment in
    CMAJ. 2008 Nov 4;179(10):1037-8; author reply 138.
    Evid Based Nurs. 2009 Jan;12(1):10.
    CMAJ. 2008 Jul 15;179(2):123-4.

Comment on
    CMAJ. 2008 Jul 15;179(2):145-6.

BACKGROUND: Many placebo-controlled trials have demonstrated the efficacy of
individual pharmacotherapies approved for smoking cessation. However, few direct
or indirect comparisons of such interventions have been conducted. We performed a
meta-analysis to compare the treatment effects of 7 approved pharmacologic
interventions for smoking cessation.
METHODS: We searched the US Centers for Disease Control and Prevention's Tobacco
Information and Prevention database as well as MEDLINE, EMBASE and the Cochrane
Library for published reports of placebo-controlled, double-blind randomized
controlled trials of pharmacotherapies for smoking cessation. We included studies
that reported biochemically validated measures of abstinence at 6 and 12 months.
We used a hierarchical Bayesian random-effects model to summarize the results for
each intervention.
RESULTS: We identified 70 published reports of 69 trials involving a total of 32
908 patients. Six of the 7 pharmacotherapies studied were found to be more
efficacious than placebo: varenicline (odds ratio [OR] 2.41, 95% credible
interval [CrI] 1.91-3.12), nicotine nasal spray (OR 2.37, 95% CrI 1.12-5.13),
bupropion (OR 2.07, 95% CrI 1.73-2.55), transdermal nicotine (OR 2.07, 95% CrI
1.69-2.62), nicotine tablet (OR 2.06, 95% CrI 1.12-5.13) and nicotine gum (OR
1.71, 95% CrI 1.35-2.21). Similar results were obtained regardless of which
measure of abstinence was used. Although the point estimate favoured nicotine
inhaler over placebo (OR 2.17), these results were not conclusive because the
credible interval included unity (95% CrI 0.95-5.43). When all 7 interventions
were included in the same model, all were more efficacious than placebo. In our
analysis of data from the varenicline trials that included bupropion control
arms, we found that varenicline was superior to bupropion (OR 2.18, 95% CrI
1.09-4.08).
INTERPRETATION: Varenicline, bupropion and the 5 nicotine replacement therapies
were all more efficacious than placebo at promoting smoking abstinence at 6 and
12 months.

PMCID: PMC2443223
PMID: 18625984  [PubMed - indexed for MEDLINE]


289. BMC Med Genet. 2008 Jun 27;9:55. doi: 10.1186/1471-2350-9-55.

Association between LRP5 polymorphism and bone mineral density: a Bayesian
meta-analysis.

Tran BN(1), Nguyen ND, Eisman JA, Nguyen TV.

Author information:
(1)Bone and Mineral Research Program, Garvan Institute of Medical Research, St
Vincent's Hospital, Sydney, Australia. b.tran@garvan.org.au

BACKGROUND: The low-density lipoprotein receptor-related protein 5 gene (LRP5)
was identified to be linked to the variation in BMD in high bone mass pedigrees.
Subsequent population-based studies of the association between the LRP5 gene and
BMD have yielded conflicting results. The present study was aimed at examining
the association between LRP5 gene and BMD by using meta-analysis.
METHODS: A systematic electronic search of literature was conducted to identify
all published studies in English on the association between LRP5 gene and
osteoporosis-related phenotypes, including bone mineral density and fracture. BMD
data were summarized from individual studies by LRP5 genotype, and a synthesis of
data was performed with random-effects meta-analyses. After excluding studies on
animal and review papers, there were 19 studies for the synthesis. Among these
studies, 10 studies used the rs3736228 (A1330V) polymorphism and reported BMD
values.
RESULTS: The 10 eligible studies comprised 16,705 individuals, with the majority
being women (n = 8444), aged between 18 - 81 years. The overall distribution of
genotype frequencies was: AA, 68%, AV and VV, 32%. However, the genotype
frequency varied significantly within as well as between ethnic populations. On
random-effects meta-analysis, lumbar spine BMD among individuals with the AA
genotype was on average 0.018 (95% confidence interval [CI]: 0.012 to 0.023)
g/cm2 higher than those with either AV or VV genotype. Similarly, femoral neck
BMD among carriers of the AA genotype was 0.011 (95%CI: 0.004 to 0.017) g/cm2
higher than those without the genotype. While there was no significant
heterogeneity in the association between the A1330V polymorphism and lumbar spine
BMD (p = 0.55), the association was heterogeneous for femoral neck BMD (p =
0.05). The probability that the difference is greater than one standard deviation
was 0.34 for femoral neck BMD and 0.54 for lumbar spine BMD.
CONCLUSION: These results suggest that there is a modest effect of the A1330V
polymorphism on BMD in the general population, and that the modest association
may limit its clinical use.

PMCID: PMC2459152
PMID: 18588671  [PubMed - indexed for MEDLINE]


290. Br J Cancer. 2008 Jun 17;98(12):1934-43. doi: 10.1038/sj.bjc.6604396. Epub 2008
May 27.

Are one or two simple questions sufficient to detect depression in cancer and
palliative care? A Bayesian meta-analysis.

Mitchell AJ(1).

Author information:
(1)Department of Cancer & Molecular Medicine, Leicester Royal Infirmary,
Leicester LE1 5WW, UK. alex.mitchell@leicspart.nhs.uk

The purpose of this study is to examine the value of one or two simple verbal
questions in the detection of depression in cancer settings. This study is a
systematic literature search of abstract and full text databases to January 2008.
Key authors were contacted for unpublished studies. Seventeen analyses were
found. Of these, 13 were conducted in late stage palliative settings. (1) Single
depression question: across nine studies, the prevalence of depression was 16%. A
single 'depression' question enabled the detection of depression in 160 out of
223 true cases, a sensitivity of 72%, and correctly reassured 964 out of 1166
non-depressed cancer sufferers, a specificity of 83%. The positive predictive
value (PPV) was 44% and the negative predictive value (NPV) 94%. (2) Single
interest question: there were only three studies examining the 'loss-of-interest'
question, with a combined prevalence of 14%. This question allowed the detection
of 60 out of 72 cases (sensitivity 83%) and excluded 394 from 459 non-depressed
cases (specificity of 86%). The PPV was 48% and the NPV 97%. (3) Two questions
(low mood and low interest): five studies examined two questions with a combined
prevalence of 17%. The two-question combination facilitated a diagnosis of
depression in 138 of 151 true cases (sensitivity 91%) and gave correct
reassurance to 645 of 749 non-cases (specificity 86%). The PPV was 57% and the
NPV 98%. Simple verbal methods perform well at excluding depression in the
non-depressed but perform poorly at confirming depression. The 'two question'
method is significantly more accurate than either single question but clinicians
should not rely on these simple questions alone and should be prepared to assess
the patient more thoroughly.

PMCID: PMC2441968
PMID: 18506146  [PubMed - indexed for MEDLINE]


291. J Vasc Surg. 2008 Jun;47(6):1364-1370. doi: 10.1016/j.jvs.2007.11.029. Epub 2008
Feb 14.

Suprarenal endograft fixation and medium-term renal function: systematic review
and meta-analysis.

Walsh SR(1), Boyle JR, Lynch AG, Sadat U, Carpenter JP, Tang TY, Gaunt ME.

Author information:
(1)Cambridge Vascular Unit, Cambridge University Hospitals NHS Trust, Cambridge,
United Kingdom. srwalsh@doctors.org.uk

BACKGROUND: Suprarenal fixation is widely used in endovascular aneurysm repair.
Numerous small, underpowered studies have concluded that it does not increase the
risk of renal impairment compared with infrarenal fixation. A recent
meta-analysis demonstrated that renal infarction is more common with suprarenal
fixation, but the effect on renal function remains unclear.
METHODS: Electronic abstract databases, article reference lists, and conference
proceedings were searched for series reporting renal function data after
suprarenal fixation. There was considerable study heterogeneity with respect to
key factors such as pre-existing renal dysfunction and length of follow-up.
Authors were contacted to obtain individual patient data for a pooled reanalysis
using standardized criteria.
RESULTS: Of 46 potentially relevant citations, only 11 were eligible for
inclusion in the meta-analysis. Complete data sets were available for four
studies (1065 patients), with a median follow-up of 33 months. Kaplan-Meier
curves were constructed for postoperative renal impairment in the suprarenal
fixation and infrarenal fixation groups and compared by the log-rank test. Median
time free of renal impairment was 38.5 months in the infrarenal fixation group
compared with 32.4 months in the suprarenal fixation group (P = .0038). However,
to account for significant methodologic differences, further analysis was
required using a Weibull regression model fitted in open Bayesian inference using
Gibbs sampling (BUGS). The pooled hazard ratio for deterioration of renal
function after suprarenal fixation was 0.6 (95% confidence interval, 0.3-10).
CONCLUSION: Currently available data are insufficient to determine the precise
effect of suprarenal fixation on medium-term renal function. Conventional
Kaplan-Meier analysis of the pooled data set suggested that suprarenal fixation
increased the risk of renal dysfunction; however, the effect disappeared when
sophisticated statistical modelling was performed to account for study
heterogeneity. A randomised controlled trial of suprarenal fixation may resolve
this issue.

PMID: 18280095  [PubMed - indexed for MEDLINE]


292. BMJ. 2008 May 3;336(7651):1006-9. doi: 10.1136/bmj.39537.939039.BE. Epub 2008 Apr
23.

Corticosteroids in the prevention and treatment of acute respiratory distress
syndrome (ARDS) in adults: meta-analysis.

Peter JV(1), John P, Graham PL, Moran JL, George IA, Bersten A.

Author information:
(1)Department of Medical Intensive Care, Christian Medical College and Hospital,
Vellore, India 632 004.

Comment in
    BMJ. 2008 May 3;336(7651):969-70.

OBJECTIVE: To systematically review the efficacy of steroids in the prevention of
acute respiratory distress syndrome (ARDS) in critically ill adults, and
treatment for established ARDS.
DATA SOURCES: Search of randomised controlled trials (1966-April 2007) of PubMed,
Cochrane central register of controlled trials, Cochrane database of systematic
reviews, American College of Physicians Journal Club, health technology
assessment database, and database of abstracts of reviews of effects.
DATA EXTRACTION: Two investigators independently assessed trials for inclusion
and extracted data into standardised forms; differences were resolved by
consensus.
DATA SYNTHESIS: Steroid efficacy was assessed through a Bayesian hierarchical
model for comparing the odds of developing ARDS and mortality (both expressed as
odds ratio with 95% credible interval) and duration of ventilator free days,
assessed as mean difference. Bayesian outcome probabilities were calculated as
the probability that the odds ratio would be > or =1 or the probability that the
mean difference would be > or =0. Nine randomised trials using variable dose and
duration of steroids were identified. Preventive steroids (four studies) were
associated with a trend to increase both the odds of patients developing ARDS
(odds ratio 1.55, 95% credible interval 0.58 to 4.05; P(odds ratio > or
=1)=86.6%), and the risk of mortality in those who subsequently developed ARDS
(three studies, odds ratio 1.52, 95% credible interval 0.30 to 5.94; P(odds ratio
> or =1)=72.8%). Steroid administration after onset of ARDS (five studies) was
associated with a trend towards reduction in mortality (odds ratio 0.62, 95%
credible interval 0.23 to 1.26; P(odds ratio > or =1)=6.8%). Steroid therapy
increased the number of ventilator free days compared with controls (three
studies, mean difference 4.05 days, 95% credible interval 0.22 to 8.71; P(mean
difference > or =0)=97.9%). Steroids were not associated with increase in risk of
infection.
CONCLUSIONS: A definitive role of corticosteroids in the treatment of ARDS in
adults is not established. A possibility of reduced mortality and increased
ventilator free days with steroids started after the onset of ARDS was suggested.
Preventive steroids possibly increase the incidence of ARDS in critically ill
adults.

PMCID: PMC2364864
PMID: 18434379  [PubMed - indexed for MEDLINE]




294. BMC Genomics. 2008 Feb 26;9:98. doi: 10.1186/1471-2164-9-98.

A non-parametric meta-analysis approach for combining independent microarray
datasets: application using two microarray datasets pertaining to chronic
allograft nephropathy.

Kong X(1), Mas V, Archer KJ.

Author information:
(1)Department of Biostatistics, Virginia Commonwealth University, Richmond, VA
23298, USA. kongx@vcu.edu

BACKGROUND: With the popularity of DNA microarray technology, multiple groups of
researchers have studied the gene expression of similar biological conditions.
Different methods have been developed to integrate the results from various
microarray studies, though most of them rely on distributional assumptions, such
as the t-statistic based, mixed-effects model, or Bayesian model methods.
However, often the sample size for each individual microarray experiment is
small. Therefore, in this paper we present a non-parametric meta-analysis
approach for combining data from independent microarray studies, and illustrate
its application on two independent Affymetrix GeneChip studies that compared the
gene expression of biopsies from kidney transplant recipients with chronic
allograft nephropathy (CAN) to those with normal functioning allograft.
RESULTS: The simulation study comparing the non-parametric meta-analysis approach
to a commonly used t-statistic based approach shows that the non-parametric
approach has better sensitivity and specificity. For the application on the two
CAN studies, we identified 309 distinct genes that expressed differently in CAN.
By applying Fisher's exact test to identify enriched KEGG pathways among those
genes called differentially expressed, we found 6 KEGG pathways to be
over-represented among the identified genes. We used the expression measurements
of the identified genes as predictors to predict the class labels for 6
additional biopsy samples, and the predicted results all conformed to their
pathologist diagnosed class labels.
CONCLUSION: We present a new approach for combining data from multiple
independent microarray studies. This approach is non-parametric and does not rely
on any distributional assumptions. The rationale behind the approach is logically
intuitive and can be easily understood by researchers not having advanced
training in statistics. Some of the identified genes and pathways have been
reported to be relevant to renal diseases. Further study on the identified genes
and pathways may lead to better understanding of CAN at the molecular level.

PMCID: PMC2276496
PMID: 18302764  [PubMed - indexed for MEDLINE]


295. J Am Coll Cardiol. 2008 Jan 1;51(1):37-45. doi: 10.1016/j.jacc.2007.06.063.

Statins for secondary prevention in elderly patients: a hierarchical bayesian
meta-analysis.

Afilalo J(1), Duque G, Steele R, Jukema JW, de Craen AJ, Eisenberg MJ.

Author information:
(1)Department of Medicine, Sir Mortimer B. Davis Jewish General Hospital, McGill
University, Montreal, Canada.

Comment in
    J Am Coll Cardiol. 2008 Jan 1;51(1):46-8.
    ACP J Club. 2008 May 20;148(3):3.
    J Fam Pract. 2008 Apr;57(4):1 p following 220.

OBJECTIVES: This study was designed to determine whether statins reduce all-cause
mortality in elderly patients with coronary heart disease.
BACKGROUND: Statins continue to be underutilized in elderly patients because
evidence has not consistently shown that they reduce mortality.
METHODS: We searched 5 electronic databases, the Internet, and conference
proceedings to identify relevant trials. In addition, we obtained unpublished
data for the elderly patient subgroups from 4 trials and for the secondary
prevention subgroup from the PROSPER (PROspective Study of Pravastatin in the
Elderly at Risk) trial. Inclusion criteria were randomized allocation to statin
or placebo, documented coronary heart disease, > or =50 elderly patients (defined
as age > or =65 years), and > or =6 months of follow-up. Data were analyzed with
hierarchical Bayesian modeling.
RESULTS: We included 9 trials encompassing 19,569 patients with an age range of
65 to 82 years. Pooled rates of all-cause mortality were 15.6% with statins and
18.7% with placebo. We estimated a relative risk reduction of 22% over 5 years
(relative risk [RR] 0.78; 95% credible interval [CI] 0.65 to 0.89). Furthermore,
statins reduced coronary heart disease mortality by 30% (RR 0.70; 95% CI 0.53 to
0.83), nonfatal myocardial infarction by 26% (RR 0.74; 95% CI 0.60 to 0.89), need
for revascularization by 30% (RR 0.70; 95% CI 0.53 to 0.83), and stroke by 25%
(RR 0.75; 95% CI 0.56 to 0.94). The posterior median estimate of the number
needed to treat to save 1 life was 28 (95% CI 15 to 56).
CONCLUSIONS: Statins reduce all-cause mortality in elderly patients and the
magnitude of this effect is substantially larger than had been previously
estimated.

PMID: 18174034  [PubMed - indexed for MEDLINE]


296. J Biopharm Stat. 2008;18(6):1063-83. doi: 10.1080/10543400802369004.

A Bayesian meta-analysis on published sample mean and variance pharmacokinetic
data with application to drug-drug interaction prediction.

Yu M(1), Kim S, Wang Z, Hall S, Li L.

Author information:
(1)Division of Biostatistics, Department of Medicine, School of Medicine, Indiana
University, Indianapolis, Indiana 46023, USA. meyu@iupui.edu

In drug-drug interaction (DDI) research, a two-drug interaction is usually
predicted by individual drug pharmacokinetics (PK). Although subject-specific
drug concentration data from clinical PK studies on inhibitor or inducer and
substrate PK are not usually published, sample mean plasma drug concentrations
and their standard deviations have been routinely reported. Hence there is a
great need for meta-analysis and DDI prediction using such summarized PK data. In
this study, an innovative DDI prediction method based on a three-level
hierarchical Bayesian meta-analysis model is developed. The three levels model
sample means and variances, between-study variances, and prior distributions.
Through a ketoconazle-midazolam example and simulations, we demonstrate that our
meta-analysis model can not only estimate PK parameters with small bias but also
recover their between-study and between-subject variances well. More importantly,
the posterior distributions of PK parameters and their variance components allow
us to predict DDI at both population-average and study-specific levels. We are
also able to predict the DDI between-subject/study variance. These statistical
predictions have never been investigated in DDI research. Our simulation studies
show that our meta-analysis approach has small bias in PK parameter estimates and
DDI predictions. Sensitivity analysis was conducted to investigate the influences
of interaction PK parameters, such as the inhibition constant Ki, on the DDI
prediction.

PMCID: PMC2737821
PMID: 18991108  [PubMed - indexed for MEDLINE]


297. J Cardiometab Syndr. 2008 Winter;3(1):45-52.

Bayesian meta-analysis of tissue angiotensin-converting enzyme inhibitors for
reduction of adverse cardiovascular events in patients with diabetes mellitus and
preserved left ventricular function.

Lang CD(1), Arora RR, Saha SA, Molnar J.

Author information:
(1)Department of Medicine, Chicago Medical School, North Chicago, IL 60064, USA.
christopher.lang@rfums.org

The role of angiotensin-converting enzyme (ACE) inhibitors in diabetic patients
with preserved ventricular function is uncertain. Tissue ACE inhibitors have been
defined by increased lipophilicity and structural characteristics that result in
greater tissue-specific ACE binding when compared with plasma ACE inhibitors. A
Bayesian meta-analysis of randomized trials was conducted to evaluate tissue ACE
inhibitors in prevention of cardiovascular disease among patients with diabetes
mellitus and preserved left ventricular function. Four trials were selected that
evaluated 2 different ACE inhibitors and included 10,328 patients (43,517
patient-years). The Perindopril Substudy in Coronary Artery Disease and Diabetes
(PERSUADE) and the Perindopril Protection Against Recurrent Stroke Study
(PROGRESS) compared the effects of perindopril vs a placebo, and the Heart
Outcomes Prevention Evaluation (HOPE) and the Non-Insulin-Dependent Diabetes,
Hypertension, Microalbuminuria, Proteinuria, Cardiovascular Events, and Ramipril
(DIABHYCAR) study investigated the impact of ramipril vs a placebo. Bayesian
meta-analysis of sequential trials and sensitivity analysis of therapeutic
response were subsequently computed. Bayesian meta-analysis determined reduced
risk of cardiovascular mortality (PB=.991), myocardial infarction (PB=.999), and
the need for invasive coronary revascularization (PB=.995) when compared with
placebo. Total mortality was also decreased (PB=.967), while the risk of stroke
(PB=.907) and hospitalization for heart failure (PB=.923) were impacted. Bayesian
meta-analysis of randomized trials suggests that tissue ACE inhibitors decrease
the probability that diabetic patients with preserved left ventricular function
will experience myocardial infarctions and cardiovascular death and reduce
overall mortality.

PMID: 18326970  [PubMed - indexed for MEDLINE]

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298. Am J Trop Med Hyg. 2007 Dec;77(6):1005-9.

Assessment of the relative advantage of various artesunate-based combination
therapies by a multi-treatment Bayesian random-effects meta-analysis.

Jansen FH(1), Lesaffre E, Penali LK, Zattera MJ, Die-Kakou H, Bissagnene E.

Author information:
(1)Fondation ACT-ion Afrique, Bruxelles, Belgium. fh.jansen@actionafrique.org

Over the years, multiple articles on Artemisinin-based Combination Therapies
(ACTs) were published, highlighting the relative advantages or drawbacks of these
combinations. Many studies were comparative. Because none of the studies compare
all combinations and methodology varies between studies, there is no homogeneity.
A multi-treatment Bayesian random-effects meta-analysis was designed to assess
the relative effect of each combination therapy to artesunate +
sulfadoxine-pyrimethamine (4 mg/kg/day for 3 days). By far the most attractive
result for the variable adequate clinical and parasitological response at day 28
PCR corrected is given by the combination artemether-lumefantrine. Annual
follow-up on the data published is intended to reveal the changes in the relative
drug efficacy values of ACTs.

PMID: 18165512  [PubMed - indexed for MEDLINE]


299. BMJ. 2007 Nov 3;335(7626):925. Epub 2007 Oct 11.

Combined resynchronisation and implantable defibrillator therapy in left
ventricular dysfunction: Bayesian network meta-analysis of randomised controlled
trials.

Lam SK(1), Owen A.

Author information:
(1)National Heart and Lung Institute, London SW3 6LY. simon.lam@medsci.oxon.org

Comment in
    BMJ. 2007 Nov 3;335(7626):895-6.

OBJECTIVE: To review the evidence base from randomised controlled trials of
combined cardiac resynchronisation therapy and implantable cardioverter
defibrillator therapy in left ventricular impairment and symptomatic heart
failure.
DESIGN: Bayesian network meta-analysis.
DATA SOURCES: Medline, Embase, and Cochrane databases up to June 2006.
REVIEW METHODS: Two reviewers independently assessed trial eligibility and
quality. Included trials compared cardiac resynchronisation therapy, implantable
cardioverter defibrillator therapy, combined resynchronisation and implantable
defibrillator therapy, and medical therapy alone, in patients with impaired left
ventricular systolic function. Bayesian random effects network models were used
to examine overall number of deaths.
RESULTS: 12 studies including 1636 events in 8307 patients were identified.
Combined cardiac resynchronisation and implantable cardioverter defibrillator
therapy reduced the number of deaths by one third compared with medical therapy
alone (odds ratio 0.57, 95% credible interval 0.40 to 0.80) but did not further
improve survival when compared with implantable defibrillator therapy (0.82, 0.57
to 1.18) or resynchronisation (0.85, 0.60 to 1.22) therapy alone.
CONCLUSION: Evidence from randomised controlled trials is insufficient to show
the superiority of combined cardiac resynchronisation and implantable
cardioverter defibrillator therapy over cardiac resynchronisation therapy alone
in patients with left ventricular impairment.

PMCID: PMC2048879
PMID: 17932160  [PubMed - indexed for MEDLINE]


300. Am J Epidemiol. 2007 Oct 1;166(7):741-51. Epub 2007 Aug 4.

Joint effects of the N-acetyltransferase 1 and 2 (NAT1 and NAT2) genes and
smoking on bladder carcinogenesis: a literature-based systematic HuGE review and
evidence synthesis.

Sanderson S(1), Salanti G, Higgins J.

Author information:
(1)Department of Public Health and Primary Care, Institute of Public Health,
University of Cambridge, Cambridge, United Kingdom.
simon.sanderson@phgfoundation.org

Bladder cancer is an increasingly important international public health problem,
with over 330,000 new cases being diagnosed each year worldwide. In a systematic
review and evidence synthesis, the authors investigated the joint effects of the
N-acetyltransferase genes NAT1 and NAT2 and cigarette smoking on bladder
carcinogenesis. Studies were identified through an exhaustive search of multiple
electronic databases and reference lists and through direct contact with study
authors and experts. Random-effects meta-analysis was used within a Bayesian
framework to investigate individual effects of NAT1 and NAT2 acetylation status
on bladder cancer risk, while a novel approach was used to investigate joint
effects of these two genes with cigarette smoking. An increased risk of bladder
cancer was found in NAT2 slow acetylators (odds ratio = 1.46, 95% credible
interval (CI): 1.26, 1.68) but not in NAT1 fast acetylators (odds ratio = 1.01,
95% CI: 0.86, 1.22). The joint effects in the highest risk category (NAT2 slow
acetylator, NAT1 fast acetylator, and current or ever cigarette smoking) as
compared with the reference category (NAT2 fast acetylator, NAT1 slow acetylator,
and never smoking) were associated with an odds ratio of 2.73 (95% CI: 1.70,
4.31). The importance of considering joint effects between genetic and
environmental factors in the etiology of common complex diseases is underlined.

PMID: 17675654  [PubMed - indexed for MEDLINE]


301. Gynecol Oncol. 2007 Oct;107(1 Suppl 1):S133-7.

Bayesian meta-analysis of Papanicolaou smear accuracy.

Cong X(1), Cox DD, Cantor SB.

Author information:
(1)Biometrics and Data Management, Boehringer Ingelheim Pharmaceuticals, Inc.,
Ridgefield, Connecticut, USA.

OBJECTIVE: To perform a Bayesian analysis of data from a previous meta-analysis
of Papanicolaou (Pap) smear accuracy (Fahey et al. Am J Epidemiol 1995;
141:680-689) and compare the results.
METHODS: We considered two Bayesian models for the same data set used in the
Fahey et al. study. Model I was a beta-binomial model which considered the number
of true positives and false negatives as independent binomial random variables
with probability parameters beta (sensitivity) and alpha (one minus specificity),
respectively. We assumed that beta and alpha are independent, each following a
beta distribution with exponential priors. Model II considered sensitivity and
specificity jointly through a bivariate normal distribution on the logits of the
sensitivity and specificity. We performed sensitivity analysis to examine the
effect of prior selection on the parameter estimates.
RESULTS: We compared the estimates of average sensitivity and specificity from
the Bayesian models with those from Fahey et al.'s summary receiver operating
characteristics (SROC) approach. Model I produced results similar to those of the
SROC approach. Model II produced point estimates higher than those of the SROC
approach, although the credible intervals overlapped and were wider. Sensitivity
analysis showed that the Bayesian models are somewhat sensitive to the variance
of the prior distribution, but their point estimates are more robust than those
of the SROC approach.
CONCLUSIONS: The Bayesian approach has advantages over the SROC approach in that
it accounts for between-study variation and allows for estimating the sensitivity
and specificity for a particular trial, taking into consideration the results of
other trials, i.e., "borrowing strength" from other trials.

PMCID: PMC2964866
PMID: 17908587  [PubMed - indexed for MEDLINE]


302. Heart. 2007 Oct;93(10):1244-50. Epub 2007 Feb 3.

Assessing the effectiveness of primary angioplasty compared with thrombolysis and
its relationship to time delay: a Bayesian evidence synthesis.

Asseburg C(1), Vergel YB, Palmer S, Fenwick E, de Belder M, Abrams KR, Sculpher
M.

Author information:
(1)Centre for Health Economics, University of York, Heslington, York, UK.

Comment in
    Heart. 2007 Oct;93(10):1167-9.
    Heart. 2007 Oct;93(10):1164-6.

BACKGROUND: Meta-analyses of trials have shown greater benefits from angioplasty
than thrombolysis after an acute myocardial infarction, but the time delay in
initiating angioplasty needs to be considered.
OBJECTIVE: To extend earlier meta-analyses by considering 1- and 6-month outcome
data for both forms of reperfusion. To use Bayesian statistical methods to
quantify the uncertainty associated with the estimated relationships.
METHODS: A systematic review and meta-analysis published in 2003 was updated.
Data on key clinical outcomes and the difference between time-to-balloon and
time-to-needle were independently extracted by two researchers. Bayesian
statistical methods were used to synthesise evidence despite differences between
reported follow-up times and outcomes. Outcomes are presented as absolute
probabilities of specific events and odds ratios (ORs; with 95% credible
intervals (CrI)) as a function of the additional time delay associated with
angioplasty.
RESULTS: 22 studies were included in the meta-analysis, with 3760 and 3758
patients randomised to primary angioplasty and thrombolysis, respectively. The
mean (SE) angioplasty-related time delay (over and above time to thrombolysis)
was 54.3 (2.2) minutes. For this delay, mean event probabilities were lower for
primary angioplasty for all outcomes. Mortality within 1 month was 4.5% after
angioplasty and 6.4% after thrombolysis (OR = 0.68 (95% CrI 0.46 to 1.01)). For
non-fatal reinfarction, OR = 0.32 (95% CrI 0.20 to 0.51); for non-fatal stroke OR
= 0.24 (95% CrI 0.11 to 0.50). For all outcomes, the benefit of angioplasty
decreased with longer delay from initiation.
CONCLUSIONS: The benefit of primary angioplasty, over thrombolysis, depends on
the former's additional time delay. For delays of 30-90 minutes, angioplasty is
superior for 1-month fatal and non-fatal outcomes. For delays of around 90
minutes thrombolysis may be the preferred option as assessed by 6-month
mortality; there is considerable uncertainty for longer time delays.

PMCID: PMC2000960
PMID: 17277350  [PubMed - indexed for MEDLINE]


303. Scand J Work Environ Health. 2007 Oct;33(5):325-35.

Estimating the relative risk of pancreatic cancer associated with exposure agents
in job title data in a hierarchical Bayesian meta-analysis.

Ojajärvi A(1), Partanen T, Ahlbom A, Hakulinen T, Kauppinen T, Weiderpass E,
Wesseling C.

Author information:
(1)Finnish Institute of Occupational Health, Good Practices and Competence,
Topeliuksenkatu 41 a A, 00250 Helsinki, Finland. anneli.ojajarvi@ttl.fi

OBJECTIVES: The study demonstrates the application of a hierarchical Bayesian
meta-analysis of epidemiologic studies that show an association between
pancreatic cancer risk and job titles, using a job-exposure matrix to estimate
risks for occupational exposure agents.
METHODS: Altogether 261 studies published from 1969 through 1998 on pancreatic
cancer and job titles were identified. When proportional studies are excluded, 77
studies were informative for 9 selected occupational agents. These studies
included more than 3799 observed pancreatic cancer cases. Hierarchical Bayesian
models were used for job titles (lower-level data) and agents (higher-level
data), the latter from a Finnish job-exposure matrix. Non-Bayesian random effects
models were applied for job titles to check consistency with the Bayesian
results.
RESULTS: The results suggest that occupational exposures to chlorinated
hydrocarbon compounds may increase the risk of pancreatic cancer; the
meta-relative risk (MRR) was 2.21 [95% credible interval (CrI) 1.31-3.68]. A
suggestive weak excess was found for exposure to insecticides (MRR 1.95, 95% CrI
0.51-7.41).
CONCLUSIONS: Hierarchical models are applicable in meta-analyses when studies
addressing the agent(s) under study are lacking or are very few, but several
studies address job titles with potential exposure to these agents. Hierarchical
meta-analytic models involving durations and intensities of exposure to
occupational agents from a job-exposure matrix should be developed.

PMID: 17973058  [PubMed - indexed for MEDLINE]






306. Curr Med Res Opin. 2007 Sep;23(9):2283-95.

Comparison of pegfilgrastim with filgrastim on febrile neutropenia, grade IV
neutropenia and bone pain: a meta-analysis of randomized controlled trials.

Pinto L(1), Liu Z, Doan Q, Bernal M, Dubois R, Lyman G.

Author information:
(1)Cerner Life Sciences, Beverly Hills, CA 90212, USA. lpinto@cerner.com

BACKGROUND AND OBJECTIVE: While head-to-head clinical trials demonstrate
pegfilgrastim to be as efficacious as filgrastim in reducing chemotherapy-induced
neutropenia, these studies lacked the statistical power to demonstrate better
outcomes with one therapy compared to the other. Our objective was to obtain a
pooled estimate of the effect of pegfilgrastim compared with filgrastim on
incidence of febrile neutropenia (FN), and related outcomes among patients with
solid tumors and malignant lymphomas receiving myelosuppressive chemotherapy.
RESEARCH DESIGN AND METHODS: We searched PubMed and EMBASE for articles published
from January 1, 1990 to August 31, 2006 reporting on randomized controlled trials
(RCTs) that compared the efficacy and safety of pegfilgrastim versus filgrastim.
We only accepted studies in which filgrastim (5 microg/kg/day) and pegfilgrastim
(100 microg/kg or a fixed dose of 6 mg) were administered at approved doses
indicated on the package insert. Pooled relative risk (RR) was estimated using
the conservative random effects, empirical Bayesian method of Hedges and Olkin.
MAIN OUTCOME MEASURES: Rates of grade IV neutropenia and of FN, time to absolute
neutrophil count (ANC) recovery, and bone pain.
RESULTS: We identified five RCTs, with a total of 617 patients, evaluating the
efficacy of a single dose of pegfilgrastim per cycle versus daily filgrastim
injections. Although only one study had a statistically significant difference in
FN reductions favoring pegfilgrastim over filgrastim (relative risk reduction of
50%; p = 0.027), the pooled RR showed a statistically significant favorable
result for pegfilgrastim (RR = 0.64; 95% CI, 0.43-0.97). Grade IV neutropenia
rates (for cycle 1: RR = 0.99; 95% CI, 0.91-1.08; cycle 2: RR = 0.88; 95% CI,
0.70-1.11; cycle 3: RR = 0.80; 95% CI, 0.47-1.36; cycle 4: RR = 0.90; 95% CI,
0.71-1.13), time to ANC (SMD = 0.11, 95% CI, -0.34-0.56), and incidence of bone
pain (RR = 0.95; 95% CI, 0.76-1.19) were similar between the two G-CSFs. The
included trials varied in the type of cancer, chemotherapy regimen and type of
trial.
CONCLUSION: A single dose of pegfilgrastim performed better than a median of
10-14 days of filgrastim in reducing FN rates for patients undergoing
myelosuppressive chemotherapy.

PMID: 17697451  [PubMed - indexed for MEDLINE]


307. Obes Rev. 2007 Sep;8(5):385-94.

Maternal obesity and risk of cesarean delivery: a meta-analysis.

Chu SY(1), Kim SY, Schmid CH, Dietz PM, Callaghan WM, Lau J, Curtis KM.

Author information:
(1)Division of Reproductive Health, Centers for Disease Control and Prevention,
Mailstop K23, 1600 Clifton Road, Atlanta, GA 30333, USA. syc1@cdc.gov

Despite numerous studies reporting an increased risk of cesarean delivery among
overweight or obese compared with normal weight women, the magnitude of the
association remains uncertain. Therefore, we conducted a meta-analysis of the
current literature to provide a quantitative estimate of this association. We
identified studies from three sources: (i) a PubMed search of relevant articles
published between January 1980 and September 2005; (ii) reference lists of
publications selected from the search; and (iii) reference lists of review
articles published between 2000 and 2005. We included cohort designed studies
that reported obesity measures reflecting pregnancy body mass, had a normal
weight comparison group, and presented data allowing a quantitative measurement
of risk. We used a Bayesian random effects model to perform the meta-analysis and
meta-regression. Thirty-three studies were included. The unadjusted odd ratios of
a cesarean delivery were 1.46 [95% confidence interval (CI): 1.34-1.60], 2.05
(95% CI: 1.86-2.27) and 2.89 (95% CI: 2.28-3.79) among overweight, obese and
severely obese women, respectively, compared with normal weight pregnant women.
The meta-regression found no evidence that these estimates were affected by
selected study characteristics. Our findings provide a quantitative estimate of
the risk of cesarean delivery associated with high maternal body mass.

PMID: 17716296  [PubMed - indexed for MEDLINE]


308. Am J Gastroenterol. 2007 Aug;102(8):1799-807. Epub 2007 Apr 24.

Ursodeoxycholic acid for patients with primary biliary cirrhosis: an updated
systematic review and meta-analysis of randomized clinical trials using Bayesian
approach as sensitivity analyses.

Gong Y(1), Huang Z, Christensen E, Gluud C.

Author information:
(1)The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Center for Clinical
Intervention Research, Department 7102, Rigshospitalet, Copenhagen University
Hospital, Copenhagen, Denmark.

Comment in
    ACP J Club. 2008 Jan-Feb;148(1):17.

OBJECTIVES: Ursodeoxycholic acid (UDCA) is used for primary biliary cirrhosis
(PBC), but the beneficial effects remain controversial.
METHODS: We performed an updated systematic review to evaluate the benefits and
harms of UDCA in patients with PBC. We included randomized clinical trials
evaluating UDCA versus placebo or no intervention in patients with PBC. The
primary outcomes, mortality and mortality or liver transplantation, were reported
as relative risk (RR) with 95% confidence interval (CI). Meta-regression was used
to investigate the associations between UDCA effects and the trial's risk of
bias, UDCA dose, duration, and PBC severity at trial entry. We used Bayesian
meta-analytic approaches as sensitivity analyses.
RESULTS: Sixteen randomized clinical trials (1,447 patients) evaluating UDCA
versus placebo or no intervention were identified. Over half of the trials had
high risk of bias. Comparing with placebo or no intervention, UDCA did not
significantly affect mortality (RR 0.97, 95% CI 0.67-1.42) and mortality or liver
transplantation (RR 0.92, 95% CI 0.71-1.21). The findings were supported by the
Bayesian meta-analyses. Meta-regression analyses suggested that UDCA effects seem
to be associated with patient's disease severity and trial duration. UDCA did not
improve pruritus, fatigue, autoimmune conditions, liver histology, or portal
pressure. UDCA seemed to improve biochemical variables, such as serum bilirubin,
and ascites and jaundice, but the findings were based on few trials with sparse
data. The use of UDCA was significantly associated with adverse events, mainly
weight gain.
CONCLUSIONS: This updated systematic review did not demonstrate any benefit of
UDCA on mortality and mortality or liver transplantation in patients with PBC.

PMID: 17459023  [PubMed - indexed for MEDLINE]


309. Diabetes Care. 2007 Aug;30(8):2070-6. Epub 2007 Apr 6.

Maternal obesity and risk of gestational diabetes mellitus.

Chu SY(1), Callaghan WM, Kim SY, Schmid CH, Lau J, England LJ, Dietz PM.

Author information:
(1)Division of Reproductive Health, Centers for Disease Control and Prevention,
Mailstop K-23, 1600 Clifton Rd., Atlanta, GA 30333, USA. syc1@cdc.gov

OBJECTIVE: Numerous studies in the U.S. and elsewhere have reported an increased
risk of gestational diabetes mellitus (GDM) among women who are overweight or
obese compared with lean or normal-weight women. Despite the number and overall
consistency of studies reporting a higher risk of GDM with increasing weight or
BMI, the magnitude of the association remains uncertain. This meta-analysis was
conducted to better estimate this risk and to explore differences across studies.
RESEARCH DESIGN AND METHODS: We identified studies from three sources: 1) a
PubMed search of relevant articles published between January 1980 and January
2006, 2) reference lists of publications selected from the PubMed search, and 3)
reference lists of review articles on obesity and maternal outcomes published
between January 2000 and January 2006. We used a Bayesian model to perform the
meta-analysis and meta-regression. We included cohort-designed studies that
reported obesity measures reflecting pregnancy body mass, that had a
normal-weight comparison group, and that presented data allowing a quantitative
measurement of risk.
RESULTS: Twenty studies were included in the meta-analysis. The unadjusted ORs of
developing GDM were 2.14 (95% CI 1.82-2.53), 3.56 (3.05-4.21), and 8.56
(5.07-16.04) among overweight, obese, and severely obese compared with
normal-weight pregnant women, respectively. The meta-regression analysis found no
evidence that these estimates were affected by selected study characteristics
(publication date, study location, parity, type of data collection [retrospective
vs. prospective], and prevalence of GDM among normal-weight women).
CONCLUSIONS: Our findings indicate that high maternal weight is associated with a
substantially higher risk of GDM.

PMID: 17416786  [PubMed - indexed for MEDLINE]




311. Bone. 2007 Apr;40(4):813-20. Epub 2006 Dec 18.

On the association between statin and fracture: a Bayesian consideration.

Nguyen ND(1), Wang CY, Eisman JA, Nguyen TV.

Author information:
(1)Bone and Mineral Research Program, Garvan Institute of Medical Research, St
Vincent's Hospital, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010,
Australia.

BACKGROUND: The association between statin use and fracture risk is
controversial, due to conflicting findings from previous studies. This study
utilized the Bayesian approach to combine existing evidence and update the
association with consideration of potential bias.
METHODS: Data on the association between statin use and fracture incidence from
11 observational studies and 4 RCTs were synthesized by both empirical Bayesian
analysis and fully Bayesian random-effects meta-analysis models.
RESULTS: Empirical Bayesian analysis showed that statin use was associated with a
reduction in hip fracture risk (OR=0.57, 95% credible interval (CrI): 0.46-0.71)
and for non-vertebral (OR=0.69, 95% CrI, 0.63-0.74). These results were
comparable with results from the fully Bayesian random-effects meta-analysis only
for hip fracture (OR 0.56, 95% CrI, 0.42-0.73), but not for non-vertebral
fracture (OR 0.77, 95% CrI, 0.58-1.03). The probability that statin use reduces
fracture risk by at least 20% was 0.995 for hip fracture and 0.61 for
non-vertebral fracture. Under the assumption that bias over-estimates the true OR
by 20%, there is still a probability of 0.97 that statin use reduces hip fracture
risk by at least 20%; however, the effect on non-vertebral fracture was much less
robust with a probability of 0.27.
CONCLUSIONS: Results of this Bayesian consideration are highly consistent with
the hypothesis that statin use reduces hip fracture, but the association between
statin use and non-vertebral fracture remains uncertain. The Bayesian approach
presented here has the ability to help updating existing evidence as new data
becomes available.

PMID: 17178257  [PubMed - indexed for MEDLINE]


312. J Clin Epidemiol. 2007 Apr;60(4):336-44. Epub 2006 Oct 23.

Hip protectors decrease hip fracture risk in elderly nursing home residents: a
Bayesian meta-analysis.

Sawka AM(1), Boulos P, Beattie K, Papaioannou A, Gafni A, Cranney A, Hanley DA,
Adachi JD, Papadimitropoulos EA, Thabane L.

Author information:
(1)Division of Endocrinology and Department of Medicine, University Health
Network, University of Toronto, Toronto, Ontario, Canada. sawkaam@yahoo.com

Erratum in
    J Clin Epidemiol. 2008 Aug;61(8):854.

OBJECTIVE: To design a Bayesian random effects model for pooling binary outcome
data from cluster randomized trials (CRTs) with individually randomized trials
(IRTs) and then use this model to determine if hip protectors decrease the risk
of hip fracture in elderly nursing home residents.
STUDY DESIGN AND SETTING: Eight electronic databases were searched; abstracts and
papers were reviewed in duplicate. Randomized controlled trials of hip protectors
in nursing homes were included. The pooled mean odds ratio (OR) of a hip fracture
in an individual allocated to hip protectors with 95% credibility interval (CRI)
was calculated.
RESULTS: We included four trials of 1,922 individuals (including three CRTs). The
pooled OR of an elderly nursing home resident sustaining one or more hip
fractures with hip protector allocation was 0.40 (95% CRI 0.25, 0.61). The model
was robust in multiple sensitivity analyses assuming alternative intracluster
correlation coefficient values.
CONCLUSION: The Bayesian approach may be used in meta-analyses of IRTs and CRTs.
Using this approach, we have determined that hip protectors decrease the risk of
hip fracture in elderly nursing home residents. Methodologic limitations of the
included trials and a possible herd effect in CRTs may have influenced these
results.

PMID: 17346606  [PubMed - indexed for MEDLINE]


313. Stat Med. 2007 Feb 28;26(5):1150-69.

Assessing the combined effect of asbestos exposure and smoking on lung cancer: a
Bayesian approach.

Wraith D(1), Mengersen K.

Author information:
(1)School of Mathematical Sciences, Queensland University of Technology,
Brisbane, Australia. s.wraith@qut.edu.au

We review the literature on the combined association between lung cancer and two
environmental exposures, asbestos exposure and smoking, and explore a Bayesian
approach to assess evidence of interaction between the exposures. The
meta-analysis combines separate indices of additive and multiplicative
relationships and multivariate relative risk estimates. By making inferences on
posterior probabilities we can explore both the form and strength of interaction.
This analysis may be more informative than providing evidence to support one
relation over another on the basis of statistical significance. Overall, we find
evidence for a more than additive and less than multiplicative relation.

Copyright (c) 2006 John Wiley & Sons, Ltd.

PMID: 16779874  [PubMed - indexed for MEDLINE]


314. Am J Obstet Gynecol. 2006 Oct;195(4):1163-73.

Diagnostic accuracy of noninvasive fetal Rh genotyping from maternal blood--a
meta-analysis.

Geifman-Holtzman O(1), Grotegut CA, Gaughan JP.

Author information:
(1)Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and
Reproductive Sciences, Temple University School of Medicine, Philadelphia, PA,
USA. geifmao@tuhs.temple.edu

Comment in
    Am J Obstet Gynecol. 2007 Jul;197(1):116-7; author reply 117-8.

OBJECTIVE: The purpose of this study was to determine the reported diagnostic
accuracy, the validity, and the current limitations of fetal Rh genotyping from
peripheral maternal blood based on the existing English-written publications.
STUDY DESIGN: A search of the English literature describing fetal RhD
determination from maternal blood was conducted. From each study, we determined
the number of samples tested, fetal RhD genotype, the source of the fetal DNA
(maternal plasma, serum, or fetal cells), gestational age, and confirmation of
fetal Rh type. The presence of alloimmunization and exclusions of tested samples
were noted. For the meta-analysis we calculated composite estimates using 2
random effects models, weighted GLM and Bayesian. Sensitivity, specificity,
positive and negative predictive values were calculated.
RESULTS: We identified 37 English-written publications that included 44 protocols
reporting noninvasive Rh genotyping using fetal DNA obtained from maternal blood
on a total of 3261 samples. A total of 183 (183/3261, 5.6%) samples were excluded
from the meta-analysis. The overall diagnostic accuracy after exclusions was
94.8%. The gestational ages ranged between 8 and 42 weeks gestation. Maternal
serum and plasma were found to be the best source for accurate diagnosis of fetal
RhD type in 394/410 (96.1%) and 2293/2377 (96.5%), respectively. There were
719/783 (91.8%) alloimmunized patients that were correctly diagnosed. There were
16 studies that reported 100% diagnostic accuracy in their fetal RhD genotyping.
CONCLUSION: The diagnostic accuracy of noninvasive fetal Rh determination using
maternal peripheral blood is 94.8%. Its use can be applicable to Rh prophylaxis
and to the management of Rh alloimmunized pregnancies. Improvements of the
technique and further study of structure and rearrangements of the RhD gene may
improve accuracy of testing and enable large-scale, risk-free fetal RhD
genotyping using maternal blood.

PMID: 17000250  [PubMed - indexed for MEDLINE]


315. Int J Technol Assess Health Care. 2006 Fall;22(4):484-96.

Reanalysis of systematic reviews: the case of invasive strategies for acute
coronary syndromes.

Kuukasjärvi P(1), Nordhausen K, Malmivaara A.

Author information:
(1)Finnish Office for Health Technology Assessment (FinOHTA), Helsinki.
pekka.kuukasjarvi@stakes.fi

OBJECTIVES: The objective of this study was to collect all systematic reviews on
invasive strategies for acute coronary syndromes (ACS) and reanalyze the data in
these reviews to reach combined estimates, as well as to make predictions on the
effectiveness and risk of harm so as to facilitate relevant decision making in
health care.
METHODS: The data sources used were the following electronic databases, searched
from 1994 to September 2004: Cochrane Database of Systematic Reviews; Cochrane
Central Register of Controlled Trials; DARE, HTA, EED (NHS CRD); MEDLINE
In-Process, Other Non-Indexed Citations, MEDLINE, and PubMed (2000 to 2004).
References to the identified systematic reviews were checked. An ancillary search
to identify recent randomized controlled trials (RCTs) covering the period from
January 2003 to January 2006 was done in MEDLINE(R). We included systematic
reviews of RCTs on patients with ACS. In unstable angina and non-ST-elevation
myocardial infarction (UA/NSTEMI), eligible reviews had to compare early routine
invasive strategy with early selective invasive strategy. In ST-elevation
myocardial infarction (STEMI), a comparison between primary percutaneous coronary
intervention (PCI) and thrombolytic therapy was required. The methodological
quality of the reviews was assessed, and a standardized data extraction form was
used. Results for the main outcomes of the RCTs in the reviews were reanalyzed.
An additional search of those RCTs not included in the meta-analyses was
performed for UA/NSTEMI and short-term morality data on STEMI. Bayesian models
were constructed to estimate the uncertainty about a possible treatment effect
and to make predictions and probability statements. Main results are based on
these analyses. Mortality was considered as the primary outcome measure.
RESULTS: One systematic review on invasive strategies was identified for
UA/NSTEMI and nine on invasive strategies for STEMI. Five reviews of the latter
that were published after the year 2000 were included for the final analysis. The
median quality score was 10.5 (range, 7-13; n = 6) on a scale from 0 to 18
points. An updated literature search identified one further RCT on UA/NSTEMI.
Regarding NSTEMI and mortality, the average risk difference favoring an early
invasive treatment strategy compared with early conservative strategy was .6
percent (95 percent credible interval [CrI], -2.1 to 1.0). Predicted risk
(relative risk/risk difference scales) of doing harm was 26.7/26.6 percent.
Regarding STEMI and mortality, the absolute risk reduction in favor of primary
PCI over thrombolysis was 4.1 percent (95 percent CrI, -7.1 to -1.1) when PCI was
compared with streptokinase and 1.2 percent (95 percent CrI, -2.7 to .2) when
compared with fibrin-specific thrombolytics. Predicted risk of harm was 8.9/5.3
percent and 8.0/13.3 percent, respectively.
CONCLUSIONS: There seems to be at present no solid evidence for survival benefit
on early invasive strategy for UA/NSTEMI as a broad diagnostic group, and the
risk of doing harm should be considered. Also, the evidence for PCI to decrease
early mortality after STEMI is scanty. Estimations of predicted harm may further
aid decisions on whether to implement the new treatment over the old one. It may
also give an additional dimension for interpreting the results of any
meta-analysis.

PMID: 16984682  [PubMed - indexed for MEDLINE]


316. Invest Ophthalmol Vis Sci. 2006 Oct;47(10):4254-61.

Variations in primary open-angle glaucoma prevalence by age, gender, and race: a
Bayesian meta-analysis.

Rudnicka AR(1), Mt-Isa S, Owen CG, Cook DG, Ashby D.

Author information:
(1)Division of Community Health Sciences, St. George's, University of London, UK.
arudnicka@sgul.ac.uk

PURPOSE: To quantify the variation in primary open-angle glaucoma (OAG)
prevalence with age, gender, race, year of publication, and survey methodology.
METHODS: Medline, EMBASE, and PubMed were searched for studies of OAG prevalence.
Studies with defined population samplings were sought. Forty-six published
observational studies of OAG prevalence (103,567 participants with 2509 cases of
OAG) were identified for inclusion in the systematic review and meta-analysis.
Data on the number of people and the number of cases of OAG by age, race, and
gender were sought for each study. Additional information was obtained regarding
whether the definition of glaucoma relied on raised intraocular pressure (IOP)
and whether visual field examination was performed routinely on all individuals.
Bayesian meta-analysis was used to model the associations between the log odds of
OAG and age, race, gender, year of publication, method of visual field testing,
and effect of reliance on IOP in the definition of OAG.
RESULTS: Black populations had the highest OAG prevalence at all ages, but the
proportional increase in prevalence of OAG with age was highest in white
populations. The odds ratio per decade increase in age was 2.05 in white
populations (95% credible interval, 1.91 to 2.18), 1.61 (95% credible interval,
1.53 to 1.70) in black populations, and 1.57 (95% credible interval, 1.46 to
1.68) in Asian populations. The average estimated prevalence in those older than
70 years of age was 6% in white populations, 16% in black populations, and 3% in
Asian populations. After adjusting for age, race, year of publication, and survey
methods, men were 1.37 (95% credible interval, 1.22 to 1.53) times more likely
than women to have OAG. The prevalence of OAG was one third lower in studies in
which routine visual fields were not assessed and that used an IOP criterion in
the definition of glaucoma; this effect was reduced to the null after adjustment
for age, racial group, and year of publication.
CONCLUSIONS: Although black populations had the highest prevalence of OAG at all
ages, white populations showed the steepest increase in OAG prevalence with age.
Men were more likely than women to have OAG.

PMID: 17003413  [PubMed - indexed for MEDLINE]


317. Stat Med. 2006 Sep 15;25(17):2886-910.

Estimating transitions between symptom severity states over time in
schizophrenia: a Bayesian meta-analytic approach.

Basu A(1), Meltzer HY, Dukic V.

Author information:
(1)Department of Medicine, Section of General Internal Medicine, University of
Chicago, 5841 S. Maryland Ave, MC 2007, AMD B201, Chicago, IL 60637, USA.
abasu@medicine.bsd.uchicago.edu

We obtain the posterior predictive distribution of transition probabilities
between symptom severity states over time for patients with schizophrenia by (i)
employing a Bayesian meta-analysis of published clinical trials and observational
studies to estimate the posterior distribution of parameters that guide changes
in Positive and Negative Syndrome Scale (PANSS) scores over time and under the
influence of various drugs and (ii) by propagating the variability from the
posterior distributions of the parameters through a micro-simulation model that
is formulated based on schizophrenia progression. Results show detailed
differences among haloperidol, risperidone and olanzapine in controlling various
levels of severities of positive, negative and joint symptoms over time. For
example, risperidone seems best in controlling severe positive symptoms while
olanzapine is the worst in that during the first quarter of drug treatment;
however, olanzapine seems to be best in controlling severe negative symptoms
across all four quarters of treatment while haloperidol is the worst in this
regard. These details may further serve to better estimate quality of life of
patients and aid in resource utilization decisions in treating schizophrenic
patients. In addition, consistent estimation of uncertainty in the time-profile
parameters also has important implications for the practice of cost-effectiveness
analysis and for future resource allocation policies in schizophrenia treatment.

Copyright 2005 John Wiley & Sons, Ltd.

PMID: 16220519  [PubMed - indexed for MEDLINE]


318. JAMA. 2006 Aug 9;296(6):679-90.

Adherence to antiretroviral therapy in sub-Saharan Africa and North America: a
meta-analysis.

Mills EJ(1), Nachega JB, Buchan I, Orbinski J, Attaran A, Singh S, Rachlis B, Wu
P, Cooper C, Thabane L, Wilson K, Guyatt GH, Bangsberg DR.

Author information:
(1)Centre for International Health and Human Rights Studies, Toronto, Ontario,
Canada. emills@cihhrs.org

CONTEXT: Adherence to antiretroviral therapy is a powerful predictor of survival
for individuals living with human immunodeficiency virus (HIV) and AIDS. Concerns
about incomplete adherence among patients living in poverty have been an
important consideration in expanding the access to antiretroviral therapy in
sub-Saharan Africa.
OBJECTIVE: To evaluate estimates of antiretroviral therapy adherence in
sub-Saharan Africa and North America.
DATA SOURCES: Eleven electronic databases were searched along with major
conference abstract databases (inclusion dates: inception of database up until
April 18, 2006) for all English-language articles and abstracts; and researchers
and treatment advocacy groups were contacted. Study Selection and Data
Abstraction To best reflect the general population, studies of mixed populations
in both North America and Africa were selected. Studies evaluating specific
populations such as men only, homeless individuals, or drug users, were excluded.
The data were abstracted in duplicate on study adherence outcomes, thresholds
used to determine adherence, and characteristics of the populations. A
random-effects meta-analysis was performed in which heterogeneity was examined
using multivariable random-effects logistic regression. A sensitivity analysis
was performed using Bayesian methods.
DATA SYNTHESIS: Thirty-one studies from North America (28 full-text articles and
3 abstracts) and 27 studies (9 full-text articles and 18 abstracts) from
sub-Saharan Africa were included. African studies represented 12 sub-Saharan
countries. Of the North American studies, 71% used patient self-report to assess
adherence; this was true of 66% of the African assessments. Studies reported
similar thresholds for adherence monitoring (eg, 100%, >95%, >90%, >80%). A
pooled analysis of the North American studies (17,573 patients total) indicated a
pooled estimate of 55% (95% confidence interval, 49%-62%; I2, 98.6%) of the
populations achieving adequate levels of adherence. Our pooled analysis of
African studies (12,116 patients total) indicated a pooled estimate of 77% (95%
confidence interval, 68%-85%; I2, 98.4%). Study continent, adherence thresholds,
and study quality were significant predictors of heterogeneity. Bayesian analysis
was used as an alternative statistical method for combining adherence rates and
provided similar findings.
CONCLUSION: Our findings indicate that favorable levels of adherence, much of
which was assessed via patient self-report, can be achieved in sub-Saharan
African settings and that adherence remains a concern in North America.

PMID: 16896111  [PubMed - indexed for MEDLINE]


319. PLoS Med. 2006 Aug;3(8):e272.

Frequency of adverse events after vaccination with different vaccinia strains.

Kretzschmar M(1), Wallinga J, Teunis P, Xing S, Mikolajczyk R.

Author information:
(1)Department of Infectious Diseases Epidemiology, Rijksinstituut voor
Volksgezondheid en Milieu/National Institute for Public Health and the
Environment, Bilthoven, Netherlands. mirjam.kretzschmar@uni-bielefeld.de

Erratum in
    PLoS Med. 2006 Oct;3(10):e429.

BACKGROUND: Large quantities of smallpox vaccine have been stockpiled to protect
entire nations against a possible reintroduction of smallpox. Planning for an
appropriate use of these stockpiled vaccines in response to a smallpox outbreak
requires a rational assessment of the risks of vaccination-related adverse
events, compared to the risk of contracting an infection. Although considerable
effort has been made to understand the dynamics of smallpox transmission in
modern societies, little attention has been paid to estimating the frequency of
adverse events due to smallpox vaccination. Studies exploring the consequences of
smallpox vaccination strategies have commonly used a frequency of approximately
one death per million vaccinations, which is based on a study of vaccination with
the New York City Board of Health (NYCBH) strain of vaccinia virus. However, a
multitude of historical studies of smallpox vaccination with other vaccinia
strains suggest that there are strain-related differences in the frequency of
adverse events after vaccination. Because many countries have stockpiled vaccine
based on the Lister strain of vaccinia virus, a quantitative evaluation of the
adverse effects of such vaccines is essential for emergency response planning. We
conducted a systematic review and statistical analysis of historical data
concerning vaccination against smallpox with different strains of vaccinia virus.
METHODS AND FINDINGS: We analyzed historical vaccination data extracted from the
literature. We extracted data on the frequency of postvaccinal encephalitis and
death with respect to vaccinia strain and age of vaccinees. Using a hierarchical
Bayesian approach for meta-analysis, we estimated the expected frequencies of
postvaccinal encephalitis and death with respect to age at vaccination for
smallpox vaccines based on the NYCBH and Lister vaccinia strains. We found large
heterogeneity between findings from different studies and a time-period effect
that showed decreasing incidences of adverse events over several decades. To
estimate death rates, we then restricted our analysis to more-recent studies. We
estimated that vaccination with the NYCBH strain leads to an average of 1.4
deaths per million vaccinations (95% credible interval, 0-6) and that vaccination
with Lister vaccine leads to an average of 8.4 deaths per million vaccinations
(95% credible interval, 0-31). We combined age-dependent estimates of the
frequency of death after vaccination and revaccination with demographic data to
obtain estimates of the expected number of deaths in present societies due to
vaccination with the NYCBH and Lister vaccinia strains.
CONCLUSIONS: Previous analyses of smallpox vaccination policies, which rely on
the commonly assumed value of one death per million vaccinations, may give
serious underestimates of the number of deaths resulting from vaccination.
Moreover, because there are large, strain-dependent differences in the frequency
of adverse events due to smallpox vaccination, it is difficult to extrapolate
from predictions for the NYCBH-derived vaccines (stockpiled in countries such as
the US) to predictions for the Lister-derived vaccines (stockpiled in countries
such as Germany). In planning for an effective response to a possible smallpox
outbreak, public-health decision makers should reconsider their strategies of
when to opt for ring vaccination and when to opt for mass vaccination.

PMCID: PMC1551910
PMID: 16933957  [PubMed - indexed for MEDLINE]


320. Am J Epidemiol. 2006 May 1;163(9):811-7. Epub 2006 Mar 22.

A Bayesian meta-analysis of prophylactic granulocyte colony-stimulating factor
and granulocyte-macrophage colony-stimulating factor in children with cancer.

Sung L(1), Beyene J, Hayden J, Nathan PC, Lange B, Tomlinson GA.

Author information:
(1)Department of Pediatrics, University of Toronto and The Hospital for Sick
Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.
Lillian.sung@sickkids.ca

The purpose of this analysis was to examine the efficacy of prophylactic
hematopoietic colony-stimulating factors (CSFs) in pediatric cancer and to
describe how a Bayesian meta-analysis can be conducted and then modified to
incorporate information not readily included in a frequentist meta-analysis.
Three Bayesian models were developed. The simplest model used the same data as a
published frequentist meta-analysis. The second model included data that could
not easily be incorporated into the frequentist meta-analysis, including data
from different courses of chemotherapy and continuous outcomes that did not
report variance estimates. The third model examined the effect of CSF type
(granulocyte CSF vs. granulocyte-macrophage CSF). Compared with the frequentist
model, the Bayesian model with the most data suggested a greater benefit of CSFs,
with a 3.2-day reduction in duration of parenteral antibiotics (95% credible
interval: -7.1, 0.7) in the expanded Bayesian model compared with a 0.8-day (95%
confidence interval: -2.3, 0.7) reduction in the frequentist model. Bayesian
meta-analysis also suggested that, compared with granulocyte-macrophage CSF,
granulocyte CSF was associated with a 4.8-day decrease in the duration of
parenteral antibiotics. Bayesian meta-analysis can readily include information
not easily incorporated in a frequentist meta-analysis. Some treatment effect
estimates were larger by a clinically important amount when additional data
contributed to the pooled estimate.

PMID: 16554346  [PubMed - indexed for MEDLINE]


321. Br J Surg. 2006 May;93(5):539-46.

Meta-analysis of sentinel lymph node biopsy after preoperative chemotherapy in
patients with breast cancer.

Xing Y(1), Foy M, Cox DD, Kuerer HM, Hunt KK, Cormier JN.

Author information:
(1)Department of Surgical Oncology, University of Texas M. D. Anderson Cancer
Center, Texas 77230, USA.

Comment in
    Br J Surg. 2006 Aug;93(8):1025-6; author reply 1026.

BACKGROUND: Women with breast cancer are more frequently being treated with
preoperative neoadjuvant chemotherapy. The reliability of sentinel lymph node
biopsy (SLNB) following chemotherapy has not been determined. This was a
meta-analysis of studies that examined the results of SLNB after preoperative
chemotherapy.
METHODS: Included articles had to meet two criteria. First, patients had to have
had operable breast cancer and to have undergone SLNB after preoperative
chemotherapy and, second, patients had to have undergone subsequent axillary
lymph node dissection. Meta-analyses were performed in which Bayesian
hierarchical models were created to estimate the identification rate (IR) and
sensitivity of SLNB in this setting.
RESULTS: Twenty-one studies were identified that included a total of 1273
patients. The IRs reported ranged from 72 to 100 per cent, with a pooled estimate
of 90 per cent. The sensitivity of SLNB ranged from 67 to 100 per cent, with a
pooled estimate of 88 (95 per cent confidence interval 85 to 90) per cent.
Meta-analyses performed using Bayesian modelling resulted in (posterior)
estimates for IR and sensitivity of 91 (95 per cent credible interval 88 to 94)
and 88 (95 per cent credible interval 84 to 91) per cent respectively.
CONCLUSION: SLNB is a reliable tool for planning treatment after preoperative
chemotherapy.

PMID: 16329089  [PubMed - indexed for MEDLINE]


322. Curr Med Res Opin. 2006 Apr;22(4):671-81.

Self-monitoring of glucose in type 2 diabetes mellitus: a Bayesian meta-analysis
of direct and indirect comparisons.

Jansen JP(1).

Author information:
(1)Mapi Values, Houten, The Netherlands. jeroen.jansen@mapivalues.com

OBJECTIVE: To evaluate the relative effectiveness of interventions with
self-monitoring blood glucose and self-monitoring of urine glucose, versus
interventions without self-monitoring, in terms of HbA(1c) reductions in type 2
diabetes mellitus.
METHODS: Thirteen published full reports on randomised controlled trials
investigating the effects of self-monitoring glucose were identified by a
systematic search of Medline, Embase, the Cochrane Library (1966-Nov 2005) and
previous reviews. Three types of studies were included: self-monitoring of blood
glucose versus no self-monitoring, self-monitoring of blood glucose versus
self-monitoring of urine glucose and self-monitoring of blood glucose with
regular feedback versus monitoring without feedback. The internal validity of
studies was assessed systematically by two reviewers, using 13 criteria of a
validated list. Results from the three types of studies were analysed
simultaneously with a Bayesian metaanalysis of direct and indirect comparisons.
RESULTS: Adjusted for baseline HbA(1c) level and internal validity, interventions
with self-monitoring of blood glucose showed a reduction in HbA(1c) of 0.40
percentage-points (%) (95% credible interval [CrI] 0.07 to 0.70%) in comparison
to interventions without self-monitoring. Regular feedback more than doubled the
HbA(1c) reduction. Self-monitoring of urine glucose showed comparable results to
interventions without self-monitoring (0.02% decrease in HbA(1c); 95% CrI -0.62
to 0.70%). There is a 88% probability that interventions with self-monitoring
blood glucose are more effective than interventions with urine glucose monitoring
(relative reduction in HbA(1c) is 0.38%, 95% CrI -0.30 to 1.00%).
CONCLUSION: The randomized clinical trials performed to date provided positive
results on the effectiveness of interventions with self-monitoring of blood
glucose in type 2 diabetes mellitus. Regular medical feedback of the monitored
HbA(1c) levels is important. Furthermore, self-monitoring of blood glucose is
likely to be more effective than self-monitoring of urine glucose.

PMID: 16684428  [PubMed - indexed for MEDLINE]


323. HIV Med. 2006 Apr;7(3):173-80.

Effect of early and late GB virus C viraemia on survival of HIV-infected
individuals: a meta-analysis.

Zhang W(1), Chaloner K, Tillmann HL, Williams CF, Stapleton JT.

Author information:
(1)Department of Biostatistics, College of Public Health, University of Iowa,
Iowa City, IA 52242, USA.

OBJECTIVES: To conduct a meta-analysis to synthesize the evidence regarding the
effect of co-infection with GB virus C (GBV-C) on survival of HIV-infected
individuals, and to estimate the effect.
METHODS: A Bayesian meta-analysis was conducted to synthesize evidence from
eligible studies. Prospective survival studies of HIV-1-infected individuals,
with outcome defined as time from baseline to all-cause death, were included and
classified by whether GBV-C status was determined in early or late HIV disease.
The primary measure was the hazard ratio (HR) of death for HIV-infected
individuals with GBV-C infection versus those without GBV-C infection.
RESULTS: Eleven studies from eight publications met the inclusion criteria. For
studies with GBV-C status measured 2 years or less after HIV seroconversion (912
subjects), the combined HR was 0.88 [95% credible interval (CI) 0.30, 1.50]. For
studies with GBV-C status measured more than 2 years after HIV seroconversion
(1294 subjects), the combined HR was 0.41 (95% CI 0.23, 0.69).
CONCLUSIONS: No conclusive evidence was found of an association between survival
and GBV-C infection early in HIV disease. However, when GBV-C infection was
present later in HIV disease, a significant reduction in the hazard for mortality
was observed for those with co-infection. Potential explanations for this
difference include a non-proportional benefit of GBV-C over time, possibly
related to clearance of GBV-C infection early in HIV disease. The timing of GBV-C
infection appears to account for the contradictory results of studies on the
effect of GBV-C coinfection on survival of HIV-infected people.

PMID: 16494631  [PubMed - indexed for MEDLINE]


324. J Bone Miner Res. 2006 Feb;21(2):340-9.

Anti-hip fracture efficacy of biophosphonates: a Bayesian analysis of clinical
trials.

Nguyen ND(1), Eisman JA, Nguyen TV.

Author information:
(1)Bone and Mineral Research Program, Garvan Institute of Medical Research, St
Vincent's Hospital, University of New South Wales, Sydney, Australia.

In postmenopausal women, the efficacy of bisphosphonates on hip fracture risk is
not clear. This Bayesian meta-analysis quantitatively reviewed data from 12
randomized clinical trials with 18,667 patients and found that bisphosphonate
treatment was associated with a reduced risk for hip fracture by
42%.INTRODUCTION: The efficacy of antiresorptive bisphosphonates therapy on
reducing hip fracture is not clear, because evidence from randomized clinical
trials (RCTs) is inconclusive. This study was undertaken to quantitatively assess
the effect of bisphosphonates on hip fracture using literature review and
meta-analysis.
MATERIALS AND METHODS: Bayesian methods of meta-analysis were applied to
synthesize data from 12 RCTs available between 1990 and 2004. The trials involved
18,667 postmenopausal women with low BMD or osteoporosis who have been followed
or treated for between 1 and 4 years. The medications used were etidronate (two
trials) alendronate (six trials), risedronate (three trials), and clodronate (one
trial). The primary endpoint was the incidence of hip fracture.
RESULTS: When data from all 12 studies were pooled, treatment with
bisphosphonates was associated with a reduced risk for hip fracture by 42%
(relative risk [RR], 0.58; 95% credible interval [CrI], 0.42-0.80). The absolute
rate reduction was 52 hip fractures per 10,000 women (95% CrI, 4-110) for a
period of 3-year treatment. The probability that bisphosphonates are better than
placebo (in reducing hip fracture risk by at least 30%) was 0.90.
CONCLUSIONS: In postmenopausal women with osteoporosis or low BMD, bisphosphonate
treatment is associated with reduced risk of hip fracture.

PMID: 16526127  [PubMed - indexed for MEDLINE]


325. Vaccine. 2006 Jan 16;24(3):272-9. Epub 2005 Aug 18.

Efficacy of inactivated hepatitis A vaccine in HIV-infected patients: a
hierarchical bayesian meta-analysis.

Shire NJ(1), Welge JA, Sherman KE.

Author information:
(1)College of Medicine, University of Cincinnati, 231 Albert Sabin Way, ML-0595,
Cincinnati, OH 45267, USA. norah.shire@uc.edu

Patients with human immunodeficiency virus-1 (HIV) have elevated risk for
hepatitis A virus (HAV) coinfection. Sequelae from coinfection include increased
risk of liver-related morbidity and mortality. This study synthesizes the results
of trials measuring response to HAV vaccine in HIV-infected patients using
Bayesian meta-analysis methodologies. PubMed, OhioLINK/Medline, and other sources
were used to search for studies analyzing response to HAV vaccine in HIV-infected
patients. Studies were evaluated for quality. A Bayesian hierarchical
random-effects model was used to estimate overall response to vaccine.
Between-study variance was calculated. Sensitivity analyses were conducted to
determine the potential for bias. The literature search yielded eight studies for
inclusion in the meta-analysis, with a combined total of 458 patients. Observed
proportions of response in individual studies ranged from 50 to 95%. The
intention-to-treat meta-analysis estimated a combined proportion of HIV+ patients
responding to vaccine of 64% (95% CI 52-75%). Heterogeneity between studies was
significant. The overall response rate to HAV vaccine in HIV-infected patients is
lower than typically cited. Up to 1/2 of HIV-infected patients may be
nonresponders. Future research will be required to better understand the
correlates of response.

PMID: 16139398  [PubMed - indexed for MEDLINE]


326. Clin Trials. 2006;3(2):73-90; discussion 91-8.

Do antidepressants cause suicidality in children? A Bayesian meta-analysis.

Kaizar EE(1), Greenhouse JB, Seltman H, Kelleher K.

Author information:
(1)Department of Statistics, Carnegie Mellon University, Pittsburgh, PA 15217,
USA.

BACKGROUND: To quantify the risk of suicidal behavior/ideation (suicidality) for
children who use antidepressants, the FDA collected randomized placebo-controlled
trials of antidepressant efficacy in children. Although none of the 4487 children
completed suicide, 1.7% exhibited suicidality. The FDA meta-analyzed these
studies and found sufficient evidence of an increased risk to require a black-box
warning on antidepressants for children.
PURPOSE: The FDA considered different drug formulations and psychiatric diagnoses
to be equivalent in their effect on suicidality. If this assumption does not
hold, the FDA analysis may have underestimated the variance of the risk estimate.
We investigate the consequences of relaxing these assumptions.
METHODS: We extend the FDA analysis using a Bayesian hierarchical model that
allows for a study-level component of variability and facilitates extensive
sensitivity analyses.
RESULTS: We found an association between antidepressant use and an increased risk
of suicidality in studies where the diagnosis was major depressive disorder (odds
ratio 2.3 [1.3, 3.8]), and where the antidepressant was an SSRI (odds ratio 2.2
[1.3, 3.6]). We did not find evidence for such an association in the complement
sets of trials. Although the results based on the hierarchical model are
insensitive to model perturbations, the robustness of the FDA's meta-analysis to
model assumptions is less clear. These data have limited generalizability due to
exclusion of patients with baseline risk of suicide and the use of relatively
short duration trials.
CONCLUSIONS: Because of model specification and interpretation issues raised in
this paper, we conclude that the evidence supporting a causal link between
antidepressant use and suicidality in children is weak. The use of Bayesian
hierarchical models for meta-analysis has facilitated the incorporation of
potentially important sources of variability and the use of sensitivity analysis
to assess the consequences of model specifications and their impact on important
regulatory decisions.

PMID: 16773951  [PubMed - indexed for MEDLINE]


327. J Womens Health (Larchmt). 2006 Jan-Feb;15(1):98-105.

Cancer incidence among female flight attendants: a meta-analysis of published
data.

Buja A(1), Mastrangelo G, Perissinotto E, Grigoletto F, Frigo AC, Rausa G, Marin
V, Canova C, Dominici F.

Author information:
(1)Department of Environmental Medicine and Public Health, University of Padua,
35128 Padua, Italy. alessandra.buja@unipd.it

BACKGROUND: Flight attendants are exposed to cosmic ionizing radiation and other
potential cancer risk factors, but only recently have epidemiological studies
been performed to assess the risk of cancer among these workers. The aim of the
present work was to evaluate the incidence of various types of cancer among
female cabin attendants by combining cancer incidence estimates reported in
published studies.
METHODS: All follow-up studies reporting standardized incidence ratio (SIR) for
cancer among female flight attendants were obtained from online databases and
analyzed. A metaanalysis was performed by applying Bayesian hierarchical models,
which take into account studies that reported SIR = 0 and natural heterogeneity
of study-specific SIRs.
RESULTS: A total of seven published studies reporting SIR for several cancer
types were extracted. Meta-analysis showed a significant excess of melanoma
(meta-SIR 2.15, 95% posterior interval [PI] 1.56-2.88) and breast carcinoma
(meta-SIR 1.40; PI 1.19-1.65) and a slight but not significant excess of cancer
incidence across types (meta-SIR 1.11, PI 0.98-1.25).
CONCLUSIONS: Although further studies are necessary to clarify the exact role of
occupational exposure, all airlines should, as some companies do, estimate
radiation dose, organize the schedules of crew members in order to reduce further
exposure in highly exposed flight attendants, inform crew members about health
risks, and give special protection to pregnant women.

PMID: 16417424  [PubMed - indexed for MEDLINE]


328. Stat Med. 2005 Dec 30;24(24):3823-44.

Meta-analysis of heterogeneously reported trials assessing change from baseline.

Abrams KR(1), Gillies CL, Lambert PC.

Author information:
(1)Centre for Biostatistics and Genetic Epidemiology, Department of Health
Sciences, University of Leicester, UK. keith.abrams@le.ac.uk

This paper considers the quantitative synthesis of published comparative study
results when the outcome measures used in the individual studies and the way in
which they are reported varies between studies. Whilst the former difficulty may
be overcome, at least to a limited extent, by the use of standardized effects,
the latter is often more problematic. Two potential solutions to this problem
are; sensitivity analyses and a fully Bayesian approach, in which pertinent
external information is included. Both approaches are illustrated using the
results of two systematic reviews and meta-analyses which consider the difference
in mean change in systolic blood pressure and the difference in physical
functioning between an intervention and control group. The two examples
illustrate that by adopting a fully Bayesian approach, as opposed to undertaking
sensitivity analyses assuming fixed values for unknown parameters, the overall
intervention effect can be estimated with greater uncertainty, but that assessing
the sensitivity of results to choice of prior distributions in such analyses is
crucial.

Copyright 2005 John Wiley & Sons, Ltd.

PMID: 16320285  [PubMed - indexed for MEDLINE]


329. Stat Med. 2005 Dec 30;24(24):3845-61.

Bayesian implementation of a genetic model-free approach to the meta-analysis of
genetic association studies.

Minelli C(1), Thompson JR, Abrams KR, Lambert PC.

Author information:
(1)Centre for Biostatistics and Genetic Epidemiology, Department of Health
Sciences, University of Leicester, Leicester, UK. cm109@le.ac.uk

A genetic model-free method for the meta-analysis of genetic association studies
is described that estimates the mode of inheritance from the data rather than
assuming that it is known. For a bi-allelic polymorphism, with G as risk allele
and g as wild-type, the genetic model depends on the ratio of the two log odds
ratios, lambda = log OR(Gg)/log OR(GG), where OR(GG) compares GG with gg and
OR(Gg) compares Gg with gg. Modelling log OR(GG) as a random effect creates a
hierarchical model that can be implemented within a Bayesian framework. In
Bayesian modelling, vague prior distributions have to be specified for all
unknown parameters when no external information is available. When the data are
sparse even supposedly vague prior distributions may have an influence on the
posterior estimates. We investigate the impact of different vague prior
distributions for the between-study standard deviation of log OR(GG) and for
lambda, by considering three published meta-analyses and associated simulations.
Our results show that depending on the characteristics of the meta-analysis the
results may indeed be sensitive to the choice of vague prior distribution for
either parameter. Genetic association studies usually use a case-control design
that should be analysed by the corresponding retrospective likelihood. However,
under some circumstances the prospective likelihood has been shown to produce
identical results and it is usually preferred for its simplicity. In our
meta-analyses the two likelihoods give very similar results.

Copyright 2005 John Wiley & Sons, Ltd.

PMID: 16320276  [PubMed - indexed for MEDLINE]


330. BMC Musculoskelet Disord. 2005 Jul 11;6:39.

Does alendronate reduce the risk of fracture in men? A meta-analysis
incorporating prior knowledge of anti-fracture efficacy in women.

Sawka AM(1), Papaioannou A, Adachi JD, Gafni A, Hanley DA, Thabane L.

Author information:
(1)Department of Medicine, St, Joseph's Healthcare and McMaster University,
Hamilton, Ontario, Canada. sawkaam@yahoo.com

BACKGROUND: Alendronate has been found to reduce the risk of fractures in
postmenopausal women as demonstrated in multiple randomized controlled trials
enrolling thousands of women. Yet there is a paucity of such randomized
controlled trials in osteoporotic men. Our objective was to systematically review
the anti-fracture efficacy of alendronate in men with low bone mass or with a
history of prevalent fracture(s) and incorporate prior knowledge of alendronate
efficacy in women in the analysis.
METHODS: We examined randomized controlled trials in men comparing the
anti-fracture efficacy of alendronate to placebo or calcium or vitamin D, or any
combination of these. Studies of men with secondary causes of osteoporosis other
than hypogonadism were excluded. We searched the following electronic databases
(without language restrictions) for potentially relevant citations: Medline,
Medline in Process (1966-May 24/2004), and Embase (1996-2004). We also contacted
the manufacturer of the drug in search of other relevant trials. Two reviewers
independently identified two trials (including 375 men), which met all inclusion
criteria. Data were abstracted by one reviewer and checked by another. Results of
the male trials were pooled using Bayesian random effects models, incorporating
prior information of anti-fracture efficacy from meta-analyses of women.
RESULTS: The odds ratios of incident fractures in men (with 95% credibility
intervals) with alendronate (10 mg daily) were: vertebral fractures, 0.44 (0.23,
0.83) and non-vertebral fractures, 0.60 (0.29, 1.44).
CONCLUSION: In conclusion, alendronate decreases the risk of vertebral fractures
in men at risk. There is currently insufficient evidence of a statistically
significant reduction of non-vertebral fractures, but the paucity of trials in
men limit the statistical power to detect such an effect.

PMCID: PMC1182376
PMID: 16008835  [PubMed - indexed for MEDLINE]


331. BMC Cardiovasc Disord. 2005 Jul 4;5:19.

Are antifibrinolytic drugs equivalent in reducing blood loss and transfusion in
cardiac surgery? A meta-analysis of randomized head-to-head trials.

Carless PA(1), Moxey AJ, Stokes BJ, Henry DA.

Author information:
(1)School of Medical Practice and Population Health, Faculty of Health,
University of Newcastle, New South Wales, Australia.
Paul.Carless@newcastle.edu.au

BACKGROUND: Aprotinin has been shown to be effective in reducing peri-operative
blood loss and the need for re-operation due to continued bleeding in cardiac
surgery. The lysine analogues tranexamic acid (TXA) and epsilon aminocaproic acid
(EACA) are cheaper, but it is not known if they are as effective as aprotinin.
METHODS: Studies were identified by searching electronic databases and
bibliographies of published articles. Data from head-to-head trials were pooled
using a conventional (Cochrane) meta-analytic approach and a Bayesian approach
which estimated the posterior probability of TXA and EACA being equivalent to
aprotinin; we used as a non-inferiority boundary a 20% increase in the rates of
transfusion or re-operation because of bleeding.
RESULTS: Peri-operative blood loss was significantly greater with TXA and EACA
than with aprotinin: weighted mean differences were 106 mls (95% CI 37 to 227
mls) and 185 mls (95% CI 134 to 235 mls) respectively. The pooled relative risks
(RR) of receiving an allogeneic red blood cell (RBC) transfusion with TXA and
EACA, compared with aprotinin, were 1.08 (95% CI 0.88 to 1.32) and 1.14 (95% CI
0.84 to 1.55) respectively. The equivalent Bayesian posterior mean relative risks
were 1.15 (95% Bayesian Credible Interval [BCI] 0.90 to 1.68) and 1.21 (95% BCI
0.79 to 1.82) respectively. For transfusion, using a 20% non-inferiority
boundary, the posterior probabilities of TXA and EACA being non-inferior to
aprotinin were 0.82 and 0.76 respectively. For re-operation the Cochrane RR for
TXA vs. aprotinin was 0.98 (95% CI 0.51 to 1.88), compared with a posterior mean
Bayesian RR of 0.63 (95% BCI 0.16 to 1.46). The posterior probability of TXA
being non-inferior to aprotinin was 0.92, but this was sensitive to the inclusion
of one small trial.
CONCLUSION: The available data are conflicting regarding the equivalence of
lysine analogues and aprotinin in reducing peri-operative bleeding, transfusion
and the need for re-operation. Decisions are sensitive to the choice of clinical
outcome and non-inferiority boundary. The data are an uncertain basis for
replacing aprotinin with the cheaper lysine analogues in clinical practice.
Progress has been hampered by small trials and failure to study clinically
relevant outcomes.

PMCID: PMC1185524
PMID: 15992412  [PubMed - indexed for MEDLINE]


332. Biostatistics. 2005 Jul;6(3):450-64. Epub 2005 Apr 14.

Accuracy of MSI testing in predicting germline mutations of MSH2 and MLH1: a case
study in Bayesian meta-analysis of diagnostic tests without a gold standard.

Chen S(1), Watson P, Parmigiani G.

Author information:
(1)Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD
21205, USA. schen46@jhmi.edu

Microsatellite instability (MSI) testing is a common screening procedure used to
identify families that may harbor mutations of a mismatch repair (MMR) gene and
therefore may be at high risk for hereditary colorectal cancer. A reliable
estimate of sensitivity and specificity of MSI for detecting germline mutations
of MMR genes is critical in genetic counseling and colorectal cancer prevention.
Several studies published results of both MSI and mutation analysis on the same
subjects. In this article we perform a meta-analysis of these studies and obtain
estimates that can be directly used in counseling and screening. In particular,
we estimate the sensitivity of MSI for detecting mutations of MSH2 and MLH1 to be
0.81 (0.73-0.89). Statistically, challenges arise from the following: (a)
traditional mutation analysis methods used in these studies cannot be considered
a gold standard for the identification of mutations; (b) studies are
heterogeneous in both the design and the populations considered; and (c) studies
may include different patterns of missing data resulting from partial testing of
the populations sampled. We address these challenges in the context of a Bayesian
meta-analytic implementation of the Hui-Walter design, tailored to account for
various forms of incomplete data. Posterior inference is handled via a Gibbs
sampler.

PMCID: PMC2274000
PMID: 15831578  [PubMed - indexed for MEDLINE]


333. Radiology. 2005 Jul;236(1):85-94. Epub 2005 Jun 13.

Indeterminate ovarian mass at US: incremental value of second imaging test for
characterization--meta-analysis and Bayesian analysis.

Kinkel K(1), Lu Y, Mehdizade A, Pelte MF, Hricak H.

Author information:
(1)Department of Radiology, University Hospital Geneva, Geneva, Switzerland.
karen.kinkel@grangettes.ch

PURPOSE: To compare value of current diagnostic strategies in assessment of
changes in posttest probability of ovarian cancer when menopausal status and
combination and sequence of diagnostic imaging tests are considered.
MATERIALS AND METHODS: Prevalence of ovarian cancer according to menopausal
status in women with an ovarian mass and performance of combined gray-scale and
Doppler ultrasonography (US), computed tomography (CT), and non-enhanced magnetic
resonance (MR) imaging and contrast material-enhanced MR imaging after
indeterminate results at gray-scale US were derived from meta-analysis by using
MEDLINE database and institutional data. Study was approved by the institutional
review board of University Hospital Geneva, Geneva, Switzerland; informed consent
was waived. Posttest probability values were computed through Bayesian analysis
and Monte Carlo simulation after initial gray-scale US and secondary combined
gray-scale and Doppler US, CT, or MR imaging, while dependence of test results
among imaging modalities was considered. Changes in posttest probability were
compared among imaging modalities with summary receiver operating characteristic
curves.
RESULTS: Prevalence of ovarian cancer was 8.75% in premenopausal women and 32.40%
in postmenopausal women with an ovarian mass. After characterization with initial
gray-scale US, posttest probability in pre- and postmenopausal women changed,
respectively, to 25% and 63% for indeterminate results and to 2% and 7% for
benign results. Subsequent use of combined gray-scale and Doppler US, CT, or MR
imaging had significant higher positive and lower negative posttest probability
than did use of gray-scale US alone. In women with an indeterminate initial US
result, posttest probability decreased after secondary testing with benign
results for all imaging modalities to 2% in premenopausal women and to 8%-10% in
postmenopausal women. After secondary testing for suspicious lesions, posttest
probability increased more after non-enhanced (premenopausal women, 70%;
postmenopausal women, 92%) or contrast-enhanced MR imaging (premenopausal women,
80%; postmenopausal women, 95%) than it did after combined gray-scale and Doppler
US (premenopausal women, 30%; postmenopausal women, 69%) or CT (premenopausal
women, 38%; postmenopausal women, 76%) (P < .001).
CONCLUSION: In women with an indeterminate ovarian mass at gray-scale US, MR
imaging results contributed to change in probability of ovarian cancer in both
pre- and postmenopausal women more than did CT or combined gray-scale and Doppler
US results.

Copyright RSNA, 2005

PMID: 15955864  [PubMed - indexed for MEDLINE]


334. Am J Clin Nutr. 2005 Mar;81(3):702-13.

Investigating heterogeneity in studies of resting energy expenditure in persons
with HIV/AIDS: a meta-analysis.

Batterham MJ(1).

Author information:
(1)Smart Foods Centre, University of Wollongong, Australia. marijka@uow.edu.au

BACKGROUND: There is conflict in the literature about the extent of alterations
of resting energy expenditure (REE) in persons with HIV.
OBJECTIVE: The study was conducted to ascertain the mean difference in REE (in
kJ) per kilogram of fat-free mass (FFM; REE/FFM) between HIV-positive subjects
and control subjects and to investigate heterogeneity in the literature.
DESIGN: A meta-analysis comparing classical and Bayesian methods was conducted.
Heterogeneity was investigated by using subgroup analysis, metaregression, and a
mixed indirect comparison.
RESULTS: Of 58 studies meeting the inclusion criteria, 32 included both
HIV-positive and control groups; 24 of these 32 were included. Thirty-seven
studies were used in the mixed indirect comparison, and 30 were used in the
subgroup comparisons of the HIV-symptomatic, lipodystrophy, weight-losing, and
weight-stable subgroups and the healthy (HIV-negative) control group. Mean
REE/FFM was significantly higher in 732 HIV-positive subjects than in 340 control
subjects [11.93 kJ/kg (95% CI: 8.44,15.43 kJ/kg) and 12.47 kJ/kg (95% CI:
8.19,16.57 kJ/kg), classical and Bayesian random effects, respectively]; the test
for heterogeneity was significant (P < 0.001). Both the mixed indirect comparison
and the subgroup analysis indicated that REE/FFM was highest in the symptomatic
subgroup; however, the small number of studies investigating symptomatic subjects
limited statistical comparisons. The presence of lipodystrophy, use of highly
active antiretroviral therapy, subject age, and method of body-composition
measurement could not explain the heterogeneity in the data with the use of
metaregression.
CONCLUSIONS: REE/FFM (kJ/kg) is significantly higher in HIV-positive subjects
than in healthy control subjects. Symptomatic HIV infection may contribute to the
variations reported in the literature.

PMID: 15755842  [PubMed - indexed for MEDLINE]
