Sources of evidence for systematic reviews of interventions in diabetes. Curcuminoids modify lipid profile in type 2 diabetes mellitus: A randomized controlled trial. The impact of cash transfers on social determinants of health and health inequalities in Sub-Saharan Africa: a systematic review protocol Efficacy of vitamin D supplementation in depression in adults: a systematic review protocol Relative citation impact of various study designs in the health sciences. Clarifying the distinction between case series and cohort studies in systematic reviews of comparative studies: potential impact on body of evidence and workload Bias due to selective inclusion and reporting of outcomes and analyses in systematic reviews of randomised trials of healthcare interventions. Systematic review data extraction: cross-sectional study showed that experience did not increase accuracy. Addressing Dichotomous Data for Participants Excluded from Trial Analysis: A Guide for Systematic Reviewers Curcuminoids exert glucose-lowering effect in type 2 diabetes by decreasing serum free fatty acids: a double-blind, placebo-controlled trial. The Medical Review Article Revisited: Has the Science Improved? Comparative Effectiveness of Dipeptidylpeptidase-4 Inhibitors in Type 2 Diabetes: A Systematic Review and Mixed Treatment Comparison Effects of supplementation with curcuminoids on dyslipidemia in obese patients: a randomized crossover trial. Seeing the forests and the trees—innovative approaches to exploring heterogeneity in systematic reviews of complex interventions to enhance health system decision-making: a protocol Highly bioavailable micellar curcuminoids accumulate in blood, are safe and do not reduce blood lipids and inflammation markers in moderately hyperlipidemic individuals. Indirect comparisons of competing interventions. Resting blood pressure reductions following isometric handgrip exercise training and the impact of age and sex: protocol for a systematic review Mitigation of Systemic Oxidative Stress by Curcuminoids in Osteoarthritis: Results of a Randomized Controlled Trial A conversation with Joseph Lau. How to write an evidence-based clinical review article. Protocol for a systematic review and economic evaluation of the clinical and cost-effectiveness of non-hospital-based non-invasive ventilation (NIV) in patients with stable end-stage COPD with hypercapnic respiratory failure Can we rely on the best trial? A comparison of individual trials and systematic reviews Effectiveness of interventions that assist caregivers to support people with dementia living in the community: a systematic review. The impact of outcome reporting bias in randomised controlled trials on a cohort of systematic reviews
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 BACKGROUND Type 2 diabetes ( T2D ) is an established risk factor for cardiovascular disease ( CVD ) and is associated with disturbed metabolism of lipids and lipoproteins . Curcuminoids are natural products with anti-diabetic and lipid-modifying actions but their efficacy in improving dyslipidemia in diabetic individuals has not been sufficiently studied . OBJECTIVE To investigate the efficacy of supplementation with curcuminoids , plus piperine as an absorption enhancer , in improving serum lipids in patients with T2D . METHODS In this 12-week r and omized double-blind placebo-controlled trial , subjects with T2D ( n=118 ) were assigned to curcuminoids ( 1000mg/day plus piperine 10mg/day ) or placebo plus st and ard of care for T2D . Serum concentrations of lipids including total cholesterol ( TC ) , low-density lipoprotein cholesterol ( LDL-C ) , high-density lipoprotein cholesterol ( HDL-C ) , triglycerides ( TG ) , lipoprotein(a ) [ Lp(a ) ] , and non-HDL-C were determined at baseline and at the end of trial . RESULTS Between-group comparison of change in the study parameters revealed significant reductions in serum levels of TC ( -21.86±25.78 versus -17.06±41.51 , respectively ; p=0.023 ) , non-HDL-C ( -23.42±25.13 versus -16.84±41.42 , respectively ; p=0.014 ) and Lp(a ) ( -1.50±1.61 versus -0.34±1.73 , respectively ; p=0.001 ) and elevations in serum HDL-C levels ( 1.56±4.25 versus -0.22±4.62 , respectively ; p=0.048 ) in the curcuminoids group as compared with the placebo group ( p<0.05 ) . Serum TG and LDL-C changes did not show any significant difference between the study groups ( p>0.05 ) . CONCLUSION Curcuminoids supplementation can reduce serum levels of atherogenic lipid indices including non-HDL-C and Lp(a ) . Therefore , curcuminoids supplementation could contribute to a reduced risk of cardiovascular events in dyslipidemic patients with T2D Background There is increasing pressure to address the social determinants of health ( SDoH ) and health inequities through the implementation of culturally acceptable interventions particularly in Sub-Saharan Africa ( SSA ) where health outcomes are generally poor . Available evaluation research on cash transfers ( CTs ) suggests that the programs may influence the wider determinants of health in SSA ; yet , there has been no attempt to synthesize the evidence regarding their contribution to tackling the SDoH and health inequalities . To date , nearly all the review s on CTs ' impact on health have predominantly featured evidence from Latin America with limited transferability to the social , cultural , and political environments in SSA . Therefore , the aim of this study is to undertake a systematic review to assess the role of CTs in tackling the wider determinants of health and health inequalities in SSA . Methods / design A systematic review of published and unpublished literature on CTs ’ impact on health and health determinants covering the period 2000–2016 will be undertaken . Studies will be considered for inclusion if they present quantitative or qualitative data , including all relevant study design s. The SDoH conceptual framework will be used to guide the data extraction process . EPPI Review er software will be used for data management and analysis . Studies included in the review will be analyzed by narrative synthesis and /or meta- analysis as appropriate for the nature of the data retrieved . Discussion This review will provide empirical evidence on the impact of CTs on SDoH to inform CT policy , implementation , and research in SSA . The protocol follows the Preferred Reporting Items for Systematic Review and Meta- Analysis Protocol s ( PRISMA -P ) . Systematic review registration This protocol has been registered with the PROSPERO international prospect i ve register of systematic review s , reference CRD42015025015 Background The role of vitamin D in management of depression is unclear . Results from observational and emerging r and omized controlled trials ( RCTs ) investigating the efficacy of vitamin D in depression lack consistency - with some suggesting a positive association while others show a negative or inconclusive association . Methods / Design The primary aim of this study is to conduct a systematic review of RCTs to assess the effect of oral vitamin D supplementation versus placebo on depression symptoms measured by scales and the proportion of patients with symptomatic improvement according to the authors ’ original definition . Secondary aims include assessing the change in quality of life , adverse events and treatment discontinuation . We will conduct the systematic review and meta- analysis according to the recommendations of the Cochrane H and book for Systematic Review s of Interventions . We will search the Cochrane Central Register of Controlled Trials ( CENTRAL ) , MEDLINE ( 1966 to present ) , EMBASE ( 1980 to present ) , CINAHL ( 1982 to present ) , PsychINFO ( 1967 to present ) and Clinical Trials.gov . Unpublished work will be identified by search ing two major conferences : the International Vitamin Conference , the Anxiety Disorders and Depression Conference , while grey literature will be acquired by contacting authors of included studies . We will use the r and om-effects meta- analysis to synthesize the data by pooling the results of included studies . Discussion The results of this systematic review will be helpful in clarifying the efficacy of vitamin D supplementation and providing evidence to establish guidelines for implementation of vitamin D for depression in general practice and other relevant setting s. Study registration Unique identifier : CRD42013003849 CONTEXT The relative merits of various study design s and their placement in hierarchies of evidence are often discussed . However , there is limited knowledge about the relative citation impact of articles using various study design s. OBJECTIVE To determine whether the type of study design affects the rate of citation in subsequent articles . DESIGN AND SETTING We measured the citation impact of articles using various study design s -- including meta-analyses , r and omized controlled trials , cohort studies , case-control studies , case reports , non systematic review s , and decision analysis or cost-effectiveness analysis --published in 1991 and in 2001 for a sample of 2646 articles . MAIN OUTCOME MEASURE The citation count through the end of the second year after the year of publication and the total received citations . RESULTS Meta-analyses received more citations than any other study design both in 1991 ( P<.05 for all comparisons ) and in 2001 ( P<.001 for all comparisons ) and both in the first 2 years and in the longer term . More than 10 citations in the first 2 years were received by 32.4 % of meta-analyses published in 1991 and 43.6 % of meta-analyses published in 2001 . R and omized controlled trials did not differ significantly from epidemiological studies and non systematic review articles in 1991 but clearly became the second-cited study design in 2001 . Epidemiological studies , non systematic review articles , and decision and cost-effectiveness analyses had relatively similar impact ; case reports received negligible citations . Meta-analyses were cited significantly more often than all other design s after adjusting for year of publication , high journal impact factor , and country of origin . When limited to studies addressing treatment effects , meta-analyses received more citations than r and omized trials . CONCLUSION Overall , the citation impact of various study design s is commensurate with most proposed hierarchies of evidence Distinguishing cohort studies from case series is difficult . We propose a conceptualization of  cohort studies  in systematic review s of comparative studies . The main aim of this conceptualization is to clarify the distinction between cohort studies and case series . We discuss the potential impact of the proposed conceptualization on the body of evidence and workload . All studies with exposure-based sampling gather multiple exposures ( with at least two different exposures or levels of exposure ) and enable calculation of relative risks that should be considered cohort studies in systematic review s , including non-r and omized studies . The term “ enables/can ” means that a predefined analytic comparison is not a prerequisite ( i.e. , the absolute risks per group and /or a risk ratio are provided ) . Instead , all studies for which sufficient data are available for re analysis to compare different exposures ( e.g. , sufficient data in the publication ) are classified as cohort studies .There are possibly large numbers of studies without a comparison for the exposure of interest but that do provide the necessary data to calculate effect measures for a comparison . Consequently , more studies could be included in a systematic review . Therefore , on the one h and , the outlined approach can increase the confidence in effect estimates and the strengths of conclusions . On the other h and , the workload would increase ( e.g. , additional data extraction and risk of bias assessment , as well as reanalyses ) 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 OBJECTIVE This study assessed the impact of systematic review and data extraction experience on the accuracy and efficiency of data extraction in systematic review s. STUDY DESIGN AND SETTING We conducted a prospect i ve cross-sectional study from October to December 2006 . Participants were classified as having minimal , moderate , or substantial experience in systematic review s and data extraction . Three studies on insomnia treatment were extracted . Our primary outcome was the accuracy of data extraction . Data sets of each experience level were analyzed for errors in data extraction and results of meta-analyses . Additionally , the time required for completion of data extraction was compared . RESULTS Error rates were similar across the various levels of experience and ranged from 28.3 % to 31.2 % . Mean rates for errors of omission ( 11.3 - 16.4 % ) were generally lower than those for errors of inaccuracy ( 13.9 - 17.9 % ) . There were no significant differences in error rates or accuracy of meta- analysis results between groups . Time required approached significance , with minimally experienced participants requiring the most time . CONCLUSION Overall , there were high error rates by participants at all experience levels ; however , time required for extraction tended to decrease with experience . These results illustrate the need to develop strategies aim ed at mastery of data extraction , rather than reliance on previous data extraction experience alone Introduction Systematic review er authors intending to include all r and omized participants in their meta-analyses need to make assumptions about the outcomes of participants with missing data . Objective The objective of this paper is to provide systematic review er authors with a relatively simple guidance for addressing dichotomous data for participants excluded from analyses of r and omized trials . Methods This guide is based on a review of the Cochrane h and book and published method ological research . The guide deals with participants excluded from the analysis who were considered ‘ non-adherent to the protocol ’ but for whom data are available , and participants with missing data . Results Systematic review er authors should include data from ‘ non-adherent ’ participants excluded from the primary study authors ' analysis but for whom data are available . For missing , unavailable participant data , authors may conduct a complete case analysis ( excluding those with missing data ) as the primary analysis . Alternatively , they may conduct a primary analysis that makes plausible assumptions about the outcomes of participants with missing data . When the primary analysis suggests important benefit , sensitivity meta-analyses using relatively extreme assumptions that may vary in plausibility can inform the extent to which risk of bias impacts the confidence in the results of the primary analysis . The more plausible assumptions draw on the outcome event rates within the trial or in all trials included in the meta- analysis . The proposed guide does not take into account the uncertainty associated with assumed events . Conclusions This guide proposes methods for h and ling participants excluded from analyses of r and omized trials . These methods can help in establishing the extent to which risk of bias impacts meta- analysis results SCOPE We previously found that curcuminoids  decreased blood glucose and improved insulin resistance by reducing serum free fatty acids ( FFAs ) and increasing fatty acid oxidation in skeletal muscle of diabetic rats . This study was to investigate whether curcuminoids have beneficial effects on type 2 diabetic patients , and its possible mechanisms . METHODS AND RESULTS Overweight/obese type 2 diabetic patients ( BMI ≥ 24.0 ; fasting blood glucose ≥ 7.0 mmol/L or postpr and ial blood glucose ≥11.1 mmol/L ) were r and omly assigned to curcuminoids ( 300 mg/day ) or placebo for 3 months . Bodyweight , glycosylated hemoglobin A1c ( HbA1c , % ) , serum fasting glucose , FFAs , lipids , and lipoprotein lipase ( LPL ) were determined . A total of 100 patients ( curcuminoids , n = 50 ; placebo , n = 50 ) completed the trial .  Curcuminoids supplementation significantly decreased fasting blood glucose ( p < 0.01 ) , HbA1c ( p = 0.031 ) , and insulin resistance index ( HOMA-IR ) ( p < 0.01 ) in type 2 diabetic patients  . Curcuminoids also led to a significant decrease in serum total FFAs ( p < 0.01 ) , triglycerides ( P = 0.018 ) , an increase in LPL activity ( p < 0.01 ) . CONCLUSION These findings suggest a glucose-lowering effect of curcuminoids in type 2 diabetes , which is partially due to decrease in serum FFAs , which may result from promoting fatty acid oxidation and utilization 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 compare the safety and efficacy of the dipeptidylpeptidase-4 ( DPP-4 ) inhibitors in patients with type 2 diabetes and inadequate glycemic control . Design Systematic review of r and omized controlled trials ( RCTs ) , health economic evaluation studies , systematic review s , and meta-analyses , followed by primary Bayesian mixed treatment comparison meta-analyses ( MTCs ) , and secondary frequentist direct-comparison meta-analyses using a r and om-effects model . Outcomes were reported as weighted mean change from baseline , or odds ratio ( OR ) with 95 % credible interval . Data sources MEDLINE , MEDLINE In-Process , EMBASE , and BIOSIS via Dialog ProQuest ; Cochrane Central Register of Controlled Trials and Cochrane Data base of Systematic Review s via EBSCO ; four diabetes and two technical congress abstract s ; and health technology assessment organization websites . Eligibility criteria Patients with type 2 diabetes and inadequate glycemic control receiving any pharmacological anti-diabetic treatment . Data extraction and analysis Title/ abstract s were review ed for eligibility , followed by full-text review of publications remaining after first pass . A three-person team filtered articles and an independent review er checked a r and om selection ( 10 % ) of filtered articles . Data extraction and quality assessment of studies were also independently review ed . Five DPP-4 inhibitors ( alogliptin , linagliptin , saxagliptin , sitagliptin , and vildagliptin ) were compared via meta- analysis ( where data were available ) as monotherapy , dual therapy ( plus metformin , sulfonylurea , pioglitazone , or insulin ) , and triple therapy ( plus metformin/sulfonylurea ) . Results The review identified 6,601 articles ; 163 met inclusion criteria and 85 publications from 83 RCTs contained sufficient or appropriate data for analysis . MTCs demonstrated no differences between DPP-4 inhibitors in mean change from baseline in glycosylated hemoglobin ( HbA1c ) or body weight , or the proportions of patients achieving HbA1c < 7 % or experiencing a hypoglycemic event , apart from in patients on alogliptin plus metformin , who achieved HbA1c < 7 % more frequently than those treated with saxagliptin plus metformin [ OR 6.41 ( 95 % CI 3.15–11.98 ) versus 2.17 ( 95 % CI 1.56–2.95 ) ] . Conclusions This systematic review and MTC showed similar efficacy and safety for DPP-4 inhibitors as treatment for type 2 diabetes , either as monotherapy or combination therapy Dyslipidemia is a leading risk factor for cardiovascular disease and is also a common feature of obesity . Curcumin is a bioactive phytochemical with well-known antioxidant , anti-inflammatory , and cardioprotective properties . The present study investigated the hypolipidemic activity of curcumin in obese individuals . Participants ( n = 30 ) were treated with curcuminoids ( 1 g/day ) , or placebo in a r and omized , double-blind , placebo-controlled , crossover trial . Serum concentrations of total cholesterol , triglycerides , low-density lipoprotein cholesterol and high-density lipoprotein cholesterol , together with anthropometric parameters and high-sensitivity C-reactive protein were measured before and after each treatment period . Anthropometric parameters including weight , BMI , waist circumference , hip circumference , arm circumference , and body fat remained statistically unchanged by the end of trial ( p > 0.05 ) . As for the lipid profile parameters , serum triglycerides were significantly reduced following curcumin supplementation ( p = 0.009 ) . However , curcuminoids were not found to affect serum levels of total cholesterol , low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , and high-sensitivity C-reactive protein ( p > 0.05 ) . In summary , the findings of the present study indicated that curcuminoid supplementation ( 1 g/day for 30 days ) leads to a significant reduction in serum triglycerides concentrations but do not have a significant influence on other lipid profile parameters as well as body mass index and body fat Background To improve quality of care and patient outcomes , health system decision-makers need to identify and implement effective interventions . An increasing number of systematic review s document the effects of quality improvement programs to assist decision-makers in developing new initiatives . However , limitations in the reporting of primary studies and current meta- analysis methods ( including approaches for exploring heterogeneity ) reduce the utility of existing syntheses for health system decision-makers . This study will explore the role of innovative meta- analysis approaches and the added value of enriched and up date d data for increasing the utility of systematic review s of complex interventions . Methods / Design We will use the data set from our recent systematic review of 142 r and omized trials of diabetes quality improvement programs  to evaluate novel approaches for exploring heterogeneity . These will include exploratory methods , such as multivariate meta-regression analyses and all-subsets combinatorial meta- analysis . We will then up date our systematic review to include new trials and enrich the data set by surveying authors of all included trials . In doing so , we will explore the impact of variables not , reported in previous publications , such as details of study context , on the effectiveness of the intervention . We will use innovative analytical methods on the enriched and up date d data set to identify key success factors in the implementation of  quality improvement interventions  for diabetes . Decision-makers will be involved throughout to help identify and prioritize variables to be explored and to aid in the interpretation and dissemination of results . Discussion This study will inform future systematic review s of complex interventions and describe the value of enriching and updating data for exploring heterogeneity in meta- analysis . It will also result in an up date d comprehensive systematic review of diabetes quality improvement interventions that will be useful to health system decision-makers in developing interventions to improve outcomes for people with diabetes . Systematic review registration PROSPERO registration no. SCOPE Curcuminoids are poorly bioavailable , but potentially lipid- and inflammation-lowering phytochemicals . We hypothesized that curcuminoids , when administered as a micellar formulation with hundredfold enhanced bioavailability , decrease blood lipids and inflammation in subjects with moderately elevated cholesterol and C-reactive protein concentrations . METHODS AND RESULTS We carried out a r and omized , double-blind , crossover study ( 4-wk washout phase ) with 42 subjects consuming 294 mg curcuminoids per day ( as micelles ) or placebo for 6 wk . At the beginning , after 3 wk and at the end ( 6 wk ) of each intervention , we collected fasting blood sample s to determine curcuminoids , blood lipids , and markers of inflammation , glucose and iron homeostasis , and liver toxicity . Daily ingestion of 98 mg micellar curcuminoids with each principal meal for as little as 3 wk result ed in fasting curcuminoid plasma concentrations of 49 nmol/L. Neither blood lipids , nor markers of inflammation , glucose and iron homeostasis , or liver enzymes differed between curcuminoid and placebo interventions . CONCLUSION Consumption of 98 mg of highly bioavailable curcuminoids with each principal meal sufficed to achieve curcuminoid accumulation in the blood , was safe , and did not alter blood lipids , inflammation , glucose , or iron homeostasis in healthy subjects with slightly elevated blood cholesterol and C-reactive protein OBJECTIVES To survey the frequency of use of indirect comparisons in systematic review s and evaluate the methods used in their analysis and interpretation . Also to identify alternative statistical approaches for the analysis of indirect comparisons , to assess the properties of different statistical methods used for performing indirect comparisons and to compare direct and indirect estimates of the same effects within review s. DATA SOURCES Electronic data bases . REVIEW METHODS The Data base of Abstract s of Review s of Effects ( DARE ) was search ed for systematic review s involving meta- analysis of r and omised controlled trials ( RCTs ) that reported both direct and indirect comparisons , or indirect comparisons alone . A systematic review of MEDLINE and other data bases was carried out to identify published methods for analysing indirect comparisons . Study design s were created using data from the International Stroke Trial . R and om sample s of patients receiving aspirin , heparin or placebo in 16 centres were used to create meta-analyses , with half of the trials comparing aspirin and placebo and half heparin and placebo . Methods for indirect comparisons were used to estimate the contrast between aspirin  and  heparin . The whole process was repeated 1000 times and the results were compared with direct comparisons and also theoretical results . Further detailed case studies comparing the results from both direct and indirect comparisons of the same effects were undertaken . RESULTS Of the review s identified through DARE , 31/327 ( 9.5 % ) included indirect comparisons . A further five review s including indirect comparisons were identified through electronic search ing . Few review s carried out a formal analysis and some based analysis on the naive addition of data from the treatment arms of interest . Few method ological papers were identified . Some valid approaches for aggregate data that could be applied using st and ard software were found : the adjusted indirect comparison , meta-regression and , for binary data only , multiple logistic regression ( fixed effect models only ) . Simulation studies showed that the naive method is liable to bias and also produces over-precise answers . Several methods provide correct answers if strong but unverifiable assumptions are fulfilled . Four times as many similarly sized trials are needed for the indirect approach to have the same power as directly r and omised comparisons . Detailed case studies comparing direct and indirect comparisons of the same effect show considerable statistical discrepancies , but the direction of such discrepancy is unpredictable . CONCLUSIONS Direct evidence from good- quality RCTs should be used wherever possible . Without this evidence , it may be necessary to look for indirect comparisons from RCTs . However , the results may be susceptible to bias . When making indirect comparisons within a systematic review , an adjusted indirect comparison method should ideally be used employing the r and om effects model . If both direct and indirect comparisons are possible within a review , it is recommended that these be done separately before considering whether to pool data . There is a need to evaluate methods for the analysis of indirect comparisons for continuous data and for empirical research into how different methods of indirect comparison perform in cases where there is a large treatment effect . Further study is needed into when it is appropriate to look at indirect comparisons and when to combine both direct and indirect comparisons . Research into how evidence from indirect comparisons compares to that from non-r and omised studies may also be warranted . Investigations using individual patient data from a meta- analysis of several RCTs using different protocol s and an evaluation of the impact of choosing different binary effect measures for the inverse variance method would also be useful Background The risk of developing cardiovascular disease is directly correlated to one ’s resting blood pressure ( BP ) , age , and biological sex . Resting BP can be reduced using h and grip exercise training , but the impact of age and sex on the effectiveness of training is not well documented . Methods / design A systematic search of the literature will be conducted for all experimental studies ( including r and omized controlled trials and prospect i ve experiments ) that report the influence of isometric h and grip exercise training on resting systolic blood pressure . The data bases Medline , Embase , Cochrane Review s , Cumulative Index to Nursing and Allied Health Literature ( CINAHL ) , SPORTD iscus , Web of Science , Allied and Complementary Medicine ( AMED ) , PubMed , and Scopus will be search ed until 1 December 2015 . Screening of potential articles , data abstract ion , and quality appraisal will be completed in duplicate independently . When necessary , corresponding authors will be contacted in order to facilitate the separation of pooled data into age and sex categories . Method ological quality will be determined using the Quality Assessment Framework developed by the Cochrane Collaboration and the Newcastle-Ottawa Quality Assessment Scale as appropriate . Any discrepancies will be resolved by a third author . Findings will be presented in accordance with the preferred reporting items for systematic review s and meta- analysis ( PRISMA ) guidelines . Discussion This systematic review will determine the overall effectiveness  of h and grip exercise training in improving resting blood pressure . A novel , focused assessment will contrast  effectiveness of h and grip training  based on the age ( younger 18–54 years , older > 55 years ) and the sex ( men , women ) of study participants . This information is essential to consoli date before moving forward with the development and implementation of h and grip exercise training programmes which are design ed to best meet the needs of particular cohorts . Systematic review registration PROSPERO ABSTRACT Oxidative stress is implicated in the pathogenesis of osteoarthritis .  Curcuminoids are natural polyphenols with strong antioxidant capacity and may thus be helpful in the treatment of osteoarthritis . The present r and omized double-blind placebo-controlled trial investigated the efficacy of curcuminoids in reducing systemic oxidative burden in patients suffering from knee osteoarthritis . Forty patients with mild-to-moderate primary knee osteoarthritis were given curcuminoid capsules ( 1500 mg/day in 3 divided doses ; n = 19 ) or matched placebo capsules ( n = 21 ) for a period of 6 weeks . Curcuminoids were co-administered with piperine ( 15 mg/day ) in order to improve the bioavailability . Serum activities of superoxide dismutase ( SOD ) and concentrations of reduced glutathione ( GSH ) and malonedialdehyde ( MDA ) were determined spectrophotometrically at baseline and at the end of the treatment period in both groups . Serum activities of SOD as well as GSH and MDA concentrations were comparable between the study groups at baseline ( p > 0.05 ) . There was a significant elevation in serum SOD activities ( mean change : 2.94 ± 3.73 vs. −0.38 ± 1.33 ; p < 0.001 ) , a borderline significant elevation in GSH concentrations ( mean change : 1.39 ± 2.78 vs. −0.02 ± 1.62 ; p = 0.064 ) and a significant reduction in MDA concentrations ( mean change : −5.26 ± 4.46 vs. −2.49 ± 3.81 ; p = 0.044 ) in the curcuminoids compared with the placebo group . Changes in serum activities of SOD and concentrations of GSH and MDA during the course of trial were significantly correlated . Short-term supplementation with curcuminoids  attenuates systemic oxidative stress in patients with osteoarthritis . These antioxidant effects may account for the reported therapeutic effects of curcuminoids in relieving osteoarthritis symptoms 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 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 Chronic obstructive pulmonary disease ( COPD ) remains a significant public health burden . Non-invasive ventilation ( NIV ) is a method of supported breathing used as st and ard care for acutely unwell patients in hospital with COPD , but there is uncertainty around the potential benefits of using NIV in the treatment of stable patients in a non-hospital setting . This is a protocol for systematic review s of the clinical and cost-effectiveness of NIV in this context , being undertaken in support of a model based economic evaluation . Methods / Design St and ard systematic review methods aim ed at minimising bias will be employed for study identification , selection and data extraction for both the clinical and economic systematic review s. Bibliographic data bases ( for example MEDLINE , EMBASE ) and ongoing trials registers will be search ed from 1980 onwards . The search strategy will combine terms for the population with those for the intervention . Studies will be selected for review if the population includes adult patients with COPD and hypercapnic respiratory failure , however defined . Systematic review s , r and omised controlled trials and observational studies ( with n > 1 ) will be included , and quality assessment will be tailored to the different study design s. The primary outcome measures of interest are survival , quality of life , and healthcare utilisations ( hospitalisation and Accident and Emergency attendances ) . Meta-analyses will be undertaken where clinical and method ological homogeneity exists , supported by predefined subgroup analyses where appropriate . A systematic review of the evidence on the cost-effectiveness of non-hospital NIV will be completed , and a model-based cost-utility analysis undertaken to determine the cost-effectiveness of non-hospital-based NIV compared with st and ard care . Discussion These review s will attempt to clarify the clinical effectiveness of non-hospital NIV in COPD patients as well as the cost-effectiveness . The findings may indicate whether NIV in a non-hospital setting should be considered more routinely in this patient group , and what the likely cost implication s will be . PROSPERO registration 2012:CRD42012003286 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 OBJECTIVES The objective of this review was to assess the effectiveness of interventions that assist caregivers to provide support for people living with dementia in the community . INCLUSION CRITERIA Types of participants Adult caregivers who provide support for people with dementia living in the community ( non-institutional care).Types of interventions Interventions design ed to support caregivers in their role such as skills training , education to assist in caring for a person living with dementia and support groups/programs . Interventions of formal approaches to care design ed to support caregivers in their role , care planning , case management and specially design ated members of the healthcare team - for example dementia nurse specialist or volunteers trained in caring for someone with dementia . Types of studies This review considered any meta-analyses , systematic review s , r and omised control trials , quasi-experimental studies , cohort studies , case control studies and observational studies without control groups that addressed the effectiveness of interventions that assist caregivers to provide support for people living with dementia in the community . SEARCH STRATEGY The search sought to identify published studies from 2000 to 2005 through the use of electronic data bases . Only studies in English were considered for inclusion . The initial search was conducted of the data bases , CINAHL , MEDLINE and PsychINFO using search strategies adapted from the Cochrane Dementia and Cognitive Improvement Group . A second more extensive search was then conducted using the appropriate Medical Subject Headings ( MeSH ) and keywords for other available data bases . Finally , h and search ing of reference lists of articles retrieved and of core dementia , geriatric and psycho geriatric journals was undertaken . ASSESSMENT OF QUALITY Method ological quality of each of the articles was assessed by two independent review ers using appraisal checklist developed by the Joanna Briggs Institute and based on the work of the Cochrane Collaboration and Centre for Review s and Dissemination . DATA COLLECTION AND ANALYSIS St and ardised mean differences or weighted mean differences and their 95 % confidence intervals were calculated for each included study reported in the meta- analysis . Results from comparable groups of studies were pooled in statistical meta- analysis using Review Manager Software from the Cochrane Collaboration . Heterogeneity between combined studies was tested using st and ard chi-square test . Where statistical pooling was not appropriate or possible , the findings are summarised in narrative form . RESULTS A comprehensive search of relevant data bases , h and search ing and cross referencing found 685 articles that were assessed for relevance to the review . Eighty-five papers appeared to meet the inclusion criteria based on title and abstract , and the full paper was retrieved . Of the 85 full papers review ed , 40 were accepted for inclusion , three were systematic review s , three were meta- analysis , and the remaining 34 were r and omised controlled trials . For the r and omised controlled trials that were able to be included in a meta- analysis , st and ardised mean differences or weighted mean differences and their 95 % confidence intervals were calculated for each . Results from comparable groups of studies were pooled in statistical meta- analysis using Review Manager Software and heterogeneity between combined studies was assessed by using the chi-square test . Where statistical pooling was not appropriate or possible , the findings are summarised in narrative form . The results are discussed in two main sections . Firstly it was possible to assess the effectiveness of different types of caregiver interventions on the outcome categories of depression , health , subjective well-being , self-efficacy and burden . Secondly , results are reported by main outcome category . For each of these sections , meta- analysis was conducted where it was possible ; otherwise , a narrative summary describes the findings . EFFECTIVENESS OF INTERVENTION TYPE Four categories of intervention were included in the review - psycho-educational , support , multi-component and other . Psycho-educational Thirteen studies used  psycho-educational interventions  , and all but one showed positive results across a range of outcomes . Eight studies were entered in a meta- analysis . No significant impact of psycho-educational interventions was found for the outcome categories of subjective well-being , self-efficacy or health . However , small but significant results were found for the categories of depression and burden . Support Seven studies discussed support only interventions and two of these showed significant results . These two studies were suitable for meta- analysis and demonstrated a small but significant improvement on caregiver burden . Multi-component Twelve of the studies report multi-component interventions and 10 of these report significant outcomes across a broad range of outcome measures including self-efficacy , depression , subjective well-being and burden . Unfortunately because of the heterogeneity of study design s and outcome measures , no meta- analysis was possible . Other interventions Other interventions included the use of exercise or nutrition which result ed in improvements in psychological distress and health benefits . Case management and a computer aided support intervention provided mixed results . One cognitive behavioural therapy study reported a reduction in anxiety and positive impacts on patient behaviour . EFFECTIVENESS OF INTERVENTIONS USING SPECIFIC OUTCOME CATEGORIES In addition to analysis by type of intervention it was possible to analyse results based on some outcome categories that were used across the studies . In particular the impact of interventions on caregiver depression was available for meta- analysis from eight studies . This indicated that multi-component and psycho-educational interventions showed a small but significant positive effect on caregiver depression . Five studies using the outcome category of caregiver burden  were entered into a meta- analysis and findings indicated that there were no significant effects of any of interventions . No meta- analysis was possible for the outcome categories of health , self-efficacy or subjective well-being . IMPLICATION S FOR PRACTICE From this review there is evidence to support the use of well- design ed psycho-educational or multi-component interventions for caregivers of people with dementia who live in the community . Factors that appear to positively contribute to effective interventions are those which : Factors which do not appear to have benefit in interventions are those which Objective To examine the prevalence of outcome reporting bias — the selection for publication of a subset of the original recorded outcome variables on the basis of the results — and its impact on Cochrane review s. Design A nine point classification system for missing outcome data in r and omised trials was developed and applied to the trials assessed in a large , unselected cohort of Cochrane systematic review s. Research ers who conducted the trials were contacted and the reason sought for the non-reporting of data . A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on review s that included a single meta- analysis of the review primary outcome . Results More than half ( 157/283 ( 55 % ) ) the review s did not include full data for the review primary outcome of interest from all eligible trials . The median amount of review outcome data missing for any reason was 10 % , whereas 50 % or more of the potential data were missing in 70 ( 25 % ) review s. It was clear from the publications for 155 ( 6 % ) of the 2486 assessable trials that the research ers had measured and analysed the review primary outcome but did not report or only partially reported the results . For reports that did not mention the review primary outcome , our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88 % ( 95 % CI 65 % to 100 % ) and specificity of 80 % ( 95 % CI 69 % to 90 % ) on the basis of responses from 62 trialists . A third of Cochrane review s ( 96/283 ( 34 % ) ) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome . In a sensitivity analysis undertaken for 81 review s with a single meta- analysis of the primary outcome of interest , the treatment effect estimate was reduced by 20 % or more in 19 ( 23 % ) . Of the 42 meta-analyses with a statistically significant result only , eight ( 19 % ) became non-significant after adjustment for outcome reporting bias and 11 ( 26 % ) would have overestimated the treatment effect by 20 % or more . Conclusions Outcome reporting bias is an under-recognised problem that affects the conclusions in a substantial proportion of Cochrane review s. Individuals conducting systematic review s need to address explicitly the issue of missing outcome data for their review to be considered a reliable source of evidence . Extra care is required during data extraction , review ers should identify when a trial reports that an outcome was measured but no results were reported or events observed , and contact with trialists should be encouraged
The effects of curcuminoids on lipids were not found to be dependent on the duration of supplementation .
Conclusion : This meta- analysis has shown that curcuminoid therapy significantly reduces plasma triglycerides and increases HDL-C levels
ABSTRACT Objective : The aim of this systematic review and meta- analysis was to determine and clarify the impact of curcuminoids on  serum lipid levels .