In the absence of adequate prospective, randomized drug-drug comparisons, the present findings provide broad, international, expert consensus-based recommendations for most clinically employed antipsychotic drugs. They can support clinical practice, trial design, and interpretation of comparative antipsychotic trials.

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Writing Committee for the REMAP-CAP Investigators IMPORTANCE The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive.OBJECTIVE To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTSThe ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021. INTERVENTIONSThe immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). MAIN OUTCOMES AND MEASURESThe primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, −1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events. RESULTS Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support-free days was 0 (IQR, -1 to 16) in the convalescent plasma group and 3 (IQR, -1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (OR <1.2) was 99.4% for the convalescent plasma group compared with the no convalescent plasma group. The treatment effects were consistent across the primary outcome and the 11...

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BackgroundLong-term sedative use is prevalent and associated with significant morbidity, including adverse events such as falls, cognitive impairment, and sedation. The development of dependence can pose significant challenges when discontinuation is attempted as withdrawal symptoms often develop. We conducted a scoping review to map and characterize the literature and determine opportunities for future research regarding deprescribing strategies for long-term benzodiazepine and Z-drug (zopiclone, zolpidem, and zaleplon) use in community-dwelling adults.MethodsWe searched PubMed, Cochrane Central Register of Controlled Trials, EMBASE, PsycINFO, CINAHL, TRIP, and JBI Ovid databases and conducted a grey literature search. Articles discussing methods for deprescribing benzodiazepines or Z-drugs in community-dwelling adults were selected.ResultsFollowing removal of duplicates, 2797 articles were reviewed for eligibility. Of these, 367 were retrieved for full-text assessment and 139 were subsequently included for review. Seventy-four (53 %) articles were original research, predominantly randomized controlled trials (n = 52 [37 %]), whereas 58 (42 %) were narrative reviews and seven (5 %) were guidelines. Amongst original studies, pharmacologic strategies were the most commonly studied intervention (n = 42 [57 %]). Additional deprescribing strategies included psychological therapies (n = 10 [14 %]), mixed interventions (n = 12 [16 %]), and others (n = 10 [14 %]). Behaviour change interventions were commonly combined and included enablement (n = 56 [76 %]), education (n = 36 [47 %]), and training (n = 29 [39 %]). Gradual dose reduction was frequently a component of studies, reviews, and guidelines, but methods varied widely.ConclusionsApproaches proposed for deprescribing benzodiazepines and Z-drugs are numerous and heterogeneous. Current research in this area using methods such as randomized trials and meta-analyses may too narrowly encompass potential strategies available to target this phenomenon. Realist synthesis methods would be well suited to understand the mechanisms by which deprescribing interventions work and why they fail.Electronic supplementary materialThe online version of this article (doi:10.1186/s40360-015-0019-8) contains supplementary material, which is available to authorized users.

BackgroundPharmacists are knowledgeable, accessible health care professionals who can provide services that improve outcomes in mental health care. Various challenges and opportunities can exist in pharmacy practice to hinder or support pharmacists’ efforts. We used a theory-informed approach to development and implementation of a capacity-building program to enhance pharmacists’ roles in mental health care.MethodsTheories and frameworks including the Consolidated Framework for Implementation Research, the Theoretical Domains Framework, and the Behaviour Change Wheel were used to inform the conceptualization, development, and implementation of a capacity-building program to enhance pharmacists’ roles in mental health care.ResultsThe More Than Meds program was developed and implemented through an iterative process. The main program components included: an education and training day; use of a train-the-trainer approach from partnerships with pharmacists and people with lived experience of mental illness; development of a community of practice through email communications, a website, and a newsletter; and use of educational outreach delivered by pharmacists. Theories and frameworks used throughout the program’s development and implementation facilitated a means to conceptualize the component parts of the program as well as its overall presence as a whole from inception through evolution in implementation. Using theoretical foundations for the program enabled critical consideration and understanding of issues related to trialability and adaptability of the program.ConclusionsTheory was essential to the underlying development and implementation of a capacity-building program for enhancing services by pharmacists for people with lived experience of mental illness. Lessons learned from the development and implementation of this program are informing current research and evolution of the program.

Disparities exist between rural and urban emergency departments with respect to knowledge resources such as online journals and clinical specialists. As knowledge is a critical element in the delivery of quality care, a web-based learning project was proposed to address the knowledge needs of emergency clinicians. One objective of this project was to evaluate the effectiveness of the online environment for knowledge exchange among rural and urban emergency clinicians. Descriptive and content analysis of the online discussion board revealed 202 postings with rural participants contributing the largest number of postings (75%; 152/202). Postings were used to establish a clinical presence (87/202), seek clinical information (52/202), and share clinical information (63/202). Postintervention survey results indicate that this modality introduced participants to new clinical experts and resources. The results provide direction for design of a virtual community of practice, which may reduce current knowledge resource disparities.

Findings indicate the effectiveness of out-of-home respite care in improving the fatigue and psychological adjustment of caregivers of children with life-threatening conditions. Study outcomes inform service provision and future research efforts in paediatric palliative care.