How effective and safe is medical cannabis as a treatment of mental disorders? A systematic review The clinical effectiveness of different parenting programmes for children with conduct problems: a systematic review of randomised controlled trials Prevention of cervical cancer in HIV-seropositive women from developing countries: a systematic review protocol A systematic review protocol examining the effect of vitamin D supplementation on endothelial function Seeing the forests and the trees—innovative approaches to exploring heterogeneity in systematic reviews of complex interventions to enhance health system decision-making: a protocol Effects of transcutaneous electrical nerve stimulation (TENS) on proinflammatory cytokines: protocol for systematic review Cost-effectiveness of interventions to control cardiovascular diseases and type 2 diabetes mellitus in South Asia: protocol for a systematic review Identifying, documenting, and examining heterogeneity in systematic reviews of complex interventions. Effect of vitamin D supplementation on inflammation: protocol for a systematic review Effects of workplace-based dietary and/or physical activity interventions for weight management targeting healthcare professionals: a systematic review of randomised controlled trials Benefits and risks of drug treatments: how to combine the best evidence on benefits with the best data about adverse effects. Addressing Dichotomous Data for Participants Excluded from Trial Analysis: A Guide for Systematic Reviewers Resting blood pressure reductions following isometric handgrip exercise training and the impact of age and sex: protocol for a systematic review Statins and Fibrates for Diabetic Retinopathy: Protocol for a Systematic Review Key Steps in Conducting Systematic Reviews for Underpinning Clinical Practice Guidelines: Methodology of the European Association of Urology. An economic evaluation of the 2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of mild-to-moderate hypertension in Greece. Can we rely on the best trial? A comparison of individual trials and systematic reviews Systematic review automation technologies Protocol for an overview of systematic reviews of interventions to reduce unscheduled hospital admissions among adults Examining the theory‐effectiveness hypothesis: A systematic review of systematic reviews Caries Removal by Chemomechanical (Carisolv™) vs. Rotary Drill: A Systematic Review The effectiveness of yoga to prevent diabetes mellitus type 2 The impact of outcome reporting bias in randomised controlled trials on a cohort of systematic reviews
We conducted a review of systematic review s ( SRs ) and r and omized-controlled trials ( RCTs ) to analyze efficacy and safety of cannabis-based medication in patients with mental disorders . Five data bases were systematic ally search ed ( 2006—August 2018 ) ; 4 SRs ( of 11 RCTs ) and 14 RCTs ( 1629 participants ) were included . Diagnoses were : dementia , cannabis and opioid dependence , psychoses/schizophrenia , general social anxiety , posttraumatic stress disorder , anorexia nervosa , attention-deficit hyperactivity disorder , and Tourette`s disorder . Outcome variables were too heterogeneous to conduct a meta- analysis . A narrative synthesis method was applied . The study quality was assessed using the risk-of-bias tool and SIGN-checklists . THC- and CBD-based medicines , given as adjunct to pharmaco- and psychotherapy , were associated with improvements of several symptoms of mental disorders , but not with remission . Side effects occurred , but severe adverse effects were mentioned in single cases only . In order to provide reliable treatment recommendations , more and larger RCTs with follow-up assessment s , consistent outcome measures and active comparisons are needed 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 Over 85 % of cervical cancer cases and deaths occur in developing countries . HIV-seropositive women are more likely to develop precancerous lesions that lead to cervical cancer than HIV-negative women . However , the literature on cervical cancer prevention in seropositive women in developing countries has not been review ed . The aim of this study is to systematic ally review cervical cancer prevention modalities available for HIV-seropositive women in developing countries . Methods / design This protocol was developed by following the Preferred Reporting Items for Systematic Review s and Meta-Analyses Protocol s ( PRISMA -P ) statement , and the systematic review will be reported in accordance with the PRISMA guidelines . Embase , MEDLINE , PubMed , CINAHL and Cochrane Library will be search ed from inception up to date of final search , and additional studies will be located through citation and reference list tracking . Eligible studies will be r and omised controlled trials , prospect i ve and retrospective cohort studies , case-control and cross-sectional studies carried out in developing countries . Studies will be included if they are published in English and examine cervical cancer prevention modalities in HIV-seropositive women . Results will be summarised in tables and , where appropriate , combined using meta- analysis . Discussion This review will address the gap in evidence by systematic ally review ing the published literature on the different prevention modalities being used to prevent  cervical cancer in HIV-seropositive women in developing countries . The findings may be used to inform evidence -based guidelines for prevention of cervical cancer in seropositive women as well as future research . Systematic review registration PROSPERO CRD42017054678 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 Background To improve quality of care and patient outcomes , health system decision-makers need to identify and implement effective interventions . An increasing number of systematic review s document the effects of quality improvement programs to assist decision-makers in developing new initiatives . However , limitations in the reporting of primary studies and current meta- analysis methods ( including approaches for exploring heterogeneity ) reduce the utility of existing syntheses for health system decision-makers . This study will explore the role of innovative meta- analysis approaches and the added value of enriched and up date d data for increasing the utility of systematic review s of complex interventions . Methods / Design We will use the data set from our recent systematic review of 142 r and omized trials of diabetes quality improvement programs  to evaluate novel approaches for exploring heterogeneity . These will include exploratory methods , such as multivariate meta-regression analyses and all-subsets combinatorial meta- analysis . We will then up date our systematic review to include new trials and enrich the data set by surveying authors of all included trials . In doing so , we will explore the impact of variables not , reported in previous publications , such as details of study context , on the effectiveness of the intervention . We will use innovative analytical methods on the enriched and up date d data set to identify key success factors in the implementation of  quality improvement interventions  for diabetes . Decision-makers will be involved throughout to help identify and prioritize variables to be explored and to aid in the interpretation and dissemination of results . Discussion This study will inform future systematic review s of complex interventions and describe the value of enriching and updating data for exploring heterogeneity in meta- analysis . It will also result in an up date d comprehensive systematic review of diabetes quality improvement interventions that will be useful to health system decision-makers in developing interventions to improve outcomes for people with diabetes . Systematic review registration PROSPERO registration no. Background Pain reduction can be achieved by lowering proinflammatory cytokine levels in the blood . Transcutaneous electrical nerve stimulation ( TENS ) is a non-invasive physiotherapeutic re source for pain management , but evidence on the effectiveness of this device at reducing proinflammatory cytokines in the blood is unclear . This study systematic ally review s the literature on the effect of TENS on proinflammatory cytokines . Methods A systematic review protocol was developed based on search es of articles in six electronic data bases and references of retrieved articles , contact with authors , and repositories of clinical trials . Eligibility criteria : publication in peer- review ed journals , r and omized clinical trials , use of TENS in the experimental group , and pre- and post- measurements of proinflammatory cytokines in the blood . Selection of the studies and extraction of the data will be carried out by two review ers independently . Characteristics of the study , participants , interventions and outcomes were extracted and described . Assessment s were performed on the risk of bias , level of evidence and the size of the intervention effect in the studies , according to GRADE guidelines and the Cochrane H and book for Systematic Review s. Clinical and statistical assessment s compared the effects of the interventions ( meta- analysis ) , taking into consideration any influencing characteristics of the studies ( e.g. , methods and application sites ) . Discussion We anticipate that this review will strengthen evidence -based knowledge of the effect of TENS on proinflammatory cytokines and , as a result , direct new studies to benefit patients with specific pathologies . Systematic review registration PROSPERO , CRD42017060379 Introduction While a number of strategies are being implemented to control cardiovascular diseases ( CVDs ) and type 2 diabetes mellitus ( T2DM ) , the cost-effectiveness of these in the South Asian context has not been systematic ally evaluated . We aim to systematic ally review the economic ( cost-effectiveness ) evidence available on the individual- , group- and population -level interventions for control of CVD and T2DM in South Asia . Methods and analysis This review will consider all relevant economic evaluations , either conducted alongside r and omised controlled trials or based on decision modelling estimates . These studies must include participants at risk of developing CVD/T2DM or with established disease in one or more of the South Asian countries ( India , Bangladesh , Pakistan , Sri Lanka , Nepal , Maldives , Bhutan and Afghanistan ) . We will identify relevant papers by systematic ally search ing all major data bases and registries . Selected articles will be screened by two independent research ers . Method ological quality of the studies will be assessed using a modified Drummond and a Phillips checklist . Cochrane guidelines will be followed for bias assessment in the effectiveness studies . Results Results will be presented in line with the PRISMA ( Preferred Reporting Items for Systematic review and Meta- analysis ) checklist , and overall quality of evidence will be presented as per the GRADE ( Grade s of Recommendation , Assessment , Development and Evaluation ) approach . Ethics and dissemination The study has received ethics approval from the All India Institute of Medical Sciences , New Delhi , India . The results of this review will provide policy-relevant recommendations for the uptake of cost-effectiveness evidence in prioritising decisions on essential chronic disease care packages for South Asia . Study registration number PROSPERO CRD42013006479 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 Introduction The extraskeletal role of vitamin D is being increasingly recognised . This has important clinical implication s , as vitamin D deficiency has reached epidemic proportions worldwide . Vitamin D has proposed anti-inflammatory properties , yet the role of vitamin D supplementation in reducing inflammation remains largely unknown . The purpose of this review is to investigate the impact of vitamin D supplementation on inflammation , and to identify relevant knowledge gaps in the field . Methods and analysis Medline , CINAHL , EMBASE and All EBM will be systematic ally search ed for r and omised controlled trials ( RCTs ) and systematic review s of RCTs , comparing vitamin D supplementation with placebo , usual care or other pharmacological or non-pharmacological interventions . One review er will assess articles for eligibility according to prespecified selection criteria , after which 2 independent review ers will perform data extraction and quality appraisal . Meta-analyses will be conducted where appropriate . Ethics and dissemination Formal ethical approval is not required as no primary data is collected . This systematic review will identify potential clinical implication s of vitamin D deficiency and supplementation , and will be disseminated through a peer- review ed publication and at conference meetings , to inform future research on the efficacy of vitamin D supplementation for inflammation and inflammatory diseases . PROSPERO registration number CRD42016037104 Background The prevalence of overweight and obesity is high amongst healthcare professionals and there is growing interest in delivering weight loss interventions in the workplace . We conducted a systematic review to ( i ) examine the effectiveness of workplace-based diet and /or physical activity interventions aim ed at healthcare professionals and to ( ii ) identify and describe key components of effective interventions . Seven electronic data bases were systematic ally search ed . Results Thirteen r and omised controlled trials met the inclusion criteria , of which seven had data available for meta- analysis . Where meta- analysis was possible , studies were grouped according to length of follow-up ( < 12 months and ≥12 months ) and behavioural target ( diet only , physical activity only or diet and physical activity ) , with outcome data pooled using a weighted r and om effects model . Nine studies reported statistically significant ( between-group ) differences . Four studies reported being informed by a behaviour change theory . Meta- analysis of all trials reporting weight data demonstrated healthcare professionals allocated to dietary and physical activity interventions lost significantly more body weight ( −3.95 Kg , [ 95 % CI −4.96 to- 2.95 Kg ] ) than controls up to 12 months follow up . Conclusions Workplace diet and /or physical activity interventions targeting healthcare professionals are limited in number and are heterogeneous . To improve the evidence base , we recommend additional evaluations of theory-based interventions and adequate reporting of intervention content THE CENTRAL THEME OF THE INSTITUTE OF MEDICINE report on the US drug safety system was the need for a life cycle approach to drug evaluation : both the benefits and the risks need to be evaluated and integrated during the entire market life of a drug . The Food and Drug Administration Amendments Act of 2007 also called on the agency to improve its methods of communicating risks and benefits to patients and physicians . The Institute of Medicine recommendation to “ develop and continually improve a systematic approach to risk-benefit analysis for use throughout the [ Food and Drug Administration ] in the preapproval and postapproval setting s ” specifically acknowledges the need for and the challenges of the development of new methods of combining evidence about risks and benefits . Information that combines the best evidence on benefits with the best data on risks is also needed for daily clinical practice . Whenever a patient and physician decide on a particular course of treatment , they do so because they expect that the likely benefits will exceed potential harms . For the benefits of drug treatments , they often have authoritative sources to provide information : r and omized trials and systematic review s and meta-analyses of such trials . For adverse effects , the situation is different . Given the average duration of r and omized trials ( often months to 1 or 2 years ) and the average number of patients in r and omized trials ( often dozens to a few hundred ) , such trials are at most able to detect and quantify frequent adverse events that occur only early during treatment . Moreover , the adverse effect has to be known beforeh and or anticipated to be recorded systematic ally in the trials . The study population in trials , which often includes young persons with a single diagnosis and without concurrent disease , is often not representative of those who will eventually use the drug in the community . The situation does not much improve in meta- analysis : the typical meta- analysis of r and omized trials covers 1000 to 2500 individuals , only half of whom will have taken the new drug . The sample size precludes good quantification of adverse effects unless they occur at least with a frequency of about 1 per 200 person-years . Meta-analyses of trials do not solve the problem of late adverse effects or the problem of the narrow population included in the trials . The information on harms from trials is incomplete , and the possibility of using and combining such information across trials in systematic review s is limited . Thus , to underst and the full spectrum of adverse effects — those that occur late , that were not known beforeh and , and that are rare but nevertheless serious— and to be able to investigate the true incidence of known adverse effects in circumstances of actual prescribing , well- design ed observational studies will always be necessary . It follows that systematic review s of drug treatments must include not only the results of r and omized trials on benefits but also evidence from observational research on harms . Although the idea to turn to observational data for evidence may be a surprise , the idea makes sense in view of what r and omization does and what r and omized trials are good at doing . R and omized trials are uniquely superior to evaluate the benefits , the intended or hoped-for effects of treatments . The r and om allocation mechanism is able to overcome the strong tendency of physicians to selectively prescribe treatments based on the perceived prognosis and likely outcomes of patients . Although prescriptions that are tailored to individual prognoses constitute desired medical practice , this effort also makes it difficult to compare the benefits of different treatments because patients who receive different treatments will have different prognoses , called “ confounding by indication . ” In general , data from routine daily practice can therefore not be used to assess the benefits of treatment , especially for the comparison between users and nonusers of a drug 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 Background The risk of developing cardiovascular disease is directly correlated to one ’s resting blood pressure ( BP ) , age , and biological sex . Resting BP can be reduced using h and grip exercise training , but the impact of age and sex on the effectiveness of training is not well documented . Methods / design A systematic search of the literature will be conducted for all experimental studies ( including r and omized controlled trials and prospect i ve experiments ) that report the influence of isometric h and grip exercise training on resting systolic blood pressure . The data bases Medline , Embase , Cochrane Review s , Cumulative Index to Nursing and Allied Health Literature ( CINAHL ) , SPORTD iscus , Web of Science , Allied and Complementary Medicine ( AMED ) , PubMed , and Scopus will be search ed until 1 December 2015 . Screening of potential articles , data abstract ion , and quality appraisal will be completed in duplicate independently . When necessary , corresponding authors will be contacted in order to facilitate the separation of pooled data into age and sex categories . Method ological quality will be determined using the Quality Assessment Framework developed by the Cochrane Collaboration and the Newcastle-Ottawa Quality Assessment Scale as appropriate . Any discrepancies will be resolved by a third author . Findings will be presented in accordance with the preferred reporting items for systematic review s and meta- analysis ( PRISMA ) guidelines . Discussion This systematic review will determine the overall effectiveness  of h and grip exercise training in improving resting blood pressure . A novel , focused assessment will contrast  effectiveness of h and grip training  based on the age ( younger 18–54 years , older > 55 years ) and the sex ( men , women ) of study participants . This information is essential to consoli date before moving forward with the development and implementation of h and grip exercise training programmes which are design ed to best meet the needs of particular cohorts . Systematic review registration PROSPERO Background Diabetic retinopathy ( DR ) is a common microvascular complication of diabetes mellitus , and more than 75 % of patients who have had diabetes for more than 20 years will have some degree of DR . This disease is highly destructive to self-esteem and puts a high burden on public health and pension systems due to the effects that it has on people of working age . The current mainstay of treatment is laser photocoagulation , which causes impairment of vision and discomfort to patients . Thus , finding a systemic drug that could act on all microcirculation and prevent direct manipulation of the eyes would be highly desirable . Objective To assess the efficacy and safety of the drugs in the statin and /or fibrate groups for the prevention and treatment of DR . Methods In this systematic review , we will select r and omized controlled trials of fibrates or statins used for the treatment or prevention of DR . Our search strategy will include free text terms and controlled vocabulary ( eg , MeSH , Emtree ) for , “ diabetic retinopathy ” , “ statins ” , “ fibrates ” , “ hypolipidemic agents ” , and for drugs from both groups . Data bases that will be used include Medical Literature Analysis and Retrieval System/ PubMed , Embase , Cochrane Central Register of Controlled Trials , Latin American and Caribbean Center on Health Sciences Information , Clinical trials.gov , World Health Organization International Clinical Trials Registry Platform , and OpenGrey , and we will not have language or date limits . Two review authors will independently select eligible studies and assess the risk of bias using the Cochrane Collaboration ’s tool . We will report structured summaries of the included studies and , if possible , conduct meta-analyses . Results This is a protocol for a systematic review , therefore results are not available . We registered a short version of this protocol before progressing in the review and we are currently in the process of selecting the studies for inclusion . Conclusions Intensive glucose control and lowering blood pressure and lipids are mechanisms that protect macrocirculation in diabetic patients . Both macrovascular and microvascular events in diabetic patients appear to have a common pathway , starting with endothelial injury . Thus , prevention and treatment of microvascular events may benefit from the same interventions . In the review for which we have written this protocol , we will assess whether the use of lipid-lowering oral drugs of the statin and /or fibrate groups may prevent and /or retard progression of DR , with the added benefit of preserving visual acuity . Trial Registration PROSPERO 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 BACKGROUND In the 2003 European Society of Hypertension-European Society of Cardiology ( ESH-ESC ) guidelines , it is concluded that the major classes of antihypertensive agents are suitable for the initiation and maintenance of antihypertensive therapy . The aim of this study was to compare the cost-effectiveness of each one of the major antihypertensive agents as monotherapy in the management of mild-to-moderate hypertension in Greece , when following the 2003 ESH-ESC guidelines . METHODS We performed a cost-effectiveness analysis based on numbers needed to treat . A decision analysis model was developed to compare chlorthalidone , propranolol , amlodipine , enalapril and losartan . Clinical inputs were derived from a meta- analysis and r and omized controlled trials and cost data from public sources . The evaluation of the cost of managing hypertension includes the cost of drug therapy , monitoring , treating side effects , poor compliance and switching . All costs were calculated from a public insurance system perspective , in 2004 Euros . Future costs and clinical benefits were discounted at 5 % . The time frame was 5 years . Extensive sensitivity analyses were also performed . RESULTS The cost ( in Euros ) of uncomplicated hypertension treatment for 5 years was 485.87 , 567.66 , 851.44 , 607.45 , and 1279.88 for chlorthalidone , propranolol , amlodipine , enalapril , and losartan , respectively . The estimated total cost ( in Euros ) to prevent one death was 60230.71 , 70369.96 , 105596.72 , 75301.40 , and 158659.35 , respectively . CONCLUSIONS In mild-to-moderate uncomplicated hypertension chlorthalidone is the most cost-effective agent . If it was the drug of choice to initiate treatment of uncomplicated hypertension , it would probably save the public insurance system organizations a great amount of expenses for benefit of the insured patients 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 Systematic review s , a cornerstone of evidence -based medicine , are not produced quickly enough to support clinical practice . The cost of production , availability of the requisite expertise and timeliness are often quoted as major contributors for the delay . This detailed survey of the state of the art of information systems design ed to support or automate individual tasks in the systematic review , and in particular systematic review s of r and omized controlled clinical trials , reveals trends that see the convergence of several parallel research projects . We surveyed literature describing informatics systems that support or automate the processes of systematic review or each of the tasks of the systematic review . Several projects focus on automating , simplifying and /or streamlining specific tasks of the systematic review . Some tasks are already fully automated while others are still largely manual . In this review , we describe each task and the effect that its automation would have on the entire systematic review process , summarize the existing information system support for each task , and highlight where further research is needed for realizing automation for the task . Integration of the systems that automate systematic review tasks may lead to a revised systematic review workflow . We envisage the optimized workflow will lead to system in which each systematic review is described as a computer program that automatically retrieves relevant trials , appraises them , extracts and synthesizes data , evaluates the risk of bias , performs meta- analysis calculations , and produces a report in real time Introduction Unscheduled hospital admissions are an increasing burden on health systems worldwide . To date , initiatives to reduce admissions have had limited success as it is unclear which strategies effectively reduce admissions and are supported by a strong evidence -base . Therefore , we will conduct an overview to find , assess and summarise all published peer- review ed systematic review s of r and omised controlled trials that examine the effect of an intervention on  unplanned admissions among adults . Methods and analysis This is a protocol for a systematic overview of review s. We will search four data bases : Ovid MEDLINE , PubMed , Cochrane Data base of Systematic Review s and the Cochrane Data base of Abstract s of Review s of Effects . We will consider systematic review s and meta-analyses of r and omised controlled trials in adults ( ≥16 years old ) evaluating the effect of any intervention on unscheduled hospital admissions including those to treat , monitor , diagnose or prevent a health problem . We will only include review s that identified unscheduled hospitalisations as a prespecified outcome . Two authors will independently screen articles for inclusion using a priori criteria . We will assess the quality of included review s and extract ratings of the quality of evidence from within each review . We will create a hierarchical list of interventions based on estimates of absolute admission reductions and the quality of the evidence . Presentation of results will align with guidelines in the Cochrane H and book of Systematic Review s of Interventions and the Preferred Reporting Items for Systematic Review s and Meta- Analysis statement . Ethics and dissemination Ethics approval is not required . We will su bmi t the results of this study for peer- review publication . The results will inform future research and could be used by healthcare managers , administrators and policymakers to guide re source allocation decisions and inform local implementation and optimisation of interventions to reduce unscheduled hospital admissions PURPOSE Health interventions based on theory may be more effective than those that are not . This review of review s synthesizes all published r and omized controlled trial ( RCT ) meta-analytic evidence from the last decade to examine whether theory-based interventions were found to be associated with more effective  adult health behaviour change interventions . METHODS Systematic review s including meta-analyses were identified by search ing Medline , CINAHL , PsycINFO , and CDSR . A narrative synthesis was used to summarize and analyse the evidence . Only review s including RCTs of health behaviour change interventions with adults aged 18 + published from 2007 to 2017 were included . RESULTS Of 8,659 articles , nine systematic review s met inclusion criteria . The majority of review s ( n = 8) suggested no increased effectiveness for theory-based compared to non-theory-based interventions for effectiveness of outcomes relating to health behaviour . Less than half of the RCTs included in the review s reported the use of theory ( 85/183 ) . Two review s suggested interventions based on control theory , motivational interviewing , or self-determination theory were associated with greater effectiveness for physical activity and /or dietary interventions and outcomes . Method ological and reporting issues limit the conclusions . CONCLUSIONS Theory-based interventions as currently operationalized in systematic review s were not found to be more effective than non-theory-based interventions . Method ological and reporting issues at study and review level may not reflect the true utility of theory use within health behaviour interventions . The promotion of theory use may benefit from using a multifaceted argument , rather than a narrow focus of increased effectiveness . Statement of contribution What is already known on this subject ? Theory use is regularly promoted by cl aim ing that it will lead to more effective behaviour change interventions . Theory use has been frequently linked to effectiveness within systematic review s of behaviour change interventions . The theory-effectiveness hypothesis has not been systematic ally examined at the systematic review level . What does this study add ? Theory use as operationalized by systematic review authors was not associated with increased effectiveness within systematic review s examining r and omized controlled trials of behaviour change interventions in adults . Interventions based on control theory , motivational interviewing , or self-determination theory were associated with greater effectiveness for physical activity and /or dietary interventions and outcomes . Theory use should be promoted using a multifaceted argument , and assertions for increased effectiveness of theory-based interventions should only be used in domains where specific evidence exists to support this cl aim Background :  Chemomechanical caries removal  is an effective alternative to the traditional rotary drilling method . The advantages of chemomechanical techniques in terms of the need for anesthesia , pain perception and patient preference are systematic ally review ed and a meta- analysis of the time required for caries removal is reported . Method : R and omized controlled studies of comparison of chemomechanical techniques with conventional rotary drill were selected from a systematic search of st and ard biomedical data bases , including the PubMed and Cochrane clinical trials . Non-repeated search results were screened for relevance and risk of bias assessment , followed by methodology assessment . Statistical models were applied to the outcome parameters - time required , pain perception , need of anesthesia and patient preference - extracted from the studies . Results : Out of the 111 non-repeated search results , 26 studies receiving a low bias score were selected for the review , and 16 r and omized clinical trials of rotary and Carisolv techniques were considered for meta- analysis . Meta- analysis by fixed effect as well as r and om effect models indicate that Carisolv takes more time ( 3.65 ± 0.05 and 4.09 ± 0.29 min ) than rotary drill ( 8.65 ± 0.09 and 8.97 ± 0.66 min ) method . Advantages of reduced pain ( 14.67 for Carisolv vs. 6.76 for rotary drill ) , need for anesthesia ( 1.59 % vs. 10.52 % ) outweigh the longer time requirement and make it the preferred ( 18.68 % vs. 4.69 % ) method . Conclusion : Chemomechanical techniques st and out as a minimally invasive and preferred method based on the meta-analyses . Evaluation of pain experienced using robust methods is needed to strengthen the evidence for their use 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 Objective To examine the prevalence of outcome reporting bias — the selection for publication of a subset of the original recorded outcome variables on the basis of the results — and its impact on Cochrane review s. Design A nine point classification system for missing outcome data in r and omised trials was developed and applied to the trials assessed in a large , unselected cohort of Cochrane systematic review s. Research ers who conducted the trials were contacted and the reason sought for the non-reporting of data . A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on review s that included a single meta- analysis of the review primary outcome . Results More than half ( 157/283 ( 55 % ) ) the review s did not include full data for the review primary outcome of interest from all eligible trials . The median amount of review outcome data missing for any reason was 10 % , whereas 50 % or more of the potential data were missing in 70 ( 25 % ) review s. It was clear from the publications for 155 ( 6 % ) of the 2486 assessable trials that the research ers had measured and analysed the review primary outcome but did not report or only partially reported the results . For reports that did not mention the review primary outcome , our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88 % ( 95 % CI 65 % to 100 % ) and specificity of 80 % ( 95 % CI 69 % to 90 % ) on the basis of responses from 62 trialists . A third of Cochrane review s ( 96/283 ( 34 % ) ) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome . In a sensitivity analysis undertaken for 81 review s with a single meta- analysis of the primary outcome of interest , the treatment effect estimate was reduced by 20 % or more in 19 ( 23 % ) . Of the 42 meta-analyses with a statistically significant result only , eight ( 19 % ) became non-significant after adjustment for outcome reporting bias and 11 ( 26 % ) would have overestimated the treatment effect by 20 % or more . Conclusions Outcome reporting bias is an under-recognised problem that affects the conclusions in a substantial proportion of Cochrane review s. Individuals conducting systematic review s need to address explicitly the issue of missing outcome data for their review to be considered a reliable source of evidence . Extra care is required during data extraction , review ers should identify when a trial reports that an outcome was measured but no results were reported or events observed , and contact with trialists should be encouraged
The effect of ARB on the improvement of the PWV level is not superior to other types of antihypertensive agents , but ARB is superior to other types of antihypertensive agents for improving the AI level .
Overall , to improve of arterial stiffness , ARB maybe is superior to other antihypertensive agents
BACKGROUND This system review and meta- analysis was conducted to systematic ally review and analyze the clinical benefits of different antihypertensive agents in improving arterial stiffness in hypertensive patients .