World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: Update 2013 on the acute and continuation treatment of unipolar depressive disorders Financial Conflicts of Interest and Conclusions About Neuraminidase Inhibitors for Influenza Opioid Modulation With Buprenorphine/Samidorphan as Adjunctive Treatment for Inadequate Response to Antidepressants: A Randomized Double-Blind Placebo-Controlled Trial. Issues related to the conduct of systematic reviews: a focus on the nutrition field. Antidepressant treatment for post-natal depression. Systematic comparison of study quality criteria. Aripiprazole augmentation in major depressive disorder: a double-blind, placebo-controlled study in patients with inadequate response to antidepressants. Improvement in functional outcomes with adjunctive aripiprazole versus placebo in major depressive disorder: a pooled post hoc analysis of 3 short-term studies. Biofeedback for treatment of awake and sleep bruxism in adults: systematic review protocol The effectiveness of yoga to prevent diabetes mellitus type 2 Is the Comparison between Exercise and Pharmacologic Treatment of Depression in the Clinical Practice Guideline of the American College of Physicians Evidence-Based? The Effectiveness of Psychosocial Interventions as Adjuncts to Orthopaedic Surgery: A Systematic Review Protocol Effectiveness of interventions that assist caregivers to support people with dementia living in the community: a systematic review. Serotonergic and Noradrenergic Modulation of Emotion Processing by Single Dose Antidepressants Interventions for domestic violence among pregnant women in low- and middle-income countries: a systematic review protocol The impact of outcome reporting bias in randomised controlled trials on a cohort of systematic reviews Effectiveness of interventions that assist caregivers to support people with dementia living in the community: a systematic review Effectiveness of parent‐centred interventions for the prevention and treatment of childhood overweight and obesity in community settings: a systematic review The B-VITAGE trial: A randomized trial of homocysteine lowering treatment of depression in later life Elusive search for effective provider interventions: a systematic review of provider interventions to increase adherence to evidence-based treatment for depression Efficacy and tolerability of flexibly-dosed adjunct TC-5214 (dexmecamylamine) in patients with major depressive disorder and inadequate response to prior antidepressant Nonoperative Management or ‘Watch and Wait’ for Rectal Cancer with Complete Clinical Response After Neoadjuvant Chemoradiotherapy: A Critical Appraisal How to write an evidence-based clinical review article.
Abstract Objectives . This 2013 up date of the practice guidelines for the biological treatment of unipolar depressive disorders was developed by an international Task Force of the World Federation of Societies of Biological Psychiatry ( WFSBP ) . The goal has been to systematic ally review all available evidence pertaining to the treatment of unipolar depressive disorders , and to produce a series of practice recommendations that are clinical ly and scientifically meaningful based on the available evidence . The guidelines are intended for use by all physicians seeing and treating patients with these conditions . Methods . The 2013 up date was conducted by a systematic up date literature search and appraisal . All recommendations were approved by the Guidelines Task Force . Results . This first part of the guidelines ( Part 1 ) covers disease definition , classification , epidemiology , and course of unipolar depressive disorders , as well as the management of the acute and continuation phase treatment . It is primarily concerned with the biological treatment ( including antidepressants , other psychopharmacological medications , electroconvulsive therapy , light therapy , adjunctive and novel therapeutic strategies ) of adults . Conclusions . To date , there is a variety of evidence -based antidepressant treatment options available . Nevertheless there is still a substantial proportion of patients not achieving full remission . In addition , somatic and psychiatric comorbidities and other special circumstances need to be more thoroughly investigated . Therefore , further high- quality informative r and omized controlled trials are urgently needed Industry funding and author financial conflicts of interest may influence the production and synthesis of scientific evidence ( 1 ) . Associations with the pharmaceutical company developing and marketing a drug have been found to influence the design of trials ( 2 ) , the conduct of trials ( 3 ) , and the reporting of trial results ( 47 ) . Furthermore , financial ties and industry funding seem to result in greater rates of favorable conclusions in clinical trials examining new drugs ( 812 ) . Fewer studies have considered the potential influence of financial conflicts of interest on the synthesis of clinical evidence in systematic review s ( 13 , 14 ) . Neuraminidase inhibitors , which are used in the prophylaxis and treatment of seasonal and p and emic influenza , have been the subject of ongoing uncertainty about their specific clinical benefits ( 15 , 16 ) . This is the result of not only the continuing emergence of strains with unknown drug responses but also the increasing awareness in the medical community that , until recently , its knowledge of the safety and efficacy of these drugs has been incomplete ( 17 ) . Despite the abundance of clinical trials and publications on neuraminidase inhibitors , the details of many key trials had not been disclosed ( 18 , 19 ) . As a result , systematic review ers analyzing and synthesizing evidence on the effectiveness of these agents have faced incomplete information , unresolved discrepancies in the data , and a high risk of publication and reporting biases among the primary clinical trials ( 20 , 21 ) . This prompted extensive efforts to access complete records of all published and unpublished clinical trials from manufacturers , culminating in the publication of several review s on the basis of comprehensive clinical study reports and potentially changing the way systematic review s will be undertaken in the future ( 2227 ) . Review s of neuraminidase inhibitors exhibit wide variation in their conclusions , ranging from strong endorsements of the use of these agents in the prophylaxis and treatment of influenza ( 28 , 29 ) to more conservative assessment s question ing the evidence on the drugs ' safety and efficacy ( 15 , 30 ) . The reasons for this discordance in review conclusions are likely multifactorial and may be related in part to the manner in which evidence is accessed , synthesized , and presented ( 23 , 27 ) , both in terms of the numerical results and the authors ' emphasis and interpretation ( 31 , 32 ) . Our aim was to determine whether there is an association between financial conflicts of interest and the favorable presentation of evidence in systematic review s on the use of neuraminidase inhibitors for the prophylaxis and treatment of influenza . Methods Data Sources Systematic review s were identified in PubMed , PubMed In Process , EMBASE , and the Cochrane Data base of Systematic Review s. Search es were done using the keywords influenza , neuraminidase inhibitors , oseltamivir , zanamivir , peramivir , and laninamivir . Articles were retrieved if the search terms appeared in the title or abstract or were included as data base-specific keywords . In PubMed and EMBASE , search es were also constrained to review publication types . We limited our search to English- language articles published since 1 January 2005 . These articles were manually review ed to identify those that focused on the use of neuraminidase inhibitors for influenza prophylaxis or treatment ( such as excluded articles primarily about drug development or other manufacturing processes ) . We selected all review s that used a systematic search protocol , which we defined as the inclusion and reporting of an explicit search strategy , including reasons for subsequent exclusion of articles . The final search es were done on 26 May 2014 . Cochrane review s are periodically up date d to incorporate new evidence , and the results and conclusions are resynthesized as indicated . The authors of these review s are typically different , and there may be differences in the methods as well as the results and language of the review . These up date d review s were included separately . Other Cochrane review s are occasionally rewritten by a subset of the authors for publication in medical journals as abridged versions to increase dissemination . These reports have separate peer review s and are prepared on the basis of a selection of the complete results . We considered these review s separately as well but also did a sensitivity analysis in which they were combined with the original Cochrane review s. Data Extraction Financial conflicts of interest were identified for all authors of the review s and included affiliations with or funding from the pharmaceutical company manufacturing any of the neuraminidase inhibitors under review . We defined financial conflicts of interest as employment , the funding of grants paid to an author or an author 's research group , and the funding of medical writers for the systematic review . These financial conflicts of interest were identified using information about affiliations or funding listed in the systematic review s , as well as in any other articles published by one of the authors during the 3 years before the publication of the index systematic review . In addition , we search ed authors ' personal and institutional Web sites ; lists of disclosures from GlaxoSmithKline ( Research Triangle Park , North Carolina ) and Roche Pharmaceuticals ( Basel , Switzerl and ) ; and performed Web search es combining the names of the authors , drugs , and pharmaceutical companies to identify any additional information about financial relationships . Details of the specific financial conflicts of interest identified for each author are listed in Appendix Table 1 . Appendix Table 1 . Financial Conflicts of Interest Among Authors of the Systematic Review s For each systematic review , we recorded whether prophylaxis or treatment was assessed , the forms of evidence to be included ( such as r and omized , controlled trials and observational studies ) , the specific clinical outcomes assessed , the population s examined , and whether meta-analyses were done . We also examined whether the review s included information about the validity or quality of the primary literature . In particular , we recorded whether there were statements addressing nonpublication of primary studies or publication bias , including tests done by the review ers to assess for bias in meta-analyses ( such as the Egger or Begg test [ 33 , 34 ] ) , difficulty in accessing comprehensive study data , and the prevalence or role of industry in conducting and funding the primary studies . Data Analysis Two investigators were provided with redacted copies of each review that did not include the review s ' authors , their affiliations , or information on financial conflicts of interest . These versions also did not contain the journal name , journal formatting , or the article 's acknowledgments or references . The investigators independently evaluated the review s and classified the prophylaxis and treatment assessment s as favorable or not favorable toward the use of neuraminidase inhibitors . They were instructed to do this grading on the basis of the entirety of the review text without restriction to conclusions or recommendations made in any specific section of the review , thus allowing them to take into account the emphasis and interpretation of the authors throughout the review . The agreement between the investigators was strong at 86 % ( Cohen , 0.72 ; P < 0.001 ) . Disagreements were resolved by a third investigator using the same redacted copies . Descriptive analyses were done to examine the associations between financial conflicts of interest and the grading of the systematic review s. A sensitivity analysis excluding the summary review s was done to further examine this association . We also assessed the association between financial conflicts of interest and the inclusion of statements addressing the validity or quality of the primary evidence . Role of the Funding Source This study was funded by the Australian National Health and Medical Research Council . The funding source had no role in the design and conduct of the study , analysis of the results , or the decision to su bmi t the manuscript for publication . Results We identified 827 published articles across the 4 data bases using the specified search criteria , with 26 systematic review s included in the final cohort ( Figure ) . Thirteen review s examined prophylaxis and 24 examined treatment of influenza , accounting for 37 distinct assessment s ( Appendix Table 2 ) . In terms of review methods , 7 were Cochrane systematic review s and 19 conducted and reported a meta- analysis ( 73 % ) . The evidence inclusion criteria were limited to r and omized , controlled trials for 14 of the systematic review s ( 54 % ) , and 5 included evidence from clinical study reports or patient-level data . The main population s examined were healthy adults ( 18 of 26 systematic review s ) , children ( 13 of 26 ) , and hospitalized patients ( 6 of 24 ) . The outcome measures for prophylaxis assessment s included influenza-like illness and laboratory-confirmed influenza . For the treatment assessment s , the outcomes were illness duration , influenza-related complications , hospitalization , and mortality , mostly in combination . Five review s were up date s of previous Cochrane review s , and 3 were summary review s based on Cochrane review s. Figure . Summary of evidence search and selection . Eligible systematic review s included those with outcomes related to the prophylaxis or treatment of influenza . Appendix Table 2 . Characteristics of Systematic Review s Examining Prophylaxis and Treatment Outcomes for Neuraminidase Inhibitors Association Between Financial Conflicts of Interest and Favorable Assessment s Seven of the 26 systematic review s ( 27 % ) , corresponding to 8 of the 37 assessment s ( 22 % ) , were associated with a financial conflict of interest ( Appendix Table 1 ) . We identified financial conflicts of interest in publications other than the index systematic review in 2 cases , and no additional OBJECTIVE Major depressive disorder has been associated with dysregulation of the endogenous opioid system . The authors sought to determine whether opioid modulation achieved through administration of ALKS 5461 , a combination of a μ- and κ-opioid partial agonist , buprenorphine , and a μ-opioid antagonist , samidorphan , would exhibit antidepressant activity in patients with major depression . METHOD A multicenter , r and omized , double-blind , placebo-controlled , two-stage sequential parallel comparison design study was conducted in adults with major depression who had an inadequate response to one or two courses of antidepressant treatment . Participants were r and omly assigned to receive adjunctive treatment with 2 mg/2 mg of buprenorphine/samidorphan ( the 2/2 dosage group ) , 8 mg/8 mg of buprenorphine/samidorphan ( the 8/8 dosage group ) , or placebo .  Antidepressant effect was measured based on change from baseline to the end of 4 weeks of treatment on the 17-item Hamilton Depression Rating Scale ( HAM-D ) , the Montgomery-Åsberg Depression Rating Scale ( MADRS ) , and the Clinical Global Impressions severity scale ( CGI-S ) . RESULTS Compared with the placebo group , there were significantly greater improvements in the 2/2 dosage group across the three depression outcome measures ( HAM-D : -2.8 , 95 % CI=-5.1 , -0.6 ; MADRS : -4.9 , 95 % CI=-8.2 , -1.6 ; CGI-S : -0.5 , 95 % CI=-0.9 , -0.1 ) . There was also evidence of improvement in the 8/8 dosage group , although it did not achieve statistical significance . Overall , the buprenorphine/samidorphan combinations were well tolerated , and there was no evidence of opioid withdrawal on treatment discontinuation . CONCLUSIONS The buprenorphine/samidorphan combination is a novel and promising c and i date for treatment of major depressive disorder in patients who have an inadequate response to st and ard antidepressants 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 BACKGROUND : Postnatal depression is a common disorder , which can have profound short and long term effects on maternal morbidity , the new infant and the family as a whole . Social factors appear to be particularly important in the aetiology and prognosis of postnatal depression and treatment is often largely social support and psychological interventions . It is not known whether antidepressants are an effective and safe choice for treatment of this disorder . OBJECTIVES : To evaluate the effectiveness of different antidepressant drugs  and compare their effectiveness with other forms of treatment . To assess any adverse effects of antidepressants in the mother or the nursing baby . SEARCH STRATEGY : The registers of clinical trials maintained and up date d by the Cochrane Depression , Anxiety and Neurosis Group and the Cochrane Pregnancy and Childbirth Group were search ed . Other data bases ( outlined below ) were also search ed and contacts were made with pharmaceutical companies and experts in the field . SELECTION CRITERIA : All trials were considered in which women with depression in the first six months postpartum were r and omised to receive antidepressants alone or in combination with another treatment , or to receive any other treatment including placebo . DATA COLLECTION AND ANALYSIS : Data was extracted independently from the trial reports by the review ers . Missing information was requested from investigators wherever possible . Data was sought to allow an " intention to treat " analysis . MAIN RESULTS : Only one trial could be included in this review , leaving most of the objectives of the review unfulfilled . Appleby et al ( 1997 ) reported that Fluoxetine was significantly more effective than placebo and , after an initial session of counselling , as effective as a full course of cognitive-behavioural counselling in the treatment of postnatal depression . There was no interaction between medication and counselling . REVIEW ER 'S CONCLUSIONS : Women with postnatal depression can be effectively treated with fluoxetine , which is as effective as a course of cognitive-behavioural counselling in the short-term . However , more trials with a longer follow-up period are needed to compare different antidepressants in the treatment of postnatal depression , and to compare antidepressant treatment with psychosocial interventions .  This is an area that has been neglected despite the large public health impact described above Approaches for the systematic review and evaluation of chemical toxicity are currently being reconsidered , with a specific focus on the evaluation of individual studies and their integration into the overall body of evidence . This renewed interest has arisen , in part , as a result of several prominent review s of these approaches by special committees of the National Research Council ( NRC ) , among others . We conducted a critical evaluation of several available frameworks for evaluating study quality . We assessed the criteria separately for human , animal , and in vitro studies as well as for systematic review s. We then evaluated commonalities across disciplines . We also considered the potential implication s of applying criteria frameworks and how they bear on fundamental risk assessment questions . We found that the available frameworks within each discipline differed in terms of their intended purpose and level of guidance for decision making . All the frameworks across disciplines shared common themes , however , including the adequate reporting of specific details of study conditions and design / protocol , selection and r and omization of study groups ( where applicable ) , outcome assessment methods and applicability ( e.g. , validity and reliability ) , avoidance of selective reporting , and the consideration of potential confounders or bias . We identified the most informative study quality considerations , which will enable research ers to implement more objective and st and ardized methods for evaluating studies and , ultimately , improve risk assessment methods INTRODUCTION Effective management of  major depressive disorder ( MDD ) continues to be a challenging task for psychiatrists and primary care physicians . This trial evaluated the efficacy and safety of adjunctive aripiprazole versus antidepressant monotherapy in patients with MDD and independently replicated the positive findings of two similar trials . METHODS Patients ( N=1,147 ) with MDD experiencing a major depressive episode and a history of inadequate response to antidepressant monotherapy were enrolled ( week 0 ) ; 827 received single-blind adjunctive placebo plus open-label antidepressant ( escitalopram , fluoxetine , paroxetine controlled release , sertraline , or venlafaxine extended release ) for 8 weeks to confirm inadequate response to antidepressants ; 349 patients with inadequate response were r and omized ( 1:1 ) to double-blind , adjunctive placebo ( n=172 ) or adjunctive aripiprazole ( n=177 ; 2 - 20 mg/day ) . Primary outcome was the mean change in Montgomery-Asberg Depression Rating Scale ( MADRS ) Total score from baseline ( week 8) to endpoint ( week 14 ) . RESULTS Clinical ly significant improvements in depressive symptoms as assessed by decreases in the MADRS Total score were greater with adjunctive aripiprazole ( -10.1 ) than placebo ( -6.4 ; P<.001 ) . Remission rates were greater for adjunctive aripiprazole than for adjunctive placebo ( week 14 , 36.8 % vs 18.9 % ; P<.001 ) . Completion rates with adjunctive aripiprazole and placebo were high ( 83 % vs. 87 % ) and discontinuations due to adverse events were low ( 6.2 % vs 1.7 % ) . CONCLUSION For some patients with MDD who do not obtain adequate symptom relief with antidepressant monotherapy , adjunctive therapies can significantly improve depressive symptoms . As reported , adjunctive aripiprazole was associated with a two-fold higher remission rate than adjunctive placebo . This , and previous studies , have shown that discontinuations due to adverse events were low and completion rates were high , and has indicated that both antidepressant and aripiprazole in combination were relatively well-tolerated and safe . This is the third consecutive clinical trial , in the absence of a failed trial , to demonstrate that aripiprazole augmentation to antidepressants is an efficacious and well-tolerated treatment for patients with MDD who do not respond adequately to st and ard antidepressant monotherapy ( Clinical Trials.gov study NCT00105196 ) OBJECTIVE To evaluate the effect of adjunctive aripiprazole to antidepressant therapy ( ADT ) on functional outcomes , as assessed by the Sheehan Disability Scale ( SDS ) . METHOD A post hoc analysis of pooled data from 3 similarly design ed r and omized , placebo-controlled trials was conducted ( CN138 - 139 [ September 2004-December 2006 ] , CN138 - 163 [ June 2004-April 2006 ] , and CN138 - 165 [ March 2005-April 2008 ] ) . Patients with DSM-IV major depressive disorder who had a prior inadequate response to ADT received adjunctive aripiprazole or placebo to st and ard ADT . The change from baseline to endpoint on total SDS score and on individual SDS domains and the distributional categorical shifts of patient-reported severity of functional impairment on the SDS were assessed . RESULTS Aripiprazole compared to placebo augmentation produced significant improvements in self-reported functioning levels in the SDS mean total score ( -1.2 vs -0.7 , P ≤ .001 ) and social life ( -1.4 vs -0.7 , P ≤ .001 ) and family life ( -1.4 vs -0.7 , P ≤ .001 ) domains . Additionally , a significant number of patients exhibited a shift from a severe/moderate level of impairment at baseline to a mild level of functional impairment after 6 weeks of adjunctive aripiprazole treatment compared with placebo in the SDS mean total score ( P = .001 ) and social life ( P ≤ .001 ) and family life ( P = .001 ) scores . CONCLUSIONS Aripiprazole augmentation of st and ard antidepressant therapy result ed in significant improvements in both total and individual domains of functioning , as assessed by the SDS , with significant categorical shifts from severe/moderate to mild levels of functioning compared with placebo augmentation . TRIAL REGISTRATION Clinical Trials.gov identifiers : NCT00095823 , NCT00095758 , and NCT00105196 Background Bruxism is a disorder of jaw-muscle activity characterised by repetitive clenching or grinding of the teeth which results in discomfort and damage to dentition . The two clinical manifestations of the condition ( sleep and awake bruxism ) are thought to have unrelated aetiologies but are palliated using similar techniques . The lack of a definitive treatment has prompted renewed interest in biofeedback , a behaviour change method that uses electronic detection to provide a stimulus whenever bruxism occurs . This systematic review aims to provide a comprehensive overview of the state of research into biofeedback for bruxism ; to assess the efficacy and acceptability of  biofeedback therapy in management of awake bruxism and , separately , sleep bruxism in adults ; and to compare findings between the two variants . Methods A systematic review of published literature examining biofeedback as an intervention directed at controlling primary bruxism in adults . We will search electronic data bases and the grey literature using a predefined search strategy to identify r and omised and non-r and omised studies , technical reports and patents . Search es will not be restricted by language or date and will be exp and ed through contact with authors and experts , and by following up reference lists and citations . Two authors , working independently , will conduct screening of search results , study selection , data extraction and quality assessment and a third will resolve any disagreements . The primary outcomes of acceptability and effectiveness will be assessed using only r and omised studies , segregated by bruxism subtype . A meta- analysis of these data will be conducted only if pre-defined conditions for quality and heterogeneity are met , otherwise the data will be summarized in narrative form . Data from non-r and omised studies will be used to augment a narrative synthesis of the state of technical developments and any safety-related issues . PROSPERO registration number : CRD42013006880 . Discussion Biofeedback is not new , but its place in the clinical management of bruxism remains unclear . New research , and the availability of miniaturized consumer- grade devices , makes a systematic review timely to guide treatment decisions and inform future research 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 Major depression disorder is most commonly treated with antidepressants . However , due to their side effects clinicians seek non-pharmacologic options , and one of these is exercise . The literature on the benefits of exercise for depression is extensive . Nevertheless , two recent review s focusing on antidepressants vs. other therapies as a basis for clinical practice guidelines recommended mainly antidepressants , excluding exercise as a viable choice for treatment of depression . The aim of this perspective is to analyze the literature exploring the reasons for this discrepancy . Two categories of publications were examined : r and omized controlled trials ( RCTs ) and meta-analyses or systematic review s. Based on this re assessment , RCTs comparing exercise to antidepressants reported that exercise and antidepressants were equally effective . RCTs comparing exercise combined with antidepressants to antidepressants only reported a significant improvement in depression following exercise as an adjunctive treatment . Almost all the review s examining exercise vs. other treatments of depression , including antidepressants , support the use of exercise in the treatment of depression , at least as an adjunctive therapy . The two review s examining pharmacologic vs. non-pharmacologic therapies as a basis for clinical practice guidelines examined limited evidence on exercise vs. antidepressants . In addition , it is possible that academics and health care practitioners are skeptical of viewing exercise as medicine . Maybe , there is a reluctance to accept that changes in lifestyle as opposed to pharmacological treatment can alter biological mechanisms . Longitudinal studies are needed for assessing the effectiveness of exercise in real clinical setting s , as well as studies exploring dose-response relationship between exercise and depression AIMS Pain and anxiety are commonly reported among those undergoing orthopaedic surgery . Improvement in anxiety and pain control might be achieved by supplementing st and ard care with psychological interventions . However , the effectiveness of adjunctive psychosocial interventions in anxiety and pain control have not been addressed sufficiently by previous systematic review s in orthopaedic surgeries . The present study aim ed to assess the effectiveness of adjunctive psychosocial techniques to improve perioperative clinical care in orthopaedic surgery , to identify the most effective intervention types and to evaluate potential moderators . METHODS We will perform a systematic review and meta- analysis to address the study aims . PubMed , PsycINFO , CINAHL and ProQuest Dissertations & Theses will be search ed between 1980 and 2015 . Prospect i ve controlled clinical trials completed in adults , contrasting st and ard care and st and ard care supplemented with psychosocial methods  , will be eligible for inclusion . Effectiveness will be assessed through the outcomes of postoperative pain intensity , analgesic requirement , perioperative anxiety , quality of life and postoperative recovery . The results of a r and om-effect meta- analysis will be reported . To aid implementation of best practice , moderating effects of the type and timing of psychosocial intervention , type of surgical intervention and type of anaesthesia will be evaluated through meta-regression . Sensitivity analyses and subgroup contrasts will follow as necessary . DISCUSSION Recommendations will be made to improve medical care in orthopaedic procedures . The quality of evidence will be rated using GRADE criteria . Copyright © 2016 John Wiley & Sons , OBJECTIVES The objective of this review was to assess the effectiveness of interventions that assist caregivers to provide support for people living with dementia in the community . INCLUSION CRITERIA Types of participants Adult caregivers who provide support for people with dementia living in the community ( non-institutional care).Types of interventions Interventions design ed to support caregivers in their role such as skills training , education to assist in caring for a person living with dementia and support groups/programs . Interventions of formal approaches to care design ed to support caregivers in their role , care planning , case management and specially design ated members of the healthcare team - for example dementia nurse specialist or volunteers trained in caring for someone with dementia . Types of studies This review considered any meta-analyses , systematic review s , r and omised control trials , quasi-experimental studies , cohort studies , case control studies and observational studies without control groups that addressed the effectiveness of interventions that assist caregivers to provide support for people living with dementia in the community . SEARCH STRATEGY The search sought to identify published studies from 2000 to 2005 through the use of electronic data bases . Only studies in English were considered for inclusion . The initial search was conducted of the data bases , CINAHL , MEDLINE and PsychINFO using search strategies adapted from the Cochrane Dementia and Cognitive Improvement Group . A second more extensive search was then conducted using the appropriate Medical Subject Headings ( MeSH ) and keywords for other available data bases . Finally , h and search ing of reference lists of articles retrieved and of core dementia , geriatric and psycho geriatric journals was undertaken . ASSESSMENT OF QUALITY Method ological quality of each of the articles was assessed by two independent review ers using appraisal checklist developed by the Joanna Briggs Institute and based on the work of the Cochrane Collaboration and Centre for Review s and Dissemination . DATA COLLECTION AND ANALYSIS St and ardised mean differences or weighted mean differences and their 95 % confidence intervals were calculated for each included study reported in the meta- analysis . Results from comparable groups of studies were pooled in statistical meta- analysis using Review Manager Software from the Cochrane Collaboration . Heterogeneity between combined studies was tested using st and ard chi-square test . Where statistical pooling was not appropriate or possible , the findings are summarised in narrative form . RESULTS A comprehensive search of relevant data bases , h and search ing and cross referencing found 685 articles that were assessed for relevance to the review . Eighty-five papers appeared to meet the inclusion criteria based on title and abstract , and the full paper was retrieved . Of the 85 full papers review ed , 40 were accepted for inclusion , three were systematic review s , three were meta- analysis , and the remaining 34 were r and omised controlled trials . For the r and omised controlled trials that were able to be included in a meta- analysis , st and ardised mean differences or weighted mean differences and their 95 % confidence intervals were calculated for each . Results from comparable groups of studies were pooled in statistical meta- analysis using Review Manager Software and heterogeneity between combined studies was assessed by using the chi-square test . Where statistical pooling was not appropriate or possible , the findings are summarised in narrative form . The results are discussed in two main sections . Firstly it was possible to assess the effectiveness of different types of caregiver interventions on the outcome categories of depression , health , subjective well-being , self-efficacy and burden . Secondly , results are reported by main outcome category . For each of these sections , meta- analysis was conducted where it was possible ; otherwise , a narrative summary describes the findings . EFFECTIVENESS OF INTERVENTION TYPE Four categories of intervention were included in the review - psycho-educational , support , multi-component and other . Psycho-educational Thirteen studies used  psycho-educational interventions  , and all but one showed positive results across a range of outcomes . Eight studies were entered in a meta- analysis . No significant impact of psycho-educational interventions was found for the outcome categories of subjective well-being , self-efficacy or health . However , small but significant results were found for the categories of depression and burden . Support Seven studies discussed support only interventions and two of these showed significant results . These two studies were suitable for meta- analysis and demonstrated a small but significant improvement on caregiver burden . Multi-component Twelve of the studies report multi-component interventions and 10 of these report significant outcomes across a broad range of outcome measures including self-efficacy , depression , subjective well-being and burden . Unfortunately because of the heterogeneity of study design s and outcome measures , no meta- analysis was possible . Other interventions Other interventions included the use of exercise or nutrition which result ed in improvements in psychological distress and health benefits . Case management and a computer aided support intervention provided mixed results . One cognitive behavioural therapy study reported a reduction in anxiety and positive impacts on patient behaviour . EFFECTIVENESS OF INTERVENTIONS USING SPECIFIC OUTCOME CATEGORIES In addition to analysis by type of intervention it was possible to analyse results based on some outcome categories that were used across the studies . In particular the impact of interventions on caregiver depression was available for meta- analysis from eight studies . This indicated that multi-component and psycho-educational interventions showed a small but significant positive effect on caregiver depression . Five studies using the outcome category of caregiver burden  were entered into a meta- analysis and findings indicated that there were no significant effects of any of interventions . No meta- analysis was possible for the outcome categories of health , self-efficacy or subjective well-being . IMPLICATION S FOR PRACTICE From this review there is evidence to support the use of well- design ed psycho-educational or multi-component interventions for caregivers of people with dementia who live in the community . Factors that appear to positively contribute to effective interventions are those which : Factors which do not appear to have benefit in interventions are those which Serotonergic and noradrenergic pathways are the main targets of antidepressants . Their differential effects on emotion processing-related brain activation are , however , to be further characterized . We aim ed at elucidating the neural sites of action of an acute differential serotonergic and noradrenergic influence on an emotion-processing task , which was earlier shown to be associated with depressiveness . In a single-blind pseudo-r and omized crossover study , 21 healthy subjects ( 16 subjects finally included in the analysis ) participated to ingest a single dose at three time points of either 40 mg citalopram , a selective serotonin-reuptake inhibitor , 8 mg reboxetine , a selective noradrenaline-reuptake inhibitor , or placebo 2–3 h before functional magnetic resonance imaging ( fMRI ) . During fMRI , subjects performed a task comprising the anticipation and perception of pictures of either ‘ known ’ ( positive , negative , neutral ) or ‘ unknown ’ valence ( r and omly 50 % positive or negative ) . In direct comparison with citalopram and with placebo , reboxetine increased brain activity in the medial thalamus . Citalopram modulated certain prefrontal and insular areas more prominently . Other frontal and parieto-occipital areas were modulated by both drugs . In conclusion , the functional network involved in emotional information processing could be modulated by the acute application of selective noradrenergic and serotonergic drugs revealing a noradrenergic effect in thalamic and frontal areas , and a prefrontal and insular focus of serotonergic modulation . These findings could have implication s for future selection criteria concerning personalized antidepressant medication in depression Background Violence during pregnancy is a global problem , associated with serious health risks for both the mother and baby . Evaluation of interventions targeted for reducing or controlling domestic violence ( DV ) is still in its infancy , and the majority of findings are primarily from high-income countries ( HICs ) . Therefore , there is an urgent need for generating evidence of DV interventions among pregnant women in low- and middle-income countries ( LMICs ) . Methods Preferred Reporting Items for Systematic Review s and Meta-Analyses ( PRISMA ) guidelines will be employed to structure the review . A comprehensive search will be carried out via electronic data bases including MEDLINE , CINAHL , Scopus , Embase , Web of Science , PsycINFO , and The Cochrane library . Gray literature will also be scrutinized for potential articles . An optimal search strategy has been developed following consultations with subject-matter experts and librarians . This search strategy will be adapted to the different data bases . Experimental studies evaluating DV interventions among pregnant women from LMICs will be included in the review . The review will only include literature written in English . Two review ers will independently screen and assess studies for inclusion in the review . A third author will resolve any discrepancies between the review ers . Risk of bias will be assessed based on the Cochrane risk of bias assessment tool , and overall quality of the evidence will be judged using Grading of Recommendations , Assessment , Development , and Evaluation ( GRADE ) criteria . Findings will be presented with the narrative synthesis , and if applicable , they will be further quantified using r and om-effects meta- analysis . Effect size , risk ratio for dichotomous variables , and st and ardized mean differences for continuous variables will be calculated for each outcome using Review Manager 5.3 . Discussion Systematic review s to evaluate the efficacy of interventions to address DV within the perinatal context have been limited . Hence , no one intervention has emerged as substantially effective towards addressing perinatal DV and associated health consequences . The evidence generated from this systematic review will inform research ers and policy makers about the effectiveness of existing DV interventions among pregnant women in LMICs and provide recommendations for future research in this area . This in turn will contribute towards violence prevention in LMICs . Systematic review registration PROSPERO 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 Objectives The objective of this review was to assess the effectiveness of interventions that assist caregivers to provide support for people living with dementia in the community . Inclusion criteria Types of participants Adult caregivers who provide support for people with dementia living in the community ( non‐institutional care ) . Types of interventions Interventions design ed to support caregivers in their role such as skills training , education to assist in caring for a person living with dementia and support groups/programs . Interventions of formal approaches to care design ed to support caregivers in their role , care planning , case management and specially design ated members of the healthcare team ‐ for example dementia nurse specialist or volunteers trained in caring for someone with dementia . Types of studies This review considered any meta‐analyses , systematic review s , r and omised control trials , quasi‐experimental studies , cohort studies , case control studies and observational studies without control groups that addressed the effectiveness of interventions that assist caregivers to provide support for people living with dementia in the community . Search strategy The search sought to identify published studies from 2000 to 2005 through the use of electronic data bases . Only studies in English were considered for inclusion . The initial search was conducted of the data bases , CINAHL , MEDLINE and PsychINFO using search strategies adapted from the Cochrane Dementia and Cognitive Improvement Group . A second more extensive search was then conducted using the appropriate Medical Subject Headings ( MeSH ) and keywords for other available data bases . Finally , h and search ing of reference lists of articles retrieved and of core dementia , geriatric and psycho geriatric journals was undertaken . Assessment of quality Method ological quality of each of the articles was assessed by two independent review ers using appraisal checklist developed by the Joanna Briggs Institute and based on the work of the Cochrane Collaboration and Centre for Review s and Dissemination . Data collection and analysis St and ardised mean differences or weighted mean differences and their 95 % confidence intervals were calculated for each included study reported in the meta‐ analysis . Results from comparable groups of studies were pooled in statistical meta‐ analysis using Review Manager Software from the Cochrane Collaboration . Heterogeneity between combined studies was tested using st and ard chi‐square test . Where statistical pooling was not appropriate or possible , the findings are summarised in narrative form . Results A comprehensive search of relevant data bases , h and search ing and cross referencing found 685 articles that were assessed for relevance to the review . Eighty‐five papers appeared to meet the inclusion criteria based on title and abstract , and the full paper was retrieved . Of the 85 full papers review ed , 40 were accepted for inclusion , three were systematic review s , three were meta‐ analysis , and the remaining 34 were r and omised controlled trials . For the r and omised controlled trials that were able to be included in a meta‐ analysis , st and ardised mean differences or weighted mean differences and their 95 % confidence intervals were calculated for each . Results from comparable groups of studies were pooled in statistical meta‐ analysis using Review Manager Software and heterogeneity between combined studies was assessed by using the chi‐square test . Where statistical pooling was not appropriate or possible , the findings are summarised in narrative form . The results are discussed in two main sections . Firstly it was possible to assess the effectiveness of different types of caregiver interventions on the outcome categories of depression , health , subjective well‐being , self‐efficacy and burden . Secondly , results are reported by main outcome category . For each of these sections , meta‐ analysis was conducted where it was possible ; otherwise , a narrative summary describes the findings . Effectiveness of intervention type Four categories of intervention were included in the review ‐ psycho‐educational , support , multi‐component and other . Psycho‐educational Thirteen studies used  psycho‐educational interventions , and all but one showed positive results across a range of outcomes . Eight studies were entered in a meta‐ analysis . No significant impact of psycho‐educational interventions was found for the outcome categories of subjective well‐being , self‐efficacy or health . However , small but significant results were found for the categories of depression and burden . Support Seven studies discussed support only interventions and two of these showed significant results . These two studies were suitable for meta‐ analysis and demonstrated a small but significant improvement on caregiver burden . Multi‐component Twelve of the studies report multi‐component interventions and 10 of these report significant outcomes across a broad range of outcome measures including self‐efficacy , depression , subjective well‐being and burden . Unfortunately because of the heterogeneity of study design s and outcome measures , no meta‐ analysis was possible . Other interventions Other interventions included the use of exercise or nutrition which result ed in improvements in psychological distress and health benefits .  Case management and a computer aided support intervention provided mixed results . One cognitive behavioural therapy study reported a reduction in anxiety and positive impacts on patient behaviour . Effectiveness of interventions using specific outcome categories In addition to analysis by type of intervention it was possible to analyse results based on some outcome categories that were used across the studies . In particular the impact of interventions on  caregiver depression was available for meta‐ analysis from eight studies . This indicated that multi‐component and psycho‐educational interventions showed a small but significant positive effect on caregiver depression . Five studies using the outcome category of caregiver burden  were entered into a meta‐ analysis and findings indicated that there were no significant effects of any of interventions . No meta‐ analysis was possible for the outcome categories of health , self‐efficacy or subjective well‐being . Implication s for practice From this review there is evidence to support the use of well‐ design ed psycho‐educational or multi‐component interventions for caregivers of people with dementia who live in the community . Factors that appear to positively contribute to effective interventions are those which : Provide opportunities within the intervention for the person with dementia as well as the caregiver to be involved Encourage active participation in educational interventions for caregivers Offer individualised programs rather than group sessions Provide information on an ongoing basis , with specific information about services and coaching regarding their new role Target the care recipient particularly by reduction in behaviours Factors which do not appear to have benefit in interventions are those which : Simply refer caregivers to support groups Only provide self help material s Only offer peer Background Worldwide in 2000 , 10 % of children aged five to 17 years were reported as being overweight with an additional 2‐3 % being obese . Overweight and obesity in childhood can adversely impact on both physical and psychological health . The rise in the prevalence of childhood obesity is a complex issue but widely recognised contributors include increased energy intake , decreased levels of physical activity and greater time spent in sedentary pursuits . A large number of environmental and cultural factors have also been identified as contributing to the problem . Evidence to support an optimal approach to treating childhood obesity is limited with many studies showing only modest results at best in the long‐term . However , the importance of family‐based treatment that combines diet , physical activity and behavioral components has been acknowledged in a recent Cochrane Systematic Review . It has also been suggested that interventions offered in the community setting may help overcome barriers to participation , by making programs more accessible and allowing the targeting of specific sub‐groups of the population . Objectives The objective of this review was to identify the effectiveness of parent‐centred interventions implemented in the community setting in modifying eating and physical activity behaviors or weight‐related outcomes of children . Inclusion criteria Types of participants This review considered studies that included free‐living children of pre‐school , primary and secondary school age and /or their parents/guardians aged > 18 years . Types of intervention(s)/phenomena of interest Intervention programs were required to have a parental component , to target eating and /or exercise behaviors for the prevention or treatment of obesity , and child weight status reported . Types of studies All intervention studies were included in the review including : r and omized controlled trials ( RCTs ) ; non‐r and omized controlled trials , longitudinal studies , cohort ( both retrospective and prospect i ve ) , case control and time series studies which had been conducted in a community setting . Types of outcomes This review considered studies that included overweight/obesity related outcomes , eating behavior outcomes , physical activity behaviour outcomes , and sedentary behavior outcomes and constructs . Search strategy A literature search of community‐based parent‐centred intervention studies to promote nutrition and physical activity for the prevention and treatment and of childhood overweight and obesity was performed in eight electronic data bases dating from 1975 to April 2009 . Method ological quality Studies were critically appraised for method ological quality using st and ardized tools . Data collection Data was extracted by one review er using a st and ardized data extraction form developed by the research ers and checked for accuracy and consistency by a second review er . Data synthesis Data in relation to setting , methodology , intervention components and effect on weight , dietary intake and physical activity was extracted , and described in a narrative synthesis . Where possible a meta‐ analysis was undertaken . Results Of the home‐based interventions , five of nine studies reported statistically significant changes in anthropometric outcomes post intervention . Of the 10 studies in the before and after school care setting , seven reported a significant decrease in a weight‐related outcome post intervention , with only one reporting an increase . Conclusions Results from the review support the after‐school setting as the most promising for community intervention setting for targeting parents as agents of change within child obesity prevention and treatment programs . Implication s for practice At this stage , interventions to support parents should target the after‐school environment as opposed to being conducted in the home , summer camps , leisure centers or churches . Targeting a decrease in energy intake and sweetened beverages in parallel with increasing number of daily steps and decreasing screen time use . Implication s for research Future studies of high quality are needed across the full range of community setting s. Given that currently most of the higher quality RCTs and the studies showing positive impacts of weight change are in the after‐school setting , further studies in this area using similar method ologies to those already published will facilitate future meta‐analyses in this area Background Depression is a leading cause of disability worldwide and depressive symptoms are common in later life . Observational evidence suggests that depression is more prevalent among people with high plasma homocysteine ( tHcy ) , but the results of r and omized trials to date have been unable to show that lowering tHcy through the supplementation of vitamins B6 , B12 and folate benefits depressive symptoms . We design ed the B-VITAGE trial to determine whether adjunctive treatment with vitamins B6 , B12 and folate increases the efficacy of st and ard antidepressant treatment . Methods / Design The B-VITAGE trial is a 12-month r and omized , double-blind , placebo-controlled trial of daily citalopram ( 20 to 40 mg ) plus B12(0.4 mg ) , B6 ( 25 mg ) and folic acid ( 2 mg ) or citalopram ( 20 to 40 mg ) plus placebo for the treatment of depression in later life . The trial aims to recruit over 300 older adults with major depression ( DSM-IV ) and has been powered to detect the impact of an intervention associated with moderate effect size . Depressive symptoms will be rated with the Montgomery-Åsberg Depression Rating Scale ( MADRS ) . The trial has two main outcomes of interest : a reduction of 50 % or more in the MADRS total score between baseline and week 12 and the remission of the depressive episode at weeks 12 , 26 and 52 according to DSM-IV criteria . We hypothesize that subjects r and omly allocated to the vitamin arm of the study will be more likely to show a clinical ly significant improvement and achieve and maintain remission of symptoms at 12 , 26 and 52 weeks . Secondary outcomes of interest include compliance with treatment , reduction in the severity of depressive symptoms , switching to different antidepressants , the use of non-pharmacological antidepressant treatments , response to treatment according to MTHFRC677 T genotype , and changes in cognitive function over 52 weeks . Conclusions The results of this trial will clarify whether the systematic use of B-vitamins improves the response of older adults to st and ard antidepressant treatment . We anticipate that our findings will have implication s for clinical practice and health policy development . Trial Registration The trial is registered with the Australian Clinical Trials Registry , trial number ( ())ACTRN12609000256279 Background Depression is a common mental health disorder for which clinical practice guidelines have been developed . Prior systematic review s have identified complex organizational interventions , such as collaborative care , as effective for guideline implementation ; yet , many healthcare delivery organizations are interested in less re source -intensive methods to increase provider adherence to guidelines and guideline -concordant practice s. The objective of this systematic review was to assess the effectiveness of  healthcare provider  interventions that aim to increase adherence to evidence -based treatment of depression in routine clinical practice . Methods We search ed five data bases through August 2017 using a comprehensive search strategy to identify English- language r and omized controlled trials ( RCTs ) in the quality improvement , implementation science , and behavior change literature that evaluated outpatient provider interventions , in the absence of practice re design efforts , to increase adherence to treatment guidelines or guideline -concordant practice s for depression . We used meta- analysis to summarize odds ratios , st and ardized mean differences , and incidence rate ratios , and assessed quality of evidence ( QoE ) using the GRADE approach . Results Twenty-two RCTs promoting adherence to clinical practice guidelines or guideline -concordant practice s met inclusion criteria . Studies evaluated diverse provider interventions , including distributing guidelines to providers , education/training such as academic detailing , and combinations of education with other components such as targeting implementation barriers . Results were heterogeneous and analyses comparing provider interventions with usual clinical practice did not indicate a statistically significant difference in guideline adherence across studies . There was some evidence that provider interventions improved individual outcomes such as medication prescribing and indirect comparisons indicated more complex provider interventions may be associated with more favorable outcomes . We did not identify types of provider interventions that were consistently associated with improvements across indicators of adherence and across studies . Effects on patients ’ health in these RCTs were inconsistent across studies and outcomes . Conclusions Existing RCTs describe a range of provider interventions to increase adherence to depression guidelines . Low QoE and lack of replication of specific intervention strategies across studies limited conclusions that can be drawn from the existing research . Continued efforts are needed to identify successful strategies to maximize the impact of provider interventions on increasing adherence to evidence -based treatment for depression . Trial registration PROSPERO record CRD42017060460 on This paper reports the efficacy and tolerability of the nicotinic channel modulator TC-5214 ( dexmecamylamine ) as adjunct therapy for patients with major depressive disorder who have an inadequate response to initial antidepressant treatment in 2 Phase III studies . These double-blind , placebo-controlled studies ( NCT01157078 , D4130C00002 [ Study 002 ] conducted in the US and India ; NCT01180400 , D4130C00003 [ Study 003 ] conducted in Europe ) comprised 8 weeks of open-label antidepressant treatment followed by 8 weeks of active treatment during which patients were r and omized to flexibly-dosed TC-5214 1 - 4 mg twice daily ( BID ) or placebo as an adjunct to ongoing therapy with SSRI/SNRI . The primary efficacy endpoint in both studies was change in Montgomery Åsberg Depression Rating Scale ( MADRS ) total score from r and omization ( week 8) to treatment end ( week 16 ) . Secondary endpoints included change in Sheehan Disability Scale and Hamilton Depression Rating Scale 17-item scores . Study 002 r and omized 319 patients and Study 003 r and omized 295 patients to TC-5214 or placebo . At treatment end , no significant differences were seen for change in MADRS total score with TC-5214 versus placebo . Furthermore , there were no significant differences in any of the secondary endpoints . The most commonly reported ( ≥ 10 % ) adverse events with TC-5214 in these studies were constipation and headache . In these 2 flexibly-dosed studies , no specific therapeutic effects were observed for TC-5214 ( 1 - 4 mg BID ) adjunct to antidepressant in the primary endpoint or any secondary endpoint ; however , TC-5214 was generally well tolerated . In conclusion , no antidepressant effect of TC-5214 was observed in these studies Background There is increasing interest in nonoperative management ( NOM ) for rectal cancer with complete clinical response ( cCR ) after neoadjuvant chemoradiation ( nCRT ) . Objective The aim of this systematic review was to summarize the available data on NOM , with the intention of formulating st and ardized protocol s on which to base future investigations . Methods A systematic review following the Preferred Reporting Items for Systematic Review s and Meta-Analyses ( PRISMA ) guidelines was conducted . A highly sensitive literature search identified all relevant studies published between January 2004 and December 2016 . Data extraction and quality assessment was performed independently by two authors , and resolved by consensus with a third review er . Results In total , 15 studies , including 920 patients , met the inclusion criteria ; 575 ( 62.5 % ) of these patients underwent NOM after cCR , with the remaining patients forming a surgical control group . The weighted mean follow-up was 39.4 ( 12.7 ) months in the NOM group and 39.8 ( 5.1 ) months in the surgery group . The pooled regrowth rate in the NOM group was 21.3 % at a mean of 15.6 ( 7.0 ) months . Surgical salvage was possible and was undertaken in 93.2 % of these patients . Overall survival in the NOM group was 91.7 % , while disease-free survival was 82.7 % . For the comparison proctectomy group , pooled rates of local recurrence , overall survival , and disease-free survival were 8.4 , 92.4 , and 87.5 % , respectively . Conclusion NOM may be a feasible option for surgically eligible rectal cancer patients with cCR after nCRT . Before such a strategy can be widely implemented , further prospect i ve data are required with st and ardized definitions , diagnostic criteria , and management protocol s , with an emphasis on shared patient – provider decision making and patient-centered outcomes 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
Mixed results were found for zinc , folic acid , vitamin C , and tryptophan , with nonsignificant results for inositol .
No major adverse effects were noted in the studies ( aside from minor digestive disturbance ) .
A meta- analysis of adjunctive omega-3 versus placebo revealed a significant and moderate to strong effect in favor of omega-3 .
Conversely , a meta- analysis of folic acid revealed a nonsignificant difference from placebo .
Current evidence supports adjunctive use of SAMe , methylfolate , omega-3 , and vitamin D with antidepressants to reduce depressive symptoms
OBJECTIVE There is burgeoning interest in augmentation strategies for improving inadequate response to antidepressants .
The adjunctive use of st and ardized pharmaceutical- grade nutrients , known as nutraceuticals , has the potential to modulate several neurochemical pathways implicated in depression .
While many studies have been conducted in this area , to date no specialized systematic review ( or meta- analysis ) has been conducted .