The impact of cash transfers on social determinants of health and health inequalities in Sub-Saharan Africa: a systematic review protocol Symposium integrating evidence-based medicine into clinical practice. Can systematic reviews with sparse data be trusted? Reporting of prognostic markers: current problems and development of guidelines for evidence-based practice in the future Sources of evidence for systematic reviews of interventions in diabetes. The Effectiveness of Psychosocial Interventions as Adjuncts to Orthopaedic Surgery: A Systematic Review Protocol A systematic review protocol examining the effect of vitamin D supplementation on endothelial function Addressing Dichotomous Data for Participants Excluded from Trial Analysis: A Guide for Systematic Reviewers Effectiveness of interventions that assist caregivers to support people with dementia living in the community: a systematic review. Effects of computerized clinical decision support systems on practitioner performance and patient outcomes: Methods of a decision-maker-researcher partnership systematic review How Quickly Do Systematic Reviews Go Out of Date? A Survival Analysis Seeing the forests and the trees—innovative approaches to exploring heterogeneity in systematic reviews of complex interventions to enhance health system decision-making: a protocol Effectiveness of interventions that assist caregivers to support people with dementia living in the community: a systematic review Examining the theory‐effectiveness hypothesis: A systematic review of systematic reviews Effects of workplace-based dietary and/or physical activity interventions for weight management targeting healthcare professionals: a systematic review of randomised controlled trials Community pharmacy interventions for public health priorities: protocol for a systematic review of community pharmacy-delivered smoking, alcohol and weight management interventions Evidence‐based management of pain after laparoscopic cholecystectomy: a PROSPECT review update Systematic reviews of evaluations of prognostic variables Protocol for a systematic review of time to antibiotics (TTA) in patients with fever and neutropenia during chemotherapy for cancer (FN) and interventions aiming to reduce TTA A systematic review of psychosocial interventions for family carers of palliative care patients Effect of vitamin D supplementation on inflammation: protocol for a systematic review A systematic appraisal of allegiance effect in randomized controlled trials of psychotherapy The impact of outcome reporting bias in randomised controlled trials on a cohort of systematic reviews Systematic reviews in endodontics--examples of GIGO? Community-based care for the management of type 2 diabetes: an evidence-based analysis. The Medical Review Article Revisited: Has the Science Improved? A conversation with Joseph Lau. Epidemiology and Reporting Characteristics of Systematic Reviews of Biomedical Research: A Cross-Sectional Study Sugammadex: when should we be giving it? Can we rely on the best trial? A comparison of individual trials and systematic reviews Bias due to selective inclusion and reporting of outcomes and analyses in systematic reviews of randomised trials of healthcare interventions. Empirical Evidence of the Importance of Comparative Studies of Diagnostic Test Accuracy Identifying, documenting, and examining heterogeneity in systematic reviews of complex interventions. The Effectiveness of Technology-Based Strategies to Promote Engagement With Digital Interventions: A Systematic Review Protocol Checklists of methodological issues for review authors to consider when including non-randomized studies in systematic reviews. Identifying effective behavioural components of Intervention and Comparison group support provided in SMOKing cEssation (IC-SMOKE) interventions: a systematic review protocol Avoidable waste of research related to outcome planning and reporting in clinical trials Indirect comparisons of competing interventions. Protocol for a systematic review of the diagnostic and prognostic utility of tests currently available for the detection of aspirin resistance in patients with established cardiovascular or cerebrovascular disease Twin–Twin Transfusion Syndrome: study protocol for developing, disseminating, and implementing a core outcome set A simplified search strategy for identifying randomised controlled trials for systematic reviews of health care interventions: a comparison with more exhaustive strategies The provision and impact of online patient access to their electronic health records (EHR) and transactional services on the quality and safety of health care: systematic review protocol. The International Society for Traumatic Stress Studies New Guidelines for the Prevention and Treatment of Posttraumatic Stress Disorder: Methodology and Development Process. Impact of non-pharmacological interventions on prevention and treatment of delirium in critically ill patients: protocol for a systematic review of quantitative and qualitative research
Background There is increasing pressure to address the social determinants of health ( SDoH ) and health inequities through the implementation of culturally acceptable interventions particularly in Sub-Saharan Africa ( SSA ) where health outcomes are generally poor . Available evaluation research on cash transfers ( CTs ) suggests that the programs may influence the wider determinants of health in SSA ; yet , there has been no attempt to synthesize the evidence regarding their contribution to tackling the SDoH and health inequalities . To date , nearly all the review s on CTs ' impact on health have predominantly featured evidence from Latin America with limited transferability to the social , cultural , and political environments in SSA . Therefore , the aim of this study is to undertake a systematic review to assess the role of CTs in tackling the wider determinants of health and health inequalities in SSA . Methods / design A systematic review of published and unpublished literature on CTs ’ impact on health and health determinants covering the period 2000–2016 will be undertaken . Studies will be considered for inclusion if they present quantitative or qualitative data , including all relevant study design s. The SDoH conceptual framework will be used to guide the data extraction process . EPPI Review er software will be used for data management and analysis . Studies included in the review will be analyzed by narrative synthesis and /or meta- analysis as appropriate for the nature of the data retrieved . Discussion This review will provide empirical evidence on the impact of CTs on SDoH to inform CT policy , implementation , and research in SSA . The protocol follows the Preferred Reporting Items for Systematic Review and Meta- Analysis Protocol s ( PRISMA -P ) . Systematic review registration This protocol has been registered with the PROSPERO international prospect i ve register of systematic review s , reference CRD42015025015 Evidence -based medicine represents the combination of the best available clinical research evidence with clinical experience and expertise and the needs and expectations of patients . Evidence -based medicine as a concept has been available for years , but it has become increasingly important over the last decade . Some evidence has suggested that it began as early as the ancient Chinese medicine practice s , while other evidence has indicated its origins were in postrevolutionary France with the systematic patient observations of Pierre Louis1 . Gordon Guyatt led a group at McMaster University in the early 1990s that introduced many of the current concepts of evidence -based medicine . This led to a major increase in interest in the area . One paper had been published in the literature in 1992 , but by 1998 over a thous and manuscripts had been published in the field1 . Evidence -based medicine utilizes the best available research evidence . In the hierarchy of medical evidence , systematic review s including meta-analyses represent the highest form of evidence if inclusion is limited to Level-I or II studies ( Table I ) . Systematic review s of Level-III or IV observational studies can be performed , but they represent Level-III or IV evidence . Frequently , in orthopaedics , systematic review s or meta-analyses may not be available and clinicians may need to rely upon r and omized controlled trials , cohorts , case-control studies , case series , or , in some areas , expert opinion . Orthopaedists may not yet recognize this hierarchy . During the 2005 Annual Meeting of the American Orthopaedic Association ( AOA ) , the audience was asked the question : “ Findings from which type of study design are most likely to influence your clinical practice ? ” The responses indicated that a r and omized controlled study design was used by 49 % ; a systematic review and /or meta- analysis of Level-I studies , by 44 % ; expert opinion , by 5 % ; and case series , by 3 % . View this table : TABLE I Medical Evidence Hierarchy At a symposium Systematic review s are increasingly used to answer clinical questions . Their popularity is partly attributable to their apparent clinical superiority in providing quick summaries of evidence from the ever-growing medical literature ( more than 750,000 items annually [ 1 ] ) , but also thanks to the great impact of the Cochrane Collaboration in promoting the use of the systematic review [ 2 ] . We also note that many scientific journals favour systematic review s because they tend to contribute to higher journal impact factors . However , the rise of systematic review s should give cause for concern ; more than 8000 are being indexed in MEDLINE annually , reflecting a three-fold increase over the last decade [ 3 ] . We write ‘ concern ’ , because many of these review s across healthcare seem to fall short of essential requirements such as incorporating risk of bias assessment in meta-analyses ( only 16 % ) , search ing for unpublished data ( only 7 % ) , or not fully following a protocol ( only one-third [ 3 ] ) . A recent study of review s published in anaesthetic journals revealed similar shortfalls [ 4 ] . Further more , the quality of reporting is lower in some countries and in journals with lower impact factors [ 5 , 6 ] . The apparent poor quality of many published systematic review s greatly increases the risk of misleading conclusions , which ultimately could harm our patients [ 7 ] . Despite their veneer of sophistication , one has to bear in mind that systematic review s are , in essence , retrospective appraisal s of the evidence . Editors , writers and readers should exercise great caution when interpreting conclusions of review s that only include very few trials , even when they fulfill the required st and ards [ 3 ] . Despite great efforts to promote adequate quality of review s through international guidelines such as PRISMA , GRADE and the Cochrane H and book [ 8 ] , the majority of review s may suffer from threats to the validity of their findings due to risk of systematic errors ( bias ) , design errors ( i.e. , erroneous selection of patients , doses of medication , comparators , analyses , outcomes ) and r and om error ( play of chance ) [ 9 ] . In a previous publication in this journal , some of the method ological issues and requirements for authors and editors were thoroughly discussed [ 10 ] . But we believe that other issues need to be addressed , in particular the amount of information included in meta-analyses from systematic review s , with the power this brings Prognostic markers help to stratify patients for treatment by identifying patients with different risks of outcome ( e.g. recurrence of disease ) , and are important tools in the management of cancer and many other diseases . Systematic review and meta-analytical approaches to identifying the most valuable prognostic markers are needed because ( sometimes conflicting ) evidence relating to markers is often published across a number of studies . To investigate the practicality of this approach , an empirical investigation of a systematic review of  tumour markers for neuroblastoma was performed ; 260 studies of prognostic markers were identified , which considered 130 different markers . The reporting of these studies was often inadequate , in terms of both statistical analysis and presentation , and there was considerable heterogeneity for many important clinical /statistical factors . These problems restricted both the extraction of data and the meta- analysis of results from the primary studies , limiting feasibility of the evidence -based approach . Guidelines for reporting the results of primary prognostic marker studies in cancer , and other diseases , are given in order to facilitate both the interpretation of individual studies and the undertaking of systematic review s , meta- analysis and , ultimately , evidence -based practice . General availability of full individual patient data is a necessary step forward and would overcome the majority of problems encountered , including poorly reported summary statistics and variability in cutoff level , outcome assessed and adjustment factors used . It would also limit the problem of reporting bias , although publication bias will remain a concern until studies are prospect ively registered . Such changes in practice would help important evidence -based review s to be conducted in order to establish the most appropriate prognostic markers for clinical use , which should ultimately improve patient care AIMS To analyse the effect on systematic review s in diabetes interventions of including only trials that are indexed in medline , and to assess the impact of adding trials from other data bases and the grey literature . METHODS All systematic review s of diabetes interventions which included a meta- analysis of r and omized controlled trials , and were published since 1996 , were selected . The impact on the meta- analysis of including only those trials indexed in medline , and the effect of then adding trials from other sources , was assessed . Where possible this was measured quantitatively , by redoing the meta- analysis , otherwise a qualitative estimate was made . RESULTS Forty-four systematic review s met our inclusion criteria . There were 120 articles reporting trial data which were not indexed in medline . These came from 52 % of the review s. In 34 % of the review s , basing a meta- analysis on a search of only medline would miss trials that could affect the result . Sources of non- medline data which had the biggest effect on the meta-analyses were journal articles from central and embase ( mainly in Diabetes , Nutrition and Metabolism ) and unpublished data ( mainly from industry ) . The exceptions were journal articles on herbal medicine , mostly indexed in Chinese language data bases . CONCLUSIONS A search of only the medline data base is insufficient for systematic review s of diabetes , because in about 34 % of review s the missed trials could affect the results of the meta- analysis . It is recommended that central ( on the Cochrane Library ) also be search ed . Scanning meeting abstract s , and seeking unpublished data are also recommended if the intervention has only recently been introduced AIMS Pain and anxiety are commonly reported among those undergoing orthopaedic surgery . Improvement in anxiety and pain control might be achieved by supplementing st and ard care with psychological interventions . However , the effectiveness of adjunctive psychosocial interventions in anxiety and pain control have not been addressed sufficiently by previous systematic review s in orthopaedic surgeries . The present study aim ed to assess the effectiveness of adjunctive psychosocial techniques to improve perioperative clinical care in orthopaedic surgery , to identify the most effective intervention types and to evaluate potential moderators . METHODS We will perform a systematic review and meta- analysis to address the study aims . PubMed , PsycINFO , CINAHL and ProQuest Dissertations & Theses will be search ed between 1980 and 2015 . Prospect i ve controlled clinical trials completed in adults , contrasting st and ard care and st and ard care supplemented with psychosocial methods  , will be eligible for inclusion . Effectiveness will be assessed through the outcomes of postoperative pain intensity , analgesic requirement , perioperative anxiety , quality of life and postoperative recovery . The results of a r and om-effect meta- analysis will be reported . To aid implementation of best practice , moderating effects of the type and timing of psychosocial intervention , type of surgical intervention and type of anaesthesia will be evaluated through meta-regression . Sensitivity analyses and subgroup contrasts will follow as necessary . DISCUSSION Recommendations will be made to improve medical care in orthopaedic procedures . The quality of evidence will be rated using GRADE criteria . Copyright © 2016 John Wiley & Sons , Introduction Vitamin D has potential benefits for extraskeletal health . These could include an anti-inflammatory effect as well as a reduction in endothelial dysfunction . We aim to provide quality evidence for the hypothesis that supplementation with vitamin D will improve endothelial function ( EF ) , possibly through the abrogation of systemic inflammation . Methods and analysis We will conduct a systematic review of all r and omised controlled trials on  vitamin D supplementation and EF lasting 12 weeks or more . The search will cover the period 2000–2015 and include studies that describe direct measures of EF  , markers of endothelial cell ( EC ) activation  and if concurrently reported , indicators of systemic inflammation  . Study selection will follow the Preferred Reporting Items for Systematic Review s and Meta-Analyses ( PRISMA ) guidelines and study quality will be assessed by the Jadad score in addition to an evaluation of allocation concealment and data analysis . If sufficient data are available , a meta- analysis will be conducted . The effect sizes will be generated using Hedges ’ g score , for both fixed and r and om effect models . I2 statistics and Galbraith plots will be used to assess heterogeneity and identify their potential sources . Potential publication and small sample size bias will be assessed by visual inspections of funnel plots and also Egger 's test . Meta-regression analysis ( if feasible ) will be conducted with restricted maximum likelihood ( REML ) estimation method , controlling for potential confounders ( demographics , study methods , location , etc ) . A backward elimination process will be applied in the regression modelling procedure . Subgroup analysis , conditional on number of studies retrieved and their sample size , will be stratified on participant disease category , total dose administered , degree of 25(OH)D change and type of supplement used . Ethics and dissemination Formal ethical approval is not required as primary data will not be collected . The results will be disseminated through a peer- review ed publication , conference presentation and the popular press . Trial registration number International Prospect i ve Register for Systematic Review s ( PROSPERO ) number CRD42014013523 Introduction Systematic review er authors intending to include all r and omized participants in their meta-analyses need to make assumptions about the outcomes of participants with missing data . Objective The objective of this paper is to provide systematic review er authors with a relatively simple guidance for addressing dichotomous data for participants excluded from analyses of r and omized trials . Methods This guide is based on a review of the Cochrane h and book and published method ological research . The guide deals with participants excluded from the analysis who were considered ‘ non-adherent to the protocol ’ but for whom data are available , and participants with missing data . Results Systematic review er authors should include data from ‘ non-adherent ’ participants excluded from the primary study authors ' analysis but for whom data are available . For missing , unavailable participant data , authors may conduct a complete case analysis ( excluding those with missing data ) as the primary analysis . Alternatively , they may conduct a primary analysis that makes plausible assumptions about the outcomes of participants with missing data . When the primary analysis suggests important benefit , sensitivity meta-analyses using relatively extreme assumptions that may vary in plausibility can inform the extent to which risk of bias impacts the confidence in the results of the primary analysis . The more plausible assumptions draw on the outcome event rates within the trial or in all trials included in the meta- analysis . The proposed guide does not take into account the uncertainty associated with assumed events . Conclusions This guide proposes methods for h and ling participants excluded from analyses of r and omized trials . These methods can help in establishing the extent to which risk of bias impacts meta- analysis results OBJECTIVES The objective of this review was to assess the effectiveness of interventions that assist caregivers to provide support for people living with dementia in the community . INCLUSION CRITERIA Types of participants Adult caregivers who provide support for people with dementia living in the community ( non-institutional care).Types of interventions Interventions design ed to support caregivers in their role such as skills training , education to assist in caring for a person living with dementia and support groups/programs . Interventions of formal approaches to care design ed to support caregivers in their role , care planning , case management and specially design ated members of the healthcare team - for example dementia nurse specialist or volunteers trained in caring for someone with dementia . Types of studies This review considered any meta-analyses , systematic review s , r and omised control trials , quasi-experimental studies , cohort studies , case control studies and observational studies without control groups that addressed the effectiveness of interventions that assist caregivers to provide support for people living with dementia in the community . SEARCH STRATEGY The search sought to identify published studies from 2000 to 2005 through the use of electronic data bases . Only studies in English were considered for inclusion . The initial search was conducted of the data bases , CINAHL , MEDLINE and PsychINFO using search strategies adapted from the Cochrane Dementia and Cognitive Improvement Group . A second more extensive search was then conducted using the appropriate Medical Subject Headings ( MeSH ) and keywords for other available data bases . Finally , h and search ing of reference lists of articles retrieved and of core dementia , geriatric and psycho geriatric journals was undertaken . ASSESSMENT OF QUALITY Method ological quality of each of the articles was assessed by two independent review ers using appraisal checklist developed by the Joanna Briggs Institute and based on the work of the Cochrane Collaboration and Centre for Review s and Dissemination . DATA COLLECTION AND ANALYSIS St and ardised mean differences or weighted mean differences and their 95 % confidence intervals were calculated for each included study reported in the meta- analysis . Results from comparable groups of studies were pooled in statistical meta- analysis using Review Manager Software from the Cochrane Collaboration . Heterogeneity between combined studies was tested using st and ard chi-square test . Where statistical pooling was not appropriate or possible , the findings are summarised in narrative form . RESULTS A comprehensive search of relevant data bases , h and search ing and cross referencing found 685 articles that were assessed for relevance to the review . Eighty-five papers appeared to meet the inclusion criteria based on title and abstract , and the full paper was retrieved . Of the 85 full papers review ed , 40 were accepted for inclusion , three were systematic review s , three were meta- analysis , and the remaining 34 were r and omised controlled trials . For the r and omised controlled trials that were able to be included in a meta- analysis , st and ardised mean differences or weighted mean differences and their 95 % confidence intervals were calculated for each . Results from comparable groups of studies were pooled in statistical meta- analysis using Review Manager Software and heterogeneity between combined studies was assessed by using the chi-square test . Where statistical pooling was not appropriate or possible , the findings are summarised in narrative form . The results are discussed in two main sections . Firstly it was possible to assess the effectiveness of different types of caregiver interventions on the outcome categories of depression , health , subjective well-being , self-efficacy and burden . Secondly , results are reported by main outcome category . For each of these sections , meta- analysis was conducted where it was possible ; otherwise , a narrative summary describes the findings . EFFECTIVENESS OF INTERVENTION TYPE Four categories of intervention were included in the review - psycho-educational , support , multi-component and other . Psycho-educational Thirteen studies used  psycho-educational interventions  , and all but one showed positive results across a range of outcomes . Eight studies were entered in a meta- analysis . No significant impact of psycho-educational interventions was found for the outcome categories of subjective well-being , self-efficacy or health . However , small but significant results were found for the categories of depression and burden . Support Seven studies discussed support only interventions and two of these showed significant results . These two studies were suitable for meta- analysis and demonstrated a small but significant improvement on caregiver burden . Multi-component Twelve of the studies report multi-component interventions and 10 of these report significant outcomes across a broad range of outcome measures including self-efficacy , depression , subjective well-being and burden . Unfortunately because of the heterogeneity of study design s and outcome measures , no meta- analysis was possible . Other interventions Other interventions included the use of exercise or nutrition which result ed in improvements in psychological distress and health benefits . Case management and a computer aided support intervention provided mixed results . One cognitive behavioural therapy study reported a reduction in anxiety and positive impacts on patient behaviour . EFFECTIVENESS OF INTERVENTIONS USING SPECIFIC OUTCOME CATEGORIES In addition to analysis by type of intervention it was possible to analyse results based on some outcome categories that were used across the studies . In particular the impact of interventions on caregiver depression was available for meta- analysis from eight studies . This indicated that multi-component and psycho-educational interventions showed a small but significant positive effect on caregiver depression . Five studies using the outcome category of caregiver burden  were entered into a meta- analysis and findings indicated that there were no significant effects of any of interventions . No meta- analysis was possible for the outcome categories of health , self-efficacy or subjective well-being . IMPLICATION S FOR PRACTICE From this review there is evidence to support the use of well- design ed psycho-educational or multi-component interventions for caregivers of people with dementia who live in the community . Factors that appear to positively contribute to effective interventions are those which : Factors which do not appear to have benefit in interventions are those which Background Computerized clinical decision support systems are information technology-based systems design ed to improve clinical decision-making . As with any healthcare intervention with cl aims to improve process of care or patient outcomes , decision support systems should be rigorously evaluated before widespread dissemination into clinical practice . Engaging healthcare providers and managers in the review process may facilitate knowledge translation and uptake . The objective of this research was to form a partnership of healthcare providers , managers , and research ers to review r and omized controlled trials assessing the effects of computerized decision support for six clinical application areas : primary preventive care , therapeutic drug monitoring and dosing , drug prescribing , chronic disease management , diagnostic test ordering and interpretation , and acute care management ; and to identify study characteristics that predict benefit . Methods The review was undertaken by the Health Information Research Unit , McMaster University , in partnership with Hamilton Health Sciences , the Hamilton , Niagara , Haldim and , and Brant Local Health Integration Network , and pertinent healthcare service teams . Following agreement on information needs and interests with decision-makers , our earlier systematic review was up date d by search ing Medline , EMBASE , EBM Review data bases , and Inspec , and review ing reference lists through 6 January 2010 . Data extraction items were exp and ed according to input from decision-makers . Authors of primary studies were contacted to confirm data and to provide additional information . Eligible trials were organized according to clinical area of application . We included r and omized controlled trials that evaluated the effect on practitioner performance or patient outcomes of patient care provided with a  computerized clinical decision support system compared with patient care without such a system . Results Data will be summarized using descriptive summary measures , including proportions for categorical variables and means for continuous variables . Univariable and multivariable logistic regression models will be used to investigate associations between outcomes of interest and study specific covariates . When reporting results from individual studies , we will cite the measures of association and p-values reported in the studies . If appropriate for groups of studies with similar features , we will conduct meta-analyses . Conclusion A decision-maker- research er partnership provides a model for systematic review s that may foster knowledge translation and uptake Context Clinicians rely on systematic review s for current , evidence -based information . Contribution This survival analysis of 100 meta-analyses indexed in ACP Journal Club from 1995 to 2005 found that new evidence that substantively changed conclusions about the effectiveness or harms of therapies arose frequently and within relatively short time periods . The median survival time without substantive new evidence for the meta-analyses was 5.5 years . Significant new evidence was already available for 7 % of the review s at the time of publication and became available for 23 % within 2 years . Implication Clinical ly important evidence that alters conclusions about the effectiveness and harms of treatments can accumulate rapidly . The Editors Systematic review s have become increasingly common in recent years ( 1 ) and are recommended by many as the best sources of evidence to guide both clinical decisions ( 2 ) and health care policy ( 3 ) . For systematic review s to fulfill these roles , their findings must remain relatively stable for at least several years or effective mechanisms must exist for alerting end users to important changes in evidence . Yet , surprisingly little research has assessed the extent to which systematic review s become out of date or the rate at which this occurs ( 47 ) . Some organizations , such as the Cochrane Collaboration , recommend updating systematic review s every 2 years , but few empirical data guide this or other recommendations about updating . We sought to determine how quickly systematic review s meet explicitly defined criteria for changes in evidence of sufficient importance to warrant updating . We also sought to identify predictors of survival time , the time to such important changes in evidence . Survival time might vary depending on many factors , including the type of question posed by the original review ( for example , therapeutic or diagnostic ) , the types of studies included ( for example , r and omized trials or observational studies ) , and whether the systematic review provided quantitative synthesis . To limit such variation , we focused on systematic review s of r and omized , controlled trials that evaluated therapeutic benefit or harm by providing quantitative synthesis ( meta- analysis ) for at least 1 outcome . Methods Study Design and Sample We used a quasi-r and om process ( alphabetical sort order by author ) to select 100 systematic review s that were indexed in ACP Journal Club with an accompanying commentary between January 1995 and December 2005 ( with a search date no later than 31 December 2004 to ensure at least 1 full year for new evidence to appear ) . We chose this sampling frame because ACP Journal Club selects systematic review s that meet explicit quality st and ards and are deemed directly relevant to clinical practice ( 8) . We regarded the sample size of 100 as sufficiently large to achieve suitably narrow confidence intervals and to permit evaluation of up to 5 potential predictors of survival . Eligibility Criteria Eligible review s evaluated the benefit or harm of a specific drug , class of drug , device , or procedure ( invasive procedure or surgery ) and included r and omized or quasi-r and omized , controlled trials . We excluded evaluations of alternative and complementary medicines because the stability of review s of such therapies might differ substantially from review s of conventional therapies . We required that review s provide a point estimate and 95 % confidence interval for at least 1 outcome in the form of a relative risk , odds ratio , or absolute risk difference for binary outcomes and weighted mean differences for continuous outcomes . We excluded meta-analyses of individual-patient data , meta-regressions , and indirect meta-analyses because of the difficulty of determining whether new data would alter previous quantitative results . Two team members independently assessed eligibility , with disagreements resolved by consensus involving a third review er . When more than 1 review on the same topic was identified , only the earliest was included . Search ing For each review , search es for new trials included identifying new systematic review s on the same topic , su bmi tting relevant content terms to the Clinical Queries function in Ovid , applying the Related Articles function in PubMed to the 3 largest and the 3 most recent trials in the original review ( up to 6 trials in total ) , and using Scopus ( www . scopus .com/ scopus /home.url ) to identify new r and omized trials that cited the original review . When these search strategies yielded no eligible new trials , we conducted more comprehensive electronic search es and review ed relevant chapters in such sources as Clinical Evidence and UpTo Date to ensure that we had not missed new trials . Team members who had background s in both medicine and clinical research screened citations retrieved by the preceding methods to identify trials that would have met the inclusion criteria in the original review . Retrieved articles were screened in chronological order to ascertain quantitative or qualitative signals for the need for updating . The review protocol stopped when any criteria for updating were met . Each systematic review was discussed in detail , with the final statussignal for updating was or was not detectedadjudicated by consensus ( Figure 1 ) . Figure 1 . Overall process for determining updating status . ACP Journal Club Signals for the Need to Up date Systematic Review s In design ing criteria for comparing new findings with those in a previous review , we adapted methods used by other investigators to address similar problems with comparing 2 sets of results relating to the same question ( 913 ) , such as r and omized and nonr and omized studies of the same intervention . These investigators identified conflicting findings among different publications using a combination of quantitative thresholds for differences in effect magnitude and qualitative judgments about the language used to describe the results . We have similarly conceptualized quantitative and qualitative signals of potential changes in evidence that are sufficiently important to warrant updating previous systematic review s. Quantitative Signals Quantitative signals consisted of a change in statistical significance or relative change in effect magnitude of at least 50 % . We restricted these changes to those involving 1 of the primary outcomes of the original review or any mortality outcome . We also ignored trivial changes in statistical significance when the original and up date d meta-analytic results both had P values between 0.04 and 0.06so that quantitative signals of changes in evidence would represent robust indicators of the need to up date previous review s. Quantitative signals were detected by combining data from eligible new trials with the previous results using a fixed-effects approach . Use of fixed-effect models allowed pooling of the new trials with the previous meta-analytic result , as opposed to having to obtain original data from all of the included trials in each of 100 systematic review s. Although r and om-effects models are usually preferred to avoid spurious precision in the face of heterogeneity , our goal was to detect potential changes in evidence that would warrant a formal up date , not produce exact estimates of the up date d results . Qualitative Signals Qualitative signals included new information about harm sufficient to affect clinical decision making , important caveats to the original results , emergence of a superior alternate therapy , and important changes in certainty or direction of effect . Qualitative signals were detected by using explicit criteria for comparing the language in the original review with descriptions of findings in new systematic review s that addressed the same topic , pivotal trials , clinical practice guidelines , or recent editions of major textbooks ( for example , UpTo Date ) . Pivotal trials were defined as trials that had a sample size at least 3 times larger than that of the previous largest trial or were published in 1 of the 5 highest-impact general medical journals ( The New Engl and Journal of Medicine , Lancet , Journal of the American Medical Association , Annals of Internal Medicine , and the British Medical Journal ) . We defined 2 levels of importance for qualitative signals : potentially invalidating changes in evidence , which would make one no longer want clinicians or policymakers to base decisions on the original findings ( such as a pivotal trial that characterized treatment effectiveness in terms opposite of those in the original systematic review ) , and major changes in evidence , which would affect clinical decision making in important ways without invalidating the previous results ( such as the identification of patient population s for whom treatment is more or less beneficial ) . Major changes also included differing characterizations of effectiveness that were less extreme than those for potentially invalidating signals but that would still affect clinical decision making ( for example , a change from possibly beneficial to definitely beneficial ) . Of importance , such characterizations as possibly effective , probably effective , and promising , were all categorized as possibly effective . Thus , qualitative signals for changes in evidence captured substantive differences in the characterization of treatment effects , not merely semantic differences . Full definitions for each of the specific signals can be found at www.ohri.ca/UpdatingSystRevs . Data Collection For each review , we characterized the clinical content area , eligibility criteria for included trials , definitions of reported outcomes , number of included trials and participants , meta-analytic result for each outcome , identification of statistical heterogeneity , and excerpted quotations of the authors ' characterizations of the main results . We also abstract ed whether a given outcome was explicitly identified as 1 of the primary or main outcomes . We discounted identification of more than 3 such outcomes as inconsistent with the Background To improve quality of care and patient outcomes , health system decision-makers need to identify and implement effective interventions . An increasing number of systematic review s document the effects of quality improvement programs to assist decision-makers in developing new initiatives . However , limitations in the reporting of primary studies and current meta- analysis methods ( including approaches for exploring heterogeneity ) reduce the utility of existing syntheses for health system decision-makers . This study will explore the role of innovative meta- analysis approaches and the added value of enriched and up date d data for increasing the utility of systematic review s of complex interventions . Methods / Design We will use the data set from our recent systematic review of 142 r and omized trials of diabetes quality improvement programs  to evaluate novel approaches for exploring heterogeneity . These will include exploratory methods , such as multivariate meta-regression analyses and all-subsets combinatorial meta- analysis . We will then up date our systematic review to include new trials and enrich the data set by surveying authors of all included trials . In doing so , we will explore the impact of variables not , reported in previous publications , such as details of study context , on the effectiveness of the intervention . We will use innovative analytical methods on the enriched and up date d data set to identify key success factors in the implementation of  quality improvement interventions  for diabetes . Decision-makers will be involved throughout to help identify and prioritize variables to be explored and to aid in the interpretation and dissemination of results . Discussion This study will inform future systematic review s of complex interventions and describe the value of enriching and updating data for exploring heterogeneity in meta- analysis . It will also result in an up date d comprehensive systematic review of diabetes quality improvement interventions that will be useful to health system decision-makers in developing interventions to improve outcomes for people with diabetes . Systematic review registration PROSPERO registration no. Objectives The objective of this review was to assess the effectiveness of interventions that assist caregivers to provide support for people living with dementia in the community . Inclusion criteria Types of participants Adult caregivers who provide support for people with dementia living in the community ( non‐institutional care ) . Types of interventions Interventions design ed to support caregivers in their role such as skills training , education to assist in caring for a person living with dementia and support groups/programs . Interventions of formal approaches to care design ed to support caregivers in their role , care planning , case management and specially design ated members of the healthcare team ‐ for example dementia nurse specialist or volunteers trained in caring for someone with dementia . Types of studies This review considered any meta‐analyses , systematic review s , r and omised control trials , quasi‐experimental studies , cohort studies , case control studies and observational studies without control groups that addressed the effectiveness of interventions that assist caregivers to provide support for people living with dementia in the community . Search strategy The search sought to identify published studies from 2000 to 2005 through the use of electronic data bases . Only studies in English were considered for inclusion . The initial search was conducted of the data bases , CINAHL , MEDLINE and PsychINFO using search strategies adapted from the Cochrane Dementia and Cognitive Improvement Group . A second more extensive search was then conducted using the appropriate Medical Subject Headings ( MeSH ) and keywords for other available data bases . Finally , h and search ing of reference lists of articles retrieved and of core dementia , geriatric and psycho geriatric journals was undertaken . Assessment of quality Method ological quality of each of the articles was assessed by two independent review ers using appraisal checklist developed by the Joanna Briggs Institute and based on the work of the Cochrane Collaboration and Centre for Review s and Dissemination . Data collection and analysis St and ardised mean differences or weighted mean differences and their 95 % confidence intervals were calculated for each included study reported in the meta‐ analysis . Results from comparable groups of studies were pooled in statistical meta‐ analysis using Review Manager Software from the Cochrane Collaboration . Heterogeneity between combined studies was tested using st and ard chi‐square test . Where statistical pooling was not appropriate or possible , the findings are summarised in narrative form . Results A comprehensive search of relevant data bases , h and search ing and cross referencing found 685 articles that were assessed for relevance to the review . Eighty‐five papers appeared to meet the inclusion criteria based on title and abstract , and the full paper was retrieved . Of the 85 full papers review ed , 40 were accepted for inclusion , three were systematic review s , three were meta‐ analysis , and the remaining 34 were r and omised controlled trials . For the r and omised controlled trials that were able to be included in a meta‐ analysis , st and ardised mean differences or weighted mean differences and their 95 % confidence intervals were calculated for each . Results from comparable groups of studies were pooled in statistical meta‐ analysis using Review Manager Software and heterogeneity between combined studies was assessed by using the chi‐square test . Where statistical pooling was not appropriate or possible , the findings are summarised in narrative form . The results are discussed in two main sections . Firstly it was possible to assess the effectiveness of different types of caregiver interventions on the outcome categories of depression , health , subjective well‐being , self‐efficacy and burden . Secondly , results are reported by main outcome category . For each of these sections , meta‐ analysis was conducted where it was possible ; otherwise , a narrative summary describes the findings . Effectiveness of intervention type Four categories of intervention were included in the review ‐ psycho‐educational , support , multi‐component and other . Psycho‐educational Thirteen studies used  psycho‐educational interventions , and all but one showed positive results across a range of outcomes . Eight studies were entered in a meta‐ analysis . No significant impact of psycho‐educational interventions was found for the outcome categories of subjective well‐being , self‐efficacy or health . However , small but significant results were found for the categories of depression and burden . Support Seven studies discussed support only interventions and two of these showed significant results . These two studies were suitable for meta‐ analysis and demonstrated a small but significant improvement on caregiver burden . Multi‐component Twelve of the studies report multi‐component interventions and 10 of these report significant outcomes across a broad range of outcome measures including self‐efficacy , depression , subjective well‐being and burden . Unfortunately because of the heterogeneity of study design s and outcome measures , no meta‐ analysis was possible . Other interventions Other interventions included the use of exercise or nutrition which result ed in improvements in psychological distress and health benefits .  Case management and a computer aided support intervention provided mixed results . One cognitive behavioural therapy study reported a reduction in anxiety and positive impacts on patient behaviour . Effectiveness of interventions using specific outcome categories In addition to analysis by type of intervention it was possible to analyse results based on some outcome categories that were used across the studies . In particular the impact of interventions on  caregiver depression was available for meta‐ analysis from eight studies . This indicated that multi‐component and psycho‐educational interventions showed a small but significant positive effect on caregiver depression . Five studies using the outcome category of caregiver burden  were entered into a meta‐ analysis and findings indicated that there were no significant effects of any of interventions . No meta‐ analysis was possible for the outcome categories of health , self‐efficacy or subjective well‐being . Implication s for practice From this review there is evidence to support the use of well‐ design ed psycho‐educational or multi‐component interventions for caregivers of people with dementia who live in the community . Factors that appear to positively contribute to effective interventions are those which : Provide opportunities within the intervention for the person with dementia as well as the caregiver to be involved Encourage active participation in educational interventions for caregivers Offer individualised programs rather than group sessions Provide information on an ongoing basis , with specific information about services and coaching regarding their new role Target the care recipient particularly by reduction in behaviours Factors which do not appear to have benefit in interventions are those which : Simply refer caregivers to support groups Only provide self help material s Only offer peer PURPOSE Health interventions based on theory may be more effective than those that are not . This review of review s synthesizes all published r and omized controlled trial ( RCT ) meta-analytic evidence from the last decade to examine whether theory-based interventions were found to be associated with more effective  adult health behaviour change interventions . METHODS Systematic review s including meta-analyses were identified by search ing Medline , CINAHL , PsycINFO , and CDSR . A narrative synthesis was used to summarize and analyse the evidence . Only review s including RCTs of health behaviour change interventions with adults aged 18 + published from 2007 to 2017 were included . RESULTS Of 8,659 articles , nine systematic review s met inclusion criteria . The majority of review s ( n = 8) suggested no increased effectiveness for theory-based compared to non-theory-based interventions for effectiveness of outcomes relating to health behaviour . Less than half of the RCTs included in the review s reported the use of theory ( 85/183 ) . Two review s suggested interventions based on control theory , motivational interviewing , or self-determination theory were associated with greater effectiveness for physical activity and /or dietary interventions and outcomes . Method ological and reporting issues limit the conclusions . CONCLUSIONS Theory-based interventions as currently operationalized in systematic review s were not found to be more effective than non-theory-based interventions . Method ological and reporting issues at study and review level may not reflect the true utility of theory use within health behaviour interventions . The promotion of theory use may benefit from using a multifaceted argument , rather than a narrow focus of increased effectiveness . Statement of contribution What is already known on this subject ? Theory use is regularly promoted by cl aim ing that it will lead to more effective behaviour change interventions . Theory use has been frequently linked to effectiveness within systematic review s of behaviour change interventions . The theory-effectiveness hypothesis has not been systematic ally examined at the systematic review level . What does this study add ? Theory use as operationalized by systematic review authors was not associated with increased effectiveness within systematic review s examining r and omized controlled trials of behaviour change interventions in adults . Interventions based on control theory , motivational interviewing , or self-determination theory were associated with greater effectiveness for physical activity and /or dietary interventions and outcomes . Theory use should be promoted using a multifaceted argument , and assertions for increased effectiveness of theory-based interventions should only be used in domains where specific evidence exists to support this cl aim Background The prevalence of overweight and obesity is high amongst healthcare professionals and there is growing interest in delivering weight loss interventions in the workplace . We conducted a systematic review to ( i ) examine the effectiveness of workplace-based diet and /or physical activity interventions aim ed at healthcare professionals and to ( ii ) identify and describe key components of effective interventions . Seven electronic data bases were systematic ally search ed . Results Thirteen r and omised controlled trials met the inclusion criteria , of which seven had data available for meta- analysis . Where meta- analysis was possible , studies were grouped according to length of follow-up ( < 12 months and ≥12 months ) and behavioural target ( diet only , physical activity only or diet and physical activity ) , with outcome data pooled using a weighted r and om effects model . Nine studies reported statistically significant ( between-group ) differences . Four studies reported being informed by a behaviour change theory . Meta- analysis of all trials reporting weight data demonstrated healthcare professionals allocated to dietary and physical activity interventions lost significantly more body weight ( −3.95 Kg , [ 95 % CI −4.96 to- 2.95 Kg ] ) than controls up to 12 months follow up . Conclusions Workplace diet and /or physical activity interventions targeting healthcare professionals are limited in number and are heterogeneous . To improve the evidence base , we recommend additional evaluations of theory-based interventions and adequate reporting of intervention content Background Community pharmacists can deliver health care advice at an opportunistic level , related to prescription or non-prescription medicines and as part of focused services design ed to reduce specific risks to health . Obesity , smoking and excessive alcohol intake are three of the most significant modifiable risk factors for morbidity and mortality in the UK , and interventions led by community pharmacists , aim ed at these three risk factors , have been identified by the government as public health priorities . In 2008 , the Department of Health for Engl and stated that ‘ a sound evidence base that demonstrates how pharmacy delivers effective , high quality and value for money services is needed ’ ; this systematic review aims to respond to this requirement . Methods / design We will search the data bases MEDLINE , Embase , CINAHL , PsycINFO , Social Sciences Citation Index , ASSIA , IBSS , Sociological Abstract s , Scopus and NHS Economic Evaluation Data base for studies that have evaluated interventions based on community pharmacies that aim to target weight management , smoking cessation and alcohol misuse . We will include all r and omised controlled trials ( RCTs ) , non-r and omised controlled trials ( N RCTs ) , controlled before-after studies ( CBAs ) and interrupted time series ( ITS ) and repeated measures studies . Data from included studies will be extracted by two independent review ers and will include study details methods , results , intervention implementation/costs and method ological quality . Meta- analysis will be conducted if appropriate ; if not , the synthesis will be restricted to a narrative overview of individual studies looking at the same question . Discussion The review aims to summarise the evidence base on the effectiveness of community pharmacy interventions on health and health behaviours in relation to weight management , smoking cessation and alcohol misuse . It will also explore if , and how , socio-economic status , gender , ethnicity and age moderate the effect of the interventions and will describe how the interventions included in the review have been organised , implemented and delivered , since context is an important factor governing the success of public health interventions . The findings from this review will have an impact on the commissioning of public health services aim ing to promote healthy weight , smoking cessation and prevent excessive alcohol consumption . Systematic review registration The review has been registered with PROSPERO ( registration no. CRD42013005943 ) . Available at : http://www.crd.york.ac.uk/ prospero /display_record.asp?ID = CRD42013005943 Background : Significant pain can be experienced after laparoscopic cholecystectomy . This systematic review aims to formulate PROSPECT ( PROcedure SPECific Postoperative Pain ManagemenT ) recommendations to reduce postoperative pain after laparoscopic cholecystectomy . Methods : R and omised controlled trials published in the English language from January 2006 ( date of last PROSPECT review ) to December 2017 , assessing analgesic , anaesthetic , or operative interventions for laparoscopic cholecystectomy in adults , and reporting pain scores , were retrieved from MEDLINE and Cochrane data bases using PRISMA ( Preferred Reporting Items for Systematic Review s and Meta‐Analyses ) search protocol s. PROSPECT methodology was used , and recommendations were formulated after review and discussion by the PROSPECT group ( an international group of leading pain specialists and surgeons ) . Results : Of 1988 r and omised controlled trials identified , 258 met the inclusion criteria and were included in this review . The studies were of mixed method ological quality , and quantitative analysis was not performed because of heterogeneous study design and how outcomes were reported . Conclusions : We recommend basic analgesic techniques : paracetamol + NSAID or cyclooxygenase‐2 specific inhibitor + surgical site local anaesthetic infiltration . Paracetamol and NSAID should be started before or during operation with dexamethasone ( GRADE A ) . Opioid should be reserved for rescue analgesia only ( GRADE B ) . Gabapentanoids , intraperitoneal local anaesthetic  , and  transversus abdominis plane blocks  are not recommended ( GRADE D ) unless basic analgesia is not possible . Surgically , we recommend low‐pressure pneumoperitoneum , postprocedure saline lavage , and aspiration of pneumoperitoneum ( GRADE A ) . Single‐port incision techniques are not recommended to reduce pain ( GRADE A ) This is the last in a series of four articles Prognostic studies include clinical studies of variables predictive of future events as well as epidemiological studies of aetiological risk factors . As multiple similar studies accumulate it becomes increasingly important to identify and evaluate all of the relevant studies to develop a more reliable overall assessment . For prognostic studies this is not straightforward . Box 1 summarises the clinical importance of information on prognostic factors . Many of the issues discussed are also relevant to aetiological studies , especially cohort ones . Some features of prognostic studies lead to particular difficulties for the systematic review er . Firstly , in most clinical prognostic studies the outcome of primary interest is the time to an event , often death . Meta- analysis of such studies is rather more difficult than that for binary data or continuous measurements . Secondly , in many context s the prognostic variable of interest is often one of several prognostic variables . When examining a variable of interest research ers should consider other prognostic variables with which it might be correlated . Thirdly , many prognostic factors are continuous variables , for which research ers use a wide variety of methods of analysis . # # # # Summary points Systematic review s are applicable to all types of research design , and studies of prognostic variables are an important additional area where appropriate methodology should be applied Prognostic variables should be evaluated in a representative sample of patients assembled at a common point in the course of their disease — ideally they should all have received the same medical treatment or been in a r and omised trial When examined critically , a high proportion of prognostic studies are found to be method ologically poor Meta- analysis of published data is hampered by difficulties in extraction of data and variation in the characteristics of the study and patients The poor quality of the published literature is a strong argument in favour Background Fever and  neutropenia ( FN ) is a common complication of chemotherapy for cancer . Prompt empiric broad-spectrum antibiotic therapy in FN is typically considered st and ard of care , but the definition of prompt is not clear . We seek to systematic ally review the available data on the association between time to antibiotics ( TTA ) administration and clinical outcomes in patients with FN being treated with chemotherapy .  There have been several efforts to reduce TTA in patients with FN , by implementing specific interventions , presuming there will be a beneficial effect on patient-important outcomes . This systematic review will also collect data on such interventions and their effect to reduce TTA and potentially change clinical outcomes . Methods / design The search will cover MEDLINE , MEDLINE In-Process & Other Non-Indexed Citations , EMBASE , CINAHL , CDSR , CENTRAL , and LILACS . A full- search strategy is provided . Lists of studies identified by references cited and forward citation search ing of included articles will also be review ed . Studies will be screened , and data extracted by one research er and independently checked by a second . Confounding biases and quality of studies will be assessed with the risk of bias in non-r and omised studies -of interventions ( ROBINS-I ) tool . Data will be presented in narrative and tabular forms ; in addition , if appropriate data is available , r and om effects meta- analysis will be used to examine TTA.A detailed analysis plan , including an assessment of heterogeneity and publication bias , is provided . Discussion This study aims to evaluate the association between TTA and patient-important clinical outcomes . Additionally , it will identify , critically appraise , and synthesis e information on performed interventions and its effect to reduce TTA as a way of gaining insight into the potential use of these approaches . This will provide better knowledge for an adjusted treatment approach of FN . Systematic review registration PROSPERO [ CRD42018092948 Background Being a family carer to a patient nearing the end of their life is a challenging and confronting experience . Studies show that caregiving can have negative consequences on the health of family carers including fatigue , sleep problems , depression , anxiety and burnout . One of the goals of palliative care is to provide psychosocial support to patients and families facing terminal illness . A systematic review of interventions for family carers of cancer and palliative care patients conducted at the start of this millennium demonstrated that there was a dearth of rigorous inquiry on this topic and consequently limited knowledge regarding the types of interventions likely to be effective in meeting the complex needs of family carers . We wanted to discern whether or not the evidence base to support family carers has improved . Furthermore , undertaking this review was acknowledged as one of the priorities for the International Palliative Care Family Carer Research Collaboration http://www.centreforpallcare.org . Methods A systematic review was undertaken in order to identify developments in family carer support that have occurred over the last decade . The focus of the review was on interventions that targeted improvements in the psychosocial support of family carers of palliative care patients . Studies were grade d to assess their quality . Results A total of fourteen studies met the inclusion criteria . The focus of interventions included  psycho-education , psychosocial support , carer coping , symptom management , sleep promotion and family meetings .  Five studies were r and omised controlled trials , three of which met the criteria for the highest quality evidence . There were two prospect i ve studies , five pre-test/post-test projects and two qualitative studies . Conclusions The systematic review identified a slight increase in the quality and quantity of psychosocial interventions conducted for family carers in the last decade . More rigorous intervention research is required in order to meet the supportive care needs of family carers of palliative care patients Introduction The extraskeletal role of vitamin D is being increasingly recognised . This has important clinical implication s , as vitamin D deficiency has reached epidemic proportions worldwide . Vitamin D has proposed anti-inflammatory properties , yet the role of vitamin D supplementation in reducing inflammation remains largely unknown . The purpose of this review is to investigate the impact of vitamin D supplementation on inflammation , and to identify relevant knowledge gaps in the field . Methods and analysis Medline , CINAHL , EMBASE and All EBM will be systematic ally search ed for r and omised controlled trials ( RCTs ) and systematic review s of RCTs , comparing vitamin D supplementation with placebo , usual care or other pharmacological or non-pharmacological interventions . One review er will assess articles for eligibility according to prespecified selection criteria , after which 2 independent review ers will perform data extraction and quality appraisal . Meta-analyses will be conducted where appropriate . Ethics and dissemination Formal ethical approval is not required as no primary data is collected . This systematic review will identify potential clinical implication s of vitamin D deficiency and supplementation , and will be disseminated through a peer- review ed publication and at conference meetings , to inform future research on the efficacy of vitamin D supplementation for inflammation and inflammatory diseases . PROSPERO registration number CRD42016037104 Background Experimenter ’s allegiance ( EA ) refers to a personal confidence of the superiority of a specific psychotherapy treatment . This factor has been linked with larger treatment effects in favor of the preferred treatment . However , various studies have displayed contradictory results between EA and the pattern of treatment effects . Aims Using a systematic approach followed by meta- analysis , we aim ed to evaluate the impact of an allegiance effect on the results of psychotherapeutic studies . Method We considered the meta-analyses of r and omized controlled trials ( RCTs ) of different types of psychotherapies in the Cochrane Data base of Systematic Review s. Eligible articles included meta-analyses of RCTs with at least one study showing evidence of EA ( i.e. , allegiant study ) . Effect sizes in allegiant RCTs were compared with non-allegiant using r and om and fixed models and a summary relative odds ratio ( ROR ) were calculated . Heterogeneity was quantified with the I2 metric . Results A total of 30 meta-analyses including 240 RCTs were analyzed . The summary ROR was 1.31 [ ( 95 % confidence interval ( CI : 1.03–1.66 ) P = 0.30 , I2 = 53 % ] indicating larger effects when allegiance exists . The impact of allegiance did not differ significantly ( P > 0.05 ) when we compared psychiatric versus medical outcomes . Allegiance effect was significant for all forms of psychotherapy except for cognitive behavioral therapy . Moreover , the impact of allegiance was significant only when the treatment integrity of delivered psychotherapy was not assessed . Allegiance effect was even stronger where the experimenter was also both the developer of the preferred treatment and supervised or trained the therapists . No significant differences were found between allegiant and non-allegiant studies in terms of overall quality of studies . Conclusions Experimenter ’s allegiance influences the effect sizes of psychotherapy RCTs and can be considered non-financial conflict of interest introducing a form of optimism bias , especially since blinding is problematic in this kind of research . A clear reporting of EA in every single study should be given an opportunity to investigators of minimizing its overestimation effects Objective To examine the prevalence of outcome reporting bias — the selection for publication of a subset of the original recorded outcome variables on the basis of the results — and its impact on Cochrane review s. Design A nine point classification system for missing outcome data in r and omised trials was developed and applied to the trials assessed in a large , unselected cohort of Cochrane systematic review s. Research ers who conducted the trials were contacted and the reason sought for the non-reporting of data . A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on review s that included a single meta- analysis of the review primary outcome . Results More than half ( 157/283 ( 55 % ) ) the review s did not include full data for the review primary outcome of interest from all eligible trials . The median amount of review outcome data missing for any reason was 10 % , whereas 50 % or more of the potential data were missing in 70 ( 25 % ) review s. It was clear from the publications for 155 ( 6 % ) of the 2486 assessable trials that the research ers had measured and analysed the review primary outcome but did not report or only partially reported the results . For reports that did not mention the review primary outcome , our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88 % ( 95 % CI 65 % to 100 % ) and specificity of 80 % ( 95 % CI 69 % to 90 % ) on the basis of responses from 62 trialists . A third of Cochrane review s ( 96/283 ( 34 % ) ) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome . In a sensitivity analysis undertaken for 81 review s with a single meta- analysis of the primary outcome of interest , the treatment effect estimate was reduced by 20 % or more in 19 ( 23 % ) . Of the 42 meta-analyses with a statistically significant result only , eight ( 19 % ) became non-significant after adjustment for outcome reporting bias and 11 ( 26 % ) would have overestimated the treatment effect by 20 % or more . Conclusions Outcome reporting bias is an under-recognised problem that affects the conclusions in a substantial proportion of Cochrane review s. Individuals conducting systematic review s need to address explicitly the issue of missing outcome data for their review to be considered a reliable source of evidence . Extra care is required during data extraction , review ers should identify when a trial reports that an outcome was measured but no results were reported or events observed , and contact with trialists should be encouraged In many areas of medicine the amount of published information is increasing at an exponential rate , making it difficult for the clinician to condense the data to a manageable amount of valuable and useful information . Systematic review s have been suggested as a remedy for this information overload . Such review s are regarded as the highest level of evidence . Certain statistical methods , e.g. , meta- analysis , have also been introduced for the calculation of a more comprehensive summation of the compiled results from studies with small sample sizes . These findings would then serve as an authoritarian guide for evidence -based practice . Endodontists have lately jumped on the b and wagon of systematic review s and meta-analyses , and papers on various topics are being published . Well done , such comprehensive information would be very useful and authoritative for the practitioner . Alarmingly , the quality of these recent publications is negatively correlated to the frequency . This can have serious consequences in the clinical arena if spurious information is given a seal of approval when communicated as facts in refereed journals . A systematic literature review is design ed to focus on a single question and to synthesize all high- quality research reports relevant to the question . In these studies , however , sources of bias are often not controlled . Therefore , even the best review and meta- analysis becomes useless if it is based on poorly design ed research . Furthermore , these review s are mostly based on published data which are too often biased toward studies that show significant differences in results and /or outcome . “ Uninteresting ” conclusions tend not to be published . Endodontic literature , thus far , is short on well design ed and executed r and omized clinical trials . Furthermore , clinical protocol s often have many important “ proprietary ” modifications that make comparison difficult . This makes it very hard to undertake a systematic review to answer a narrow question . Such GIGO ( garbage in , garbage out ) can easily lead to biased conclusions and reinforce already existing biased comclusions . An example of such bias can be illustrated by a meta- analysis recently published . The study focused on assessing if there were differences in outcome between 1 and 2 treatment visits when treating teeth with apical periodontitis . Relevant publications on this topic are rare , and with the narrow inclusion criteria only 3 investigations were available for the review . However , the only factors connecting these 3 studies was the words “ single ” and “ two visits ” in the title . Beyond that , the selected studies are too different and inadequate for the study . Only 1 study is somewhat demonstrably r and omized , and outcome assessment s are based on 3 vastly different criteria . Two of the studies use calcium hydroxide as intracanal dressing , whereas the third uses no intervisit medication . Complexity of initial pathology and healing time are also clearly factors of great importance but not controlled . In addition , sample sizes in the component studies as well as the final cohort are all too small for the conclusions that there was no significant difference between 1or 2-visit treatment protocol s. To undertake and publish a meta- analysis on such an incomplete sample is counterproductive . Although the publication noted its numerous limitations , it will still communicate erroneous conclusions with a poor scientific foundation to the less informed reader . There are other examples of recently published systematic review s that are very ambiguous and tend to communicate spurious facts . One of these studies looks at the effect of smear-layer removal on sealing ability of root canal obturation . The study is entirely limited to laboratory experiments , with the majority of evaluations using dye leakage which is generally considered to be unreliable . This is an example of review ers lacking content expertise . The authors draw the conclusion , using defective review material , that removal of smear layer enhances the seal of the root filling . We may generally believe that this is the truth UNLABELLED In June 2008 , the Medical Advisory Secretariat began work on the Diabetes Strategy Evidence Project , an evidence -based review of the literature surrounding strategies for successful management and treatment of diabetes . This project came about when the Health System Strategy Division at the Ministry of Health and Long-Term Care subsequently asked the secretariat to provide an evidentiary platform for the Ministry 's newly released Diabetes Strategy .After an initial review of the strategy and consultation with experts , the secretariat identified five key areas in which evidence was needed . Evidence -based analyses have been prepared for each of these five areas : insulin pumps , behavioural interventions , bariatric surgery , home telemonitoring , and community based care . For each area , an economic analysis was completed where appropriate and is described in a separate report . To review these titles within the Diabetes Strategy Evidence series , please visit the Medical Advisory Secretariat Web site , http://www.health.gov.on.ca/english/providers/program/mas/mas_about.html,DIABETES STRATEGY EVIDENCE PLATFORM : Summary of Evidence -Based AnalysesContinuous Subcutaneous Insulin Infusion Pumps for Type 1 and Type 2 Adult Diabetics : An Evidence -Based Analysis Behavioural Interventions for Type 2 Diabetes : An Evidence -Based Analysis BARIATRIC SURGERY FOR PEOPLE WITH DIABETES AND MORBID OBESITY : An Evidence -Based Summary Community-Based Care for the Management of Type 2 Diabetes : An Evidence -Based Analysis Home Telemonitoring for Type 2 Diabetes  : An Evidence -Based Analysis Application of the Ontario Diabetes Economic Model ( ODEM ) to Determine the Cost-effectiveness and Budget Impact of Selected Type 2 Diabetes Interventions in Ontario OBJECTIVE The objective of this report is to determine the efficacy of specialized multidisciplinary community care for the management of type 2 diabetes compared to usual care . CLINICAL NEED TARGET POPULATION AND CONDITION Diabetes ( i.e. diabetes mellitus ) is a highly prevalent chronic metabolic disorder that interferes with the body 's ability to produce or effectively use insulin . The majority ( 90 % ) of diabetes patients have type 2 diabetes . ( 1 ) Based on the United Kingdom Prospect i ve Diabetes Study ( UKPDS ) , intensive blood glucose and blood pressure control significantly reduce the risk of microvascular and macrovascular complications in type 2 diabetics . While many studies have documented that patients often do not meet the glycemic control targets specified by national and international guidelines , factors associated with glycemic control are less well studied , one of which is the provider(s ) of care . Multidisciplinary approaches to care may be particularly important for diabetes management . According guidelines from the Canadian Diabetes Association ( CDA ) , the diabetes health care team should be multi- and interdisciplinary . Presently in Ontario , the core diabetes health care team consists of at least a family physician and /or diabetes specialist , and diabetes educators ( registered nurse and registered dietician ) . Increasing the role played by allied health care professionals in diabetes care and their collaboration with physicians may represent a more cost-effective option for diabetes management . Several systematic review s and meta-analyses have examined multidisciplinary care programs , but these have either been limited to a specific component of multidisciplinary care ( e.g. intensified education programs ) , or were conducted as part of a broader disease management program , of which not all were multidisciplinary in nature . Most review s also do not clearly define the intervention(s ) of interest , making the evaluation of such multidisciplinary community programs challenging . EVIDENCE -BASED ANALYSIS METHODS RESEARCH QUESTIONS What is the evidence of efficacy of specialized multidisciplinary community care provided by at least a registered nurse , registered dietician and physician ( primary care and /or specialist ) for the management of type 2 diabetes compared to usual care ? [ Henceforth referred to as Model 1]What is the evidence of efficacy of specialized multidisciplinary community care provided by at least a pharmacist and a primary care physician for the management of type 2 diabetes compared to usual care ? [ Henceforth referred to as Model 2 ] INCLUSION CRITERIA English language full-reportsPublished between January 1 , 2000 and September 28 , 2008R and omized controlled trials ( RCTs ) , systematic review s and meta-analysesType 2 diabetic adult population ( ≥18 years of age)Total sample size ≥30Describe specialized multidisciplinary community care defined as ambulatory-based care provided by at least two health care disciplines ( of which at least one must be a specialist in diabetes ) with integrated communication between the care providers . Compared to usual care ( defined as health care provision by non-specialist(s ) in diabetes , such as primary care providers ; may include referral to other health care professionals/services as necessary)≥6 months follow-up EXCLUSION CRITERIA Studies where discrete results on diabetes can not be abstract edPredominantly home-based interventions Inpatient-based interventions OUTCOMES OF INTEREST The primary outcomes for this review were glycosylated hemoglobin ( rHbA1c ) levels and systolic blood pressure ( SBP ) . SEARCH STRATEGY A literature search was performed on September 28 , 2008 using OVID MEDLINE , MEDLINE In-Process and Other Non-Indexed Citations , EMBASE , the Cumulative Index to Nursing & Allied Health Literature ( CINAHL ) , the Cochrane Library , and the International Agency for Health Technology Assessment ( INAHTA ) for studies published between January 1 , 2000 and September 28 , 2008 . Abstract s were review ed by a single review er and , for those studies meeting the eligibility criteria , full-text articles were obtained . Reference lists were also examined for any additional relevant studies not identified through the search . Articles with unknown eligibility were review ed with a second clinical epidemiologist , then a group of epidemiologists until consensus was established . The quality of evidence was assessed as high , moderate , low or very low according to GRADE methodology . Given the high clinical heterogeneity of the articles that met the inclusion criteria , specific models of specialized multidisciplinary community care were examined based on models of care that are currently being supported in Ontario , models of care that were commonly reported in the literature , as well as suggestions from an Expert Advisory Panel Meeting held on January 21 , 2009 . SUMMARY OF FINDINGS The initial search yielded 2,116 unique citations , from which 22 RCTs trials and nine systematic review s published were identified as meeting the eligibility criteria . Of these , five studies focused on care provided by at least a nurse , dietician , and physician ( primary care and /or specialist ) model of care ( Model 1 ; see Table ES 1 ) , while three studies focused on care provided by at least a pharmacist and primary care physician ( Model 2 ; see Table ES 2 ) . Based on moderate quality evidence , specialized multidisciplinary community care Model 2 has demonstrated a statistically and clinical ly significant reduction in HbA1c of 1.0 % compared with usual care . The effects of this model on SBP , however , are uncertain compared with usual care , based on very-low quality evidence . Specialized multidisciplinary community care Model 2 has demonstrated a statistically and clinical ly significant reduction in both HbA1c of 1.05 % ( based on high quality evidence ) and SBP of 7.13 mm Hg ( based on moderate quality evidence ) compared to usual care . For both models , the evidence does not suggest a preferred setting of care delivery ( i.e. , primary care vs. hospital outpatient clinic vs. community clinic ) . Table ES1 : Summary of Results of Meta-Analyses of the Effects of Multidisciplinary Care Model 1 Outcome Estimate of effect(95 % CI)Heterogeneity I(2)(p-value ) GRADE Glycosylated Hemoglobin ( HbA1c [%])-1.00 [ -1.27 , -0.73]4 % (p=0.37)Moderate- quality Subgroup : Moderate-to-High Quality -0.91 [ -1.19 , -0.62]0 % (p=0.74)Systolic Blood Pressure ( mm Hg)-2.04 [ -13.80 , 9.72]89 % (p=0.002)Very-low quality * Mean change from baseline to follow-up between intervention and control groupsTable ES2 : Summary of Results of Meta-Analyses of the Effects of Multidisciplinary Care Model 2 Outcome Estimate of effect(95 % CI)Heterogeneity I(2)(p-value ) GRADE Glycosylated Hemoglobin ( HbA1c [%])-1.05 [ -1.57 , -0.52]0 % (p=0.75)High- quality Systolic Blood Pressure ( mm Hg)-7.13 [ -11.78 , -2.48]46 % (p=0.17)Moderate quality * Mean change from baseline to follow-up between intervention and control groups Review articles are an important element of most medical journals and a popular source of information for clinicians ( 1 ) . Given the increasing volume of medical literature and the limited time for reading that busy clinicians have , reliance on review articles is likely to increase . However , concerns have been raised that narrative , non systematic review articles may produce biased conclusions ( 2 , 3 ) . Mulrow ( 4 ) examined 50 review articles published in four major medical journals ( The New Engl and Journal of Medicine , Annals of Internal Medicine , JAMA , and Archives of Internal Medicine ) in 1985 - 1986 and found that none fulfilled 8 explicit criteria for scientifically sound summaries of the evidence . As a result , she and others ( 5 , 6 ) proposed criteria for conducting and evaluating review articles that would improve their quality ; these criteria are the first 10 listed in the Appendix Table . In a study of 36 review articles done by nine content experts and method ologists , these criteria were shown to yield reliable and valid estimates of the scientific quality of review s ( 7 , 8) . We sought to describe the methods used in recently published review articles and determine whether the attention paid to the method ologic shortcomings of review articles has led to improvements in their scientific quality . Methods By using the Science Citation Index ( 9 ) , we stratified the 12 general medicine journals that are considered core journals for ACP Journal Club ( 10 ) into those with high impact factors ( scores 5 ) and those with lower impact factors . We r and omly selected 3 ( The New Engl and Journal of Medicine , Annals of Internal Medicine , and JAMA ) of the 4 high-impact core journals and 3 ( British Medical Journal , American Journal of Medicine , and Journal of Internal Medicine ) of the 8 core journals with lower impact factors . The sampling frame included 3 of the 4 journals examined in Mulrow 's original study ( 4 ) . All 6 journals were h and - search ed by two of the investigators independently , and review articles published between January and December 1996 were retrieved . Review articles were defined as full-text articles published under the banner review that dealt with disease states ; had the words review , overview , or meta- analysis in the title or abstract ; or indicated in the text that the intention was to review or summarize the literature about a clinical topic . Editorials , correspondence , and conference summaries were excluded . Disagreements on article eligibility ( which occurred in five cases ) were resolved by consensus . After training with a test set of articles , five of the authors used explicit criteria ( Appendix Table ) to rate the identified review articles . So that the raters ' assessment s would be blinded , the articles ' authors , author affiliations , and sources of articles were masked . The first 10 criteria in the Appendix Table ( hereafter referred to as method ologic criteria ) have been previously vali date d ( 7 ) and assess method ologic rigor , whereas the last five criteria were developed for this study to evaluate the scientific basis of treatment recommendations . Because inter-rater agreement was excellent on the test set ( overall agreement , 94 % ) , each rater was assigned a r and om sample of 20 % of the articles . One rater independently evaluated a r and om sample of five articles from each rater to assess inter-rater reliability for the criteria . The mean value was 0.79 , indicating substantial agreement ; overall agreement was 95 % and ranged from 84 % for criteria 1 and 6 to 100 % for criteria 2 , 3 , and 5 . After we determined the number of criteria fulfilled by each article , the number of articles meeting each criterion was ascertained . The proportion of review s from high-impact journals and from lower-impact journals that met each criterion were compared . Only the subset of review s containing treatment recommendations were used for the comparisons for criteria 7 to 15 . The chi-square test was used and 95 % CIs for the observed differences were calculated for all comparisons . In addition , articles identified as meta-analyses , systematic review s , or overviews in their title , abstract , or text were compared with the remaining review articles for each criterion ( again by using the chi-square test and by limiting analysis to those that included treatment recommendations for criteria 7 to 15 ) . Logistic regression analysis was used to adjust for journal of publication . The funding organizations were not involved in the design , conduct , analysis , or reporting of this study . Results A total of 158 review articles were identified : 60 from The New Engl and Journal of Medicine , 33 from Annals of Internal Medicine , 24 from British Medical Journal , 18 from American Journal of Medicine , 13 from JAMA , and 10 from Journal of Internal Medicine . ( A full list of the included articles is available from Dr. McAlister on request . ) Most review s were written by more than one author ( median number of authors , 2 [ range , 1 to 10 authors ] ) , and 111 review s ( 70 % ) made treatment recommendations . Although most articles had sections review ing the relevant pathophysiology and pharmacodynamics , 19 articles ( 12 % ) were largely basic science review s. Only 2 review s met all 10 method ologic criteria ; the median number of criteria fulfilled was one ( Figure ) . Nineteen ( 12 % ) of the review articles were described as meta- analysis , systematic review , or overview in the title or abstract ; 12 of these 19 articles were published in high-impact journals . A higher proportion of these articles met the method ologic criteria ( Appendix Table ) ; the comparisons for all but criterion 6 were statistically significant , even after adjustment for journal of publication ( P<0.005 for all comparisons ) . Although there was significant heterogeneity among journals ( P<0.005 for criteria 1 to 5 , 7 , and 8) , review articles published in high-impact journals did not meet method ologic criteria more frequently than those published in other journals ( Table ) . Exclusion of the review s from one journal with method ologic scores that were significantly lower than the rest ( P<0.001 for all comparisons ) resolved much of the interjournal heterogeneity and revealed that review s published in the remaining high-impact journals more often met some ( but not all ) of the method ologic criteria ( Table ) . Figure . Percentage of 158 review articles published in 1996 that fulfilled specific method ologic criteria . Table . Comparison of Methods Used in 1996 Review Articles , by Journal Impact Factor The 44 articles that described how evidence was located used the following sources ( which were not mutually exclusive ) : MEDLINE ( 42 articles ) , h and search of reference lists from published studies or review articles ( 30 articles ) , other electronic data bases ( 14 articles ) , contact with experts in the field ( 10 articles ) , h and search of relevant journals ( 7 articles ) , and contact with the pharmaceutical industry ( 5 articles ) . Of the 22 review s that included a description of the electronic search strategy , the search was restricted to English- language publications in 11 . Of the 111 review s in which treatment recommendations were made , a median of 3 therapies ( range , 1 to 23 therapies ) were discussed . The 16 meta-analyses that included treatment recommendations were more focused , examining a median of 1 therapy ( range , 1 to 6 therapies ) . The scientific basis of these recommendations is outlined in the last five criteria of the Appendix Table . Discussion In summary , only a minority of the review articles published in six widely read general medical journals specified rigorous , systematic methods of identifying , evaluating , and synthesizing the evidence , thereby raising concerns about the validity of their conclusions and recommendations ( 11 ) . Furthermore , although most review articles made recommendations for therapeutic options , their clinical relevance may be limited : Only one third discussed benefits and harms of the treatment options , only 6 % mentioned the relative or absolute costs of the various options , less than half provided an estimate of the anticipated treatment effect , and very few presented the results in clinical ly relevant formats that would be easily understood by clinicians . Although there is still substantial room for improvement , these results do represent progress from the situation in 1985 - 1986 ( Appendix Table ) . A higher proportion of recently published review s specify how the evidence was identified and synthesized . This same pattern was observed in a recent study of oncology review articles published in a single journal between 1983 and 1995 ( 12 ) . Similarly , our findings for meta-analyses published in these journals in 1996 are consistent with contemporaneous investigations in other fields and represent substantial improvement over the state of affairs in the mid-1980s ( 13 , 14 ) . Our study had several potential limitations . First , the authors of articles in which systematic methods were not specified may have used such methods but not reported them ( or the journal may have removed the details of the methods in prepublication ) . However , preliminary evidence suggests that there is little difference between the conduct of studies and their published methods ( 7 , 15 ) . In other words , if what was done is not reported , there is a good chance that it was not done rigorously ( 7 ) . Second , our finding that meta-analyses are more scientifically rigorous than other review s may be seen as tautological because the criteria used in this study may be used by meta-analysts in performing their studies . However , meta-analysts disagree over some issues of methodology , and published meta-analyses often vary in the quality of their reports ( 13 ) . Third , the practical importance of the method ologic flaws identified in these review s is difficult to ascertain . We lack empirical evidence that review s with explicit , systematic methods yield results closer to the truth , but it is known that non systematic review s are more prone to r and om and Dr. Joseph Lau is a world-leading expert in meta- analysis and systematic review s. Currently a professor in the Department of Health Services , Policy and Practice and co-director of the Center for Evidence -based Medicine at Brown University , Professor Lau has applied evidence -based methods to a variety of clinical , biomedical and healthcare topics ; has developed reliable and efficient methods and tools to conduct systematic review s and meta-analyses ; and has advanced an underst and ing on the impact of factors that may contribute to differences of results in scientific studies . His past research includes cumulative meta- analysis of r and omized controlled trials , comparison of results from large trials and meta-analyses of small trials , effect of baseline risk in the interpretation of clinical trial results , and empirical evaluation of existing methods of combining data . His current focus is on a Web-based repository of systematic review data , review s of diagnostic tests , nutrition , clinical practice guidelines , and dissemination of evidence -based methods to varied health-care disciplines . This report is a conversation from an adapted version of an interview , more or less chronologically arranged , between Joseph C. Cappelleri as interviewer and Joseph Lau as interviewee , with Meghan Ingerick recording and transcribing the interview Background Systematic review s ( SRs ) can help decision makers interpret the deluge of published biomedical literature . However , a SR may be of limited use if the methods used to conduct the SR are flawed , and reporting of the SR is incomplete . To our knowledge , since 2004 there has been no cross-sectional study of the prevalence , focus , and completeness of reporting of SRs across different specialties . Therefore , the aim of our study was to investigate the epidemiological and reporting characteristics of a more recent cross-section of SRs . Methods and Findings We search ed MEDLINE to identify potentially eligible SRs indexed during the month of February 2014 . Citations were screened using prespecified eligibility criteria . Epidemiological and reporting characteristics of a r and om sample of 300 SRs were extracted by one review er , with a 10 % sample extracted in duplicate . We compared characteristics of Cochrane versus non-Cochrane review s , and the 2014 sample of SRs versus a 2004 sample of SRs . We identified 682 SRs , suggesting that more than 8,000 SRs are being indexed in MEDLINE annually , corresponding to a 3-fold increase over the last decade . The majority of SRs addressed a therapeutic question and were conducted by authors based in China , the UK , or the US ; they included a median of 15 studies involving 2,072 participants .  Meta- analysis was performed in 63 % of SRs , mostly using st and ard pairwise methods . Study risk of bias/ quality assessment was performed in 70 % of SRs but was rarely incorporated into the analysis ( 16 % ) . Few SRs ( 7 % ) search ed sources of unpublished data , and the risk of publication bias was considered in less than half of SRs . Reporting quality was highly variable ; at least a third of SRs did not report use of a SR protocol , eligibility criteria relating to publication status , years of coverage of the search , a full Boolean search logic for at least one data base , methods for data extraction , methods for study risk of bias assessment , a primary outcome , an abstract conclusion that incorporated study limitations , or the funding source of the SR . Cochrane SRs , which accounted for 15 % of the sample , had more complete reporting than all other types of SRs . Reporting has generally improved since 2004 , but remains suboptimal for many characteristics . Conclusions An increasing number of SRs are being published , and many are poorly conducted and reported . Strategies are needed to help reduce this avoidable waste in research 2011 ; 14 : 371–380 . 6 . Senn S , Gavini F , Magrez D , Scheen A. Issues in performing a network meta analysis . Statistical Methods in Medical Research 2013 ; 22 : 169–89 . 7 . Salanti G , Higgins JP , Ades A , Ioannidis JP . Evaluation of networks of r and omized trials . Statistical Methods in Medical Research 2008 ; 17 : 279– 301 . 8 . Song F , Clark A , Bachmann MO , Maas J. Simulation evaluation of statistical properties  of methods for indirect and mixed treatment comparisons . BMC Medical Research Methodology 2012 ; 12 : 1–14 . 9 . Jansen JP , Naci H. Is network meta- analysis as valid as st and ard pairwise meta- analysis ? It all depends on the distribution of effect modifers . BMC Medicine 2013 ; 11 : 1 . 10 . The Guidelines Manual . London : National Institute for Health and Clinical Excellence . 2012 . https://www . nice.org.uk/process/pmg6/chapter/6 review ing-the- evidence ( accessed 27/ 05/2017 ) . 11 . Kanters S , Ford N , Druyts E , et al. Use of network meta- analysis  in clinical guidelines . Bulletin of the World Health Organization 2016 ; 94 : 782–4 . 12 . Kiefer C , Sturtz S , Bender R. Indirect comparisons and network meta-analyses : estimation of effects in the absence of head-to-head trials . Deutsches € Arzteblatt International 2015 ; 112 : 803–8 . 13 . Imberger G , Gluud C , Boylan J , Wetterslev J. Systematic review s of anesthesiologic interventions reported as statistically significant : problems with power , precision , and type 1 error protection . Anesthesia and Analgesia 2015 ; 121 : 1611–22 . 14 . Afshari A , Wetterslev J , Smith AF . Can systematic review s with sparse data be trusted ? Anaesthesia 2017 ; 72 : 12–6 . 15 . Jakobsen JC , Wetterslev J , Lange T , Gluud C. Viewpoint : taking into account risks of r and om errors when analysing multiple outcomes in systematic review s. Cochrane Data base of Systematic Review s 2016 ; 3 : ED000111 . 16 . Jakobsen JC , Wetterslev J , Winkel P , Lange T , Gluud C. Thresholds for statistical and clinical significance in systematic review s with meta-analytic methods . BMC Medical Research Methodology 2014 ; 14 : 120 . 17 . Wetterslev J , Jakobsen JC , Gluud C. Trial Sequential Analysis in systematic review s with meta- analysis . BMC Medical Research Methodology 2017 ; 17 : 39 . 18 . Smith AF , Carlisle JC . Review s , systematic review s and Anaesthesia . Anaesthesia 2015 ; 70 : 644–70 . 19 . Cook TM , Kelly FE . The Difficult Airway Society 2015 guidelines and the sacred cows of routine airway management . Anaesthesia 2016 ; 71 : 466–7 . 20 . Schmitz S , Adams R , Walsh C. Incorporating data from various trial design s into a mixed treatment comparison model . Statistics in Medicine 2013 ; 32 : 2935–49 . 21 . Marshall SD , P and it JJ . Radical evolution : the 2015 Difficult Airway Society guidelines for managing unanticipated difficult or failed tracheal intubation . Anaesthesia 2016 ; 71 : 131–7 . 22 . Black AE , Flynn PE , Smith HL , Thomas ML , Wilkinson KA . Association of Pediatric Anaesthetists of Great Britain and Irel and . Development of a guideline for the management of the unanticipated difficult airway in pediatric practice . Pediatric Anaesthesia 2015 ; 25 : 346–62 . 23 . Hagberg CA , Gabel JC , Connis RT . Difficult Airway Society 2015 guidelines for the management of unanticipated difficult intubation in adults : not just another algorithm . British Journal of Anaesthesia 2015 ; 115 : 812–4 . 24 . Martin-Castro C , Montero A.  Flexible laryngeal mask as an alternative to reinforced tracheal tube for upper chest , head and neck oncoplastic surgery . European Journal of Anaesthesiology 2008 ; 25 : 261–6 . 25 . Maclennan A , Smith AF . An analysis of critical incidents relevant to paediatric anaesthesia reported to the UK National Reporting and Learning System , 2006 - 2008 . Pediatric Anesthesia 2011 ; 21 : 841–7 . 26 . P and it JJ , Popat MT , Cook TM , et al. The Difficult Airway Society ‘ ADEPT ’ Guidance on selecting airway devices : the basis of a strategy for equipment evaluation . Anaesthesia 2011 ; 66 : 726–37 Background The ideal evidence to answer a question about the effectiveness of treatment is a systematic review . However , for many clinical questions a systematic review will not be available , or may not be up to date . One option could be to use the evidence from an individual trial to answer the question ? Methods We assessed how often ( a ) the estimated effect and ( b ) the p-value in the most precise single trial in a meta- analysis agreed with the whole meta- analysis . For a r and om sample of 200 completed Cochrane Review s ( January , 2005 ) we identified a primary outcome and extracted : the number of trials , the statistical weight of the most precise trial , the estimate and confidence interval for both the highest weighted trial and the meta- analysis overall . We calculated the p-value for the most precise trial and meta- analysis . Results Of 200 review s , only 132 provided a meta- analysis of 2 or more trials , with a further 35 effect estimates based on single trials . The average number of trials was 7.3 , with the most precise trial contributing , on average , 51 % of the statistical weight to the summary estimate from the whole meta- analysis . The estimates of effect from the most precise trial and the overall meta-analyses were highly correlated ( rank correlation of 0.90).There was an 81 % agreement in statistical conclusions . Results from the most precise trial were statistically significant in 60 of the 167 evaluable review s , with 55 of the corresponding systematic review s also being statistically significant . The five discrepant results were not strikingly different with respect to their estimates of effect , but showed considerable statistical heterogeneity between trials in these meta-analyses . However , among the 101 cases in which the most precise trial was not statistically significant , the corresponding meta-analyses yielded 31 statistically significant results . Conclusions Single most precise trials provided similar estimates of effects to those of the meta-analyses to which they contributed , and statistically significant results are generally in agreement . However , " negative " results were less reliable , as may be expected from single underpowered trials . For systematic review ers we suggest that : ( 1 ) key trial(s ) in a review deserve greater attention ( 2 ) systematic review ers should check agreement of the most precise trial and the meta analysis . For clinicians using trials we suggest that when a meta- analysis is not available , a focus on the most precise trial is reasonable provided it is adequately powered BACKGROUND Systematic review s may be compromised by selective inclusion and reporting of outcomes and analyses . Selective inclusion occurs when there are multiple effect estimates in a trial report that could be included in a particular meta- analysis ( e.g. from multiple measurement scales and time points ) and the choice of effect estimate to include in the meta- analysis is based on the results ( e.g. statistical significance , magnitude or direction of effect ) . Selective reporting occurs when the reporting of a subset of outcomes and analyses in the systematic review is based on the results ( e.g. a protocol -defined outcome is omitted from the published systematic review ) . OBJECTIVES To summarise the characteristics and synthesis e the results of empirical studies that have investigated the prevalence of selective inclusion or reporting in systematic review s of r and omised controlled trials ( RCTs ) , investigated the factors ( e.g. statistical significance or direction of effect ) associated with the prevalence and quantified the bias . SEARCH METHODS We search ed the Cochrane Methodology Register ( to July 2012 ) , Ovid MEDLINE , Ovid EMBASE , Ovid PsycINFO and ISI Web of Science ( each up to May 2013 ) , and the US Agency for Healthcare Research and Quality ( AHRQ ) Effective Healthcare Program 's Scientific Re source Center ( SRC ) Methods Library ( to June 2013 ) . We also search ed the abstract books of the 2011 and 2012 Cochrane Colloquia and the article alerts for method ological work in research synthesis published from 2009 to 2011 and compiled in Research Synthesis Methods . SELECTION CRITERIA We included both published and unpublished empirical studies that investigated the prevalence and factors associated with selective inclusion or reporting , or both , in systematic review s of RCTs of healthcare interventions . We included empirical studies assessing any type of selective inclusion or reporting , such as investigations of how frequently RCT outcome data is selectively included in systematic review s based on the results , outcomes and analyses are discrepant between protocol and published review or non-significant outcomes are partially reported in the full text or summary within systematic review s. DATA COLLECTION AND ANALYSIS Two review authors independently selected empirical studies for inclusion , extracted the data and performed a risk of bias assessment . A third review author resolved any disagreements about inclusion or exclusion of empirical studies , data extraction and risk of bias . We contacted authors of included studies for additional unpublished data . Primary outcomes included overall prevalence of selective inclusion or reporting , association between selective inclusion or reporting and the statistical significance of the effect estimate , and association between selective inclusion or reporting and the direction of the effect estimate . We combined prevalence estimates and risk ratios ( RRs ) using a r and om-effects meta- analysis model . MAIN RESULTS Seven studies met the inclusion criteria . No studies had investigated selective inclusion of results in systematic review s , or discrepancies in outcomes and analyses between systematic review registry entries and published systematic review s. Based on a meta- analysis of four studies ( including 485 Cochrane Review s ) , 38 % ( 95 % confidence interval ( CI ) 23 % to 54 % ) of systematic review s added , omitted , up grade d or down grade d at least one outcome between the protocol and published systematic review . The association between statistical significance and discrepant outcome reporting between protocol and published systematic review was uncertain . The meta-analytic estimate suggested an increased risk of adding or upgrading ( i.e. changing a secondary outcome to primary ) when the outcome was statistically significant , although the 95 % CI included no association and a decreased risk as plausible estimates ( RR 1.43 , 95 % CI 0.71 to 2.85 ; two studies , n = 552 meta-analyses ) . Also , the meta-analytic estimate suggested an increased risk of downgrading ( i.e. changing a primary outcome to secondary ) when the outcome was statistically significant , although the 95 % CI included no association and a decreased risk as plausible estimates ( RR 1.26 , 95 % CI 0.60 to 2.62 ; two studies , n = 484 meta-analyses ) . None of the included studies had investigated whether the association between statistical significance and adding , upgrading or downgrading of outcomes was modified by the type of comparison , direction of effect or type of outcome ; or whether there is an association between direction of the effect estimate and discrepant outcome reporting . Several secondary outcomes were reported in the included studies . Two studies found that reasons for discrepant outcome reporting were infrequently reported in published systematic review s ( 6 % in one study and 22 % in the other ) . One study ( including 62 Cochrane Review s ) found that 32 % ( 95 % CI 21 % to 45 % ) of systematic review s did not report all primary outcomes in the abstract . Another study ( including 64 Cochrane and 118 non-Cochrane review s ) found that statistically significant primary outcomes were more likely to be completely reported in the systematic review abstract than non-significant primary outcomes ( RR 2.66 , 95 % CI 1.81 to 3.90 ) . None of the studies included systematic review s published after 2009 when reporting st and ards for systematic review s ( Preferred Reporting Items for Systematic review s and Meta-Analyses ( PRISMA ) Statement , and Method ological Expectations of Cochrane Intervention Review s ( MECIR ) ) were disseminated , so the results might not be generalisable to more recent systematic review s. AUTHORS ' CONCLUSIONS Discrepant outcome reporting between the protocol and published systematic review is fairly common , although the association between statistical significance and discrepant outcome reporting is uncertain . Complete reporting of outcomes in systematic review abstract s is associated with statistical significance of the results for those outcomes . Systematic review outcomes and analysis plans should be specified prior to seeing the results of included studies to minimise post-hoc decisions that may be based on the observed results . Modifications that occur once the review has commenced , along with their justification , should be clearly reported . Effect estimates and CIs should be reported for all systematic review outcomes regardless of the results . The lack of research on selective inclusion of results in systematic review s needs to be addressed and studies that avoid the method ological weaknesses of existing research are also needed BACKGROUND Systematic review s that " compare " the accuracy of 2 or more tests often include different sets of studies for each test . PURPOSE To investigate the availability of direct comparative studies of test accuracy and to assess whether summary estimates of accuracy differ between meta-analyses of noncomparative and comparative studies . DATA SOURCES Systematic review s in any language from the Data base of Abstract s of Review s of Effects and the Cochrane Data base of Systematic Review s from 1994 to October 2012 . STUDY SELECTION 1 of 2 assessors selected review s that evaluated at least 2 tests and identified meta-analyses that included both noncomparative studies and comparative studies . DATA EXTRACTION 1 of 3 assessors extracted data about review and study characteristics and test performance . DATA SYNTHESIS 248 review s compared test accuracy ; of the 6915 studies , 2113 ( 31 % ) were comparative . Thirty-six review s ( with 52 meta-analyses ) had adequate studies to compare results of noncomparative and comparative studies by using a hierarchical summary receiver-operating characteristic meta-regression model for each test comparison . In 10 meta-analyses , noncomparative studies ranked tests in the opposite order of comparative studies . A total of 25 meta-analyses showed more than a 2-fold discrepancy in the relative diagnostic odds ratio between noncomparative and comparative studies . Differences in accuracy estimates between noncomparative and comparative studies were greater than expected by chance ( P < 0.001 ) . LIMITATION A paucity of comparative studies limited exploration of direction in bias . CONCLUSION Evidence derived from noncomparative studies often differs from that derived from comparative studies . Robustly design ed studies in which all patients receive all tests or are r and omly assigned to receive one or other of the tests should be more routinely undertaken and are preferred for evidence to guide test selection . PRIMARY FUNDING SOURCE National Institute for Health Research ( United Kingdom ) This article describes approaches for planning , dealing , and analyzing heterogeneity in a systematic review of complex interventions . Approaches aim to generate a priori hypotheses of the mechanism of action of a complex intervention to identify the key variables that might contribute to variation among studies and guide statistical analysis . In addition to characteristics related to the population , intervention , and outcomes , we describe study -related variables , such as the way the interventions have been implemented and the context and conduct of studies . These approaches will guide review ers planning a meta- analysis and provide a rationale for not meta-analyzing data if there is too much variability . Potential difficulties in applying meta-analytical techniques to examine statistical association among study results and sources of potential heterogeneity are described ; these include the selection of a fixed or r and om-effects model , the risk of multiple testing and confounding when studies include different aspects of a complex intervention or different sub sample s of the intended participant pool Background Digital interventions provide effective and potentially cost-effective models for improving health outcomes as they deliver health information and services that are widely disseminated , confidential , and can be tailored to needs of the individual user . Digital interventions have been used successfully for health promotion , mental health , and for enabling self-management of long-term conditions . However , their effectiveness is limited by low usage rates , with non-engagement a major challenge . Hence , it is crucial to find effective strategies to increase user engagement with digital interventions . Objective This systematic review will aim to evaluate the effectiveness of technology-based strategies  to promote engagement with digital interventions . Methods We will follow Cochrane Collaboration guidelines on systematic review methodology . The search strategy will be executed across seven e- data bases ( including MEDLINE , EMBASE , PsycINFO , CINAHL ) using the concepts “ digital intervention ” and “ engagement ” , limited by study type ( r and omized controlled trial ) . Grey literature and reference lists of included studies will be search ed . Titles and abstract s will be independently screened by 2 authors . Then the full text of potentially eligible papers will be obtained and double screened . Data from eligible papers will be extracted by 1 author and checked for accuracy by another author . Bias will be assessed using the Cochrane bias assessment tool . Narrative synthesis will report on all included studies , and where appropriate , data will be pooled using meta- analysis . All findings will be reported according to the Preferred Reporting Items for Systematic Review s and Meta-Analyses guidelines . Sources of heterogeneity will be further investigated if required . Results Our research is in progress . The final draft of the systematic review is being written and will be su bmi tted before the end of 2015 . Conclusions The review findings will inform research ers and digital intervention providers about optimal use of technology-based strategies to promote engagement with digital interventions . Trial Registration PROSPERO International Prospect i ve Register of Systematic Review s : CRD42014010164 ; http://www.crd.york.ac.uk/ PROSPERO /display_record.asp?ID = CRD42014010164#.VTZmmiFViko ( Archived by WebCite at http://www.webcitation.org/6XxQC8fT8 ) BACKGROUND There is increasing interest from review authors about including  non-r and omized studies  ( NRS ) in their systematic review s of health care interventions . This series from the Ottawa Non-R and omized Studies Workshop consists of six papers identifying method ological issues when doing this . AIM To format the guidance from the preceding papers on study design and bias , confounding and meta- analysis , selective reporting , and applicability/directness into checklists of issues for review authors to consider when including NRS in a systematic review . CHECKLISTS Checklists were devised providing frameworks to describe/assess : ( 1 ) study design s based on study design features ; ( 2 ) risk of residual confounding and when to consider meta-analysing data from NRS ; ( 3 ) risk of selective reporting based on the Cochrane framework for detecting selective outcome reporting in trials but extended to selective reporting of analyses ; and ( 4 ) directness of evidence contributed by a study to aid integration of NRS findings into summary of findings tables . SUMMARY The checklists described will allow review groups to operationalize the inclusion of NRS in systematic review s in a more consistent way . The next major step is extending the existing Cochrane Risk of Bias tool so that it can assess the risk of bias to NRS included in a review . Copyright © 2013 John Wiley & Sons , Background Systematic review s of behaviour change interventions for  smoking cessation  vary in scope , quality , and applicability . The current review aims to generate more accurate and useful findings by ( 1 ) a detailed analysis of intervention elements that change behaviour ( i.e. behaviour change techniques ( BCTs ) ) and potential moderators of behaviour change ( i.e. other intervention and sample characteristics ) and ( 2 ) assessing and controlling for variability in support provided to comparison groups in smoking cessation trials . Methods A systematic review will be conducted of r and omized controlled trials of behaviour change interventions for smoking cessation in adults ( with or without pharmacological support ) , with a minimum follow-up of 6 months , published after 1995 . Eligible articles will be identified through the Cochrane Tobacco Addiction Group Specialized Register . Study authors will be asked for detailed descriptions of smoking cessation support provided to intervention and comparison groups . All data will be independently coded by two research ers . The BCT taxonomy v1 ( tailored to smoking cessation interventions ) and template for intervention description and replication criteria will be used to code intervention characteristics . Data collection will further include sample and trial characteristics and outcome data ( smoking cessation rates ) . Multilevel mixed-effects meta-regression models will be used to examine which BCTs and /or BCT clusters delivered to intervention and comparison groups explain smoking cessation rates in treatment arms ( and effect sizes ) and what key moderators of behaviour change are . Predicted effect sizes of each intervention will be computed assuming all interventions are compared against comparison groups receiving the same levels of behavioural support ( i.e. low , medium , and high levels ) . Multi-disciplinary advisory board members ( policymakers , health care providers , and (ex-)smokers ) will provide strategic input throughout the project to ensure the review ’s applicability to policy and practice . Discussion By capturing BCTs in intervention and comparison groups , this systematic review will provide more accurate estimates of the effectiveness of smoking cessation interventions , the most promising BCTs and /or BCT clusters associated with smoking cessation rates in intervention and comparison arms , and important moderators of behaviour change . The results could set new st and ards for conducting meta-analyses of behaviour change interventions and improve research , service delivery , and training in the area of smoking cessation . Systematic review registration PROSPERO Background Inadequate planning , selective reporting , and incomplete reporting of outcomes in r and omized controlled trials ( RCTs ) contribute to the problem of waste of research . We aim ed to describe such a waste and to examine to what extent this waste could be avoided . Methods This research -on- research study was based on RCTs included in Cochrane review s with a summary of findings ( SoF ) table . We considered the outcomes reported in the SoF tables as surrogates for important outcomes for patients and other decision makers . We used a three-step approach . ( 1 ) First , in each review , we identified , for each important outcome , RCTs that were excluded from the corresponding meta- analysis . ( 2 ) Then , for these RCTs , we systematic ally search ed for registration s and protocol s to distinguish between inadequate planning ( an important outcome was not reported in registries or protocol s ) , selective reporting ( an important outcome was reported in registries or protocol s but not in publications ) , and incomplete reporting ( an important outcome was incompletely reported in publications ) . ( 3 ) Finally , we assessed , with the consensus of five experts , the feasibility and cost of measuring the important outcomes that were not planned . We considered inadequately planned or selectively or incompletely reported important outcomes as avoidable waste if the outcome could have been easily measured at no additional cost based on expert evaluation . Results Of the 2711 RCTs included in the main comparison of 290 review s , 2115 ( 78 % ) were excluded from at least one meta- analysis of important outcomes . Every trial contributed to 55 % , on average , of the meta-analyses of important outcomes . Of the 310 RCTs published in 2010 or later , 156 were registered . Inadequate planning affected 79 % of these RCTs , whereas incomplete and selective reporting affected 41 % and 15 % , respectively . For 63 % of RCTs , we found at least one missing important outcome for which the waste was avoidable and for 30 % , the waste was avoidable for all important outcomes . Conclusions Most of the RCTs included in our sample did not contribute to all the important outcomes in meta-analyses , mostly because of inadequate planning or incomplete reporting . A large part of this waste of research seemed to be avoidable OBJECTIVES To survey the frequency of use of indirect comparisons in systematic review s and evaluate the methods used in their analysis and interpretation . Also to identify alternative statistical approaches for the analysis of indirect comparisons , to assess the properties of different statistical methods used for performing indirect comparisons and to compare direct and indirect estimates of the same effects within review s. DATA SOURCES Electronic data bases . REVIEW METHODS The Data base of Abstract s of Review s of Effects ( DARE ) was search ed for systematic review s involving meta- analysis of r and omised controlled trials ( RCTs ) that reported both direct and indirect comparisons , or indirect comparisons alone . A systematic review of MEDLINE and other data bases was carried out to identify published methods for analysing indirect comparisons . Study design s were created using data from the International Stroke Trial . R and om sample s of patients receiving aspirin , heparin or placebo in 16 centres were used to create meta-analyses , with half of the trials comparing aspirin and placebo and half heparin and placebo . Methods for indirect comparisons were used to estimate the contrast between aspirin  and  heparin . The whole process was repeated 1000 times and the results were compared with direct comparisons and also theoretical results . Further detailed case studies comparing the results from both direct and indirect comparisons of the same effects were undertaken . RESULTS Of the review s identified through DARE , 31/327 ( 9.5 % ) included indirect comparisons . A further five review s including indirect comparisons were identified through electronic search ing . Few review s carried out a formal analysis and some based analysis on the naive addition of data from the treatment arms of interest . Few method ological papers were identified . Some valid approaches for aggregate data that could be applied using st and ard software were found : the adjusted indirect comparison , meta-regression and , for binary data only , multiple logistic regression ( fixed effect models only ) . Simulation studies showed that the naive method is liable to bias and also produces over-precise answers . Several methods provide correct answers if strong but unverifiable assumptions are fulfilled . Four times as many similarly sized trials are needed for the indirect approach to have the same power as directly r and omised comparisons . Detailed case studies comparing direct and indirect comparisons of the same effect show considerable statistical discrepancies , but the direction of such discrepancy is unpredictable . CONCLUSIONS Direct evidence from good- quality RCTs should be used wherever possible . Without this evidence , it may be necessary to look for indirect comparisons from RCTs . However , the results may be susceptible to bias . When making indirect comparisons within a systematic review , an adjusted indirect comparison method should ideally be used employing the r and om effects model . If both direct and indirect comparisons are possible within a review , it is recommended that these be done separately before considering whether to pool data . There is a need to evaluate methods for the analysis of indirect comparisons for continuous data and for empirical research into how different methods of indirect comparison perform in cases where there is a large treatment effect . Further study is needed into when it is appropriate to look at indirect comparisons and when to combine both direct and indirect comparisons . Research into how evidence from indirect comparisons compares to that from non-r and omised studies may also be warranted . Investigations using individual patient data from a meta- analysis of several RCTs using different protocol s and an evaluation of the impact of choosing different binary effect measures for the inverse variance method would also be useful Background The benefits of aspirin as an anti-platelet agent are well established ; however , there has been much debate about the lack of uniformity in the efficacy of aspirin to inhibit platelet function . In some patients , aspirin fails to inhibit platelets even where compliance has been verified , a phenomenon which has been termed “ aspirin resistance ” . These patients may in turn be at a higher risk of future vascular events . The proportion of “ resistant ” patients identified depends on the type of platelet function test . Therefore , the aim of this systematic review is to determine which , if any , platelet function test has utility in terms of identifying patients with a high risk of vascular events . The review has been registered with PROSPERO ( CRD42012002151 ) . Methods Relevant studies will be sought from bibliographic data bases . Trials registers will be search ed for ongoing studies . Reference lists will be checked and subject experts contacted . There will be no date or language restrictions . St and ard review ing methodology to minimise bias will be employed . Any prospect i ve studies in patients on aspirin therapy and assessing platelet function in relation to relevant clinical outcomes will be included , as will studies reporting prognostic models . Risk of bias assessment will be based on the Quality Assessment of Diagnostic Accuracy Studies guidelines , and suitable criteria for assessing quality of prognostic studies . Data on test accuracy measures , relative risks , odds or hazard ratios will be extracted and meta-analysed , where possible , using a r and om-effects model to account for between- study heterogeneity . Where appropriate , the causes of heterogeneity will be explored through meta-regression and sub-group or sensitivity analyses . If platelet function testing is demonstrated to have diagnostic/predictive utility in a specific population , the potential for a cost-effectiveness analysis will be considered and , if possible , an economic model constructed . This will be supported by a systematic review of existing economic evaluation studies . Discussion The results of the review could indicate if platelet function test(s ) could lead to a reliable prediction of the risk of clinical ly important events in a defined population , and thus support investigations into adjustments to therapy in order to compensate for a predicted poor response to st and ard aspirin Background Twin – Twin Transfusion Syndrome ( TTTS ) is associated with an increased risk of perinatal mortality and morbidity . Several treatment interventions have been described for TTTS , including fetoscopic laser surgery , amnioreduction , septostomy , expectant management , and pregnancy termination . Over the last decade , fetoscopic laser surgery has become the primary treatment . The literature to date reports on many different outcomes , making it difficult to compare results or combine data from individual studies , limiting the value of research to guide clinical practice . With the advent and ongoing development of new therapeutic techniques , this is more important than ever . The development and use of a core outcome set has been proposed to address these issues , prioritising outcomes important to the key stakeholders , including patients . We aim to produce , disseminate , and implement a core outcome set for TTTS . Methods An international steering group has been established to oversee the development of this core outcome set . This group includes healthcare professionals , research ers and patients . A systematic review is planned to identify previously reported outcomes following treatment for TTTS . Following completion , the identified outcomes will be evaluated by stakeholders using an international , multi-perspective online modified Delphi method to build consensus on core outcomes . This method encourages the participants towards consensus ‘ core ’ outcomes . All key stakeholders will be invited to participate . The steering group will then hold a consensus meeting to discuss results and form a core outcome set to be introduced and measured . Once core outcomes have been agreed , the next step will be to determine how they should be measured , disseminated , and implemented within an international context . Discussion The development , dissemination , and implementation of a core outcome set in TTTS will enable its use in future clinical trials , systematic review s and clinical practice guidelines . This is likely to advance the quality of research studies and their effective use in order to guide clinical practice and improve patient care , maternal , short-term perinatal outcomes and long-term neurodevelopmental outcomes .Trial registration Core Outcome Measures in Effectiveness Trials ( COMET ) , 921 Registered on July 2016.International Prospect i ve Register of Systematic Review s ( PROSPERO ) , CRD42016043999 . Registered on 2 August 2016 Background It is generally believed that exhaustive search es of bibliographic data bases are needed for systematic review s of health care interventions . The CENTRAL data base of controlled trials ( RCTs ) has been built up by exhaustive search ing . The CONSORT statement aims to encourage better reporting , and hence indexing , of RCTs . Our aim was to assess whether developments in the CENTRAL data base , and the CONSORT statement , mean that a simplified RCT search strategy for identifying RCTs now suffices for systematic review s of health care interventions . Methods RCTs used in the Cochrane review s were identified . A brief RCT search strategy ( BRSS ) , consisting of a search of CENTRAL , and then for variants of the word r and om across all fields ( r and om$.af . ) in MEDLINE and EMBASE , was devised and run . Any trials included in the meta-analyses , but missed by the BRSS , were identified . The meta-analyses were then re-run , with and without the missed RCTs , and the differences quantified . The proportion of trials with variants of the word r and om in the title or abstract was calculated for each year . The number of RCTs retrieved by search ing with " r and om$.af . " was compared to the highly sensitive search strategy ( HSSS ) . Results The BRSS had a sensitivity of 94 % . It found all journal RCTs in 47 of the 57 review s. The missing RCTs made some significant differences to a small proportion of the total outcomes in only five review s , but no important differences in conclusions result ed . In the post-CONSORT years , 1997–2003 , the percentage of RCTs with r and om in the title or abstract was 85 % , a mean increase of 17 % compared to the seven years pre-CONSORT ( 95 % CI , 8.3 % to 25.9 % ) . The search using r and om$.af . reduced the MEDLINE retrieval by 84 % , compared to the HSSS , thereby reducing the workload of checking retrievals . Conclusion A brief RCT search strategy is now sufficient to locate RCTs for systematic review s in most cases . Exhaustive search ing is no longer cost-effective , because in effect it has already been done for CENTRAL BACKGROUND Innovators have piloted improvements in communication , changed patterns of practice and patient empowerment from online access to electronic health records ( EHR ) . International studies of online services , such as prescription ordering , online appointment booking and secure communications with primary care , show good uptake of email consultations , accessing test results and booking appointments ; when technologies and business process are in place . Online access and transactional services are due to be rolled out across Engl and by 2015 ; this review seeks to explore the impact of online access to health records and other online services on the quality and safety of primary health care . OBJECTIVE To assess the factors that may affect the provision of  online patient access to their EHR and transactional services , and the impact of such access on the quality and safety of health care . METHOD Two review ers independently search ed 11 international data bases during the period 1999 - 2012 . A range of papers including descriptive studies using qualitative or quantitative methods , hypothesis-testing studies and systematic review s were included . A detailed eligibility criterion will be used to shape study inclusion . A team of experts will review these papers for eligibility , extract data using a customised extraction form and use the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) instrument to determine the quality of the evidence and the strengths of any recommendation . Data will then be descriptively summarised and thematically synthesis ed . Where feasible , we will perform a quantitative meta- analysis . Prospero ( International Prospect i ve Register of Systematic Review s ) registration number : crd42012003091 Over the last two decades , treatment guidelines have become major aids in the delivery of evidence -based care and improvement of clinical outcomes . The International Society for Traumatic Stress Studies ( ISTSS ) produced the first guidelines for the prevention and treatment of posttraumatic stress disorder ( PTSD ) in 2000 and published its latest recommendations , along with position papers on complex PTSD ( CPTSD ) , in November 2018 . A rigorous methodology was developed and followed ; scoping questions were posed , systematic review s were undertaken , and 361 r and omized controlled trials were included according to the a priori agreed inclusion criteria . In total , 208 meta-analyses were conducted and used to generate 125 recommendations ( 101 for adults and 24 for children and adolescents ) for specific prevention and treatment interventions , using an agreed definition of clinical importance and recommendation setting algorithm . There were eight strong , eight st and ard , five low effect , 26 emerging evidence , and 78 insufficient evidence to recommend recommendations . The inclusion of separate scoping questions on treatments for complex presentations of PTSD was considered but decided against due to definitional issues and the virtual absence of studies specifically design ed to clearly answer possible scoping questions in this area . Narrative review s were undertaken and position papers prepared ( one for adults and one for children and adolescents ) to consider the current issues around CPTSD and make recommendations to facilitate further research . This paper describes the methodology and results of the ISTSS Guideline process and considers the interpretation and implementation of the recommendations Background Critically ill patients have an increased risk of developing delirium during their intensive care stay . To date , pharmacological interventions have not been shown to be effective for delirium management but non-pharmacological interventions have shown some promise . The aim of this systematic review is to identify effective non-pharmacological interventions for reducing the incidence or the duration of delirium in critically ill patients . Methods We will search MEDLINE , EMBASE , CINAHL , Web of Science , AMED , psycINFO and the Cochrane Library . We will include studies of critically ill adults and children . We will include r and omised trials and controlled trials which measure the effectiveness of one or more non-pharmacological interventions in reducing incidence or duration of delirium in critically ill patients . We will also include qualitative studies that provide an insight into patients and their families ’ experiences of delirium and non-pharmacological interventions . Two independent review ers will assess studies for eligibility , extract data and appraise quality . We will conduct meta-analyses if possible or present results narratively . Qualitative studies will also be review ed by two independent review ers , and a specially design ed quality assessment tool incorporating the CASP framework and the POPAY framework will be used to assess quality . Discussion Although non-pharmacological interventions have been studied in population s outside of intensive care units and multicomponent interventions have successfully reduced incidence and duration of delirium , no systematic review of non-pharmacological interventions specifically targeting delirium in critically ill patients have been undertaken to date . This systematic review will provide evidence for the development of a multicomponent intervention for delirium management of critically ill patients that can be tested in a subsequent multicentre r and omised trial . Systematic review registration PROSPERO
Less frequently reported were quality of life , patient satisfaction , self-care , and healthcare utilization .
Most care management modalities were carved out from primary care .
Conclusions Most care management programs for patients with type 2 diabetes are ' carved-out ' , accomplish limited effects on metabolic outcomes , and have unknown effects on patient important outcomes .
Background This systematic review and meta- analysis aims at assessing the composition and performance of care management models evaluated in the last decade and their impact on patient important outcomes .