Treating schizophrenia: the quality of evidence behind treatment recommendations and how it can improve.

OBJECTIVE: To assess the methodological and reporting quality of systematic reviews that comprise the American Psychiatric Association (APA) Practice Guideline for the Treatment of Patients with Schizophrenia and to determine the extent to which results from Cochrane systematic reviews published after guideline development would alter or confirm current recommendations. PARTICIPANTS: Systematic reviews that underpinned recommendations in the APA guidelines and Cochrane systematic reviews. MAIN OUTCOME: Three independent reviewers scored all systematic reviews referenced in the guideline for quality and reporting using AMSTAR and PRISMA checklist, respectively. Items in both tools were individually graded and compared to identify consistently low-performing areas within the systematic reviews. Post hoc analysis of the Cochrane systematic reviews since the latest revision of APA's guidelines were performed to determine whether their findings were congruent with recent recommendations. RESULTS: The mean score of the 57 reviews on the PRISMA checklist was 70%. The mean AMSTAR score was 6.8, correlating with a moderate quality score. Post hoc analysis revealed that 171 Cochrane reviews had been published since the APA guideline release. Only half of the reviews of pharmacological interventions confirmed current recommendations. CONCLUSIONS AND RELEVANCE: The methodological quality of the systematic reviews included in the APA guideline was deficient in key areas. Our study brings to light the importance of using high-quality evidence in the development of clinical practice guidelines. An updated APA guideline (last updated in 2009) is necessary to provide the highest quality treatment recommendations for clinicians in the management of schizophrenia. TRIAL REGISTRATION NUMBER: UMIN-CTR, UMIN000023099.

Methodological quality of systematic reviews referenced in clinical practice guidelines for the treatment of opioid use disorder.

INTRODUCTION: With efforts to combat opioid use disorder, there is an increased interest in clinical practice guidelines (CPGs) for opioid use disorder treatments. No literature exists examining the quality of systematic reviews used in opioid use disorder CPGs. This study aims to describe the methodological quality and reporting clarity of systematic reviews (SRs) used to create CPGs for opioid use disorder. METHODS: From June to July 2016 guideline clearinghouses and medical literature databases were searched for relevant CPGs used in the treatment of opioid use disorder. Included CPGs must have been recognized by a national organization. SRs from the reference section of each CPG was scored by using AMSTAR (a measurement tool to assess the methodological quality of systematic reviews) tool and PRISMA (preferred reporting items for systematic reviews and meta-analyses) checklist. RESULTS: Seventeen CPGs from 2006-2016 were included in the review. From these, 57 unique SRs were extracted. SRS comprised 0.28% to 17.92% of all references found in the CPGs. All SRs obtained moderate or high methodological quality score on the AMSTAR tool. All reviews met at least 70% of PRISMA criteria. In PRISMA, underperforming areas included accurate title labeling, protocol registration, and risk of bias. Underperforming areas in AMSTAR included conflicts of interest, funding, and publication bias. A positive correlation was found between AMSTAR and PRISMA scores (r = .79). CONCLUSION: Although the SRs in the CPGs were of good quality, there are still areas for improvement. Systematic reviewers should consult PRISMA and AMSTAR when conducting and reporting reviews. It is important for CPG developers to consider methodological quality as a factor when developing CPG recommendations, recognizing that the quality of systematic reviews underpinning guidelines does not necessarily correspond to the quality of the guideline itself.

Variable methodological quality and use found in systematic reviews referenced in STEMI clinical practice guidelines.

BACKGROUND: The objective of this study was to assess the methodological quality and clarity of reporting of the systematic reviews (SRs) supporting clinical practice guideline (CPG) recommendations in the management of ST-elevation myocardial infarction (STEMI) across international CPGs. METHODS: We searched 13 guideline clearinghouses including the National Guideline Clearinghouse and Guidelines International Network (GIN). To meet inclusion criteria CPGs must be pertinent to the management of STEMI, endorsed by a governing body or national organization, and written in English. We retrieved SRs from the reference sections using a combination of keywords and hand searching. Two investigators scored eligible SRs using AMSTAR and PRISMA. RESULTS: We included four CPGs. We extracted 71 unique SRs. These SRs received AMSTAR scores ranging from 1 (low) to 9 (high) on an 11-point scale. All CPGs consistently underperformed in areas including disclosure of funding sources, risk of bias, and publication bias according to AMSTAR. PRISMA checklist completeness ranged from 44% to 96%. The PRISMA scores indicated that SRs did not provide a full search strategy, study protocol and registration, assessment of publication bias or report funding sources. Only one SR was referenced in all four CPGs. All CPGs omitted a large subset of available SRs cited by other guidelines. CONCLUSIONS: Our study demonstrates the variable quality of SRs used to establish recommendations within guidelines included in our sample. Although guideline developers have acknowledged this variability, it remains a significant finding that needs to be addressed further. FUNDING: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Database selection in systematic reviews: an insight through clinical neurology.

BACKGROUND: Failure to perform a comprehensive search when designing a systematic review (SR) can lead to bias, reducing the validity of review's conclusions. OBJECTIVE: We examined the frequency and choice of databases used by reviewers in clinical neurology. METHODS: Ninety-five SRs and/or meta-analyses were located across five prominent neurology journals between 2008 and 2014. Methods sections were reviewed, and all bibliographic databases were coded. RESULTS: On average, 2.59 databases were used in SR searches. Seven reviews included an information specialist, and these reviews reported a greater number of information sources used during the search process. Thirty-nine databases were reported across studies. PubMed/MEDLINE® and EMBASE were cited most frequently. DISCUSSION: Searching too few databases may reduce the validity and generalisability of SR results. We found that the majority of systematic reviewers in clinical neurology do not search an adequate number of databases, which may yield a biased sample of primary studies and, thus, may influence the accuracy of summary effects. CONCLUSIONS: Systematic reviewers should aim to search a sufficient number of databases to minimise selection bias. Additionally, systematic reviewers should include information specialists in designing SR methodology, as this may improve systematic review quality.

Systematic Reviewers in Clinical Neurology Do Not Routinely Search Clinical Trials Registries.

We examined the use of clinical trials registries in published systematic reviews and meta-analyses from clinical neurology. A review of publications between January 1, 2008 and December 31, 2014 from five neuroscience journals (Annals of Neurology, Brain, Lancet Neurology, Neurology, and The Neuroscientist) was performed to identify eligible systematic reviews. The systematic reviews comprising the final sample were independently appraised to determine if clinical trials registries had been included as part of the search process. Studies acknowledging the use of a trials registry were further examined to determine whether trial data had been incorporated into the analysis. The initial search yielded 194 studies, of which 78 systematic reviews met the selection criteria. Of those, five acknowledged the use of a specific clinical trials registry: four reviewed unpublished trial data and two incorporated unpublished trial data into their results. Based on our sample of systematic reviews, there was no increase in the use of trials registries in systematic review searches over time. Few systematic reviews published in clinical neurology journals included data from relevant clinical trials registries.

Food deprivation reduces and leptin increases the amplitude of an active sensory and communication signal in a weakly electric fish.

Energetic demands of social communication signals can constrain signal duration, repetition, and magnitude. The metabolic costs of communication signals are further magnified when they are coupled to active sensory systems that require constant signal generation. Under such circumstances, metabolic stress incurs additional risk because energy shortfalls could degrade sensory system performance as well as the social functions of the communication signal. The weakly electric fish Eigenmannia virescens generates electric organ discharges (EODs) that serve as both active sensory and communication signals. These EODs are maintained at steady frequencies of 200-600Hz throughout the lifespan, and thus represent a substantial metabolic investment. We investigated the effects of metabolic stress (food deprivation) on EOD amplitude (EODa) and EOD frequency (EODf) in E. virescens and found that only EODa decreases during food deprivation and recovers after restoration of feeding. Cortisol did not alter EODa under any conditions, and plasma cortisol levels were not changed by food deprivation. Both melanocortin hormones and social challenges caused transient EODa increases in both food-deprived and well-fed fish. Intramuscular injections of leptin increased EODa in food-deprived fish but not well-fed fish, identifying leptin as a novel regulator of EODa and suggesting that leptin mediates EODa responses to metabolic stress. The sensitivity of EODa to dietary energy availability likely arises because of the extreme energetic costs of EOD production in E. virescens and also could reflect reproductive strategies of iteroparous species that reduce social signaling and reproduction during periods of stress to later resume reproductive efforts when conditions improve.