The effectiveness of yoga to prevent diabetes mellitus type 2 Inhibition of COX-1 and COX-2 activity by plasma of human volunteers after ingestion of French maritime pine bark extract (Pycnogenol). Chemotherapy and targeted therapy for women with human epidermal growth factor receptor 2-negative (or unknown) advanced breast cancer: American Society of Clinical Oncology Clinical Practice Guideline. An examination of the effects of the antioxidant Pycnogenol® on cognitive performance, serum lipid profile, endocrinological and oxidative stress biomarkers in an elderly population Effectiveness of female condom in preventing HIV and sexually transmitted infections: a systematic review protocol Epidemiologic analysis of breast cancer incidence, prevalence, and mortality in India Antimicrobially impregnated catheters: An overview of randomized controlled trials. Key Steps in Conducting Systematic Reviews for Underpinning Clinical Practice Guidelines: Methodology of the European Association of Urology. Addressing Dichotomous Data for Participants Excluded from Trial Analysis: A Guide for Systematic Reviewers A conversation with Joseph Lau. INVITED COMMENTARY: Rating the Quality of Trials in Systematic Reviews of Physical Therapy Interventions [Practice of systematic reviews. VII. Pooling of results from observational studies]. How to write an evidence-based clinical review article. Issues related to the conduct of systematic reviews: a focus on the nutrition field. Mineral Trioxide Aggregate vs. Calcium Hydroxide in Primary Molar Pulpotomy: A Systematic Review Supplementation with a pine bark extract rich in polyphenols increases plasma antioxidant capacity and alters the plasma lipoprotein profile The clinical effectiveness of different parenting programmes for children with conduct problems: a systematic review of randomised controlled trials Can we rely on the best trial? A comparison of individual trials and systematic reviews A systematic review protocol examining the effect of vitamin D supplementation on endothelial function Identifying, documenting, and examining heterogeneity in systematic reviews of complex interventions. Summarizing systematic reviews: methodological development, conduct and reporting of an umbrella review approach Efficacy of vitamin D supplementation in depression in adults: a systematic review protocol The effects of exercise on cognition in Parkinson’s disease: a systematic review
Background : Type 2 diabetes mellitus ( T2DM ) is becoming a leading problem worldwide . Emerging reports reveal alarming evidence of increasing prevalence of T2DM that has reached p and emic levels . Despite the significant incidence , there are limited reliable data re sources and comprehensive systematic review and meta- analysis on the effects of yoga on people who are a prediabetic or high risk for developing T2DM . Objective : The objective of this protocol is to conduct a full-scale systematic review and meta-analyses on the effects of yoga on people who are prediabetes or high risk of developing T2DM . Methods : The articles enrolled in the study will be retrieved from the online data bases between 2002 and the date the search es are executed . The search es will be repeated just before the final analyses and further relevant studies for inclusion . We will conduct a bibliographic search in data bases : Medline / PubMed , Scopus , Cochrane Library , EBSCO , and IndMED using keywords including prediabetes state , high risk for diabetes , metabolic syndrome , and yoga . A defined search strategy will be implemented along with selection criteria to obtain full-text articles of relevant studies . This study protocol was prepared according to the Preferred Reporting Items for Systematic Review s and Meta- Analysis for Protocol s 2015 guidelines . There will be no language restrictions . Ethics and dissemination : The proposed study will be based on published studies and publicly available anonymized data without directly involving human participants and therefore requires neither formal human ethical review nor approval by a human research ethics committee . We published an outline of the protocol in the International Prospect i ve Register of Systematic Review s ( PROSPERO ) in 2018 . We plan to disseminate the findings of this systematic review and meta- analysis through publication in a peer- review ed journal and presentation at relevant conference proceedings . In addition , we believe the results of the systematic review will have implication s for policy and practice . We will prepare policymaker summary using a vali date d format , disseminate through social media and email discussion groups . Review registration number : PROSPERO registration number CRD There is evidence from several studies that supplementation with French maritime pine bark extract ( Pycnogenol ) improves inflammatory symptoms in vivo . However , the molecular pharmacological basis for the observed effects has not been fully uncovered yet . Direct inhibitory effects of plant extracts or components upon cyclooxygenase ( COX ) activity have been repeatedly reported , but the question remained whether sufficiently high in vivo concentrations of bioactive compounds could be achieved in humans . The purpose of the present study was to determine a possible inhibition of the enzymatic activity of COX-1 and COX-2 by serum sample s of human volunteers after intake of French maritime pine bark extract .  This methodology considered that the serum sample s would contain any bioavailable active principle . Therefore , we obtained blood sample s before and after 5 days administration of 200 mg  Pycnogenol to five healthy humans . The plasma moderately inhibited both COX-1 and COX-2 activities ex vivo . In a second approach , 10 volunteers received a single dose of 300 mg Pycnogenol . Only 30 min after ingestion of the pine bark extract the serum sample s induced a statistically significant increase in the inhibition of both COX-1 ( P < 0.02 ) and COX-2 ( P < 0.002 ) . This suggests a strikingly rapid bioavailability of bioeffective compounds after oral intake of the extract . Thus , we provide evidence that Pycnogenol exerts effects by inhibition of eicosanoid generating enzymes which is consistent with reported clinical anti-inflammatory and platelet inhibitory effects in vivo . The next challenge is to identify the active principle(s ) that are rapidly bioavailable in human plasma PURPOSE To identify optimal chemo- and targeted therapy for women with human epidermal growth factor 2 (HER2)- negative ( or unknown ) advanced breast cancer . METHODS A systematic review of r and omized evidence ( including systematic review s and meta-analyses ) from 1993 through to current was completed . Outcomes of interest included survival , progression-free survival , response , quality of life , and adverse effects . Guideline recommendations were evidence based and were agreed on by the Expert Panel via consensus . RESULTS Seventy-nine studies met the inclusion criteria , comprising 20 systematic review s and /or meta-analyses , 30 trials on first-line treatment , and 29 trials on second-line and subsequent treatment . These trials form the evidence base for the guideline recommendations . RECOMMENDATIONS Endocrine therapy is preferable to chemotherapy as first-line treatment for patients with estrogen receptor-positive metastatic breast cancer unless improvement is medically necessary ( eg , immediately life-threatening disease ) . Single agent is preferable to combination chemotherapy , and longer planned duration improves outcome but must be balanced against toxicity . There is no single optimal first-line or subsequent line chemotherapy , and choice of treatment will be determined by multiple factors including prior therapy , toxicity , performance status , comorbid conditions , and patient preference . The role of bevacizumab remains controversial . Other targeted therapies have not so far been shown to enhance chemotherapy outcome in HER2-negative breast cancer The study examines the effects of the antioxidant flavonoid Pycnogenol on a range of cognitive and biochemical measures in healthy elderly individuals . The study used a double-blind , placebo-controlled , matched-pair design , with 101 elderly participants ( 60—85 years ) consuming a daily dose of 150 mg of Pycnogenol for a three-month treatment period . Participants were assessed at baseline , then at 1 , 2 , and 3 months of the treatment . The control ( placebo ) and Pycnogenol groups were matched by age , sex , body mass index , micronutrient intake , and intelligence . The cognitive tasks comprised measures of attention , working memory , episodic memory , and psychomotor performance . The biological measures comprised levels of clinical hepatic enzymes , serum lipid profile , human growth hormone , and lipid peroxidation products . Statistically significant interactions were found for memory-based cognitive variables and lipid peroxidation products , with the Pycnogenol group displaying improved working memory and decreased concentrations of F2-isoprostanes relative to the control group Introduction The HIV p and emic continues to evolve with young women being the most vulnerable group to acquire infection . The presence of sexually transmitted infections ( STIs ) further enhances HIV susceptibility and also leads to long-term complications such as infertility and cervical cancer . The female condom is a self-initiated method for STI and HIV prevention but there are controversies on its effects . We aim to assess the effectiveness , safety and acceptability of the use of female condoms for prevention of STI and HIV acquisition among women . Methods and analysis We will search Cochrane Central Register of Controlled Trials , PubMed , EMBASE , Scopus , WHO International Clinical Trials Registry and reference lists of relevant publications for potentially eligible studies . We will screen search outputs , select eligible studies , extract data and assess risk of bias in duplicate ; resolving discrepancies through discussion and consensus or arbitration . We will combine data from clinical ly homogenous studies in a fixed effect meta- analysis and assess the certainty of the evidence using the method for Grading of Recommendations Assessment , Development and Evaluation . We registered the planned systematic review with the International Prospect i ve Register of Systematic Review s ( PROSPERO ) in March 2018 and will finalise the search strategy in August 2018 ; conduct the search es and select eligible studies between August and October 2018 ; and collect data , conduct statistical analyses and prepare and su bmi t the manuscript for consideration by a peer- review ed journal between November 2018 and April 2019 . Ethics and dissemination We will use publicly available data ; hence no formal ethical approval is required for this review . We will disseminate the findings of this review through conference presentations and publication in an open-access peer- review ed journal . PROSPERO registration number CRD42018090710 Background : Breast Cancer ( BC ) is the leading cause of deaths in Indian women . Emerging reports reveal alarming evidence of increasing incidence and mortality of BC among young Indian women in addition to the late presentation and poor prognosis . Despite the significant incidence , there is a lack of reliable data re sources and comprehensive epidemiologic studies relating to BC . The objective of this protocol is to conduct a full-scale systematic review and meta-analyses on the incidence , prevalence , and mortality of BC in 29 states and seven union territories of India . Methods : Data sources used will be Cochrane Review , MEDLINE , PubMed , Scopus , Science Direct , Web of Science , and international and national cancer registries such as World Health Organization , International Agency for Research on Cancer ( IARC ) , and National Centre for Disease Information and Research (NCDIR)-National Cancer Registry Program initiated by Indian Council of Medical Research . Relevant data will be extracted using a predefined data collection form . A defined search strategy will be implemented along with selection criteria to obtain full-text articles of relevant studies . This study protocol was prepared according to the Preferred Reporting Items for Systematic Review s and Meta- Analysis for Protocol s 2015 guidelines . Odds ratios ( ORs ) will be used to measure effect size . The r and om or fixed-effects meta-analyses model will be employed to aggregate the pooled estimates ( ORs ) with 95 % confidence intervals ( CIs ) separately . A forest plot will be produced to assess ORs and 95 % CIs . Publication bias will be assessed using funnel plot , and Egger regression will be applied to test the symmetry of the funnel plot . Ethics and dissemination : This proposed study will be based on published studies and the data from cancer registries . Therefore , human research ethics approval is not required . The results of this study will be published in a peer- review ed journal . PROSPERO registration no : CRD42018084003 In order to acquire an overview of the effectiveness of  antimicrobially impregnated catheters  on the prevention of  catheter related bloodstream infections ( CRI )  , we conducted a systematic review concentrating on r and omized controlled trials ( RCTs ) . The analysis end point was CRI ; therefore , studies focussing only on catheter colonization were excluded . We did not consider abstract s for analysis . We identified 24 RCTs investigating the effectiveness of  antimicrobially impregnated catheters .  In addition , we discovered five meta-analyses and four studies investigating cost effectiveness . For the majority of antimicrobially impregnated catheter types only a few studies were available , and not enough to draw conclusions . Therefore , despite a relatively large number of RCTs available , the routine use of antimicrobially impregnated catheters as a measure for CRI prevention remains controversial , with a need for more high quality studies CONTEXT The findings of systematic review s ( SRs ) and meta-analyses ( MAs ) are used for clinical decision making . The European Association of Urology has committed increasing re sources into the development of high quality clinical guidelines based on such SRs and MAs . OBJECTIVE In this paper , we have summarised the process of conducting SRs for underpinning clinical practice guidelines under the auspices of the European Association of Urology Guidelines Office . EVIDENCE ACQUISITION The process involves explicit methods and the findings should be reproducible . When conducting a SR , the essential first step is to formulate a clear and answerable research question . An extensive literature search lays the foundation for evidence synthesis . Data are extracted independently by two review ers and any disagreements are resolved by discussion or arbitration by a third review er . EVIDENCE SYNTHESIS In SRs , data for particular outcomes in individual r and omised controlled trials may be combined statistically in a meta- analysis to increase power when the studies are similar enough . Biases in studies included in a SR/MA can lead to either an over estimation or an under estimation of true intervention effect size , result ing in heterogeneity in outcome between studies . A number of different tools are available such as Cochrane Risk of Bias assessment tool for r and omised controlled trials . In circumstances where there is too much heterogeneity , or when a review has included nonr and omised comparative studies , it is more appropriate to conduct a narrative synthesis . The GRADE tool for assessing quality of evidence strives to be a structured and transparent system , which can be applied to all evidence , regardless of quality . A SR not only identifies , evaluates , and summarises the best available evidence , but also the gaps to be targeted by future studies . CONCLUSIONS SRs and MAs are integral in developing sound clinical practice guidelines and recommendations . PATIENT SUMMARY Clinical practice guidelines should be evidence based , and systematic review s and meta-analyses are essential in their production . We have discussed the key steps of conducting systematic review s and meta-analyses in this paper 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 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 & NA ; Physical therapists seeking to use evidence to guide their practice may have limited time to read research reports . One way to reduce the time required to identify and read about the research that is relevant to a particular clinical question is to read a systematic review that summarizes multiple studies . This paper explains the process that is used to conduct systematic review s , which includes the establishment of a protocol , comprehensive search ing , appraisal of the quality of the included studies , data extraction and meta analysis , and consideration of the clinical and research implication s of the findings . We also consider how the reader of a systematic review can determine whether the review is likely to provide an unbiased ( believable ) estimate of the treatment effect . A systematic review of r and omized trials of a  cardiopulmonary physical therapy intervention is used as an example . The issue of appraisal of quality is then discussed further , with a demonstration of how one vali date d tool for quality appraisal ‐‐the PEDro scale‐‐can be used to evaluate a r and omized trial in cardiopulmonary physical therapy Knowledge concerning aetiologic hypotheses can be obtained through systematic review s of observational studies . In observational studies , heterogeneity between studies is expected , because of differences in study design and analysis . Data from observational studies have to be made comparable before pooling of results from component studies is possible . In this , definition of exposure and disease and adjustment for confounding have to be taken into account . Three methods to deal with heterogeneity are presented : ignoring ( fixed effects model ) , modelling ( r and om effects model ) and exploring ( meta regression ) . Any combination of data in meta- analysis of observational studies has to be based on statistical , method ological and clinical considerations . The same considerations are applied for the choice which method is used 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 Systematic review s ( SRs ) are an increasingly popular evidence -based tool and are often used to answer complex research questions across many different research domains . Early SR methodology was advanced by social scientists , and the term meta- analysis was coined by a social scientist who also conducted research in psychology . SRs have recently become popular in healthcare and are likely to be beneficial in any field . The aim of this report is to highlight issues in SR conduct with a focus on the field of nutrition and to make recommendations on improving SR conduct in this area . Development of the research question is probably the most important step in conducting an SR . The 4 main components of an answerable question are 1 ) the patient , population , or problem ; 2 ) the intervention , independent variable , or exposure ; 3 ) the comparators ; and 4 ) the dependent variables or outcomes of interest . The question will be used to determine the optimal methods for conducting the SR . SRs often include study design s beyond r and omized trials and do not always include a meta- analysis of the results . Other topics explored include underst and ing and interpreting discordant review s and the importance of reporting tools [ eg , QUality Of Reporting Of Meta-analyses ( QUOROM Statement ) or CONsoli date d St and ards Of Reporting of Trials ( CONSORT Statement ) ] . Recommendations are then provided , such as developing a capacity-building program , search ing the primary literature for research gaps , and extending reporting tools such as the QUOROM Statement to the field of nutrition 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 Pycnogenol ® ( PYC ) , an extract of French maritime pine bark ( Pinus pinaster ) , is a potent antioxidant with potential health benefits . Its bioavailabilty has previously been shown by urinary excretion studies of constituents and metabolites of PYC . The aim of this study was to test the effect of PYC supplementation on measures of oxidative stress and the lipid profile in humans . Twenty-five healthy subjects received  PYC  ( 150 mg/d ) for 6 wk . Fasting blood was collected at baseline , after 3 and 6 wk of supplementation , and again after a 4-wk washout period . After 6 wk of supplementation with PYC , a significant increase in plasma polyphenol levels was detectable , which was reversed after the 4-wk washout phase . The antioxidant effect of PYC was demonstrated by a significant increase in oxygen radical absorbance capacity ( ORAC ) in plasma throughout the supplementation period ( P<0.05 ) . The ORAC value returned to baseline after the 4-wk washout period . Moreover , in addition to its antioxidant effects  , PYC significantly reduced LDL-cholesterol levels and increased HDL-cholesterol levels in plasma of two-thirds of the subjects . While the LDL changes reversed during washout , the HDL increase did not . There was no significant difference in LDL oxidizability or plasma lipid peroxides following PYC supplementation . Hence , following oral supplementation in humans  , PYC significantly increases antioxidant capacity of plasma , as determined by ORAC , and exerts favorable effects on the lipid profile Background Conduct problems are common , disabling and costly . The prognosis for children with conduct problems is poor , with outcomes in adulthood including criminal behaviour , alcoholism , drug abuse , domestic violence , child abuse and a range of psychiatric disorders . There has been a rapid expansion of group based parent-training programmes for the treatment of children with conduct problems  in a number of countries over the past 10 years . Existing review s of parent training have method ological limitations such as inclusion of non-r and omised studies , the absence of investigation for heterogeneity prior to meta- analysis or failure to report confidence intervals . The objective of the current study was to systematic ally review r and omised controlled trials of parenting programmes for the treatment of children with conduct problems .  Methods St and ard systematic review methods were followed including duplicate inclusion decisions , data extraction and quality assessment . Twenty electronic data bases from the fields of medicine , psychology , social science and education were comprehensively search ed for RCTs and systematic review s to February 2006 . Inclusion criteria were : r and omised controlled trial ; of structured , repeatable parenting programmes ; for parents/carers of children up to the age of 18 with a conduct problem ; and at least one measure of child behaviour . Meta- analysis and qualitative synthesis were used to summarise included studies . Results 57 RCTs were included . Studies were small with an average group size of 21 . Meta-analyses using both parent ( SMD -0.67 ; 95 % CI : -0.91 , -0.42 ) and independent ( SMD -0.44 ; 95 % CI : -0.66 , -0.23 ) reports of outcome showed significant differences favouring the intervention group . There was insufficient evidence to determine the relative effectiveness of different approaches to delivering parenting programmes . Conclusion Parenting programmes are an effective treatment for children with conduct problems . The relative effectiveness of different parenting programmes requires further research Background The ideal evidence to answer a question about the effectiveness of treatment is a systematic review . However , for many clinical questions a systematic review will not be available , or may not be up to date . One option could be to use the evidence from an individual trial to answer the question ? Methods We assessed how often ( a ) the estimated effect and ( b ) the p-value in the most precise single trial in a meta- analysis agreed with the whole meta- analysis . For a r and om sample of 200 completed Cochrane Review s ( January , 2005 ) we identified a primary outcome and extracted : the number of trials , the statistical weight of the most precise trial , the estimate and confidence interval for both the highest weighted trial and the meta- analysis overall . We calculated the p-value for the most precise trial and meta- analysis . Results Of 200 review s , only 132 provided a meta- analysis of 2 or more trials , with a further 35 effect estimates based on single trials . The average number of trials was 7.3 , with the most precise trial contributing , on average , 51 % of the statistical weight to the summary estimate from the whole meta- analysis . The estimates of effect from the most precise trial and the overall meta-analyses were highly correlated ( rank correlation of 0.90).There was an 81 % agreement in statistical conclusions . Results from the most precise trial were statistically significant in 60 of the 167 evaluable review s , with 55 of the corresponding systematic review s also being statistically significant . The five discrepant results were not strikingly different with respect to their estimates of effect , but showed considerable statistical heterogeneity between trials in these meta-analyses . However , among the 101 cases in which the most precise trial was not statistically significant , the corresponding meta-analyses yielded 31 statistically significant results . Conclusions Single most precise trials provided similar estimates of effects to those of the meta-analyses to which they contributed , and statistically significant results are generally in agreement . However , " negative " results were less reliable , as may be expected from single underpowered trials . For systematic review ers we suggest that : ( 1 ) key trial(s ) in a review deserve greater attention ( 2 ) systematic review ers should check agreement of the most precise trial and the meta analysis . For clinicians using trials we suggest that when a meta- analysis is not available , a focus on the most precise trial is reasonable provided it is adequately powered Introduction Vitamin D has potential benefits for extraskeletal health . These could include an anti-inflammatory effect as well as a reduction in endothelial dysfunction . We aim to provide quality evidence for the hypothesis that supplementation with vitamin D will improve endothelial function ( EF ) , possibly through the abrogation of systemic inflammation . Methods and analysis We will conduct a systematic review of all r and omised controlled trials on  vitamin D supplementation and EF lasting 12 weeks or more . The search will cover the period 2000–2015 and include studies that describe direct measures of EF  , markers of endothelial cell ( EC ) activation  and if concurrently reported , indicators of systemic inflammation  . Study selection will follow the Preferred Reporting Items for Systematic Review s and Meta-Analyses ( PRISMA ) guidelines and study quality will be assessed by the Jadad score in addition to an evaluation of allocation concealment and data analysis . If sufficient data are available , a meta- analysis will be conducted . The effect sizes will be generated using Hedges ’ g score , for both fixed and r and om effect models . I2 statistics and Galbraith plots will be used to assess heterogeneity and identify their potential sources . Potential publication and small sample size bias will be assessed by visual inspections of funnel plots and also Egger 's test . Meta-regression analysis ( if feasible ) will be conducted with restricted maximum likelihood ( REML ) estimation method , controlling for potential confounders ( demographics , study methods , location , etc ) . A backward elimination process will be applied in the regression modelling procedure . Subgroup analysis , conditional on number of studies retrieved and their sample size , will be stratified on participant disease category , total dose administered , degree of 25(OH)D change and type of supplement used . Ethics and dissemination Formal ethical approval is not required as primary data will not be collected . The results will be disseminated through a peer- review ed publication , conference presentation and the popular press . Trial registration number International Prospect i ve Register for Systematic Review s ( PROSPERO ) number CRD42014013523 This article describes approaches for planning , dealing , and analyzing heterogeneity in a systematic review of complex interventions . Approaches aim to generate a priori hypotheses of the mechanism of action of a complex intervention to identify the key variables that might contribute to variation among studies and guide statistical analysis . In addition to characteristics related to the population , intervention , and outcomes , we describe study -related variables , such as the way the interventions have been implemented and the context and conduct of studies . These approaches will guide review ers planning a meta- analysis and provide a rationale for not meta-analyzing data if there is too much variability . Potential difficulties in applying meta-analytical techniques to examine statistical association among study results and sources of potential heterogeneity are described ; these include the selection of a fixed or r and om-effects model , the risk of multiple testing and confounding when studies include different aspects of a complex intervention or different sub sample s of the intended participant pool Aims : With the increase in the number of systematic review s available , a logical next step to provide decision makers in healthcare with the evidence they require has been the conduct of review s of existing systematic review s. Syntheses of existing systematic review s are referred to by many different names , one of which is an umbrella review . An umbrella review allows the findings of review s relevant to a review question to be compared and contrasted . An umbrella review 's most characteristic feature is that this type of evidence synthesis only considers for inclusion the highest level of evidence , namely other systematic review s and meta-analyses . A methodology working group was formed by the Joanna Briggs Institute to develop method ological guidance for the conduct of an umbrella review , including diverse types of evidence , both quantitative and qualitative . The aim of this study is to describe the development and guidance for the conduct of an umbrella review . Methods : Discussion and testing of the elements of methods for the conduct of an umbrella review were held over a 6-month period by members of a methodology working group . The working group comprised six participants who corresponded via teleconference , e-mail and face-to-face meeting during this development period . In October 2013 , the methodology was presented in a workshop at the Joanna Briggs Institute Convention . Workshop participants , review authors and method ologists provided further testing , critique and feedback on the proposed methodology . Results : This study describes the methodology and methods developed for the conduct of an umbrella review that includes published systematic review s and meta-analyses as the analytical unit of the review . Details are provided regarding the essential elements of an umbrella review , including presentation of the review question in a Population , Intervention , Comparator , Outcome format , nuances of the inclusion criteria and search strategy . A critical appraisal tool with 10 questions to help assess risk of bias in systematic review s and meta-analyses was also developed and tested . Relevant details to extract from included review s and how to best present the findings of both quantitative and qualitative systematic review s in a reader friendly format are provided . Conclusions : Umbrella review s provide a ready means for decision makers in healthcare to gain a clear underst and ing of a broad topic area . The umbrella review methodology described here is the first to consider review s that report other than quantitative evidence derived from r and omized controlled trials . The methodology includes an easy to use and informative summary of evidence table to readily provide decision makers with the available , highest level of evidence relevant to the question posed 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 Cognitive impairments are highly prevalent in Parkinson ’s disease ( PD ) and can substantially affect a patient ’s quality of life . These impairments remain difficult to manage with current clinical therapies , but exercise has been identified as a possible treatment . The objective of this systematic review was to accumulate and analyze evidence for the effects of exercise on cognition in both animal models of PD and human disease . This systematic review was conducted according to the Preferred Reporting Items for Systematic review s and Meta-Analyses ( PRISMA ) statement . Fourteen original reports were identified , including six pre- clinical animal studies and eight human clinical studies . These studies used various exercise interventions and evaluated many different outcome measures ; therefore , only a qualitative synthesis was performed . The evidence from animal studies supports the role of exercise to improve cognition in humans through the promotion of neuronal proliferation , neuroprotection and neurogenesis . These findings warrant more research to determine what roles these neural mechanisms play in clinical population s. The reports on cognitive changes in clinical studies demonstrate that a range of exercise programs can improve cognition in humans . While each clinical study demonstrated improvements in a marker of cognition , there were limitations in each study , including non-r and omized design s and risk of bias . The Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) system was used and the quality of the evidence for human studies were rated from “ low ” to “ moderate ” and the strength of the recommendations were rated from “ weak ” to “ strong ” . Studies that assessed executive function , compared to general cognitive abilities , received a higher GRADE rating . Overall , this systematic review found that in animal models exercise  results in behavioral and corresponding neurobiological changes in the basal ganglia related to cognition . The clinical studies showed that various types of exercise , including aerobic , resistance and dance can improve cognitive function , although the optimal type , amount , mechanisms , and duration of exercise are unclear . With growing support for exercise to improve not only motor symptoms , but also cognitive impairments in PD , health care providers and policy makers should recommend exercise as part of routine management and neurorehabilitation for this disorder
The results indicate that pycnogenol supplementation improves levels of HDL-C ; however , the changes in TC , TAG , and LDL-C were not clinical ly relevant .
Since there are few phytochemicals that have a significant increasing effect on HDL-C levels  , pycnogenol may have important role in prevention of cardiovascular diseases
The effects of pycnogenol on plasma lipids are controversial .
A systematic review and meta- analysis of clinical trials were conducted to obtain a conclusive result in humans .