Avoidable waste of research related to outcome planning and reporting in clinical trials A simplified search strategy for identifying randomised controlled trials for systematic reviews of health care interventions: a comparison with more exhaustive strategies Mineral Trioxide Aggregate vs. Calcium Hydroxide in Primary Molar Pulpotomy: A Systematic Review Sources of evidence for systematic reviews of interventions in diabetes. Common statistical errors in the design and analysis of subfertility trials. Efficacy of vitamin D supplementation in depression in adults: a systematic review protocol A systematic appraisal of allegiance effect in randomized controlled trials of psychotherapy Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Disease Risk in Adults: Synopsis of the 2013 American College of Cardiology/American Heart Association Cholesterol Guideline Comparative Effectiveness of Dipeptidylpeptidase-4 Inhibitors in Type 2 Diabetes: A Systematic Review and Mixed Treatment Comparison Effectiveness of workplace interventions in rehabilitating musculoskeletal disorders and preventing its consequences among workers with physical and sedentary employment: systematic review protocol Reporting trends of randomised controlled trials in heart failure with preserved ejection fraction: a systematic review Dietetic guidelines: diet in secondary prevention of cardiovascular disease. Poor Reliability between Cochrane Reviewers and Blinded External Reviewers When Applying the Cochrane Risk of Bias Tool in Physical Therapy Trials Cluster Randomised Trials in Cochrane Reviews: Evaluation of Methodological and Reporting Practice Effects of pravastatin and rosuvastatin on the generation of adiponectin in the visceral adipose tissue in patients with coronary artery disease. What are the most effective behaviour change techniques to promote physical activity and/or reduce sedentary behaviour in inactive adults? A systematic review protocol Community pharmacy interventions for public health priorities: protocol for a systematic review of community pharmacy-delivered smoking, alcohol and weight management interventions How to write an evidence-based clinical review article. Protocol for a systematic review of psychological interventions for cancer-related fatigue in post-treatment cancer survivors Preoperative or postoperative therapy for resectable oesophageal cancer: an updated practice guideline. Systemic therapy in the curative treatment of head-and-neck squamous cell cancer: Cancer Care Ontario clinical practice guideline. Examining the theory‐effectiveness hypothesis: A systematic review of systematic reviews The Effectiveness of Psychosocial Interventions as Adjuncts to Orthopaedic Surgery: A Systematic Review Protocol
Background Inadequate planning , selective reporting , and incomplete reporting of outcomes in r and omized controlled trials ( RCTs ) contribute to the problem of waste of research . We aim ed to describe such a waste and to examine to what extent this waste could be avoided . Methods This research -on- research study was based on RCTs included in Cochrane review s with a summary of findings ( SoF ) table . We considered the outcomes reported in the SoF tables as surrogates for important outcomes for patients and other decision makers . We used a three-step approach . ( 1 ) First , in each review , we identified , for each important outcome , RCTs that were excluded from the corresponding meta- analysis . ( 2 ) Then , for these RCTs , we systematic ally search ed for registration s and protocol s to distinguish between inadequate planning ( an important outcome was not reported in registries or protocol s ) , selective reporting ( an important outcome was reported in registries or protocol s but not in publications ) , and incomplete reporting ( an important outcome was incompletely reported in publications ) . ( 3 ) Finally , we assessed , with the consensus of five experts , the feasibility and cost of measuring the important outcomes that were not planned . We considered inadequately planned or selectively or incompletely reported important outcomes as avoidable waste if the outcome could have been easily measured at no additional cost based on expert evaluation . Results Of the 2711 RCTs included in the main comparison of 290 review s , 2115 ( 78 % ) were excluded from at least one meta- analysis of important outcomes . Every trial contributed to 55 % , on average , of the meta-analyses of important outcomes . Of the 310 RCTs published in 2010 or later , 156 were registered . Inadequate planning affected 79 % of these RCTs , whereas incomplete and selective reporting affected 41 % and 15 % , respectively . For 63 % of RCTs , we found at least one missing important outcome for which the waste was avoidable and for 30 % , the waste was avoidable for all important outcomes . Conclusions Most of the RCTs included in our sample did not contribute to all the important outcomes in meta-analyses , mostly because of inadequate planning or incomplete reporting . A large part of this waste of research seemed to be avoidable Background It is generally believed that exhaustive search es of bibliographic data bases are needed for systematic review s of health care interventions . The CENTRAL data base of controlled trials ( RCTs ) has been built up by exhaustive search ing . The CONSORT statement aims to encourage better reporting , and hence indexing , of RCTs . Our aim was to assess whether developments in the CENTRAL data base , and the CONSORT statement , mean that a simplified RCT search strategy for identifying RCTs now suffices for systematic review s of health care interventions . Methods RCTs used in the Cochrane review s were identified . A brief RCT search strategy ( BRSS ) , consisting of a search of CENTRAL , and then for variants of the word r and om across all fields ( r and om$.af . ) in MEDLINE and EMBASE , was devised and run . Any trials included in the meta-analyses , but missed by the BRSS , were identified . The meta-analyses were then re-run , with and without the missed RCTs , and the differences quantified . The proportion of trials with variants of the word r and om in the title or abstract was calculated for each year . The number of RCTs retrieved by search ing with " r and om$.af . " was compared to the highly sensitive search strategy ( HSSS ) . Results The BRSS had a sensitivity of 94 % . It found all journal RCTs in 47 of the 57 review s. The missing RCTs made some significant differences to a small proportion of the total outcomes in only five review s , but no important differences in conclusions result ed . In the post-CONSORT years , 1997–2003 , the percentage of RCTs with r and om in the title or abstract was 85 % , a mean increase of 17 % compared to the seven years pre-CONSORT ( 95 % CI , 8.3 % to 25.9 % ) . The search using r and om$.af . reduced the MEDLINE retrieval by 84 % , compared to the HSSS , thereby reducing the workload of checking retrievals . Conclusion A brief RCT search strategy is now sufficient to locate RCTs for systematic review s in most cases . Exhaustive search ing is no longer cost-effective , because in effect it has already been done for CENTRAL Introduction : The aim of this quantitative systematic review /meta- analysis was to compare the treatment outcomes of mineral trioxide aggregate ( MTA ) and calcium hydroxide ( CH ) in pulpotomy of human primary molars . The focused PICO question was “ in case of pulp exposure in vital primary molars , how does MTA pulpotomy compare to CH in terms of clinical /radiographic success ? ” Methods and Material s : We retrieved published r and omized clinical trials ( RCTs ) of at least 6-month duration ; our search included articles published up to March 2013 in five following data bases : PubMed ( Medline ) , Cochrane data base of systematic review s , Science Citation Index , EMBASE , and Google Scholar . Mantel Haenszel and Inverse Variance-weighted methods were applied by STATA ; the relative risk ( RR ) was calculated with 95 % confidence intervals ( CI ) . Results : A total of 282 English articles were collected . Two authors independently screened the articles and five RCTs were selected ; data extraction and quality assessment were then carried out . Four RCTs were appropriate for meta- analysis according to their follow-up times by Mantel Haenszel method . Statistically significant difference was found between success rate of MTA compared to CH , with RR=0.08 ( 95 % CI , 0.02 - 0.39 ) , RR=0.19 ( 95 % CI , 0.08 - 0.46 ) , and RR=0.38 ( 95 % CI , 0.21 - 0.68 ) for 6- , 12- , and 24-month follow-ups , respectively . A significant difference was also observed for all included RCTs after analyses using the Inverse Variance-weighted method ( RR=0.44 ; 95 % CI , 0.27 - 0.72 ) . Conclusions : Systematic review /meta- analysis of included RCTs revealed that for pulpotomy of vital primary molars , MTA has better treatment outcomes compared to CH 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 The quality of clinical trials has received increasing attention with the growth of evidence -based medicine and systematic review s. We aim ed to identify whether errors and omissions commonly encountered when undertaking Cochrane review s in this field are still passing peer review . METHODS We undertook a review of trials published in 2001 by two major journals . We selected from Medline only trials in which authors compared pregnancy rates under two interventions by allocating women to different groups . RESULTS We identified 39 trials meeting our criteria . Six trials were fatally flawed by design , either by inappropriate use of a cross-over design or by systematic allocation described by the authors as ' r and om ' . Only six reports cl aim ed to apply the intention-to-treat principle , and the principle was misunderstood by four of these . Only five trials reported live birth rates sufficiently to allow valid meta- analysis . Most trials ( 82 % ) included at least one ' unit of analysis ' error . CONCLUSIONS We selected simple trials from respected journals , assuming that our sample would represent trials of highest method ological quality in the field . Nevertheless , the st and ards of design , analysis and reporting of many subfertility trials are not sufficient to allow reliable interpretation of results , or inclusion in meta-analyses 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 Background Experimenter ’s allegiance ( EA ) refers to a personal confidence of the superiority of a specific psychotherapy treatment . This factor has been linked with larger treatment effects in favor of the preferred treatment . However , various studies have displayed contradictory results between EA and the pattern of treatment effects . Aims Using a systematic approach followed by meta- analysis , we aim ed to evaluate the impact of an allegiance effect on the results of psychotherapeutic studies . Method We considered the meta-analyses of r and omized controlled trials ( RCTs ) of different types of psychotherapies in the Cochrane Data base of Systematic Review s. Eligible articles included meta-analyses of RCTs with at least one study showing evidence of EA ( i.e. , allegiant study ) . Effect sizes in allegiant RCTs were compared with non-allegiant using r and om and fixed models and a summary relative odds ratio ( ROR ) were calculated . Heterogeneity was quantified with the I2 metric . Results A total of 30 meta-analyses including 240 RCTs were analyzed . The summary ROR was 1.31 [ ( 95 % confidence interval ( CI : 1.03–1.66 ) P = 0.30 , I2 = 53 % ] indicating larger effects when allegiance exists . The impact of allegiance did not differ significantly ( P > 0.05 ) when we compared psychiatric versus medical outcomes . Allegiance effect was significant for all forms of psychotherapy except for cognitive behavioral therapy . Moreover , the impact of allegiance was significant only when the treatment integrity of delivered psychotherapy was not assessed . Allegiance effect was even stronger where the experimenter was also both the developer of the preferred treatment and supervised or trained the therapists . No significant differences were found between allegiant and non-allegiant studies in terms of overall quality of studies . Conclusions Experimenter ’s allegiance influences the effect sizes of psychotherapy RCTs and can be considered non-financial conflict of interest introducing a form of optimism bias , especially since blinding is problematic in this kind of research . A clear reporting of EA in every single study should be given an opportunity to investigators of minimizing its overestimation effects Atherosclerotic cardiovascular disease ( ASCVD ) is the leading cause of death , decreased quality of life , and medical costs in the United States . Nearly 1 in 3 Americans die of heart disease and stroke ( 1 ) . Most ASCVD is preventable through a healthy lifestyle and effective treatment of cholesterol and blood pressure . The 2013 Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults from the American College of Cardiology and American Heart Association ( ACC/AHA ) provides an evidence -based approach to reducing ASCVD risk ( 2 ) . Guideline Development Process In 2008 , the National Heart , Lung , and Blood Institute ( NHLBI ) convened the Adult Treatment Panel ( ATP ) IV to up date the 2001 ATP-III cholesterol guidelines using a rigorous systematic process to identify and review r and omized , controlled trials ( RCTs ) with cardiovascular outcomes and meta-analyses of these RCTs . The panel comprised experts and clinicians from the fields of cardiology , epidemiology , primary care , and endocrinology ( 2 ) and received support from the Lifestyle Management and Risk Assessment Work Groups ( 3 , 4 ) . Systematic evidence review s conducted according to principles recommended by the Institute of Medicine ( 5 ) were performed to answer 3 questions relevant to clinical care . Two questions focused on the evidence supporting low-density lipoprotein cholesterol ( LDL-C ) and nonhigh-density lipoprotein cholesterol ( HDL-C ) levels as targets of treatment . One question examined the reduction in ASCVD events and adverse effects for each cholesterol-lowering drug class . The panel synthesized the evidence from these 3 review s as well as from Lifestyle Management and Risk Assessment Work Groups review s ( 3 , 4 ) that addressed 5 additional critical questions . Systematic electronic search es of relevant data bases of the peer- review ed English- language literature published from 1 January 1995 through 1 December 2009 for each critical question were conducted by an NHLBI-selected independent contractor and focused on RCTs and systematic review s and meta-analyses of RCTs assessed as fair to good quality . In addition , RCTs with ASCVD outcomes that included coronary heart disease , stroke , and cardiovascular deaths published after that date were eligible for consideration through July 2013 . Evidence tables were constructed , and the strength of evidence was rated according to the NHLBI ( Table 1 of the Supplement ) . Recommendations were grade d according to criteria from the NHLBI ( Table 2 of the Supplement ) and ACC/AHA ( Table 3 of the Supplement ) . Because of the inherent differences in grading systems and the clinical questions driving the recommendations , alignment between the NHLBI and ACC/AHA formats was imperfect . A complete description of the methods used and results of the evidence review are provided in the guideline ( 2 ) and the NHLBI evidence report ( www.nhlbi.nih.gov/ guidelines /cholesterol/ser/index.htm ) . Supplement . NHLBI and ACC/AHA Criteria for Rating Strength of Evidence To help clinicians estimate ASCVD risk , the risk assessment working group developed the Pooled Cohort Equations using data from 5 NHLBI-sponsored longitudinal , population -based cohorts of African American and non-Hispanic white men and women to estimate risk for a first myocardial infa rct ion , coronary heart disease death , or fatal or nonfatal stroke on the basis of age , sex , race , smoking status , total cholesterol level , HDL-C level , systolic blood pressure , antihypertensive therapy , and diabetes ( 4 , 6 ) . These equations significantly advance ASCVD risk estimation by providing sex- and race-specific estimates and including stroke as an outcome . The earlier Framingham equations calculated only coronary heart disease risk for non-Hispanic whites . The draft recommendations were review ed by 23 experts and representatives of federal agencies identified by the NHLBI . In September 2013 , the recommendations developed by the panel were transitioned to the ACC/AHA and had additional review by 4 experts nominated by the ACC Foundation and the AHA . The governing bodies of the ACC and AHA approved the guideline , which also received endorsement from the American Association of Cardiovascular and Pulmonary Rehabilitation , American Pharmacists Association , American Society for Preventive Cardiology , Association of Black Cardiologists , Preventive Cardiovascular Nurses Association , and WomenHeart : The National Coalition for Women with Heart Disease . Recommendations The guideline focuses on treatment of blood cholesterol to reduce ASCVD risk in adults . Major recommendations are summarized here and in Table 1 . The guideline report provides a complete listing of recommendations and supporting evidence behind each recommendation ( 2 ) . Table 1 . Major Recommendations for the Treatment of Blood Cholesterol to Reduce ASCVD Risk in Adults * 1 . Encourage Adherence to a Healthy Lifestyle A healthy lifestyle is the foundation for cardiovascular health . The panel endorsed the 2013 ACC/AHA Lifestyle Management Guideline ( 3 ) for a diet that is low in saturated fat , trans fat , and sodium ; emphasizes vegetables , fruits , whole grains , low-fat dairy products , poultry , fish , legumes , nontropical vegetable oils , and nuts ; and limits sweets , sugar-sweetened beverages , and red meats and engage in regular aerobic physical activity . Adults also should maintain a healthy body weight , avoid smoking , and control hypertension and diabetes when present . 2 . Statin Therapy Is Recommended for Adults in Groups Demonstrated to Benefit Strong RCT evidence shows that reduction in ASCVD events from statin therapy exceeds adverse events for 4 patient groups : those with clinical ASCVD ( acute coronary syndromes , myocardial infa rct ion , stable angina , coronary or other arterial revascularization , stroke , transient ischemic attack , or peripheral arterial disease of atherosclerotic origin ) when  statins are used for secondary prevention , and those with LDL-C levels 190 mg/dL ; those aged 40 to 75 years with diabetes and LDL-C levels 70 to 189 mg/dL ; and those aged 40 to 75 years without diabetes and with a 10-year ASCVD risk 7.5 % when statins are used for primary prevention . Moderate evidence supports consideration of statin therapy for primary prevention in individuals with a 10-year ASCVD risk of 5 % to < 7.5 % . Routine initiation of statin therapy is not recommended in adults with New York Heart Association heart failure class II to IV or those receiving maintenance hemodialysis . R and omized , controlled trials in these groups showed no reduction in ASCVD . 3 . Statins have an Acceptable Margin of Safety When Used in Properly Selected Individuals and Appropriately Monitored Strong RCT evidence supports safety of statins when they are used as directed in conjunction with regular follow-up assessment s in properly selected patients . Adjustment of statin intensity is recommended in individuals older than 75 years with a history of statin intolerance or other characteristics ( 2 ) or those receiving drug therapy that may increase statin adverse events . Routine monitoring of hepatic aminotransferase level or creatine kinase level is not recommended unless clinical ly indicated by symptoms suggesting hepatotoxicity or myopathy . Given the potential for decreasing ASCVD events and death , the relationship of muscle and other symptoms to statin treatment must be confirmed . Therefore , eliciting a history of muscle symptoms before statin initiation and carefully monitoring symptoms during statin discontinuation and rechallenge is recommended . Severe myopathy , rhabdomyolysis , and possibly hemorrhagic stroke are rare complications of statin therapy . Although statin therapy modestly increases the risk for type 2 diabetes , ASCVD risk reduction outweighs the excess risk for diabetes for high-intensity statins in secondary prevention or for 10-year ASCVD risk 7.5 % . Similarly , ASCVD risk reduction outweighs the excess risk for diabetes for moderate-intensity statin therapy in adults with a 10-year ASCVD risk 5 % . 4 . Engage in a ClinicianPatient Discussion Before Initiating Statin Therapy , Especially for Primary Prevention in Patients With Lower ASCVD Risk Decisions to initiate statin therapy in primary prevention should be based on clinical judgment and preferences of informed patients . In adults without clinical ASCVD or diabetes whose LDL-C level is < 190 mg/dL , calculating the estimated 10-year ASCVD risk should be the start of the clinicianpatient discussion and should not automatically lead to statin initiation . As the absolute risk for ASCVD events decreases , so does the net benefit of the intervention . Therefore , discussion of the potential for ASCVD event reduction , adverse effects , drugdrug interactions , and patient preferences is especially important for lower-risk primary prevention . The discussion provides the opportunity to encourage healthy lifestyle habits and control other risk factors . Additional factors may be considered when a risk-based decision is uncertain , including LDL-C levels 160 mg/dL , family history of premature ASCVD , elevated  lifetime ASCVD risk  , high-sensitivity C-reactive protein level 2.0 mg/L ,  coronary artery calcification score  > 300 Agatston units , and anklebrachial index < 0.9 . After age 75 years , comorbid conditions , anticipated longevity , safety considerations , and patient preferences should play a large role in decision making . 5 . Use the Newly Developed Pooled Cohort Equations for Estimating 10-Year ASCVD Risk The Pooled Cohort Equations are currently the best available method for estimating 10-year ASCVD risk to guide statin initiation ( 4 , 6 ) . Application of the inclusion and exclusion criteria from RCTs is cumbersome and results in underidentifying high-risk and overidentifying low-risk individuals for statin treatment . The Pooled Cohort Equations were developed using recent data from 5 NHLBI-sponsored , longitudinal , population -based cohorts of African American and white men and women ( ARIC [ 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 Background Musculoskeletal disorders ( MSDs ) are the leading cause of work disability and sickness absence worldwide . The prevalence of MSDs increases with age , consequently challenging sustainable employability among the growing ageing workforce . Knowledge of feasible and efficient workplace-based interventions to rehabilitate MSD or prevent its consequences is therefore warranted . This systematic review will evaluate the effectiveness of workplace-based interventions on MSDs and its consequences among adult workers with physical and sedentary work tasks , respectively . Methods We will search the following bibliographic data bases : PubMed ( including the data base ‘ MEDLINE ’ ) and Web of Science Core Collection ( including the data bases ‘ Science Citation Index Exp and ed ’ , ‘ Social Sciences Citation Index ’ and ‘ Arts & Humanities Citation Index ’ ) . Manual search es will also be performed . We will include r and omised controlled trials ( RCTs ) and non- RCTs reported in English in which ( 1 ) participants are adult workers with MSD , ( 2 ) interventions are aim ing at rehabilitating pain symptoms of MSD or preventing the consequences of MSD and ( 3 ) interventions are initiated and /or carried out at the workplace . The review will adhere to the ‘ Preferred Reporting Items for Systematic review s and Meta-Analyses ’ ( PRISMA ) guidelines for reporting systematic review s and the Institute for Work and Health ( IWH ) guidelines for workplace-based interventions . For the primary evaluation of the review , the quality assessment and evidence synthesis will conform to the IWH guidelines . Secondary evaluation will include a meta- analysis ( unless the included studies do not allow this due to heterogeneity ) and employ the risk of bias domains recommended by Cochrane along with the Grading of Recommendations , Assessment , Development and Evaluations ( GRADE ) approach on the studies with pain intensity as an outcome . Discussion This systematic review will provide knowledge on effective workplace-based interventions among physical and sedentary workers with MSD . RCTs are considered the most powerful experimental design in clinical trials , but solely including these may be too restrictive to underst and effective workplace-based interventions where r and omised and carefully controlled trials ( RCTs ) are not always possible . In order to maximize practical relevance , the selection process will , therefore , include both RCTs and non- RCTs and the quality assessment and evidence synthesis will conform to IWH guidelines focusing on developing practical guidelines for stakeholders . The result of this work will form the basis for industry-specific evidence -based recommendations on effective workplace-based interventions for rehabilitation of MSDs and its consequences that will later be operationalised into concrete and user-friendly practical tools for workplaces . Systematic review registration International Prospect i ve Register of Systematic Review s ( PROSPERO ) number CRD42018116752 Background Heart failure with preserved ejection fraction ( HFpEF ) causes significant cardiovascular morbidity and mortality . Current consensus guidelines reflect the neutral results from r and omised controlled trials ( RCTs ) . Adequate trial reporting is a fundamental requirement before concluding on RCT intervention efficacy and is necessary for accurate meta- analysis and to provide insight into future trial design . The Consoli date d St and ards of Reporting Trials ( CONSORT ) 2010 statement provides a framework for complete trial reporting . Reporting quality of HFpEF RCTs has not been previously assessed , and this represents an important validation of reporting qualities to date . Objectives The aim was to systematic ally identify RCTs investigating the efficacy of pharmacological therapies in HFpEF and to assess the quality of reporting using the CONSORT 2010 statement . Methods MEDLINE , EMBASE and CENTRAL data bases were search ed from January 1996 to November 2015 , with RCTs assessing pharmacological therapies on clinical outcomes in HFpEF patients included . The quality of reporting was assessed against the CONSORT 2010 checklist . Results A total of 33 RCTs were included . The mean CONSORT score was 55.4 % ( SD 17.2 % ) . The CONSORT score was strongly correlated with journal impact factor ( r=0.53 , p=0.003 ) and publication year ( r=0.50 , p=0.003 ) . Articles published after the introduction of CONSORT 2010 statement had a significantly higher mean score compared with those published before ( 64 % vs 50 % , p=0.02 ) . Conclusions Although the CONSORT score has increased with time , a significant proportion of HFpEF RCTs showed inadequate reporting st and ards . The level of adherence to CONSORT criteria could have an impact on the validity of trials and hence the interpretation of intervention efficacy . We recommend improving compliance with the CONSORT statement for future RCTs AIM To produce dietetic guidelines summarizing the systematic review evidence on dietary advice for secondary prevention of cardiovascular disease . METHODS The Cochrane Library , MEDLINE and EMBASE were comprehensively search ed for systematic review s on aspects of diet and heart health . Review s were included if they search ed systematic ally for r and omised controlled trials relating to diet and secondary prevention of cardiovascular disease . Two members of the UK Heart Health and Thoracic Dietitians Group critically appraised each review . The quality and results of each review were discussed and summarized in a whole group meeting . The guidelines were trialled in seven dietetic departments and modified where necessary . RESULTS Providing evidence -based dietary information ( including increasing omega-3 fat plus fruit and vegetable intake ) to all people after myocardial infa rct ion will save more lives than concentrating dietary advice on those in need of weight loss or lipid lowering . The practice of prioritizing dietetic time to those with raised lipids is out of date since the advent of statin therapy . CONCLUSION There is good systematic review evidence that dietary advice to those with cardiovascular disease can reduce mortality and morbidity as well as modify risk factors .  Dietary advice that does this most effectively should be prioritized Objectives To test the inter-rater reliability of the RoB tool applied to Physical Therapy ( PT ) trials by comparing ratings from Cochrane review authors with those of blinded external review ers . Methods R and omized controlled trials ( RCTs ) in PT were identified by search ing the Cochrane Data base of Systematic Review s for meta- analysis of PT interventions .  RoB assessment s were conducted independently by 2 review ers blinded to the RoB ratings reported in the Cochrane review s. Data on RoB assessment s from Cochrane review s and other characteristics of review s and trials were extracted . Consensus assessment s between the two review ers were then compared with the RoB ratings from the Cochrane review s. Agreement between Cochrane and blinded external review ers was assessed using weighted kappa ( κ ) . Results In total , 109 trials included in 17 Cochrane review s were assessed . Inter-rater reliability on the overall RoB assessment between Cochrane review authors and blinded external review ers was poor ( κ = 0.02 , 95%CI : −0.06 , 0.06 ] ) . Inter-rater reliability on individual domains of the RoB tool was poor ( median κ = 0.19 ) , ranging from κ = −0.04 ( “ Other bias ” ) to κ = 0.62 ( “ Sequence generation ” ) . There was also no agreement ( κ = −0.29 , 95%CI : −0.81 , 0.35 ] ) in the overall RoB assessment at the meta- analysis level . Conclusions Risk of bias assessment s of RCTs using the RoB tool are not consistent across different research groups . Poor agreement was not only demonstrated at the trial level but also at the meta- analysis level . Results have implication s for decision making since different recommendations can be reached depending on the group analyzing the evidence . Improved guidelines to consistently apply the RoB tool and revisions to the tool for different health areas are needed Objective Systematic review s can include cluster-r and omised controlled trials ( C- RCTs ) , which require different analysis compared with st and ard individual-r and omised controlled trials . However , it is not known whether review authors follow the method ological and reporting guidance when including these trials . The aim of this study was to assess the method ological and reporting practice of Cochrane review s that included C- RCTs against criteria developed from existing guidance . Methods Criteria were developed , based on method ological literature and personal experience supervising review production and quality . Criteria were grouped into four themes : identifying , reporting , assessing risk of bias , and analysing C- RCTs . The Cochrane Data base of Systematic Review s was search ed ( 2nd December 2013 ) , and the 50 most recent review s that included C- RCTs were retrieved . Each review was then assessed using the criteria . Results The 50 review s we identified were published by 26 Cochrane Review Groups between June 2013 and November 2013 . For identifying C- RCTs , only 56 % identified that C- RCTs were eligible for inclusion in the review in the eligibility criteria . For reporting C- RCTs , only eight ( 24 % ) of the 33 review s reported the method of cluster adjustment for their included C- RCTs . For assessing risk of bias , only one review assessed all five C- RCT -specific risk-of-bias criteria . For analysing C- RCTs , of the 27 review s that presented unadjusted data , only nine ( 33 % ) provided a warning that confidence intervals may be artificially narrow . Of the 34 review s that reported data from unadjusted C- RCTs , only 13 ( 38 % ) excluded the unadjusted results from the meta-analyses . Conclusions The method ological and reporting practice s in Cochrane review s incorporating C- RCTs could be greatly improved , particularly with regard to analyses . Criteria developed as part of the current study could be used by review authors or editors to identify errors and improve the quality of published systematic review s incorporating C- RCTs Pravastatin increases the plasma adiponectin level . We examined whether this is a statins ' class effect or specific to pravastatin . Of 50 patients undergoing cardiac surgery for coronary artery disease ( CAD , n = 36 ) and valvular heart disease ( VHD , n = 14 ) , 23 with CAD and serum LDL-cholesterol level > 100 mg/dL were r and omized  to pravastatin at 10 mg/day ( PRAVA , n = 12 ) or rosuvastatin at 2.5 mg/day ( ROSUVA , n = 11 ) for 2 months , and the other 13 with CAD and LDL-cholesterol ≤100 mg/dL were not treated with statin ( Non-statin , n = 13 ) . Patients with VHD did not have CAD and were not treated with statin . Blood was sample d at baseline and surgery . Visceral ( VIS ) and subcutaneous ( SC ) adipose tissues were harvested during surgery . At baseline , the plasma adiponectin level was low in patients with CAD compared with that of patients with VHD . At surgery , adiponectin level in PRAVA was increased to the level in VHD , whereas those in ROSUVA and Non-statin were unchanged . VIS contents and gene expressions of adiponectin in PRAVA and VHD were similar to each other and were both higher than those in Non-statin and ROSUVA . SC content and gene expression of adiponectin were similar among 4 groups . Protein carbonyl ( PC ) level , an indicator of oxidative stress , in VIS was lower in PRAVA and VHD than in ROSUVA and Non-statin . There was a negative correlation between the plasma adiponectin and VIS PC levels ( r = -0.41 , P < 0.05 ) . Thus , pravastatin  increases adiponectin generation , whereas rosuvastatin does not Introduction Large proportions of the population are not meeting recommended levels of physical activity and have increasingly sedentary lifestyles . Low levels of physical activity are predictive of poor health outcomes and time spent sedentary is related to a host of risk factors independently of physical activity levels . Building an evidence base of the best approaches to intervene in the lifestyles of inactive individuals is crucial in preventing long-term disease , disability and higher mortality rates . Methods and analysis Systematic search es will be conducted on all relevant data bases ( eg , PubMed , Scopus , CINAHL , PsycINFO ) . Studies will be included if they assess interventions aim ed at changing physical activity or sedentary behaviour levels in adults ( over 18 ) who are inactive and do not suffer from chronic conditions . Studies must also be r and omised controlled trials ( RCTs ) , have a primary outcome of physical activity or sedentary behaviour , and measure outcomes at least 6 months after intervention completion . Studies will be coded using the Behaviour Change Technique ( BCT ) taxonomy v1 and Template for Intervention Description and Replication ( TIDieR ) guidelines . 2 review ers will independently screen full-text articles and extract data on study characteristics , participants , BCTs , intervention features and outcome measures . Study quality will also be assessed independently by 2 review ers using the Cochrane risk of bias tool . A meta- analysis will be considered if there is sufficient homogeneity across outcomes . GRADE criteria will be used to assess quality of evidence . Dissemination This will be the first review to systematic ally appraise interventions aim ed at changing the physical activity or sedentary behaviour of inactive individuals using RCT design s with a 6-month follow-up post-intervention . This review will better inform intervention design ers targeting inactive population s and inform the design of a future complex intervention . Review registration number This protocol was registered with the International Prospect i ve Register of Systematic Review s ( PROSPERO ) on 17 October 2014 ( registration number : CRD42014014321 ) Background Community pharmacists can deliver health care advice at an opportunistic level , related to prescription or non-prescription medicines and as part of focused services design ed to reduce specific risks to health . Obesity , smoking and excessive alcohol intake are three of the most significant modifiable risk factors for morbidity and mortality in the UK , and interventions led by community pharmacists , aim ed at these three risk factors , have been identified by the government as public health priorities . In 2008 , the Department of Health for Engl and stated that ‘ a sound evidence base that demonstrates how pharmacy delivers effective , high quality and value for money services is needed ’ ; this systematic review aims to respond to this requirement . Methods / design We will search the data bases MEDLINE , Embase , CINAHL , PsycINFO , Social Sciences Citation Index , ASSIA , IBSS , Sociological Abstract s , Scopus and NHS Economic Evaluation Data base for studies that have evaluated interventions based on community pharmacies that aim to target weight management , smoking cessation and alcohol misuse . We will include all r and omised controlled trials ( RCTs ) , non-r and omised controlled trials ( N RCTs ) , controlled before-after studies ( CBAs ) and interrupted time series ( ITS ) and repeated measures studies . Data from included studies will be extracted by two independent review ers and will include study details methods , results , intervention implementation/costs and method ological quality . Meta- analysis will be conducted if appropriate ; if not , the synthesis will be restricted to a narrative overview of individual studies looking at the same question . Discussion The review aims to summarise the evidence base on the effectiveness of community pharmacy interventions on health and health behaviours in relation to weight management , smoking cessation and alcohol misuse . It will also explore if , and how , socio-economic status , gender , ethnicity and age moderate the effect of the interventions and will describe how the interventions included in the review have been organised , implemented and delivered , since context is an important factor governing the success of public health interventions . The findings from this review will have an impact on the commissioning of public health services aim ing to promote healthy weight , smoking cessation and prevent excessive alcohol consumption . Systematic review registration The review has been registered with PROSPERO ( registration no. CRD42013005943 ) . Available at : http://www.crd.york.ac.uk/ prospero /display_record.asp?ID = CRD42013005943 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 Fatigue is a common symptom in cancer patients that can persist beyond the curative treatment phase . Some evidence has been reported for interventions for fatigue during active treatment . However , to date , there is no systematic review on psychological interventions for fatigue after the completion of curative treatment for cancer . This is a protocol for a systematic review that aims to evaluate the effectiveness of psychological interventions for cancer-related fatigue in post-treatment cancer survivors . This systematic review protocol was registered with the International Prospect i ve Register of Systematic Review s ( PROSPERO ) data base . Methods / design We will search the Cochrane Central Register of Controlled Trials ( CENTRAL ; The Cochrane Library ) , PubMed , MEDLINE , EMBASE , CINAHL , PsycINFO , and relevant sources of grey literature . R and omised controlled trials ( RCTs ) which have evaluated psychological interventions in adult cancer patients after the completion of treatment , with fatigue as an outcome measure , will be included . Two review authors will independently extract data from the selected studies and assess the method ological quality using the Cochrane Collaboration Risk of Bias Tool . Discussion Most existing evidence on cancer-related fatigue is from those in active cancer treatment . This systematic review and meta- analysis will build upon previous evaluations of psychological interventions in people during and after cancer treatment . With the growing need for stage-specific research in cancer , this review seeks to highlight a gap in current practice and to strengthen the evidence base of r and omised controlled trials in the area . Systematic review registration PROSPERO CRD42014015219 AIMS Oesophageal cancer is an aggressive disease and the optimal therapy for patients with resectable tumours remains unclear . A systematic review and companion practice guideline were published in 2004 ; however , new evidence has become available since the publication of the original report . An up date of the literature search and a revision of the recommendations were undertaken to incorporate the new data . The following research question was addressed : should patients with resectable oesophageal cancer receive preoperative or postoperative therapy together with surgery ? The outcomes of interest were survival , adverse effects and quality of life . MATERIAL S AND METHODS The literature search of the original systematic review was up date d to April 2007 . MEDLINE , EMBASE , Cochrane Library and abstract s from the American Society of Clinical Oncology and the American Society for Therapeutic Radiology and Oncology were search ed for reports of r and omised controlled trials and meta-analyses comparing preoperative or postoperative therapy with surgery alone or other preoperative or postoperative therapy . After the completion of the draft systematic review and practice guideline , the report was distributed through a mailed survey to 133 health care providers in Ontario for review and feedback . RESULTS The up date d literature search yielded eight new r and omised controlled trial reports and seven new meta- analysis reports for consideration , together with the evidence review ed in the original review publication . Of the 31 practitioners who responded to the mailed survey , 80 % agreed with the draft recommendations as stated , 83 % agreed that the report should be approved as a practice guideline and 86 % indicated that they would probably use the guideline in their own practice . CONCLUSIONS Preoperative cisplatin-based chemotherapy plus radiotherapy is recommended as the preferred modality for the management of surgically resectable patients with oesophageal cancer .  Preoperative cisplatin-based chemotherapy alone is an alternative choice for the management of these patients OBJECTIVE The aim of the present work was to make recommendations about the use of systemically administered drugs in combination or in sequence with radiation ( rt ) or surgery , or both , for cure or organ preservation , or both , in patients with locally advanced nonmetastatic ( stages iii-ivb ) squamous cell carcinoma of the head and neck ( lascchn ) . METHODS The Meta- analysis of Chemotherapy in Head and Neck Cancer ( mach-nc ) reports have , de facto , guided practice since 2000 , and so we search ed the literature for systematic review s published from January 2000 to February 2015 in reference to five research questions . A search was also conducted up to February 2015 for r and omized trials ( rcts ) not included in the meta-analyses . Recommendations were constructed using the Cancer Care Ontario Program in Evidence -Based Care practice guidelines development cycle . RESULTS In addition to up date d mach-nc reports , five additional meta-analyses and thirty rcts were identified . Five recommendations for lascchn treatment were generated based on those data . Concurrent chemoradiation ( ccrt ) is recommended to maximize the chance of cure in patients less than 71 years of age when rt is used as definitive treatment . The same recommendation also applies to patients with resected lascchn considered to be at high risk for locoregional recurrence . For lascchn patients who are c and i date s for organ preservation strategies and would otherwise require total laryngectomy , either ccrt or induction chemotherapy , followed by rt or surgery based on tumour response is recommended . The addition of cetuximab to intensified rt ( concomitant boost or hyperfractionated schedule ) is an alternative to ccrt . Routine use of induction chemotherapy to improve overall survival is not recommended . CONCLUSIONS We were able to use high-level evidence from patients receiving rt as definitive or postoperative treatment to generate recommendations for the use of systemic therapy in the treatment of lascchn . A limitation is a lack of stratification for human papillomavirus-related cancers of the oropharynx . One rct provided evidence for the use of cetuximab as an alternative to chemotherapy in the definitive rt setting . Concurrent chemoradiation provides one strategy for larynx preservation , but the best strategy is unclear . Use of induction chemotherapy does not improve overall survival , and its use should be limited to patients requiring immediate tumour downsizing before local therapy PURPOSE Health interventions based on theory may be more effective than those that are not . This review of review s synthesizes all published r and omized controlled trial ( RCT ) meta-analytic evidence from the last decade to examine whether theory-based interventions were found to be associated with more effective  adult health behaviour change interventions . METHODS Systematic review s including meta-analyses were identified by search ing Medline , CINAHL , PsycINFO , and CDSR . A narrative synthesis was used to summarize and analyse the evidence . Only review s including RCTs of health behaviour change interventions with adults aged 18 + published from 2007 to 2017 were included . RESULTS Of 8,659 articles , nine systematic review s met inclusion criteria . The majority of review s ( n = 8) suggested no increased effectiveness for theory-based compared to non-theory-based interventions for effectiveness of outcomes relating to health behaviour . Less than half of the RCTs included in the review s reported the use of theory ( 85/183 ) . Two review s suggested interventions based on control theory , motivational interviewing , or self-determination theory were associated with greater effectiveness for physical activity and /or dietary interventions and outcomes . Method ological and reporting issues limit the conclusions . CONCLUSIONS Theory-based interventions as currently operationalized in systematic review s were not found to be more effective than non-theory-based interventions . Method ological and reporting issues at study and review level may not reflect the true utility of theory use within health behaviour interventions . The promotion of theory use may benefit from using a multifaceted argument , rather than a narrow focus of increased effectiveness . Statement of contribution What is already known on this subject ? Theory use is regularly promoted by cl aim ing that it will lead to more effective behaviour change interventions . Theory use has been frequently linked to effectiveness within systematic review s of behaviour change interventions . The theory-effectiveness hypothesis has not been systematic ally examined at the systematic review level . What does this study add ? Theory use as operationalized by systematic review authors was not associated with increased effectiveness within systematic review s examining r and omized controlled trials of behaviour change interventions in adults . Interventions based on control theory , motivational interviewing , or self-determination theory were associated with greater effectiveness for physical activity and /or dietary interventions and outcomes . Theory use should be promoted using a multifaceted argument , and assertions for increased effectiveness of theory-based interventions should only be used in domains where specific evidence exists to support this cl aim AIMS Pain and anxiety are commonly reported among those undergoing orthopaedic surgery . Improvement in anxiety and pain control might be achieved by supplementing st and ard care with psychological interventions . However , the effectiveness of adjunctive psychosocial interventions in anxiety and pain control have not been addressed sufficiently by previous systematic review s in orthopaedic surgeries . The present study aim ed to assess the effectiveness of adjunctive psychosocial techniques to improve perioperative clinical care in orthopaedic surgery , to identify the most effective intervention types and to evaluate potential moderators . METHODS We will perform a systematic review and meta- analysis to address the study aims . PubMed , PsycINFO , CINAHL and ProQuest Dissertations & Theses will be search ed between 1980 and 2015 . Prospect i ve controlled clinical trials completed in adults , contrasting st and ard care and st and ard care supplemented with psychosocial methods  , will be eligible for inclusion . Effectiveness will be assessed through the outcomes of postoperative pain intensity , analgesic requirement , perioperative anxiety , quality of life and postoperative recovery . The results of a r and om-effect meta- analysis will be reported . To aid implementation of best practice , moderating effects of the type and timing of psychosocial intervention , type of surgical intervention and type of anaesthesia will be evaluated through meta-regression . Sensitivity analyses and subgroup contrasts will follow as necessary . DISCUSSION Recommendations will be made to improve medical care in orthopaedic procedures . The quality of evidence will be rated using GRADE criteria . Copyright © 2016 John Wiley & Sons ,
The meta- analysis showed a significant increase in plasma adiponectin levels following statin therapy .
Although statins are known to increase the risk for new onset diabetes mellitus , our data might suggest that the mechanism for this is unlikely to be due to a reduction in adiponectin expression
BACKGROUND AND AIMS The effect of statin therapy on plasma adiponectin levels has not been conclusively studied .
Therefore , we aim ed to evaluate this effect through a systematic review and meta- analysis of available r and omized controlled trials ( RCTs ) .