A conversation with Joseph Lau. All in the Family: systematic reviews, rapid reviews, scoping reviews, realist reviews, and more Spine surgery research: on and beyond current strategies. Tackling inequalities in obesity: a protocol for a systematic review of the effectiveness of public health interventions at reducing socioeconomic inequalities in obesity among adults Systematic reviews in endodontics--examples of GIGO? The Medical Review Article Revisited: Has the Science Improved? How to write an evidence-based clinical review article. Effects of workplace-based dietary and/or physical activity interventions for weight management targeting healthcare professionals: a systematic review of randomised controlled trials Bias due to selective inclusion and reporting of outcomes and analyses in systematic reviews of randomised trials of healthcare interventions. Financial Conflicts of Interest and Conclusions About Neuraminidase Inhibitors for Influenza Balancing the strengths of systematic and narrative reviews. Calcium intake in health maintenance – a systematic review Sources of evidence for systematic reviews of interventions in diabetes. Where do all the undergraduate and new graduate nurses go and why? A search for empirical research evidence. Examining the theory‐effectiveness hypothesis: A systematic review of systematic reviews Can we rely on the best trial? A comparison of individual trials and systematic reviews Protocol for an overview of systematic reviews of interventions to reduce unscheduled hospital admissions among adults Key Steps in Conducting Systematic Reviews for Underpinning Clinical Practice Guidelines: Methodology of the European Association of Urology. Symposium integrating evidence-based medicine into clinical practice. Tackling inequalities in obesity: a protocol for a systematic review of the effectiveness of public health interventions at reducing socioeconomic inequalities in obesity amongst children Reproducible Research Practices and Transparency across the Biomedical Literature Treatment of surgical patients is evidence-based. Editorial: Standards of Reporting: The CONSORT, QUORUM, and STROBE Guidelines
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 Three years ago , we founded this journal focusing on publishing systematic review s , systematic review protocol s , and associated method ological development papers . Systematic review s , which developed in the social sciences in the 1970s , began to gain rapid momentum during the 1990s in response to concerns by policymakers and clinicians about the scientific validity of the prevailing paradigm of traditional narrative review s written by authoritative experts . What distinguished systematic review s was the use of formal explicit methods , in other words pre-specification , of what exactly was the question to be answered , how evidence was search ed for and assessed , and how it was synthesized in order to reach the conclusion . Importantly , these formal methods were described as part of the review itself in a Methods section . In turn , these methods themselves became the subject of hypothesis-testing studies , as investigators sought how best to search for evidence , assess studies for quality or risk of bias , determine under what conditions meta- analysis was justified , and how to best determine and characterize our confidence in the conclusions . The results of these hypothesis-testing studies led over time to improvements in the methods we use for systematic review s. Thus , systematic review s and this journal are part of an ever-evolving process whose foundations are rooted in the scientific method . Today , new forms of review s are appearing . These have emerged in response to policymakers and other stakeholders ’ needs for information , sometimes emergently or urgently , for which the existing systematic review model does not quite fit . Hence , the rapid review , when time is of the essence ; the scoping review , when what is needed is not detailed answers to specific questions but rather an overview of a broad field ; the evidence map , a cousin of scoping review s that commonly has a specific visual presentation of the evidence across a broad field ; and the realist review , where the question of interest includes how and why complex social interventions work in certain situations , rather than assume they either do or do not work at all . As Editors , we regularly get contacted by prospect i ve authors asking whether realist review s , or scoping review s , etc . , are “ within the scope ” for Systematic Review s , and therefore we judge it an opportune time to state our position on this matter . It is our view that all of these new forms of review s are related to systematic review s , similar to the way that different biological Species within the same Family are related to each other . We consider “ systematic review s ” to be the Family and the different forms of review s to be the different species . Just as in the biological classification , where the related organisms must share certain characteristics , so too must the different types of review s share a common characteristic . In this case , what is shared is their foundation in the scientific method , with their methods articulated in advance in sufficient detail that the review can be reproduced by others . A further defining feature is that there are scholars devoted to improving the methods over time via hypothesis-testing studies . Systematic Review s has responded to these emerging techniques and already publishes papers reporting methods and findings from the systematic review family and has for example published an extremely popular series on rapid review s. We would like to consoli date this position and invite su bmi ssion of these new species of review s , as long as they meet the qualifications just listed . We expect this process of evolution to continue and to refine the methods such that in 10 years ’ time , there will appear new , as yet unimagined species of review s— and perhaps some current species of review will become extinct . Thus , it is with the scientific method , which we believe is the foundation that unites the Family of systematic review BACKGROUND CONTEXT Systematic review s of the literature are powerful tools in evidence -based medicine . However , the design and report of systematic review s in spinal surgery contain many aspects amenable to improvement . PURPOSE To discuss the issues especially relevant for systematic review s in spinal surgery . METHODS From our experience of systematic review s and meta-analyses of clinical trials in  spinal surgery  , we infer guidance for the design and execution of systematic literature review s. RESULTS There are many difficulties associated with the design as well as conduct of clinical trials and consequently appraising evidence in spinal surgery . New treatments should be compared with the gold st and ard before other comparisons are investigated . Studies should present data as thoroughly as possible regarding all subgroups and follow-up moments , possibly in supplementary material . To provide the highest level of evidence , systematic review s should be as rigorously design ed as possible . CONCLUSIONS Gathering information on clinical effectiveness in spinal surgery can be improved both at the clinical study level and at the systematic review level . Alternatives to r and omized controlled trials such as comparative studies can be valuable tools on the clinical effectiveness of treatments in spinal surgery . The experience reflected in this article can support the scientific efforts in this field Background Socioeconomic inequalities in obesity and associated risk factors for obesity are widening throughout developed countries worldwide . Tackling obesity is high on the public health agenda both in the United Kingdom and internationally . However , what works in terms of interventions that are able to reduce inequalities in obesity is lacking . Methods / Design The review will examine public health interventions at the individual , community and societal level that might reduce inequalities in  obesity among adults aged 18 years and over , in any setting and in any country . The following electronic data bases will be search ed : MEDLINE , EMBASE , CINAHL , PsycINFO , Social Science Citation Index , ASSIA , IBSS , Sociological Abstract s , and the NHS Economic Evaluation Data base . Data base search es will be supplemented with website and gray literature search es . No studies will be excluded based on language , country or publication date . R and omized and non-r and omized controlled trials , prospect i ve and retrospective cohort studies ( with/without control groups ) and prospect i ve repeat cross-sectional studies ( with/without control groups ) that have a primary outcome that is a proxy for body fatness and have examined differential effects with regard to socioeconomic status ( education , income , occupation , social class , deprivation , poverty ) or where the intervention has been targeted specifically at disadvantaged groups or deprived areas will be included . Study inclusion , data extraction and quality appraisal will be conducted by two review ers . Meta- analysis and narrative synthesis will be conducted . The main analysis will examine the effects of 1 ) individual , 2 ) community and 3 ) societal level public health interventions on socioeconomic inequalities in adult obesity . Interventions will be characterized by their level of action and their approach to tackling inequalities . Context ual information on how such public health interventions are organized , implemented and delivered will also be examined . Discussion The review will provide evidence , and reveal any gaps in the evidence base , of public health strategies which reduce and prevent inequalities in the prevalence of obesity in adults and provide information on the organization , implementation and delivery of such interventions . Systematic review registration PROSPERO registration number : 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 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 Traditional clinical review articles , also known as up date s , differ from systematic review s and meta-analyses . Up date s selectively review the medical literature while discussing a topic broadly . Non-quantitative systematic review s comprehensively examine the medical literature , seeking to identify and synthesize all relevant information to formulate the best approach to diagnosis or treatment . Meta-analyses ( quantitative systematic review s ) seek to answer a focused clinical question , using rigorous statistical analysis of pooled research studies . This article presents guidelines for writing an evidence -based clinical review article for American Family Physician . First , the topic should be of common interest and relevance to family practice . Include a table of the continuing medical education objectives of the review . State how the literature search was done and include several sources of evidence -based review s , such as the Cochrane Collaboration , BMJ 's Clinical Evidence , or the InfoRetriever Web site . Where possible , use evidence based on clinical outcomes relating to morbidity , mortality , or quality of life , and studies of primary care population s. In articles su bmi tted to American Family Physician , rate the level of evidence for key recommendations according to the following scale : level A ( r and omized controlled trial [ RCT ] , meta- analysis ) ; level B ( other evidence ) ; level C ( consensus/expert opinion ) . Finally , provide a table of key summary points 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 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 Industry funding and author financial conflicts of interest may influence the production and synthesis of scientific evidence ( 1 ) . Associations with the pharmaceutical company developing and marketing a drug have been found to influence the design of trials ( 2 ) , the conduct of trials ( 3 ) , and the reporting of trial results ( 47 ) . Furthermore , financial ties and industry funding seem to result in greater rates of favorable conclusions in clinical trials examining new drugs ( 812 ) . Fewer studies have considered the potential influence of financial conflicts of interest on the synthesis of clinical evidence in systematic review s ( 13 , 14 ) . Neuraminidase inhibitors , which are used in the prophylaxis and treatment of seasonal and p and emic influenza , have been the subject of ongoing uncertainty about their specific clinical benefits ( 15 , 16 ) . This is the result of not only the continuing emergence of strains with unknown drug responses but also the increasing awareness in the medical community that , until recently , its knowledge of the safety and efficacy of these drugs has been incomplete ( 17 ) . Despite the abundance of clinical trials and publications on neuraminidase inhibitors , the details of many key trials had not been disclosed ( 18 , 19 ) . As a result , systematic review ers analyzing and synthesizing evidence on the effectiveness of these agents have faced incomplete information , unresolved discrepancies in the data , and a high risk of publication and reporting biases among the primary clinical trials ( 20 , 21 ) . This prompted extensive efforts to access complete records of all published and unpublished clinical trials from manufacturers , culminating in the publication of several review s on the basis of comprehensive clinical study reports and potentially changing the way systematic review s will be undertaken in the future ( 2227 ) . Review s of neuraminidase inhibitors exhibit wide variation in their conclusions , ranging from strong endorsements of the use of these agents in the prophylaxis and treatment of influenza ( 28 , 29 ) to more conservative assessment s question ing the evidence on the drugs ' safety and efficacy ( 15 , 30 ) . The reasons for this discordance in review conclusions are likely multifactorial and may be related in part to the manner in which evidence is accessed , synthesized , and presented ( 23 , 27 ) , both in terms of the numerical results and the authors ' emphasis and interpretation ( 31 , 32 ) . Our aim was to determine whether there is an association between financial conflicts of interest and the favorable presentation of evidence in systematic review s on the use of neuraminidase inhibitors for the prophylaxis and treatment of influenza . Methods Data Sources Systematic review s were identified in PubMed , PubMed In Process , EMBASE , and the Cochrane Data base of Systematic Review s. Search es were done using the keywords influenza , neuraminidase inhibitors , oseltamivir , zanamivir , peramivir , and laninamivir . Articles were retrieved if the search terms appeared in the title or abstract or were included as data base-specific keywords . In PubMed and EMBASE , search es were also constrained to review publication types . We limited our search to English- language articles published since 1 January 2005 . These articles were manually review ed to identify those that focused on the use of neuraminidase inhibitors for influenza prophylaxis or treatment ( such as excluded articles primarily about drug development or other manufacturing processes ) . We selected all review s that used a systematic search protocol , which we defined as the inclusion and reporting of an explicit search strategy , including reasons for subsequent exclusion of articles . The final search es were done on 26 May 2014 . Cochrane review s are periodically up date d to incorporate new evidence , and the results and conclusions are resynthesized as indicated . The authors of these review s are typically different , and there may be differences in the methods as well as the results and language of the review . These up date d review s were included separately . Other Cochrane review s are occasionally rewritten by a subset of the authors for publication in medical journals as abridged versions to increase dissemination . These reports have separate peer review s and are prepared on the basis of a selection of the complete results . We considered these review s separately as well but also did a sensitivity analysis in which they were combined with the original Cochrane review s. Data Extraction Financial conflicts of interest were identified for all authors of the review s and included affiliations with or funding from the pharmaceutical company manufacturing any of the neuraminidase inhibitors under review . We defined financial conflicts of interest as employment , the funding of grants paid to an author or an author 's research group , and the funding of medical writers for the systematic review . These financial conflicts of interest were identified using information about affiliations or funding listed in the systematic review s , as well as in any other articles published by one of the authors during the 3 years before the publication of the index systematic review . In addition , we search ed authors ' personal and institutional Web sites ; lists of disclosures from GlaxoSmithKline ( Research Triangle Park , North Carolina ) and Roche Pharmaceuticals ( Basel , Switzerl and ) ; and performed Web search es combining the names of the authors , drugs , and pharmaceutical companies to identify any additional information about financial relationships . Details of the specific financial conflicts of interest identified for each author are listed in Appendix Table 1 . Appendix Table 1 . Financial Conflicts of Interest Among Authors of the Systematic Review s For each systematic review , we recorded whether prophylaxis or treatment was assessed , the forms of evidence to be included ( such as r and omized , controlled trials and observational studies ) , the specific clinical outcomes assessed , the population s examined , and whether meta-analyses were done . We also examined whether the review s included information about the validity or quality of the primary literature . In particular , we recorded whether there were statements addressing nonpublication of primary studies or publication bias , including tests done by the review ers to assess for bias in meta-analyses ( such as the Egger or Begg test [ 33 , 34 ] ) , difficulty in accessing comprehensive study data , and the prevalence or role of industry in conducting and funding the primary studies . Data Analysis Two investigators were provided with redacted copies of each review that did not include the review s ' authors , their affiliations , or information on financial conflicts of interest . These versions also did not contain the journal name , journal formatting , or the article 's acknowledgments or references . The investigators independently evaluated the review s and classified the prophylaxis and treatment assessment s as favorable or not favorable toward the use of neuraminidase inhibitors . They were instructed to do this grading on the basis of the entirety of the review text without restriction to conclusions or recommendations made in any specific section of the review , thus allowing them to take into account the emphasis and interpretation of the authors throughout the review . The agreement between the investigators was strong at 86 % ( Cohen , 0.72 ; P < 0.001 ) . Disagreements were resolved by a third investigator using the same redacted copies . Descriptive analyses were done to examine the associations between financial conflicts of interest and the grading of the systematic review s. A sensitivity analysis excluding the summary review s was done to further examine this association . We also assessed the association between financial conflicts of interest and the inclusion of statements addressing the validity or quality of the primary evidence . Role of the Funding Source This study was funded by the Australian National Health and Medical Research Council . The funding source had no role in the design and conduct of the study , analysis of the results , or the decision to su bmi t the manuscript for publication . Results We identified 827 published articles across the 4 data bases using the specified search criteria , with 26 systematic review s included in the final cohort ( Figure ) . Thirteen review s examined prophylaxis and 24 examined treatment of influenza , accounting for 37 distinct assessment s ( Appendix Table 2 ) . In terms of review methods , 7 were Cochrane systematic review s and 19 conducted and reported a meta- analysis ( 73 % ) . The evidence inclusion criteria were limited to r and omized , controlled trials for 14 of the systematic review s ( 54 % ) , and 5 included evidence from clinical study reports or patient-level data . The main population s examined were healthy adults ( 18 of 26 systematic review s ) , children ( 13 of 26 ) , and hospitalized patients ( 6 of 24 ) . The outcome measures for prophylaxis assessment s included influenza-like illness and laboratory-confirmed influenza . For the treatment assessment s , the outcomes were illness duration , influenza-related complications , hospitalization , and mortality , mostly in combination . Five review s were up date s of previous Cochrane review s , and 3 were summary review s based on Cochrane review s. Figure . Summary of evidence search and selection . Eligible systematic review s included those with outcomes related to the prophylaxis or treatment of influenza . Appendix Table 2 . Characteristics of Systematic Review s Examining Prophylaxis and Treatment Outcomes for Neuraminidase Inhibitors Association Between Financial Conflicts of Interest and Favorable Assessment s Seven of the 26 systematic review s ( 27 % ) , corresponding to 8 of the 37 assessment s ( 22 % ) , were associated with a financial conflict of interest ( Appendix Table 1 ) . We identified financial conflicts of interest in publications other than the index systematic review in 2 cases , and no additional The m and ate of Human Reproduction Up date involves several roles : ( i ) to provide a synthesis of evidence that can aid scientists and clinicians in their daily work ; ( ii ) to help reproductive specialists underst and concepts from related disciplines ; and ( iii ) to summarize current knowledge generated by basic science as the foundation of future scientific and clinical advancement . Given that review and synthesis are central to good scientific and clinical practice , and that a grasp of the current state of knowledge is a prerequisite to design ing new studies , it is pertinent to ask which review s are most likely to fulfil the needs of readers . A related question concerns whether systematic review s meet the needs of all review topics and all readers . Summarizing evidence or knowledge is a difficult problem in reproductive medicine , as in other branches of science and medical care ( Eddy et al. , 1992 ) . For each question there may be multiple studies that use different design s and inclusion criteria . For clinical questions , the interventions , outcomes and measures of effect may vary : the effect measures in treatment studies include odds ratios , relative risks and absolute differences . For scientific questions , the experimental species , models and design s may differ . Moreover , it is always uncertain whether all of the relevant evidence has been evaluated . Even when the search has been exhaustive , there are no simple guides on how to interpret conflicting results and whether to accept apparently outlying studies . The choices that the review er makes to address the variable conditions and uncertainties may be conservative , strict and exclusive , or liberal , open and inclusive . The decisions made by the review er may not be consistent throughout and these choices may or may not satisfy the reader who seeks out the review to address a clinical or research question . Faced with uncertainty and doubt , readers nonetheless must form an impression of the evidence and synthesize the state of knowledge in order to address the clinical or research question that stimulated their interest in the review . We argue that the reader is better served when the choices made in the review , regardless of whether they are strict or open , should be explicit , transparent , clearly stated and reproducible by interested readers . This list of objectives for review s is more easily satisfied by systematic review s , which use explicit methods to method ically search , critically appraise and synthesize the available literature on a specific issue . The question or issue need not be clinical : indeed , the concept evolved primarily in psychology studies ( Light and Pillemer , 1984 ) . The systematic review attempts to reduce review er bias through the use of objective , reproducible criteria to select relevant individual publications and assess their validity . A systematic review may include a meta- analysis or statistical summary of the individual study results : the aggregate of effects from several studies yields an average treatment effect that is more precise than the individual study results ( Schlesselman and Collins , 2003 ) . Thus , the systematic review involves explicit , transparent methods which are clearly stated , and reproducible by others . Whether a systematic review of r and omized controlled trials adheres to the guidelines can easily be evaluated by means of a widely used checklist ( the QUORUM statement ) ( Moher et al. , 1999 ) . The strengths of the systematic review include the narrow focus of the question , the comprehensive search for evidence , the criterion-based selection of relevant evidence , the rigorous appraisal of validity , the objective or quantitative summary , and the evidence -based inferences ( Cook et al. , 1997 ) . For some review topics , however , the strengths of the systematic review may turn into weaknesses . The primary problem is that the narrow focus and prescribed methods of the systematic review do not allow for comprehensive coverage . For example , the historical review is an irreplaceable means of tracing the development of a scientific principle or clinical concept , but the narrative thread could be lost in the strict rules of systematic review . As other examples , it would be burdensome to apply systematic methods to a survey on  aneuploidy and fertility in the aging female or to an assessment of mouse knockout models and polycystic ovarian phenotype . Such topics would require the wider scope of a traditional narrative review , in Human Reproduction Up date , Vol.11 , No.2 pp . 103–104 , 2005 doi:10.1093/humupd/dmh058 Advance Access publication December 23 , Background Calcium ( Ca ) is an essential nutrient for the human body . Despite lively research , there is uncertainty about Ca requirements in terms of desirable health outcomes including an upper intake level above which the potential for harm increases . Objectives The aim was to conduct a review to up date requirements and desirable or harmful health effects of Ca on the current scientific evidence . Methods We search ed Medline and Swemed from January 2000 to December 2011 and included all systematic review s that reported Ca supplementation or usual Ca intake on health outcomes . Meta-analyses , r and omized clinical trials and cohort studies were included in the second search between May 2009 and March 2011 and an additional search covering studies till the end of 2011 . This review concentrated on studies reporting independent effects of Ca , although a few recent trials report sole effects of Ca on health outcomes , most trials use Ca in combination with vitamin D vs. placebo . Results In total , we review ed 38 studies addressing the effects of Ca on bone , pregnancy-related outcomes , cancers , cardiovascular outcomes , obesity , and mortality .  There was a lot of heterogeneity in the study protocol s , which made it difficult to draw any strong conclusions . According to the literature , high Ca intake seems to have a small positive effect on bone mineral content ( BMC ) or bone mineral density ( BMD ) in children and postmenopausal women . We did not find any consistent evidence on the effects of Ca on bone health in premenopausal women or men . Also , the evidence that Ca supplementation reduces fracture incidence is scarce and inconsistent . Maternal diet may influence the peak bone mass of offspring but more studies are required . There was no overall effect of Ca intake on cancers . Ca was associated with a decreased risk of breast cancer and a slightly increased risk of prostate cancer in two of the three studies . No associations were found with other cancers . We found no consistent association between cardiovascular outcomes and  Ca  intake except for blood pressure . A small decrease of 2–4 mmHg in systolic blood pressure was found in pregnant and in hypertensive subjects with Ca supplementation . Review ed studies did not show consistent evidence relating Ca intake to either mortality or obesity . Conclusion Based on this evidence , there is no need to change the Nordic recommendations for Ca intake . However , due to heterogeneity in the studies it is difficult to interpret the results and provide single summary statement 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 OBJECTIVE To review the published scientific literature for studies quantifying or examining factors associated with the attrition of undergraduate nursing students in pre- registration programs and the retention of graduate nurses in the workforce . METHODS The following selection criteria were used to systematic ally search the literature : target population s were either students in pre- registration nursing programs or registered nurses in their graduate year ; the studies were to be primary observational or analytical ( cross-sectional , case-control or prospect i ve cohort studies ) in design ; and outcome measures were attrition in undergraduate programs and /or retention of graduates within the workforce . Three authors guided by a st and ardised procedure performed data extraction and quality assessment independently . Synthesis of the data appears in text and tabular format . Due to the heterogenic nature of the study methods , meta- analysis was not possible . RESULTS This review found only four studies that met all inclusion criteria . All four studies examined undergraduate attrition as an outcome with two studies reporting a range of 25 - 27 % attrition within the first year . No studies were found that quantified or examined retention of new graduates as an outcome measure . Only two of the four studies followed cohorts of students prospect ively and were able to provide a high level of evidence , although each of these studies was design ed to assess specific exposures as potential predictors of attrition , rather than assess actual factors associated with students leaving their program . CONCLUSION There is a paucity of research studies in the literature from which evidence quantifying attrition and retention and the reasons why students leave undergraduate nursing programs or new graduates leave the profession can be obtained . Clearly there is a need to systematic ally track undergraduates and new graduates to quantify and underst and attrition , retention and workforce choices within the nursing profession and begin to build this evidence -base 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 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 Introduction Unscheduled hospital admissions are an increasing burden on health systems worldwide . To date , initiatives to reduce admissions have had limited success as it is unclear which strategies effectively reduce admissions and are supported by a strong evidence -base . Therefore , we will conduct an overview to find , assess and summarise all published peer- review ed systematic review s of r and omised controlled trials that examine the effect of an intervention on  unplanned admissions among adults . Methods and analysis This is a protocol for a systematic overview of review s. We will search four data bases : Ovid MEDLINE , PubMed , Cochrane Data base of Systematic Review s and the Cochrane Data base of Abstract s of Review s of Effects . We will consider systematic review s and meta-analyses of r and omised controlled trials in adults ( ≥16 years old ) evaluating the effect of any intervention on unscheduled hospital admissions including those to treat , monitor , diagnose or prevent a health problem . We will only include review s that identified unscheduled hospitalisations as a prespecified outcome . Two authors will independently screen articles for inclusion using a priori criteria . We will assess the quality of included review s and extract ratings of the quality of evidence from within each review . We will create a hierarchical list of interventions based on estimates of absolute admission reductions and the quality of the evidence . Presentation of results will align with guidelines in the Cochrane H and book of Systematic Review s of Interventions and the Preferred Reporting Items for Systematic Review s and Meta- Analysis statement . Ethics and dissemination Ethics approval is not required . We will su bmi t the results of this study for peer- review publication . The results will inform future research and could be used by healthcare managers , administrators and policymakers to guide re source allocation decisions and inform local implementation and optimisation of interventions to reduce unscheduled hospital admissions CONTEXT The findings of systematic review s ( SRs ) and meta-analyses ( MAs ) are used for clinical decision making . The European Association of Urology has committed increasing re sources into the development of high quality clinical guidelines based on such SRs and MAs . OBJECTIVE In this paper , we have summarised the process of conducting SRs for underpinning clinical practice guidelines under the auspices of the European Association of Urology Guidelines Office . EVIDENCE ACQUISITION The process involves explicit methods and the findings should be reproducible . When conducting a SR , the essential first step is to formulate a clear and answerable research question . An extensive literature search lays the foundation for evidence synthesis . Data are extracted independently by two review ers and any disagreements are resolved by discussion or arbitration by a third review er . EVIDENCE SYNTHESIS In SRs , data for particular outcomes in individual r and omised controlled trials may be combined statistically in a meta- analysis to increase power when the studies are similar enough . Biases in studies included in a SR/MA can lead to either an over estimation or an under estimation of true intervention effect size , result ing in heterogeneity in outcome between studies . A number of different tools are available such as Cochrane Risk of Bias assessment tool for r and omised controlled trials . In circumstances where there is too much heterogeneity , or when a review has included nonr and omised comparative studies , it is more appropriate to conduct a narrative synthesis . The GRADE tool for assessing quality of evidence strives to be a structured and transparent system , which can be applied to all evidence , regardless of quality . A SR not only identifies , evaluates , and summarises the best available evidence , but also the gaps to be targeted by future studies . CONCLUSIONS SRs and MAs are integral in developing sound clinical practice guidelines and recommendations . PATIENT SUMMARY Clinical practice guidelines should be evidence based , and systematic review s and meta-analyses are essential in their production . We have discussed the key steps of conducting systematic review s and meta-analyses in this paper 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 Background There is growing evidence of the impact of overweight and obesity on short- and long-term functioning , health and well-being . Internationally , childhood obesity rates continue to rise in some countries ( for example , Mexico , India , China and Canada ) , although there is emerging evidence of a slowing of this increase or a plateauing in some age groups . In most European countries , the United States and Australia , however , socioeconomic inequalities in relation to obesity and risk factors for obesity are widening . Addressing inequalities in obesity , therefore , has a very high profile on the public health and health services agendas . However , there is a lack of accessible policy-ready evidence on what works in terms of interventions to reduce inequalities in obesity . Methods and design This article describes the protocol for a National Health Service Trust ( NHS ) National Institute for Health Research -funded systematic review of public health interventions at the individual , community and societal levels which might reduce socioeconomic inequalities in relation to obesity amongst children ages 0 to 18 years . The studies will be selected only if ( 1 ) they included a primary outcome that is a proxy for body fatness and ( 2 ) examined differential effects with regard to socioeconomic status ( education , income , occupation , social class , deprivation and poverty ) or the intervention was targeted specifically at disadvantaged groups ( for example , children of the unemployed , lone parents , low income and so on ) or at people who live in deprived areas . A rigorous and inclusive international literature search will be conducted for r and omised and nonr and omised controlled trials , prospect i ve and retrospective cohort studies ( with and /or without control groups ) and prospect i ve repeat cross-sectional studies ( with and /or without control groups ) . The following electronic data bases will be search ed : MEDLINE , Embase , CINAHL , PsycINFO , Social Science Citation Index , ASSIA , IBSS , Sociological Abstract s and the NHS Economic Evaluation Data base . Data base search es will be supplemented with website and grey literature search es . No studies will be excluded on the basis of language , country of origin or publication date . Study inclusion , data extraction and quality appraisal will be conducted by two review ers . Meta- analysis and narrative synthesis will be conducted . The main analysis will examine the effects of ( 1 ) individual , ( 2 ) community and ( 3 ) societal level public health interventions on socioeconomic inequalities in childhood obesity . Interventions will be characterised by their level of action and their approach to tackling inequalities . Context ual information on how such public health interventions are organised , implemented and delivered will also be examined . Discussion In this review , we consider public health strategies which reduce and prevent inequalities in the prevalence of childhood obesity , highlight any gaps in the evidence base and seek to establish how such public health interventions are organised , implemented and delivered . PROSPERO registration number : There is a growing movement to encourage reproducibility and transparency practice s in the scientific community , including public access to raw data and protocol s , the conduct of replication studies , systematic integration of evidence in systematic review s , and the documentation of funding and potential conflicts of interest . In this survey , we assessed the current status of reproducibility and transparency addressing these indicators in a r and om sample of 441 biomedical journal articles published in 2000–2014 . Only one study provided a full protocol and none made all raw data directly available . Replication studies were rare ( n = 4 ) , and only 16 studies had their data included in a subsequent systematic review or meta- analysis . The majority of studies did not mention anything about funding or conflicts of interest . The percentage of articles with no statement of conflict decreased substantially between 2000 and 2014 ( 94.4 % in 2000 to 34.6 % in 2014 ) ; the percentage of articles reporting statements of conflicts ( 0 % in 2000 , 15.4 % in 2014 ) or no conflicts ( 5.6 % in 2000 , 50.0 % in 2014 ) increased . Articles published in journals in the clinical medicine category versus other fields were almost twice as likely to not include any information on funding and to have private funding . This study provides baseline data to compare future progress in improving these indicators in the scientific literature OBJECTIVES To assess the type of evidence that supported our management of surgical patients . DESIGN Retrospective audit . SETTING Teaching hospital , Republic of Irel and . PATIENTS All 222 patients admitted by two surgical teams during one month . Patients admitted for diagnostic procedures were included if they were treated as a result . MAIN OUTCOME MEASURES Diagnosis and treatment were established from the notes . Evidence for each intervention was then sought in MEDLINE 1986 - 1999 , Best Evidence 1991 - 1999 , and the Cochrane Data base of Systematic Review s Issue 3 , 1999 , and grade d into one of five categories : systematic review , meta- analysis , r and omised controlled trial , prospect i ve study , or retrospective study . RESULTS Treatment was supported by systematic review in 14 , by meta- analysis in 12 , by r and omised controlled trial in 75 , by prospect i ve studies in 55 , by retrospective studies in 58 , and by no evidence in 8 . CONCLUSIONS Everyday surgical practice in our unit is supported by good quality evidence from recent publications St and ards of scientific reporting have evolved from the very beginning of scientific reporting . Virtually all journals now publish instructions for authors and most medical journals adhere to certain st and ards of publication . Such st and ards have been promoted by international groups such as the International Committee of Medical Journal Editors ( ICMJE ) and Committee on Publication Ethics ( COPE ) . The ICMJE has published general st and ards for crafting scientific articles : the “ Uniform Requirements for Manuscripts Su bmi tted to Biomedical Journals : Writing and Editing for Biomedical Publication ” [ 7 ] . These guidelines include suggestions not only for manuscript preparation , but also guidelines for ethical issues related to publishing . COPE , however , focuses on ethical issues [ 1 ] . CORR adheres to these guidelines ; authors may find links to these guidelines in our online Instructions for Authors . Such guidelines , as important as they are , lack sufficient detail to ensure all important information is included . Therefore , in addition to these general guidelines for preparing a manuscript , numerous international groups have published guidelines to ensure various sorts of studies contain all essential information . These include the CONSORT ( Consoli date d St and ards of Reporting Trials ) guidelines for r and omized trials [ 2 , 3 , 8 ] , QUORUM ( Quality of Reporting of Meta-analyses ) [ 6 ] and MOOSE ( Meta- analysis Of Observational Studies in Epidemiology ) [ 13 ] for meta-analyses , and STROBE ( Strengthening the Reporting of Observational Studies in Epidemiology ) for various sorts of observational studies ( the majority of clinical studies in surgical disciplines ) [ 12 , 15 ] . In essence , these guidelines tell investigators and authors what information is required to ensure readers ( and review ers ) can properly evaluate the study . Despite these st and ards , most reports of clinical studies lack such critical information . I suspect this is less by intent than lack of awareness of what information is required . In addition , although many journals , including CORR require a Level of Evidence [ 5 , 10 , 16 ] for studies involving patients , most clinical articles published in surgical journals have a relatively low level ; prospect i ve , r and omized trials are uncommon ( and often impractical ) , and even sufficiently large retrospective cohort studies to control for confounding variables may be unachievable for many conditions or treatments in single institutions . In the absence of high levels of evidence , systematic review s [ 9 , 11 , 17 ] and meta-analyses [ 4 ] have become increasingly common . My search of PubMed for articles limited to meta- analysis yielded 276 articles from 1950–1989 , 2116 from 1990–1994 , 3736 from 1995–1999 , 7920 from 2000–2004 , and 9313 from 2005 to 2009 . Most of these analyses undoubtedly collected information from lower level studies , thereby incurring the limitations of the individual studies . Virtually all systematic and meta-analyses we have recently published noted missing and variably reported data . In contrast to medical disciplines , surgical disciplines do not have the advantage of being able to conduct tightly design ed prospect i ve , r and omized , blinded , controlled trials . ( A PubMed search limited to r and omized controlled trials suggested The Journal of Bone and Joint Surgery and CORR had together published 556 RCTs and although I did not individually check these for quality , they reflect a small fraction of the articles both journals publish . ) For the foreseeable future , most of our information will arise from observational studies rather than prospect i ve trials . In this setting , it is especially important that each article contain all relevant information for future systematic review s and meta-analyses . The STROBE guidelines [ 12 ] provide authors with lists of critical information for reporting three sorts of observational studies : cohort ( longitudinal studies typically reporting outcomes of treatment in one or more cohorts ) , case-control ( studies identifying factors in outcomes ) , and cross-sectional studies ( studies to identify prevalence of factors or characteristics in a population at a single time ) . CORR now requires authors to adhere to CONSORT guidelines for r and omized clinical trials , QUORUM guidelines for meta-analyses , and STROBE guidelines for observational clinical studies . Authors will be able to download from our Instructions to Authors convenient templates for the various sorts of articles we publish ; these templates contain the information required . In addition , we request authors read and follow the guidelines in the Cochrane H and book for Systematic Review s of Interventions 4.2.6 [ 14 ] . Adherence to these st and ards will enhance our ability to answer key clinical questions in more definitive ways than we have in the past , and to answer more questions
There is no consistent result in the relationship between obesity and timing of pubertal onset in boys .
Obesity may contribute to early onset of puberty in girls , while in boys , there is insufficient data .
This systematic review and meta- analysis examined the associations between obesity and puberty timing based on scientific evidence .