Caries-preventive effect of glass ionomer and resin-based fissure sealants on permanent teeth: An update of systematic review evidence Systematic reviews in endodontics--examples of GIGO? Use of Pit-and-Fissure Sealants. Structural brain alterations following adult non-CNS cancers: a systematic review of the neuroimaging literature Evidence-based Clinical Practice Guideline for the Use of Pit-and-Fissure Sealants. Research gaps identified during systematic reviews of clinical trials: glass-ionomer cements From the Editors’ Desk: Bias in Systematic Reviews—Let the Reader Beware Retention and caries preventive effects of a GIC and a resin-based fissure sealant. The Medical Review Article Revisited: Has the Science Improved? Chiropractic care for patients with asthma: A systematic review of the literature. Financial Conflicts of Interest and Conclusions About Neuraminidase Inhibitors for Influenza Sealing versus partial caries removal in primary molars: a randomized clinical trial Controversies around Xylitol Wasted research when systematic reviews fail to provide a complete and up-to-date evidence synthesis: the example of lung cancer Dietary and physical activity strategies to prevent type 2 diabetes in South Asian adults: protocol for a systematic review Systematic Reviews of Diagnostic Test Accuracy Discussion sections in reports of controlled trials published in general medical journals: islands in search of continents? How Quickly Do Systematic Reviews Go Out of Date? A Survival Analysis
Background This article constitutes a partial up date of the original systematic review evidence by Yengopal et al. from 15 January 2008 ( published in the Journal of Oral Science in 2009 ) with primary focus on research quality in regard to bias risk in trials . Its aim is to up date the existing systematic review evidence from the English literature as to whether caries occurrence on pits and fissures of teeth sealed with either GIC or resin is the same . Methods In addition to the 12 trials included during the original systematic review , 5 new trials were identified during the data base search ( up to 26 August 2010 ) and 2 further trials were included from a h and search and reference check . Of these , 3 trials were excluded and 16 were accepted for data extraction and quality assessment . The quality of accepted trials was assessed , using up date d quality criteria , and the risk of bias was investigated in more depth than previously reported . In addition , the focus of quantitative synthesis was shifted to single data sets that were extracted from the accepted trials . Results Twenty-six dichotomous and 4 continuous data sets were extracted . Meta- analysis and cumulative meta- analysis were used in combining clinical ly homogenous data sets . The overall outcome of the computed data sets suggest no difference between the caries-preventive effects of GIC- and resin-based fissure sealants . Conclusions This overall outcome is in agreement with the conclusions of the original systematic review . Although the findings of the trials identified in this up date may be considered to be less affected by attrition- and publication bias , their risk of selection - and detection-/performance bias is high . Thus , verification of the currently available results requires further high quality r and omised control trials 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 BACKGROUND This article presents evidence -based clinical recommendations for the use of pit- and -fissure sealants on the occlusal surfaces of primary and permanent molars in children and adolescents . A guideline panel convened by the American Dental Association ( ADA ) Council on Scientific Affairs and the American Academy of Pediatric Dentistry conducted a systematic review and formulated recommendations to address clinical questions in relation to the efficacy , retention , and potential side effects of sealants to prevent dental caries ; their efficacy compared with fluoride varnishes ; and a head-to-head comparison of the different types of sealant material used to prevent caries on pits- and -fissures of occlusal surfaces . TYPES OF STUDIES REVIEW ED This is an up date of the ADA 2008 recommendations on the use of pit- and -fissure sealants on the occlusal surfaces of primary and permanent molars . The authors conducted a systematic search in MEDLINE , Embase , Cochrane Central Register of Controlled Trials , and other sources to identify r and omized controlled trials reporting on the effect of sealants ( available on the U.S. market ) when applied to the occlusal surfaces of primary and permanent molars . The authors used the Grading of Recommendations Assessment , Development , and Evaluation approach to assess the quality of the evidence and to move from the evidence to the decisions . RESULTS The guideline panel formulated 3 main recommendations . They concluded that sealants are effective in preventing and arresting pit- and -fissure occlusal carious lesions of primary and permanent molars in children and adolescents compared with the nonuse of sealants or use of fluoride varnishes . They also concluded that sealants could minimize the progression of non-cavitated occlusal carious lesions ( also referred to as initial lesions ) that receive a sealant . Finally , based on the available limited evidence , the panel was unable to provide specific recommendations on the relative merits of 1 type of sealant material over the others . Conclusions and practical implication s : These recommendations are design ed to inform practitioners during the clinical decision-making process in relation to the prevention of occlusal carious lesions in children and adolescents . Clinicians are encouraged to discuss the information in this guideline with patients or the parents of patients . The authors recommend that clinicians re-orient their efforts toward increasing the use of sealants on the occlusal surfaces of primary and permanent molars in children and adolescents Abstract Background : Cancer and cancer treatments may impact the brain through several pathways leading to cognitive impairment . Neuroimaging evidence has begun to eluci date the neurobiological underpinnings of cancer-related cognitive impairment . The aim of this paper was to systematic ally review available literature on structural brain alterations following adult non- central nervous system ( CNS ) cancers and associated treatments . Methods : This review followed PRISMA guidelines and was registered in PROSPERO ( ID#107387 ) . Comprehensive search es were conducted in June 2018 using PubMed and Web of Science . Inclusion criteria were English peer- review ed journal articles of formal , controlled studies that examined structural neuroimaging outcomes in adult non-CNS cancer patients and survivors . Selected articles were assessed for quality and risk of bias using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies . Results : Thirty-six publications of prospect i ve and cross-sectional studies met inclusion criteria and were included . Structural brain alterations following cancer and its treatment were reported in a majority of the publications as evidence d by reduced global and local gray matter volumes , impaired white matter microstructural integrity , and brain network alterations . Structural alterations were most often evident when cancer-treated groups were compared with healthy controls , and more subtle when compared with cancer controls . Regarding the existence of pretreatment impairments , the evidence was equivocal . There was significant between- study heterogeneity in imaging analytical approaches and use of statistical adjustments . Over half reported associations with cognitive outcomes , though regions and associated cognitive domains were heterogeneous . Conclusions : Structural brain alterations following cancer and cancer treatments were reported in a majority of the review ed studies . However , the extent of observed alterations depended on the choice of comparison groups . Method ological issues exist that will need to be addressed systematic ally to ensure the validity of findings . Large-scale prospect i ve studies with extended assessment points are warranted to replicate and build upon initial findings BACKGROUND This article presents evidence -based clinical recommendations for the use of pit- and -fissure sealants on the occlusal surfaces of primary and permanent molars in children and adolescents . A guideline panel convened by the American Dental Association ( ADA ) Council on Scientific Affairs and the American Academy of Pediatric Dentistry conducted a systematic review and formulated recommendations to address clinical questions in relation to the efficacy , retention , and potential side effects of sealants to prevent dental caries ; their efficacy compared with fluoride varnishes ; and a head-to-head comparison of the different types of sealant material used to prevent caries on pits- and -fissures of occlusal surfaces . TYPES OF STUDIES REVIEW ED This is an up date of the ADA 2008 recommendations on the use of pit- and -fissure sealants on the occlusal surfaces of primary and permanent molars . The authors conducted a systematic search in MEDLINE , Embase , Cochrane Central Register of Controlled Trials , and other sources to identify r and omized controlled trials reporting on the effect of sealants ( available on the U.S. market ) when applied to the occlusal surfaces of primary and permanent molars . The authors used the Grading of Recommendations Assessment , Development , and Evaluation approach to assess the quality of the evidence and to move from the evidence to the decisions . RESULTS The guideline panel formulated 3 main recommendations . They concluded that sealants are effective in preventing and arresting pit- and -fissure occlusal carious lesions of primary and permanent molars in children and adolescents compared with the nonuse of sealants or use of fluoride varnishes . They also concluded that sealants could minimize the progression of non-cavitated occlusal carious lesions ( also referred to as initial lesions ) that receive a sealant . Finally , based on the available limited evidence , the panel was unable to provide specific recommendations on the relative merits of 1 type of sealant material over the others . Conclusions and practical implication s : These recommendations are design ed to inform practitioners during the clinical decision-making process in relation to the prevention of occlusal carious lesions in children and adolescents . Clinicians are encouraged to discuss the information in this guideline with patients or the parents of patients . The authors recommend that clinicians re-orient their efforts toward increasing the use of sealants on the occlusal surfaces of primary and permanent molars in children and adolescents Background To report the results of an audit concerning research gaps in clinical trials that were accepted for appraisal in authored and published systematic review s regarding the application of glass-ionomer cements ( GIC ) in dental practice Methods Information concerning research gaps in trial precision was extracted , following a framework that included classification of the research gap reasons : ‘ imprecision of information ( results ) ’ , ‘ biased information ’ , ‘ inconsistency or unknown consistency ’ and ‘ not the right information ’ , as well as research gap characterization using PICOS elements : population ( P ) , intervention ( I ) , comparison ( C ) , outcomes ( O ) and setting ( S ) . Internal trial validity assessment was based on the underst and ing that successful control for systematic error can not be assured on the basis of inclusion of adequate methods alone , but also requires empirical evidence about whether such attempt was successful . Results A comprehensive and interconnected coverage of GIC-related clinical topics was established . The most common reasons found for gaps in trial precision were lack of sufficient trials and lack of sufficient large sample size . Only a few research gaps were ascribed to ‘ Lack of information ’ caused by focus on mainly surrogate trial outcomes . According to the chosen assessment criteria , a lack of adequate r and omisation , allocation concealment and blinding/masking in trials covering all review ed GIC topics was noted ( selection - and detection/performance bias risk ) . Trial results appear to be less affected by loss-to-follow-up ( attrition bias risk ) . Conclusion This audit represents an adjunct of the systematic review articles it has covered . Its results do not change the systematic review ’s conclusions but highlight existing research gaps concerning the precision and internal validity of review ed trials in detail . These gaps should be addressed in future GIC-related clinical research S ystematic review s are relied upon by clinicians and policymakers as high- quality evidence for decision-making . In some hierarchies of evidence quality , systematic review s are ranked at the top , higher than r and omized controlled trials . A properly conducted systematic review that is based on high- quality articles provides very strong evidence ; policymakers recognize this value and solicit many such review s. Busy clinicians rely on well-executed systematic review s to quickly synthesize the literature and guide them in managing patients . However , there are important inherent weaknesses that can limit the quality of systematic review s and can lead to erroneous conclusions . Consumers of systematic review s should approach them with a healthy sense of skepticism . Unfortunately , many of these weaknesses may not be obvious to the various stakeholders who routinely invest their trust in such review s. The first bias one encounters is inherent in the research enterprise . Generally , research ers design studies to demonstrate maximum effect ; hence they are careful about the population selected , the interventions tested , and the outcomes assessed . For example , interventions are often tested in population s that are at high risk for experiencing the outcome in question and are likely to respond to the intervention . Not only can this make results difficult to generalize , but it often results in studies that overstate the benefit ; subsequent studies frequently find less benefit . This is particularly common when the pool of available studies consists of small , single-center investigations , trials that are particularly likely to show large effects . While usually not intentional , the combination of careful selection of population and outcomes can distort clinical research and obscure truth . This inherent bias in the research enterprise can not be fixed ; however , if there are a sufficient number of studies , conducted across different setting s and population s , this problem can be partially ameliorated with systematic review s. Systematic review s are vulnerable to a number of biases . First , the question may not be well-defined . A marker of a high- quality systematic review is the inclusion of a purpose statement in which the specific research question is clearly articulated . Specificity is key : what are they willing to accept as evidence , what population , what intervention , what duration , what doses , what outcomes and when ? Second , the search strategy should be broad enough to reassure readers that no studies were left out . Research ers commonly limit their search to English- language articles . However , there is no difference between the quality of articles in English and those in other language s , and limiting the search to English-only should be a red flag to readers . The bibliographies of retrieved articles should also be review ed . All search strategies should include input from an experienced medical librarian . Third , the quality of included articles must be carefully assessed . The higher the quality of articles that provide the bulk of the systematic review ’s conclusions , the more confident readers can be in those conclusions . Readers should be wary of review s that are based on observational data or uncontrolled clinical trials . A statistical package will analyze whatever data the analyst feeds it , and will provide an estimate of an overall effect and a 95 % confidence interval . This can mislead readers into believing that our underst and ing of the effect is more concrete than it is . Pooling of observational data can lead to answers that differ material ly from the results of r and omized controlled trials . Readers should also be wary of systematic review s built on low sample numbers , either few studies or small sample s within each study . The number of studies necessary to produce believable results is an area of ongoing debate . A recent article discussed the benefits of  Trial Sequential Analysis ( TSA )  , a method that allows metaanalysts to determine the likelihood that the review contains either a type I error ( finding a difference that does not exist ) or a type II error ( reporting no difference when in fact one exists ) . TSA theory is similar to the principles governing stopping rules for interventional trials . It takes the total sample size and the size of the effect , and establishes boundaries . These boundaries provide confidence that the sample size is large enough to avoid type I or II errors . We strongly recommend routinely including them in meta-analyses . Fourth , very careful attention must be paid to the issue of publication bias . Most readers recognize that studies with nonsignificant results face greater publication hurdles . This is a wellrecognized phenomenon ; protocol s with non-significant results are both less likely to be published and , when published , more likely to encounter significant delays than studies with significant Published online December 12 , Abstract Fissure sealing using partially filled resins is an established caries preventive practice . Glass ionomer cement ( GIC ) sealants may offer additional advantages due to their ability to bond chemically to enamel and release fluoride . The aim of this study was to compare the caries preventive effect and retention of a GIC and a resin-based sealant . Ketac-fil ® was tested against a chemically cured resin-based material ( Delton ® ) using a split mouth design . Perth ( Western Australia ) schoolchildren ( n= 465 ) , mean age 7 yr±0.72 ( S.D. ) , received sealants  on the occlusal surfaces of sound homologous permanent first molar pairs .  Test ( GIC ) and control ( resin ) sealants were systematic ally allocated to left and right sides based on the child 's month of birth , and were placed by dental therapists . After 3.64±0.11 yr , 415 children were examined by different clinicians , and the clinical status of the teeth and the extent of sealant retention recorded . Sealants were deemed retained when at least 2/3 of the fissure pattern was still sealed . In 252 tooth pairs , neither sealant was retained to this extent . In 71 pairs , the GIC was not retained and the resin sealant retained . In 40 pairs the reverse occurred ( McNemar 's test , χ2= 8.66 , P < 0.005 ) . Net gain ( additional lesions prevented by the test agent per 100 treatments ) was 6.1%(95 % CI 3.3 % , 8.9 % ) . Effectiveness of the GIC was 80.6 % ( 95 % CI 59.6 % , 90.7 % ) . The relative risk of caries in test teeth was 0.19 ( 95 % CI 0.09 , 0.40 ) . The study suggests that complete retention of GIC sealant is not necessary for caries prevention in newly erupted permanent first molars 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 OBJECTIVE To provide a review of the literature and rate the quality of published studies regarding chiropractic care , including spinal manipulation , for asthmatic patients . METHODS A multimodal search strategy was conducted , including multiple data base search es , along with reference and journal h and - search ing . Studies were limited to those published in English and in peer- review ed journals or conference proceedings between January 1980 and March 2009 . All study design s were considered except personal narratives or review s. Retrieved articles that met the inclusion criteria were rated for quality by using the Downs and Black checklist . A brief summary was also written for each retrieved study . RESULTS Eight articles met the inclusion criteria of this review in the form of one case series , one case study , one survey , two r and omized controlled trials ( RCTs ) , one r and omized patient and observer blinded cross-over trial , one single blind cross study design , and one self-reported impairment question naire . Their quality scores ranged from 5 to 22 out of 27 . CONCLUSION Results of the eight retrieved studies indicated that chiropractic care showed improvements in subjective measures and , to a lesser degree objective measures , none of which were statistically significant . It is evident that some asthmatic patients may benefit from this treatment approach ; however , at this time , the evidence suggests chiropractic care should be used as an adjunct , not a replacement , to traditional medical therapy 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 Background The resin-based pit and fissure sealant is considered a successful tool in caries prevention , however there is a growing evidence of its use in controlling already established caries in posterior teeth . The aim of this clinical trial is to verify the efficacy of pit and fissure sealants in arresting dentinal caries lesions compared to partial excavation and restorative treatment in primary molar teeth . Methods Thirty six patients with occlusal cavitated primary molar reaching outer half of dentin were selected . The patients were r and omly allocated into two groups : sealant application ( experimental group – n = 17 ) and restoration with composite resin ( control group – n = 19 ) . Clinical and radiograph evaluation were performed after 6 , 12 and 18 months . The chi-square test was used to verify the distribution of characteristics variables of the sample among the groups . The survival rate of treatments was evaluated using Kaplan – Meier survival and log-rank test . Fisher ’s Exact and logistic regression tests were calculated in each evaluation period ( α = 5 % ) . Results The control group showed significantly better clinical survival after 18 months ( p = 0.0025 ) . In both groups , no caries progression was registered on the radiographic evaluations . Conclusions Sealing had similar efficacy in the arrestment of caries progression of cavitated occlusal lesions compared to partial excavation of the lesions , even though the frequency of re-treatments was significantly higher in sealed lesions . Trial registration Registro Brasileiro de Ensaios Clínicos ( ReBEC ) : Xylitol research has been conducted since the early 70 ’s ; at the beginning of 2009 there were almost 500 PubMed - indexed papers on “ xylitol and dental ” . Xylitol research was initiated in Finl and , but nowadays the majority of papers are published by non-Finnish authors . Xylitol studies have been criticized mainly by European research ers . This criticism is reflected for example in the most recent textbook of cariology , Dental Caries – The Disease and its Clinical Management ( 2008 ) , used by students in all Nordic countries . It shows a figure with reduction in caries occurrence in the Turku Sugar Studies as an example , not of the effect of total substitution of dietary sugars with xylitol , but rather “ indicating the importance of removal of sugar from the diet , rather than starch , in caries control “ . Moreover , a frequently cited review in Caries Research in 2004 came to the conclusion that “ there is no evidence for a caries-therapeutic effect of xylitol”.1 Xylitol studies are easy to criticize especially by authors who have never been involved in field trials . For example , to avoid exchange of test products between children of the same class r and omisation has to be done by schools or school classes . This is rarely recognized by the critics of xylitol studies . In addition , it is hard to find volunteers to comply with 2–3 years chewing of a hard and tasteless gum base , which is the control often suggested for chewing gum trials . Polyols like maltitol and sorbitol are by no means inert and are thus not valid controls for xylitol . Fortunately , US dental experts have critically , but positively , conducted research and review ed the literature on xylitol.2–5 One consequence of practical problems associated with field trials is that in systematic review s of methods for caries control and prevention the strict exclusion criteria leave only few xylitol studies for evaluation . For example , the inclusion criteria for a Swedish systematic review on methods of caries prevention ( SBU ; www.sbu.se ) were so strict that hardly any recommendations concerning caries prevention could be made . This also applied to xylitol : according to the report , the evidence on the clinical efficacy for xylitol was inconclusive . In a critical evaluation of the SBU report , the following question was asked “ where does this leave the confused dental practitioner , who has to offer chairside advice to patients , but can not wait of further ( good- quality ) research to be conducted and published , providing a more solid evidence -base ? ” ( Stillman-Lowe , 2005 ) . On the other h and , xylitol has been recommended for use in caries control and prevention by several dental associations . Also the European Food Safety Authority evaluated the literature on xylitol in 2008 and came to the conclusion that “ xylitol chewing gum reduces the risk of caries in children ” . The cl aim had to be reformulated since chewing gum is not a medicine and can thus not be cl aim ed to reduce the risk of a disease , caries . In Europe , there is a strong interest not to give xylitol a better status than for other polyol sweeteners . Xylitol differs from other polyols as is obvious to all experts familiar with microbiology . Xylitol has beneficial effects on the oral flora not shared by other polyols . The evidence so far supports specific xylitol-effects on oral bacteria , but not on saliva .  Xylitol can not be metabolized by plaque bacteria , contrary to sorbitol and other 6-carbon polyols , and may thus favour mineralization . The accumulated evidence suggests that 1 ) mutans streptococci are the target organisms of xylitol in vivo , 2 ) mutans streptococci are reduced and stay on a lower level even during long-term xylitol consumption as long as the consumption lasts , 3 ) xylitol consumption reduces the accumulation of plaque , 4 ) xylitol consumed by mothers reduces the mother-child transmission of mutans streptococci and consequently , caries occurrence in their children,6,7 and 5 ) xylitol consumption reduces the risk of caries in children.4 In clinical trials on xylitol mostly chewing gum with high xylitol concentrations has been used . Studies with low daily doses of xylitol are known as a rule to fail to show any caries-preventive effects . To obtain beneficial xylitol-effects on mutans streptococci , on plaque and caries occurrence xylitol must be consumed three times or more per day , with a daily dose of 5–6 grams.4,7 When using chewing gums or pastilles , saliva stimulation always occurs due to chewing or sucking . Some authors have cl aim ed that the beneficial effects of xylitol are solely based on saliva stimulation and that all sugar-free gums are similar in this respect . In fact , in conditions where caries occurrence is high , even sorbitol gum can prevent caries.8 A recent study elegantly shows caries prevention with xylitol without any saliva stimulation . In this study fifteen-month-old children were given xylitol or sorbitol syrup with a syringe for 12 months.9 The xylitol syrup prevented  early childhood caries  effectively , while sorbitol had no effect . In spite of the abundant literature still more studies are needed on the action of xylitol . Biofilm models could be very useful in xylitol research . There is a clear need for properly design ed , r and omized , controlled , clinical trials to demonstrate 1 ) the feasibility of  xylitol prevention in different population s with different dietary and oral hygiene habits , 2 ) suitable vehicles to deliver xylitol , 3 ) the extent to which xylitol can be “ diluted ” with other polyols without losing the caries preventive effects , and 4 ) the minimum daily xylitol dose and frequency of xylitol are needed to obtain the expected xylitol-effects on mutans streptococci , plaque and most importantly , on caries occurrence . Clinical trials often aim to improve treatment methods . When several clinical trials give similar results , clinicians can be given treatment guidelines based on findings verified by research . In this way research serves the clinicians in treating patients according to evidence -based solid information . Systematic review s are currently required to up date guidelines for caries prevention . As such , critical evaluation of the existing literature is a positive goal , but if it leads to a situation where no treatment guidelines can be given , something is wrong . This also applies to xylitol studies . Though strict inclusion criteria prevent conclusions based on systematic review s of the literature , evidence -based treatment guidelines can still be given for the use of xylitol . Xylitol is a useful adjunct to traditional methods for caries control and prevention . Caries prevention with xylitol has been cl aim ed to be expensive , but if true primary prevention is obtained , as demonstrated in the mother-child study , 6,7 it may be worth it Background Multiple treatments are frequently available for a given condition , and clinicians and patients need a comprehensive , up-to- date synthesis of evidence for all competing treatments . We aim ed to quantify the waste of research related to the failure of systematic review s to provide a complete and up-to- date evidence synthesis over time . Methods We performed a series of systematic overviews and networks of r and omized trials assessing the gap between evidence covered by systematic review s and available trials of second-line treatments for advanced non-small cell lung cancer . We search ed the Cochrane Data base of Systematic Review s , Data base of Abstract s of Review s of Effects , MEDLINE , EMBASE , and other re sources sequentially by year from 2009 to March 2 , 2015 . We sequentially compared the amount of evidence missing from systematic review s to the r and omized evidence available for inclusion each year . We constructed cumulative networks of r and omized evidence over time and evaluated the proportion of trials , patients , treatments , and treatment comparisons not covered by systematic review s on December 31 each year from 2009 to 2015 . Results We identified 77 trials ( 28,636 patients ) assessing 47 treatments with 54 comparisons and 29 systematic review s ( 13 published after 2013 ) . From 2009 to 2015 , the evidence covered by existing systematic review s was consistently incomplete : 45 % to 70 % of trials ; 30 % to 58 % of patients ; 40 % to 66 % of treatments ; and 38 % to 71 % of comparisons were missing . In the cumulative networks of r and omized evidence , 10 % to 17 % of treatment comparisons were partially covered by systematic review s and 55 % to 85 % were partially or not covered . Conclusions We illustrate how systematic review s of a given condition provide a fragmented , out-of- date panorama of the evidence for all treatments . This waste of research might be reduced by the development of live cumulative network meta-analyses Introduction Type 2 diabetes ( T2D ) is a major health concern among population s of South Asian ethnicity . Although dietary and physical activity interventions may reduce the risk of T2D , the effectiveness has been moderate among South Asians . This might ( in part ) be because this subgroup follows strategies that were originally developed for interventions among other population s. Therefore , this review aims to assess the evidence for the current dietary and physical activity strategies recommended in T2D prevention intervention studies and guidelines for South Asians . Methods and analysis Included will be all studies and guidelines on dietary and /or physical activity strategies to prevent T2D in adult South Asians . Two review ers will search online data bases from their start until the present date for published and unpublished experimental/quasiexperimental studies , with at least an abstract in English . References of identified articles and key review s will be screened for additional studies . Guidelines will be identified by search es in online data bases and websites of public organisations . Finally , expert consultations will be held to supplement any missing information . Trial quality will be assessed with the Quality Assessment Tool for Quantitative Studies Data , and guidelines with the Appraisal of Guidelines for Research & Evaluation II . Data on the strategies recommended , targeting and evidence on effectiveness will be extracted by two review ers and presented in tabular and narrative forms . Recommendations will be compared with the National Institute for Health and Care Excellence guidelines [ PH35 ] . Overall findings on  dietary and physical activity recommendations , as well as findings for specific subgroups ( eg , by sex ) , will be discussed . Ethics and dissemination Ethics assessment is not required . Start date : 1 January 2016 , finishing and reporting date 31 July 2016 . Results will be published in a peer- review ed scientific journal , the project report of EuroDHYAN ( www.eurodhyan.eu ) and in a PhD dissertation . Trial registration number The protocol is registered with the International Prospect i ve Register of Systematic Review s ( PROSPERO ) registration number CRD42015027067 Diagnosis is a critical component of health care , and clinicians , policymakers , and patients routinely face a range of questions regarding diagnostic tests . They want to know whether testing improves outcome ; what test to use , purchase , or recommend in practice guidelines ; and how to interpret test results . Well- design ed  diagnostic test accuracy studies can help in making these decisions , provided that they transparently and fully report their participants , tests , methods , and results as facilitated , for example , by the STARD ( St and ards for Reporting of Diagnostic Accuracy ) statement ( 1 ) . That 25-item checklist was published in many journals and is now adopted by more than 200 scientific journals worldwide . As in other areas of science , systematic review s and meta- analysis of accuracy studies can be used to obtain more precise estimates when small studies addressing the same test and patients in the same setting are available . Review s can also be useful to establish whether and how scientific findings vary by particular subgroups , and may provide summary estimates with a stronger generalizability than estimates from a single study . Systematic review s may help identify the risk for bias that may be present in the original studies and can be used to address questions that were not directly considered in the primary studies , such as comparisons between tests . The Cochrane Collaboration is the largest international organization preparing , maintaining , and promoting systematic review s to help people make well-informed decisions about health care ( 2 ) . The Collaboration decided in 2003 to make preparations for including systematic review s of diagnostic test accuracy in their Cochrane Data base of Systematic Review s. To enable this , a working group ( Appendix ) . was formed to develop methodology , software , and a h and book The first diagnostic test accuracy review was published in the Cochrane Data base in October 2008 . In this paper , we review recent method ological developments concerning problem formulation , location of literature , quality assessment , and meta- analysis of diagnostic accuracy studies by using our experience from the work on the Cochrane H and book . The information presented here is based on the recent literature and up date s previously published guidelines by Irwig and colleagues ( 3 ) . Definition of the Objectives of the Review Diagnostic test accuracy refers to the ability of a test to distinguish between patients with disease ( or more generally , a specified target condition ) and those without . In a study of test accuracy , the results of the test under evaluation , the index test , are compared with those of the reference st and ard determined in the same patients . The reference st and ard is an agreed-on and accurate method for identifying patients who have the target condition . Test results are typically categorized as positive or negative for the target condition . By using such binary test outcomes , the accuracy is most often expressed as the test 's sensitivity ( the proportion of patients with positive results on the reference st and ard that are also positive on the index test ) and specificity ( the proportion of patients with negative results on the reference st and ard that are also negative on the index test ) . Other measures have been proposed and are in use ( 46 ) . It has long been recognized that test accuracy is not a fixed property of a test . It can vary between patient subgroups , with their spectrum of disease , with the clinical setting , or with the test interpreters and may depend on the results of previous testing . For this reason , inclusion of these elements in the study question is essential . In order to make a policy decision to promote use of a new index test , evidence is required that using the new test increases test accuracy over other testing options , including current practice , or that the new test has equivalent accuracy but offers other advantages ( 79 ) . As with the evaluation of interventions , systematic review s need to include comparative analyses between alternative testing strategies and should not focus solely on evaluating the performance of a test in isolation . In relation to the existing situation , 3 possible roles for a new test can be defined : replacement , triage , and add-on ( 7 ) . If a new test is to replace an existing test , then comparing the accuracy of both tests on the same population and with the same reference st and ard provides the most direct evidence . In triage , the new test is used before the existing test or testing pathway , and only patients with a particular result on the triage test continue the testing pathway . When a test is needed to rule out disease in patients who then need no further testing , a test that gives a minimal proportion of falsenegative results and thus a relatively high sensitivity should be used . Triage tests may be less accurate than existing ones , but they have other advantages , such as simplicity or low cost . A third possible role of a new test is add-on . The new test is then positioned after the existing testing pathway to identify false-positive or false-negative results after the existing pathway . The review should provide data to assess the incremental change in accuracy made by adding the new test . An example of a replacement question can be found in a systematic review of the diagnostic accuracy of urinary markers for primary bladder cancer ( 10 ) . Clinicians may use cytology to triage patients before they undergo invasive cystoscopy  , the reference st and ard for bladder cancer . Because cytology combines high specificity with low sensitivity ( 11 ) , the goal of the review was to identify a tumor marker with sufficient accuracy to either replace cytology or be used in addition to cytology . For a marker to replace cytology , it has to achieve equally high specificity with improved sensitivity . New markers that are sensitive but not specific may have roles as adjuncts to conventional testing . The review included studies in which the test under evaluation ( several different tumor markers and cytology ) was evaluated against cystoscopy or histopathology . Included studies compared 1 or more of the markers , cytology only , or a combination of markers and cytology . Although information on accuracy can help clinicians make decisions about tests , good diagnostic accuracy is a desirable but not sufficient condition for the effectiveness of a test ( 8) . To demonstrate that using a new test does more good than harm to patients tested , r and omized trials of test- and -treatment strategies and review s of such trials may be necessary . However , with the possible exception of screening , in most cases , such r and omized trials are not available and systematic review s of test accuracy may provide the most useful evidence available to guide clinical and health policy decision making and use as input for decision and cost-effectiveness analysis ( 12 ) . Identification and Selection of Studies Identifying test accuracy studies is more difficult than search ing for r and omized trials ( 13 ) . There is not a clear , unequivocal keyword or indexing term for an accuracy study in literature data bases comparable with the term r and omized , controlled trial . The Medical Subject Heading sensitivity and specificity may look suitable but is inconsistently applied in most electronic bibliographic data bases . Furthermore , data on diagnostic test accuracy may be hidden in studies that did not have test accuracy estimation as their primary objective . This complicates the efficient identification of diagnostic test accuracy studies in electronic data bases , such as MEDLINE . Until indexing systems properly code studies of test accuracy , search ing for them will remain challenging and may require additional manual search es , such as screening reference lists . In the development of a comprehensive search strategy , review authors can use search strings that refer to the test(s ) under evaluation , the target condition , and the patient description or a subset of these . For tests with a clear name that are used for a single purpose , search ing for publications in which those tests are mentioned may suffice . For other review s , adding the patient description may be necessary , although this is also often poorly indexed . A search strategy in MEDLINE should contain both Medical Subject Headings and free text words . A search strategy for articles about tests for bladder cancer , for example , should include as many synonyms for bladder cancer as possible in the search strategy , including neoplasm , carcinoma , transitional cell , and hematuria . Several method ological electronic search filters for diagnostic test accuracy studies have been developed , each attempting to restrict the search to articles that are most likely to be test accuracy studies ( 1316 ) . These filters rely on indexing terms for research methodology and text words used in reporting results , but they often miss relevant studies and are unlikely to decrease the number of articles one needs to screen . Therefore , they are not recommended for systematic review s ( 17 , 18 ) . The incremental value of search ing in language s other than English and in the gray literature has not yet been fully investigated . In systematic review s of intervention studies , publication bias is an important and well-studied form of bias in which the decision to report and publish studies is linked to their findings . For clinical trials , the magnitude and determinants of publication bias have been identified by tracing the publication history of cohorts of trials review ed by ethics committees and research boards ( 19 ) . A consistent observation has been that studies with significant results are more likely to be published than studies with nonsignificant findings ( 19 ) . Investigating publication bias for diagnostic tests is problematic , because many studies are done without ethical review or study registration ; therefore , identification of cohorts of studies from registration to final publication status CONTEXT Several journals have adopted the Consoli date d St and ards of Reporting Trials ( CONSORT ) recommendations to make assessment of the quality of r and omized controlled trials ( RCTs ) easier . One of these recommendations is that the trial 's results be discussed in light of the totality of the available evidence . OBJECTIVE To assess the extent to which reports of RCTs published in 5 general medical journals have discussed new results in light of all available evidence . DESIGN Assessment of the discussion sections in all 26 reports of RCTs published during May 1997 in Annals of Internal Medicine , BMJ , JAMA , The Lancet , and The New Engl and Journal of Medicine . MAIN OUTCOME MEASURE The inclusion or mention of a systematic review in the discussion section of each article . RESULTS In only 2 articles were the RCT 's results discussed in the context of an up date d systematic review of earlier trials . In a further 4 articles , references were made to relevant systematic review s , but no attempts were made to integrate the results of the new trials in up date d versions of these review s. One article was probably the first published trial to address the question studied . The remaining 19 articles included no evidence that any systematic attempt had been made to set the reported trial 's results in the context of previous trials . CONCLUSION There is little evidence that journals have adequately implemented the CONSORT recommendation that results of an RCT be discussed in light of the totality of the available evidence 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
The overall outcome of the computed data sets suggest no difference between the caries-preventive effects of GIC- and resin-based fissure sealants .
Background This article constitutes a partial up date of the original systematic review evidence by Yengopal et al. from 15 January 2008 ( published in the Journal of Oral Science in 2009 ) with primary focus on research quality in regard to bias risk in trials .
Its aim is to up date the existing systematic review evidence from the English literature as to whether caries occurrence on pits and fissures of teeth sealed with either GIC or resin is the same .