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Highlights • Lifestyle intervention lowers type 2 diabetes risk in people with prediabetes. • Weight loss is commonly achieved but there is great variation between studies. • The majority of studies concluded that lifestyle intervention is cost-effective. • Lifestyle intervention is most cost-effective over a lifelong analysis period. • More research is necessary to compare different types of lifestyle intervention. Abstract Aims To assess the efficacy, safety, and cost-effectiveness of lifestyle intervention, compared with treatment as usual in people with prediabetes as defined by the American Diabetes Association. For older studies, we used the 1985 World Health Organization definition. Methods We systematically searched multiple electronic databases and referenced lists of pertinent review articles from January 1980 through November 2015. We performed an update search in MEDLINE on April 26, 2017. Based on a priori established eligibility criteria, we dually reviewed the literature, extracted data, and rated the risk of bias of included studies with validated checklists. To assess the efficacy of lifestyle intervention to prevent or delay further progression to type 2 diabetes, we conducted a random-effects meta-analysis. We assessed the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Result Pooled results of 16 randomized controlled trials showed that people with prediabetes who received lifestyle intervention had a lower rate of progression to type 2 diabetes after one (4% vs. 10%, RR 0.46 [CI 0.32, 0.66]) and three years of follow-up (14% vs. 23%, RR 0.64 [95% CI 0.53, 0.77]). The majority of the studies also showed a greater weight loss in lifestyle intervention participants, with a great variation between studies. Costs per quality-adjusted life-year were lower when the benefits of lifestyle intervention were analyzed over a lifelong time horizon compared to only the period of lifestyle intervention (three years) or to modeling over a ten-year period. Conclusion Lifestyle intervention is an efficacious, safe, and cost-effective measure to reduce the risk of progression to type 2 diabetes in people diagnosed with prediabetes. More research is necessary to compare the efficacy of various modes, frequencies, and intensities of lifestyle intervention across studies. [ABSTRACT FROM AUTHOR]

Objectives: We sought to determine whether producers or users of systematic reviews using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach or a close variation give the same meanings to terms intended to convey uncertainty about treatment effects when interpreting grades for the quality or strength of evidence. Study Design and Setting: Following exploratory interviews with stakeholders and user testing, we conducted an international Webbased survey among producers and users of systematic reviews. For each quality grade (high, moderate, low, very low/insufficient), we asked participants to assign a minimum likelihood that treatment effects will not change substantially as new studies emerge. Using multivariate analysis of covariance, we tested whether the estimated likelihoods differed between producers and users. Results: In all, 244 participants completed the survey. The associated minimum likelihoods that treatment effects will not change substantially for high, moderate, and low grades of quality of evidence (QOE) were 86% [95% confidence interval (CI): 85%, 87%], 61% (95% CI: 59%, 63%), and 34% (95% CI: 32%, 36%), respectively (very low was preset at 0%). Likelihoods for each grade were similar between producers and users of systematic reviews (P O 0.05 for all comparisons). Conclusion: GRADE is, in general, a suitable method to convey uncertainties for systematic review producers to users. The wide ranges of likelihoods associated with GRADE terms suggest that current definitions of levels of QOE that rely exclusively on qualitative certainty expressions should be augmented by numerical predictions once such data are available. [ABSTRACT FROM AUTHOR]

Context: Traumatic events are prevalent worldwide; trauma victims seek help in numerous clinical and emergency settings. Using effective interventions to prevent post-traumatic stress disorder (PTSD) is increasingly important. This review assessed the efficacy, comparative effectiveness, and harms of psychological, pharmacologic, and emerging interventions to prevent PTSD. Evidence acquisition: The following sources were searched for research on interventions to be included in the review: MEDLINE; Cochrane Library; CINAHL; EMBASE; PILOTS (Published International Literature on Traumatic Stress); International Pharmaceutical Abstracts; PsycINFO; Web of Science; reference lists of published literature; and unpublished literature (January 1, 1980 to July 30, 2012). Two reviewers independently selected studies, extracted data or checked accuracy, assessed study risk of bias, and graded strength of evidence. All data synthesis occurred between January and September 2012. Evidence synthesis: Nineteen studies covered various populations, traumas, and interventions. In meta-analyses of three trials (from the same team) for people with acute stress disorder, brief trauma-focused cognitive behavioral therapy was more effective than supportive counseling in reducing the severity of PTSD symptoms (moderate-strength); these two interventions had similar results for incidence of PTSD (low-strength); depression severity (low-strength); and anxiety severity (moderate-strength). PTSD symptom severity after injury decreased more with collaborative care than usual care (single study; low-strength). Debriefing did not reduce incidence or severity of PTSD or psychological symptoms in civilian traumas (low-strength). Evidence about relevant outcomes was unavailable for many interventions or was insufficient owing to methodologic shortcomings. Conclusions: Evidence is very limited regarding best practices to treat trauma-exposed individuals. Brief cognitive behavioral therapy may reduce PTSD symptom severity in people with acute stress disorder; collaborative care may help decrease symptom severity post-injury. [Copyright &y& Elsevier]

Zusammenfassung: Evidenzbasierte Medizin (EbM) fordert, dass bei klinischen Entscheidungen das weltweit beste verfügbare Wissen berücksichtigt wird, um eine optimale Behandlung der Patienten zu garantieren. Aufgrund der rasanten Entwicklung der medizinischen Forschung mit mehr als 3 Millionen publizierten Artikeln pro Jahr ist es jedoch unmöglich, auf dem aktuellen Stand der Wissenschaft zu bleiben. Systematische Übersichtsarbeiten fassen Resultate einer Vielzahl von Studien zusammen, bewerten die methodische Qualität und die Aussagekraft für die medizinische Praxis. Dieser Artikel fasst Konzepte der EbM sowie methodische Aspekte von systematischen Übersichtsarbeiten und Meta-Analysen zusammen und bietet Lesern eine Anleitung, wie Resultate systematischer Übersichtsarbeiten kritisch gelesen und bewertet werden können. [ABSTRACT FROM AUTHOR]

Abstract: Objective: This article is to establish recommendations for conducting quantitative synthesis, or meta-analysis, using study-level data in comparative effectiveness reviews (CERs) for the Evidence-based Practice Center (EPC) program of the Agency for Healthcare Research and Quality. Study Design and Setting: We focused on recurrent issues in the EPC program and the recommendations were developed using group discussion and consensus based on current knowledge in the literature. Results: We first discussed considerations for deciding whether to combine studies, followed by discussions on indirect comparison and incorporation of indirect evidence. Then, we described our recommendations on choosing effect measures and statistical models, giving special attention to combining studies with rare events; and on testing and exploring heterogeneity. Finally, we briefly presented recommendations on combining studies of mixed design and on sensitivity analysis. Conclusion: Quantitative synthesis should be conducted in a transparent and consistent way. Inclusion of multiple alternative interventions in CERs increases the complexity of quantitative synthesis, whereas the basic issues in quantitative synthesis remain crucial considerations in quantitative synthesis for a CER. We will cover more issues in future versions and update and improve recommendations with the accumulation of new research to advance the goal for transparency and consistency. [Copyright &y& Elsevier]

Abstract: Objective: The objective of this study was to determine the effect of industry bias in a systematically reviewed body of evidence of head-to-head trials. Study Design and Setting: We limited our analysis to published head-to-head randomized controlled trials of selective serotonin reuptake inhibitors (SSRIs) identified in a comparative effectiveness review. Two reviewers independently determined the status of funding for each trial. We classified drugs into one of two groups: (1) drugs associated with the funding source and (2) drugs not associated with the funding source. To determine the effect of any underlying industry bias, we conducted relative-benefit meta-analyses comparing the response rates of drugs when associated with the funding source with response rates of the same drugs when not associated with the funding source. Results: Thirteen out of 20 studies (65%) numerically favored drugs associated with the funding source over drugs used as controls. The pooled response rates of SSRIs, when associated with the funding source, are significantly greater than those of the same SSRIs when not associated with the sponsor (relative benefit=1.07; 95% confidence interval=1.02–1.11). The difference, however, is likely to be not of clinical importance. Conclusions: The effect of industry bias in comparative effectiveness reviews might play a lesser role than in systematic reviews of placebo-controlled trials. [Copyright &y& Elsevier]

Background & Aims: Serious adverse events such as bowel obstruction, heart failure, infection, lymphoma, and neuropathy have been reported with infliximab. The aims of this study were to explore adverse event signals with infliximab by using a long period of post-marketing experience, stratifying by indication. Methods: The relative reporting of infliximab adverse events to the U.S. Food and Drug Administration (FDA) was assessed with the public release version of the adverse event reporting system (AERS) database from 1968 to third quarter 2005. On the basis of a systematic review of adverse events, Medical Dictionary for Regulatory Activities (MedDRA) terms were mapped to predefined categories of adverse events, including death, heart failure, hepatitis, infection, infusion reaction, lymphoma, myelosuppression, neuropathy, and obstruction. Disproportionality analysis was used to calculate the empiric Bayes geometric mean (EBGM) and corresponding 90% confidence intervals (EB05, EB95) for adverse event categories. Results: Infliximab was identified as the suspect medication in 18,220 reports in the FDA AERS database. We identified a signal for lymphoma (EB05 = 6.9), neuropathy (EB05 = 3.8), infection (EB05 = 2.9), and bowel obstruction (EB05 = 2.8). The signal for granulomatous infections was stronger than the signal for non-granulomatous infections (EB05 = 12.6 and 2.4, respectively). The signals for bowel obstruction and infusion reaction were specific to patients with IBD; this suggests potential confounding by indication, especially for bowel obstruction. Conclusions: In light of this additional evidence of risk of lymphoma, neuropathy, and granulomatous infections, clinicians should stress this risk in the shared decision-making process. [Copyright &y& Elsevier]

Abstract: Objective: To propose and test a simple instrument based on seven criteria of study design to distinguish effectiveness (pragmatic) from efficacy (explanatory) trials. Study Design: Currently no validated definition of effectiveness studies exists. We asked the directors of 12 Evidence-based Practice Centers to select six studies each: four that they considered to be examples of effectiveness trials and two considered efficacy studies. We then applied our proposed criteria to test the construct validity using the selected studies as if they had been identified by a gold standard. Results: Based on the rationale to identify effectiveness studies reliably with minimal false positives (i.e., a high specificity), a cutoff of six criteria produced the most desirable balance between sensitivity and specificity. This setting produced a specificity of 0.83 and a sensitivity of 0.72. Conclusion: When applied in a standardized manner, our proposed criteria can provide a valid and simple tool to distinguish effectiveness from efficacy studies. The applicability of systematic reviews can improve when analysts place more emphasis on the generalizability of included studies. In addition, clinicians can also use our criteria to determine the external validity of individual studies, given an appropriate population of interest. [Copyright &y& Elsevier]

Abstract: Background: The Z0011-study, a landmark randomised controlled trial (RCT) challenged the benefits of complete axillary lymph node dissection (ALND) compared with sentinel lymph node dissection only (SLND) in breast cancer patients with positive sentinel nodes. The study, however, has been criticised for lack of power and low applicability. The aim of this review was to systematically assess the evidence on the comparative benefits and harms of ALND versus SLND for sentinel node positive breast cancer patients. Methods: We systematically searched PubMed, Embase, the Cochrane Library, and reference lists of pertinent review articles from January 2006 to August 2011. We dually reviewed the literature and rated the risk of bias of each study. For effectiveness, we included RCTs and observational studies of at least 1year follow-up. In addition, we considered studies conducted in sentinel node-negative women to assess the risk of harms. If data were sufficient, we conducted random effects meta-analysis of outcomes of interest. Results: Meta-analysis of three studies with 50,120 patients indicated similar 5-year survival and regional recurrence rates between patients treated with ALND or SLND, although prognostic tumour characteristics varied among the 3 study-populations. Results from 6 studies on more than 11,500 patients reported a higher risk for harms for ALND than SLND. Long-term evidence on pertinent health outcomes is missing. Conclusion: The available evidence indicates that for some women with early invasive breast cancer SLND appears to be a justifiable alternative to ALND. Surgeons need to discuss advantages and disadvantages of both approaches with their patients. [Copyright &y& Elsevier]

Abstract: Objective: To describe a systematic approach for identifying, reporting, and synthesizing information to allow consistent and transparent consideration of the applicability of the evidence in a systematic review according to the Population, Intervention, Comparator, Outcome, Setting domains. Study Design and Setting: Comparative effectiveness reviews need to consider whether available evidence is applicable to specific clinical or policy questions to be useful to decision makers. Authors reviewed the literature and developed guidance for the Effective Health Care program. Results: Because applicability depends on the specific questions and needs of the users, it is difficult to devise a valid uniform scale for rating the overall applicability of individual studies or body of evidence. We recommend consulting stakeholders to identify the factors most relevant to applicability for their decisions. Applicability should be considered separately for benefits and harms. Observational studies can help determine whether trial populations and interventions are representative of “real world” practice. Reviewers should describe differences between available evidence and the ideally applicable evidence for the question being asked and offer a qualitative judgment about the importance and potential effect of those differences. Conclusion: Careful consideration of applicability may improve the usefulness of systematic reviews in informing practice and policy. [Copyright &y& Elsevier]

Objectives: To determine the effectiveness of interventions designed to prevent or reduce publication and related biases. Study Design and Setting: We searched multiple databases and performed manual searches using terms related to publication bias and known interventions against publication bias. We dually reviewed citations and assessed risk of bias. We synthesized results by intervention and outcomes measured and graded the quality of the evidence (QoE). Results: We located 38 eligible studies. The use of prospective trial registries (PTR) has increased since 2005 (seven studies, moderate QoE); however, positive outcome-reporting bias is prevalent (14 studies, low QoE), and information in nonmandatory fields is vague (10 studies, low QoE). Disclosure of financial conflict of interest (CoI) is inadequate (five studies, low QoE). Blinding peer reviewers may reduce geographical bias (two studies, very low QoE), and open-access publishing does not discriminate against authors from lowincome countries (two studies, very low QoE). Conclusion: The use of PTR and CoI disclosures is increasing; however, the adequacy of their use requires improvement. The effect of open-access publication and blinding of peer reviewers on publication bias is unclear, as is the effect of other interventions such as electronic publication and authors' rights to publish their results. [ABSTRACT FROM AUTHOR]

Objectives: Pooled-studies publications (PSPs) present statistical analyses of multiple randomized controlled trials without a systematic literature search or critical appraisal. We explored the characteristics of PSPs and their potential impact on a systematic review (SR). Study Design and Setting: We systematically evaluated PSPs excluded from an SR of second-generation antidepressants. We analyzed their basic characteristics, risk of bias, and the effect of new data on review conclusions. Results: We identified 57 PSPs containing a median of five trials (range, 2-11) and 1,233 patients (range, 117 2,919). Ninety-six percent of PSPs were industry funded, and 49% of PSPs contained unpublished data. The median number of citations for PSPs was 29 (range, 0-549). Only 7% planned pooling a priori, and 19% combined trials with identical protocols. Fifty-nine percent of PSPs eligible e for general efficacy provided no new data. For some subgroups and accompanying symptoms (e.g., anxiety, insomnia, melancholia, fatigue, sex, and race), more than 30% of PSPs presented entirely new data or data that could alter the strength of the evidence available in the SR. Conclusion: In this case study, PSPs provided new information on subgroups and secondary outcomes; however, guidance for reviewers and development of a system to assess their susceptibility to bias are required. [ABSTRACT FROM AUTHOR]