Integrating fragmented evidence by network meta-analysis: relative effectiveness of psychological interventions for adults with post-traumatic stress disorder

BACKGROUND To summarize the available evidence on the effectiveness of psychological interventions for patients with post-traumatic stress disorder (PTSD). METHOD We searched bibliographic databases and reference lists of relevant systematic reviews and meta-analyses for randomized controlled trials that compared specific psychological interventions for adults with PTSD symptoms either head-to-head or against control interventions using non-specific intervention components, or against wait-list control. Two investigators independently extracted the data and assessed trial characteristics. RESULTS The analyses included 4190 patients in 66 trials. An initial network meta-analysis showed large effect sizes (ESs) for all specific psychological interventions (ESs between -1.10 and -1.37) and moderate effects of psychological interventions that were used to control for non-specific intervention effects (ESs -0.58 and -0.62). ES differences between various types of specific psychological interventions were absent to small (ES differences between 0.00 and 0.27). Considerable between-trial heterogeneity occurred (τ 2 = 0.30). Stratified analyses revealed that trials that adhered to DSM-III/IV criteria for PTSD were associated with larger ESs. However, considerable heterogeneity remained. Heterogeneity was reduced in trials with adequate concealment of allocation and in large-sized trials. We found evidence for small-study bias. CONCLUSIONS Our findings show that patients with a formal diagnosis of PTSD and those with subclinical PTSD symptoms benefit from different psychological interventions. We did not identify any intervention that was consistently superior to other specific psychological interventions. However, the robustness of evidence varies considerably between different psychological interventions for PTSD, with most robust evidence for cognitive behavioral and exposure therapies.

Initial orthodontic alignment effectiveness with self-ligating and conventional appliances: a network meta-analysis in practice.

Systematic reviews of well-designed trials constitute a high level of scientific evidence and are important for medical decision making. Meta-analysis facilitates integration of the evidence using a transparent and systematic approach, leading to a broader interpretation of treatment effectiveness and safety than can be attained from individual studies. Traditional meta-analyses are limited to comparing just 2 interventions concurrently and cannot combine evidence concerning multiple treatments. A relatively recent extension of the traditional meta-analytical approach is network meta-analysis, which allows, under certain assumptions, the quantitative synthesis of all evidence under a unified framework and across a network of all eligible trials. Network meta-analysis combines evidence from direct and indirect information via common comparators; interventions can therefore be ranked in terms of the analyzed outcome. In this article, the network meta-analysis approach is introduced in a nontechnical manner using a worked example on the treatment effectiveness of conventional and self-ligating appliances.

Active surveillance for rheumatic heart disease in endemic regions: a systematic review and meta-analysis of prevalence among children and adolescents

BACKGROUND Rheumatic heart disease accounts for up to 250 000 premature deaths every year worldwide and can be regarded as a physical manifestation of poverty and social inequality. We aimed to estimate the prevalence of rheumatic heart disease in endemic countries as assessed by different screening modalities and as a function of age. METHODS We searched Medline, Embase, the Latin American and Caribbean System on Health Sciences Information, African Journals Online, and the Cochrane Database of Systematic Reviews for population-based studies published between Jan 1, 1993, and June 30, 2014, that reported on prevalence of rheumatic heart disease among children and adolescents (≥5 years to <18 years). We assessed prevalence of clinically silent and clinically manifest rheumatic heart disease in random effects meta-analyses according to screening modality and geographical region. We assessed the association between social inequality and rheumatic heart disease with the Gini coefficient. We used Poisson regression to analyse the effect of age on prevalence of rheumatic heart disease and estimated the incidence of rheumatic heart disease from prevalence data. FINDINGS We included 37 populations in the systematic review and meta-analysis. The pooled prevalence of rheumatic heart disease detected by cardiac auscultation was 2·9 per 1000 people (95% CI 1·7-5·0) and by echocardiography it was 12·9 per 1000 people (8·9-18·6), with substantial heterogeneity between individual reports for both screening modalities (I(2)=99·0% and 94·9%, respectively). We noted an association between social inequality expressed by the Gini coefficient and prevalence of rheumatic heart disease (p=0·0002). The prevalence of clinically silent rheumatic heart disease (21·1 per 1000 people, 95% CI 14·1-31·4) was about seven to eight times higher than that of clinically manifest disease (2·7 per 1000 people, 1·6-4·4). Prevalence progressively increased with advancing age, from 4·7 per 1000 people (95% CI 0·0-11·2) at age 5 years to 21·0 per 1000 people (6·8-35·1) at 16 years. The estimated incidence was 1·6 per 1000 people (0·8-2·3) and remained constant across age categories (range 2·5, 95% CI 1·3-3·7 in 5-year-old children to 1·7, 0·0-5·1 in 15-year-old adolescents). We noted no sex-related differences in prevalence (p=0·829). INTERPRETATION We found a high prevalence of rheumatic heart disease in endemic countries. Although a reduction in social inequalities represents the cornerstone of community-based prevention, the importance of early detection of silent rheumatic heart disease remains to be further assessed. FUNDING UBS Optimus Foundation.

Effects of acupuncture on sensory perception: a systematic review and meta-analysis.

BACKGROUND The effect of acupuncture on sensory perception has never been systematically reviewed; although, studies on acupuncture mechanisms are frequently based on the idea that changes in sensory thresholds reflect its effect on the nervous system. METHODS Pubmed, EMBASE and Scopus were screened for studies investigating the effect of acupuncture on thermal or mechanical detection or pain thresholds in humans published in English or German. A meta-analysis of high quality studies was performed. RESULTS Out of 3007 identified articles 85 were included. Sixty five studies showed that acupuncture affects at least one sensory threshold. Most studies assessed the pressure pain threshold of which 80% reported an increase after acupuncture. Significant short- and long-term effects on the pressure pain threshold in pain patients were revealed by two meta-analyses including four and two high quality studies, respectively. In over 60% of studies, acupuncture reduced sensitivity to noxious thermal stimuli, but measuring methods might influence results. Few but consistent data indicate that acupuncture reduces pin-prick like pain but not mechanical detection. Results on thermal detection are heterogeneous. Sensory threshold changes were equally frequent reported after manual acupuncture as after electroacupuncture. Among 48 sham-controlled studies, 25 showed stronger effects on sensory thresholds through verum than through sham acupuncture, but in 9 studies significant threshold changes were also observed after sham acupuncture. Overall, there is a lack of high quality acupuncture studies applying comprehensive assessments of sensory perception. CONCLUSIONS Our findings indicate that acupuncture affects sensory perception. Results are most compelling for the pressure pain threshold, especially in pain conditions associated with tenderness. Sham acupuncture can also cause such effects. Future studies should incorporate comprehensive, standardized assessments of sensory profiles in order to fully characterize its effect on sensory perception and to explore the predictive value of sensory profiles for the effectiveness of acupuncture.

A systematic review and meta-analysis of factors associated with anthelmintic resistance in sheep.

BACKGROUND Anthelmintic drugs have been widely used in sheep as a cost-effective means for gastro-intestinal nematode (GIN) control. However, growing anthelmintic resistance (AHR) has created a compelling need to identify evidence-based management recommendations that reduce the risk of further development and impact of AHR. OBJECTIVE To identify, critically assess, and synthesize available data from primary research on factors associated with AHR in sheep. METHODS Publications reporting original observational or experimental research on selected factors associated with AHR in sheep GINs and published after 1974, were identified through two processes. Three electronic databases (PubMed, Agricola, CAB) and Web of Science (a collection of databases) were searched for potentially relevant publications. Additional publications were identified through consultation with experts, manual search of references of included publications and conference proceedings, and information solicited from small ruminant practitioner list-serves. Two independent investigators screened abstracts for relevance. Relevant publications were assessed for risk of systematic bias. Where sufficient data were available, random-effects Meta-Analyses (MAs) were performed to estimate the pooled Odds Ratio (OR) and 95% Confidence Intervals (CIs) of AHR for factors reported in ≥2 publications. RESULTS Of the 1712 abstracts screened for eligibility, 131 were deemed relevant for full publication review. Thirty publications describing 25 individual studies (15 observational studies, 7 challenge trials, and 3 controlled trials) were included in the qualitative synthesis and assessed for systematic bias. Unclear (i.e. not reported, or unable to assess) or high risk of selection bias and confounding bias was found in 93% (14/15) and 60% (9/15) of the observational studies, respectively, while unclear risk of selection bias was identified in all of the trials. Ten independent studies were included in the quantitative synthesis, and MAs were performed for five factors. Only high frequency of treatment was a significant risk factor (OR=4.39; 95% CI=1.59, 12.14), while the remaining 4 variables were marginally significant: mixed-species grazing (OR=1.63; 95% CI=0.66, 4.07); flock size (OR=1.02; 95% CI=0.97, 1.07); use of long-acting drug formulations (OR=2.85; 95% CI=0.79, 10.24); and drench-and-shift pasture management (OR=4.08; 95% CI=0.75, 22.16). CONCLUSIONS While there is abundant literature on the topic of AHR in sheep GINs, few studies have explicitly investigated the association between putative risk or protective factors and AHR. Consequently, several of the current recommendations on parasite management are not evidence-based. Moreover, many of the studies included in this review had a high or unclear risk of systematic bias, highlighting the need to improve study design and/or reporting of future research carried out in this field.

Enduring effects of evidence-based psychotherapies in acute depression and anxiety disorders versus treatment as usual at follow-up — A longitudinal meta-analysis

This meta-analysis examined the enduring efficacy of evidence-based psychotherapies (EBP) in comparison to treatment as usual (TAU) by examining effects from termination to follow-up for acute anxiety and depression in an adult outpatient population. It was hypothesized that EBPs might extend their efficacy at follow-up assessment (Tolin, 2010). METHOD: Longitudinal multilevel meta-analyses were conducted that examined the magnitude of difference between EBP and TAU. Targeted (disorder-specific) outcomes were examined, along with dropout rates at follow-up assessments. RESULTS: A total of 15 comparisons (including 30 repeated effect sizes [ES]) were included in this meta-analysis (average of 8.9 month follow-up). Small to moderate ES differences were found to be in favor of EBPs at 0-4 month assessments (Hedges' g=0.40) and up to 12-18 month assessments (g=0.20), indicating no extended efficacy at follow-up. However, the TAU-conditions were heterogeneous, ranging from absence of minimal mental health treatment to legitimate psychotherapeutic interventions provided by trained professionals, the latter of which resulted in smaller ES differences. Furthermore, samples where substance use comorbidities were not actively excluded indicated smaller ES differences. TAU-conditions produced slightly higher dropout rates than EBP-conditions. CONCLUSION: Findings indicate small and no extended superiority of EBP for acute depression and anxiety disorders in comparison to TAU at follow-up assessment. There are a limited number of studies investigating the transportability and lasting efficacy of EBP compared to TAU, especially to TAU with equivalent conditions between treatment groups.

Metamizole-associated adverse events: a systematic review and meta-analysis.

BACKGROUND Metamizole is used to treat pain in many parts of the world. Information on the safety profile of metamizole is scarce; no conclusive summary of the literature exists. OBJECTIVE To determine whether metamizole is clinically safe compared to placebo and other analgesics. METHODS We searched CENTRAL, MEDLINE, EMBASE, CINAHL, and several clinical trial registries. We screened the reference lists of included trials and previous systematic reviews. We included randomized controlled trials that compared the effects of metamizole, administered to adults in any form and for any indication, to other analgesics or to placebo. Two authors extracted data regarding trial design and size, indications for pain medication, patient characteristics, treatment regimens, and methodological characteristics. Adverse events (AEs), serious adverse events (SAEs), and dropouts were assessed. We conducted separate meta-analyses for each metamizole comparator, using standard inverse-variance random effects meta-analysis to pool the estimates across trials, reported as risk ratios (RRs). We calculated the DerSimonian and Laird variance estimate T2 to measure heterogeneity between trials. The pre-specified primary end point was any AE during the trial period. RESULTS Of the 696 potentially eligible trials, 79 trials including almost 4000 patients with short-term metamizole use of less than two weeks met our inclusion criteria. Fewer AEs were reported for metamizole compared to opioids, RR = 0.79 (confidence interval 0.79 to 0.96). We found no differences between metamizole and placebo, paracetamol and NSAIDs. Only a few SAEs were reported, with no difference between metamizole and other analgesics. No agranulocytosis or deaths were reported. Our results were limited by the mediocre overall quality of the reports. CONCLUSION For short-term use in the hospital setting, metamizole seems to be a safe choice when compared to other widely used analgesics. High-quality, adequately sized trials assessing the intermediate- and long-term safety of metamizole are needed.

PEDro or Cochrane to Assess the Quality of Clinical Trials? A Meta-Epidemiological Study.

OBJECTIVE There is debate on how the methodological quality of clinical trials should be assessed. We compared trials of physical therapy (PT) judged to be of adequate quality based on summary scores from the Physiotherapy Evidence Database (PEDro) scale with trials judged to be of adequate quality by Cochrane Risk of Bias criteria. DESIGN Meta-epidemiological study within Cochrane Database of Systematic Reviews. METHODS Meta-analyses of PT trials were identified in the Cochrane Database of Systematic Reviews. For each trial PeDro and Cochrane assessments were extracted from the PeDro and Cochrane databases. Adequate quality was defined as adequate generation of random sequence, concealment of allocation, and blinding of outcome assessors (Cochrane criteria) or as trials with a PEDro summary score ≥5 or ≥6 points. We combined trials of adequate quality using random-effects meta-analysis. RESULTS Forty-one Cochrane reviews and 353 PT trials were included. All meta-analyses included trials with PEDro scores ≥5, 37 (90.2%) included trials with PEDro scores ≥6 and only 22 (53.7%) meta-analyses included trials of adequate quality according to the Cochrane criteria. Agreement between PeDro and Cochrane was poor for PeDro scores of ≥5 points (kappa = 0.12; 95% CI 0.07 to 0.16) and slight for ≥6 points (kappa 0.24; 95% CI 0.16-0.32). When combining effect sizes of trials deemed to be of adequate quality according to PEDro or Cochrane criteria, we found that a substantial difference in the combined effect size (≥0.15) was evident in 9 (22%) out of the 41 meta-analyses for PEDro cutoff ≥5 and 10 (24%) for cutoff ≥6. CONCLUSIONS The PeDro and Cochrane approaches lead to different sets of trials of adequate quality, and different combined treatment estimates from meta-analyses of these trials. A consistent approach to assessing RoB in trials of physical therapy should be adopted.

What is the influence of randomisation sequence generation and allocation concealment on treatment effects of physical therapy trials? A meta-epidemiological study.

OBJECTIVE To determine if adequacy of randomisation and allocation concealment is associated with changes in effect sizes (ES) when comparing physical therapy (PT) trials with and without these methodological characteristics. DESIGN Meta-epidemiological study. PARTICIPANTS A random sample of randomised controlled trials (RCTs) included in meta-analyses in the PT discipline were identified. INTERVENTION Data extraction including assessments of random sequence generation and allocation concealment was conducted independently by two reviewers. To determine the association between sequence generation, and allocation concealment and ES, a two-level analysis was conducted using a meta-meta-analytic approach. PRIMARY AND SECONDARY OUTCOME MEASURES association between random sequence generation and allocation concealment and ES in PT trials. RESULTS 393 trials included in 43 meta-analyses, analysing 44 622 patients contributed to this study. Adequate random sequence generation and appropriate allocation concealment were accomplished in only 39.7% and 11.5% of PT trials, respectively. Although trials with inappropriate allocation concealment tended to have an overestimate treatment effect when compared with trials with adequate concealment of allocation, the difference was non-statistically significant (ES=0.12; 95% CI -0.06 to 0.30). When pooling our results with those of Nuesch et al, we obtained a pooled statistically significant value (ES=0.14; 95% CI 0.02 to 0.26). There was no difference in ES in trials with appropriate or inappropriate random sequence generation (ES=0.02; 95% CI -0.12 to 0.15). CONCLUSIONS Our results suggest that when evaluating risk of bias of primary RCTs in PT area, systematic reviewers and clinicians implementing research into practice should pay attention to these biases since they could exaggerate treatment effects. Systematic reviewers should perform sensitivity analysis including trials with low risk of bias in these domains as primary analysis and/or in combination with less restrictive analyses. Authors and editors should make sure that allocation concealment and random sequence generation are properly reported in trial reports.

Non-selective beta-blockers may reduce risk of hepatocellular carcinoma: a meta-analysis of randomized trials

BACKGROUND & AIMS Non-selective beta-blockers (NSBB) are used in patients with cirrhosis and oesophageal varices. Experimental data suggest that NSBB inhibit angiogenesis and reduce bacterial translocation, which may prevent hepatocellular carcinoma (HCC). We therefore assessed the effect of NSBB on HCC by performing a systematic review with meta-analyses of randomized trials. METHODS Electronic and manual searches were combined. Authors were contacted for unpublished data. Included trials assessed NSBB for patients with cirrhosis; the control group could receive any other intervention than NSBB. Fixed and random effects meta-analyses were performed with I(2) as a measure of heterogeneity. Subgroup, sensitivity, regression and sequential analyses were performed to evaluate heterogeneity, bias and the robustness of the results after adjusting for multiple testing. RESULTS Twenty-three randomized trials on 2618 patients with cirrhosis were included, of which 12 reported HCC incidence and 23 reported HCC mortality. The mean duration of follow-up was 26 months (range 8-82). In total, 47 of 694 patients randomized to NSBB developed HCC vs 65 of 697 controls (risk difference -0.026; 95% CI-0.052 to -0.001; number needed to treat 38 patients). There was no heterogeneity (I(2) = 7%) or evidence of small study effects (Eggers P = 0.402). The result was not confirmed in sequential analysis, which suggested that 3719 patients were needed to achieve the required information size. NSBB did not reduce HCC-related mortality (RD -0.011; 95% CI -0.040 to 0.017). CONCLUSIONS Non-selective beta-blockers may prevent HCC in patients with cirrhosis.

Comparative analysis of meta-analysis methods: when to use which?

Background: Several meta-analysis methods can be used to quantitatively combine the results of a group of experiments, including the weighted mean difference, statistical vote counting, the parametric response ratio and the non-parametric response ratio. The software engineering community has focused on the weighted mean difference method. However, other meta-analysis methods have distinct strengths, such as being able to be used when variances are not reported. There are as yet no guidelines to indicate which method is best for use in each case. Aim: Compile a set of rules that SE researchers can use to ascertain which aggregation method is best for use in the synthesis phase of a systematic review. Method: Monte Carlo simulation varying the number of experiments in the meta analyses, the number of subjects that they include, their variance and effect size. We empirically calculated the reliability and statistical power in each case Results: WMD is generally reliable if the variance is low, whereas its power depends on the effect size and number of subjects per meta-analysis; the reliability of RR is generally unaffected by changes in variance, but it does require more subjects than WMD to be powerful; NPRR is the most reliable method, but it is not very powerful; SVC behaves well when the effect size is moderate, but is less reliable with other effect sizes. Detailed tables of results are annexed. Conclusions: Before undertaking statistical aggregation in software engineering, it is worthwhile checking whether there is any appreciable difference in the reliability and power of the methods. If there is, software engineers should select the method that optimizes both parameters.

The Effectiveness of Art Therapy in Decreasing Depressive Symptomology: A Meta-Analysis

Art therapy is an increasingly popular treatment modality with various mental health professionals; however, despite its increasing popularity and utilization, the field suffers from a continued lack of empirically validated studies that demonstrate its effectiveness. Thus, this study performed a meta-analysis on studies that utilized therapeutic art interventions with depressive symptoms in order to produce an overall effect size (ES) regarding the effectiveness of art therapy on depression. Additionally, this study attempted to determine moderating factors that might influence the magnitude of the ES. The present meta-analysis included 18 published and unpublished studies that produced a significant (p=0.001) ES of -1.10 (95% Confidence Interval (CI) of -1.64 to -0.56), thus demonstrating that art therapy has a large effect on the reduction of depression-related symptoms in participants. The results of this analysis are comparable to other meta-analyses of psychotherapeutic treatments for depression (Mazzucchelli, Kane, & Rees, 2009; Gloaguen, Cottraux, Cucherat, & Blackburn, 1998; Cuijper, van Straten, Andersson, & van Oppen, 2008). This study also covers clinically relevant issues regarding treating depression with art therapy and makes recommendations for further research.

Reducing the risk of sexually transmitted infections in genitourinary medicine clinic patients:A systematic review and meta-analysis of behavioural interventions

Objectives: Are behavioural interventions effective in reducing the rate of sexually transmitted infections (STIs) among genitourinary medicine (GUM) clinic patients? Design: Systematic review and meta-analysis of published articles. Data sources: Medline, CINAHL, Embase, PsychINFO, Applied Social Sciences Index and Abstracts, Cochrane Library Controlled Clinical Trials Register, National Research Register (1966 to January 2004). Review methods: Randomised controlled trials of behavioural interventions in sexual health clinic patients were included if they reported change to STI rates or self reported sexual behaviour. Trial quality was assessed using the Jadad score and results pooled using random effects meta-analyses where outcomes were consistent across studies. Results: 14 trials were included; 12 based in the United States. Experimental interventions were heterogeneous and most control interventions were more structured than typical UK care. Eight trials reported data on laboratory confirmed infections, of which four observed a greater reduction in their intervention groups (in two cases this result was statistically significant, p<0.05). Seven trials reported consistent condom use, of which six observed a greater increase among their intervention subjects. Results for other measures of sexual behaviour were inconsistent. Success in reducing STIs was related to trial quality, use of social cognition models, and formative research in the target population. However, effectiveness was not related to intervention format or length. Conclusions: While results were heterogeneous, several trials observed reductions in STI rates. The most effective interventions were developed through extensive formative research. These findings should encourage further research in the United Kingdom where new approaches to preventing STIs are urgently required.

Efficacy and safety of second-generation antipsychotic long-acting injections (SGA LAIs) in maintenance treatment of bipolar disorder:protocol for a systematic review and meta-analysis

INTRODUCTION: Bipolar disorder requires long-term treatment but non-adherence is a common problem. Antipsychotic long-acting injections (LAIs) have been suggested to improve adherence but none are licensed in the UK for bipolar. However, the use of second-generation antipsychotics (SGA) LAIs in bipolar is not uncommon albeit there is a lack of systematic review in this area. This study aims to systematically review safety and efficacy of SGA LAIs in the maintenance treatment of bipolar disorder. METHODS AND ANALYSIS: The protocol is based on Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and will include only randomised controlled trials comparing SGA LAIs in bipolar. PubMed, EMBASE, CINAHL, Cochrane Library (CENTRAL), PsychINFO, LiLACS, http://www.clinicaltrials.gov will be searched, with no language restriction, from 2000 to January 2016 as first SGA LAIs came to the market after 2000. Manufacturers of SGA LAIs will also be contacted. Primary efficacy outcome is relapse rate or delayed time to relapse or reduction in hospitalisation and primary safety outcomes are drop-out rates, all-cause discontinuation and discontinuation due to adverse events. Qualitative reporting of evidence will be based on 21 items listed on standards for reporting qualitative research (SRQR) focusing on study quality (assessed using the Jadad score, allocation concealment and data analysis), risk of bias and effect size. Publication bias will be assessed using funnel plots. If sufficient data are available meta-analysis will be performed with primary effect size as relative risk presented with 95% CI. Sensitivity analysis, conditional on number of studies and sample size, will be carried out on manic versus depressive symptoms and monotherapy versus adjunctive therapy.

To move or not to move, that is the question! Body schema and non-action oriented body representations:an fMRI meta-analytic study

Many studies have attempted to identify the different cognitive components of body representation (BR). Due to methodological issues, the data reported in these studies are often confusing. Here we summarize the fMRI data from previous studies and explore the possibility of a neural segregation between BR supporting actions (body-schema, BS) or not (non-oriented-to-action-body-representation, NA). We performed a general activation likelihood estimation meta-analysis of 59 fMRI experiments and two individual meta-analyses to identify the neural substrates of different BR. Body processing involves a wide network of areas in occipital, parietal, frontal and temporal lobes. NA selectively activates the somatosensory primary cortex and the supramarginal gyrus. BS involves the primary motor area and the right extrastriate body area. Our data suggest that motor information and recognition of body parts are fundamental to build BS. Instead, sensory information and processing of the egocentric perspective are more important for NA. In conclusion, our results strongly support the idea that different and segregated neural substrates are involved in body representations orient or not to actions.