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Background Valid assessment of drug efficacy and safety requires an evidence base free of reporting bias. Using trial reports in Food and Drug Administration (FDA) drug approval packages as a gold standard, we previously found that the published literature inflated the apparent efficacy of antidepressant drugs. The objective of the current study was to determine whether this has improved with recently approved drugs. Methods and findings Using medical and statistical reviews in FDA drug approval packages, we identified 30 Phase II/III double-blind placebo-controlled acute monotherapy trials, involving 13,747 patients, of desvenlafaxine, vilazodone, levomilnacipran, and vortioxetine; we then identified corresponding published reports. We compared the data from this newer cohort of antidepressants (approved February 2008 to September 2013) with the previously published dataset on 74 trials of 12 older antidepressants (approved December 1987 to August 2002). Using logistic regression, we examined the effects of trial outcome and trial cohort (newer versus older) on transparent reporting (whether published and FDA conclusions agreed). Among newer antidepressants, transparent publication occurred more with positive (15/15 = 100%) than negative (7/15 = 47%) trials (OR 35.1, CI.sub.95% 1.8 to 693). Controlling for trial outcome, transparent publication occurred more with newer than older trials (OR 6.6, CI.sub.95% 1.6 to 26.4). Within negative trials, transparent reporting increased from 11% to 47%. We also conducted and contrasted FDA- and journal-based meta-analyses. For newer antidepressants, FDA-based effect size (ES.sub.FDA) was 0.24 (CI.sub.95% 0.18 to 0.30), while journal-based effect size (ES.sub.Journals) was 0.29 (CI.sub.95% 0.23 to 0.36). Thus, effect size inflation, presumably due to reporting bias, was 0.05, less than for older antidepressants (0.10). Limitations of this study include a small number of trials and drugs-belonging to a single class-and a focus on efficacy (versus safety). Conclusions Reporting bias persists but appears to have diminished for newer, compared to older, antidepressants. Continued efforts are needed to further improve transparency in the scientific literature., Author(s): Erick H. Turner 1,2,*, Andrea Cipriani 3,4,5, Toshi A. Furukawa 6, Georgia Salanti 7, Ymkje Anna de Vries 8,9 Introduction Reporting bias can lead to overestimates of efficacy and/or [...]

Background: Internet-based cognitive behavioral therapy (iCBT) shows promise in the prevention of depression. However, the specific iCBT components that contribute to its effectiveness remain unclear. Objective: We aim to evaluate the effects of iCBT components in preventing depression among university students. Methods: Using a smartphone cognitive behavioral therapy (CBT) app, we randomly allocated university students to the presence or absence of 5 different iCBT components: self-monitoring, behavioral activation, cognitive restructuring, assertiveness training, and problem-solving. The active intervention lasted 8 weeks but the app remained accessible through the follow-up. The primary outcome was the onset of a major depressive episode (MDE) between baseline and the follow-up after 52 weeks, as assessed with the computerized World Health Organization Composite International Diagnostic Interview. Secondary outcomes included changes in the 9-item Patient Health Questionnaire, 7-item General Anxiety Disorder, and CBT Skills Scale. Results: During the 12-month follow-up, 133 of 1301 (10.22%) participants reported the onset of an MDE. There were no significant differences in the incidence of MDEs between the groups with or without each component (hazard ratios ranged from 0.85, 95% CI 0.60-1.20, for assertiveness training to 1.26, 95% CI 0.88-1.79, for self-monitoring). Furthermore, there were no significant differences in the changes on the 9-item Patient Health Questionnaire, 7-item General Anxiety Disorder, or for CBT Skills Scale between component allocation groups. However, significant reductions in depression and anxiety symptoms were observed among all participants at the 52-week follow-up. Conclusions: In this study, we could not identify any specific iCBT components that were effective in preventing depression or the acquisition of CBT skills over the 12-month follow-up period, but all participants with and without intervention of each iCBT component demonstrated significant improvements in depressive and anxiety symptoms. Further research is needed to explore the potential impact of frequency of psychological assessments, nonspecific intervention effects, natural change in the mental state, and the baseline depression level. [ABSTRACT FROM AUTHOR]

Background and Objectives: Only 10% of Americans with substance use disorders (SUDs) receive treatment with insufficient treatment access and screening practices proposed and potential contributing factors. Methods: This retrospective cross‐sectional study used National Survey on Drug Use and Health (NSDUH) data to assess individuals with SUDs receiving treatment between 2016 and 2019 (survey n = 12,111; weighted n = 12,394,214). Demographic, access, and screening characteristics were investigated as predictors of treatment receipt using time‐series logistic regression analyses to test trends and assessed treatment receipt odds, controlling for demographic and treatment characteristics. Results: For those with past‐year SUDs, 13.0% reported receiving past‐year SUD treatment (survey n = 1605; weighted n = 1,612,154). The SUD treatment receipt rate remained statistically stable from 2016 to 2019, with a nonsignificant treatment receipt trend declining from 14% to 12%. Treatment changes were notable among Native Americans (+53.80%), Pacific Islanders (+94.10%), multiracial (−59.96%), ages 65+ (−70.18%), and ages 12−17 (−50.70%). In the regression model, race, sex, age, insurance status, and receiving mental health treatment were associated with SUD treatment receipt. Discussion and Conclusions: The treatment gap remains substantial and stable. Annually, about 87% of Americans with SUDs are not receiving the treatment they need. Asian Americans were less likely and those attending general mental health services were more likely to receive treatment. Scientific Significance: We present an updated SUD treatment gap evaluation, and identify access and screening characteristics associated with SUD treatment receipt. Policymakers, clinicians, and researchers must continue improving access and identification of those in need of care. [ABSTRACT FROM AUTHOR]

Purpose Polymyxin B-immobilized hemoperfusion (PMX-HP) is an adjuvant therapy for sepsis or septic shock that clears circulating endotoxin. Prior trials have shown that PMX-HP improves surrogate endpoints. We aimed to conduct an evidence synthesis to evaluate the efficacy and safety of PMX-HP in critically ill adult patients with sepsis or septic shock. Methods We searched for randomized controlled trials (RCTs) in MEDLINE, EMBASE, the Cochrane Library, the Health Technology Assessment Database, CINAHL, 'Igaku Chuo Zasshi', the National Institute of Health Clinical Trials Register, the World Health Organization International Clinical Trials Registry Platform, the University Hospital Medical Information Network Clinical Trials Registry, the reference lists of retrieved articles, and publications by manufacturers of PMX-HP. The primary outcomes were 28-day all-cause mortality, the number of patients with at least one serious adverse event, and organ dysfunction scores. The GRADE methodology for the certainty of evidence was used. Results Six trials (857 participants; weighted mean age 62.5 years) proved eligible. Patient-oriented primary outcomes were assessed. The pooled risk ratio (RR) for 28-day mortality associated with PMX-HP was 1.03 [95% confidence interval (CI) 0.78-1.36; I.sup.2 = 25%; n = 797]. The pooled RR for adverse events was 2.17 (95% CI 0.68-6.94; I.sup.2 = 0%; n = 717). Organ dysfunction scores over 24-72 h after PMX-HP treatment did not change significantly (standardized mean difference - 0.26; 95% CI - 0.64 to 0.12; I.sup.2 = 78%; n = 797). The certainty of the body of evidence was judged as low for both benefit and harm using the GRADE methodology. Conclusions There is currently insufficient evidence to support the routine use of PMX-HP to treat patients with sepsis or septic shock. Registration PROSPERO International Prospective Register of Systematic Reviews (CRD42016038356)., Author(s): Tomoko Fujii [sup.1] [sup.2], Riki Ganeko [sup.3], Yuki Kataoka [sup.4], Toshi A. Furukawa [sup.5], Robin Featherstone [sup.6], Kent Doi [sup.7], Jean-Louis Vincent [sup.8], Daniela Pasero [sup.9], René Robert [sup.10], [...]

Objective: Relapses and rehospitalization prevent the recovery of individuals with schizophrenia or related psychoses. We aimed to build a model to predict the risk of rehospitalization among people with schizophrenia or related psychoses, including those with multiple episodes. Methods: This retrospective cohort study included individuals aged 18 years or older, with schizophrenia or related psychoses, and discharged between January 2014 and December 2018 from one of three Japanese psychiatric hospital acute inpatient care ward. We collected nine predictors at the time of recruitment, followed up with the participants for 12 months, and observed whether psychotic relapse had occurred. Next, we applied the Cox regression model and used an elastic net to avoid overfitting. Then, we examined discrimination using bootstrapping, Steyerberg’s method, and “leave-one-hospital-out” crossvalidation. We also constructed a bias-corrected calibration plot. Results: Data from a total of 805 individuals were analyzed. The significant predictors were the number of previous hospitalizations (HR 1.42, 95% CI 1.22– 1.64) and the current length of stay in days (HR 1.31, 95% CI 1.04–1.64). In model development for relapse, Harrell’s c-index was 0.59 (95% CI 0.55–0.63). The internal and internal-external validation for rehospitalization showed Harrell’s c-index to be 0.64 (95% CI 0.59–0.69) and 0.66 (95% CI 0.57–0.74), respectively. The calibration plot was found to be adequate. Conclusion: The model showed moderate discrimination of readmission after discharge. Carefully defining a research question by seeking needs among the population with chronic schizophrenia with multiple episodes may be key to building a useful model. [ABSTRACT FROM AUTHOR]