Safety of acamprosate for alcohol use disorder Post-Liver transplant: a pilot randomized controlled trial.

INTRODUCTION: Acamprosate is a therapy for alcohol use disorder but data on feasibility and safety in liver transplant (LT) recipients are lacking. METHODS: This was a single-center unblinded prospective pilot randomized controlled trial of adults (≥18 years) with LT for ALD enrolled between 2021-2023 who were randomized 2:1 to the intervention of acamprosate (666mg dose three times daily) or standard of care (SOC) over 14 weeks. Outcomes included safety [prevalence of adverse events (AE)], feasibility (weekly survey response rate >60%), adherence (self-reported acamprosate use>60%), and efficacy (reduction in Penn Alcohol Craving Scale [PACS]) and relapse-blood phosphatidylethanol≥20ng/mL/reported alcohol use) evaluated by standardized weekly surveys. The efficacy analysis was done in both the intention to treat (ITT) (excluding withdrawals before medication administration) and per-protocol (PP) population (excluding withdrawals/<4 weeks participation). RESULTS: Of 78 participants approached, 30 enrolled (19 acamprosate, 11 SOC) with similar baseline characteristics. Eight participants withdrew (6 acamprosate prior to medication administration and 2 SOC). AEs were similar between acamprosate and SOC groups (92.3% vs. 90.0%, p>0.99), including Grade 3 AEs (53.9% vs. 60.0%, p>0.99) with no reported grade 4/5 AEs. Survey response rates were similar in acamprosate vs SOC groups (61.0% vs. 76.0%, p=0.19), and 69.0% were acamprosate adherent. Baseline PACS values were low with no difference by group in median absolute change in PACS for ITT (0, IQR:-4-0 vs. 0, IQR:0-0, p=0.32) and PP analyses (-1, IQR:-6-0 vs. 0, IQR:0-0, p=0.36). There were no reported or biochemical evidence of alcohol relapse. CONCLUSION: In this pilot study, preliminary data suggests that acamprosate may be safe and feasible. These data can inform larger studies and clinician efforts to address alcohol use disorder in post-LT care. (ClinicalTrials.gov, Number: NCT06471686).

Impact of Varying Active Learning Time on Student Performance on a Standardized Exam in the Psychiatry Clerkship.

OBJECTIVE: As medical schools reform clinical curricula, an increasing amount of time is spent in active learning activities. The authors hypothesized that students who spent more time in active learning educational activities (e.g., team-based learning, small group activities, clinical simulation) would receive higher NBME Subject Exam scores compared to students with less. METHODS: This cohort study included 518 students from 2014 to 2016 who completed at least six contiguous weeks of a psychiatry clerkship. Active learning time percent was calculated by dividing the amount of time in active learning by the total in-classroom time during the clerkship. Analysis was conducted using ANOVA and linear regression. RESULTS: Analysis found that increasing the amount of active learning was not significantly associated with student scores on the NBME Subject Exam in psychiatry (F = 0.91, p = 0.402). However, when controlling for possible confounding variables (including clerkship length and order), clerkship order was a significant predictor of student performance (r = 0.19, ß = 0.18, p < 0.0001); students who took the clerkship later in the academic year-and after the internal medicine rotation-performed significantly better on the exam. CONCLUSIONS: This study found that increasing the amount of active learning did not improve student performance on the NBME Subject Exam in psychiatry. This study provides preliminary, but unexpected, evidence of interest to medical educators and curriculum reformers that increasing the amount of active learning is not significantly associated with improved student test performance.

Pharmacological promotion of inclusion formation: a therapeutic approach for Huntington's and Parkinson's diseases.

Misfolded proteins accumulate in many neurodegenerative diseases, including huntingtin in Huntington's disease and alpha-synuclein in Parkinson's disease. The disease-causing proteins can take various conformations and are prone to aggregate and form larger cytoplasmic or nuclear inclusions. One approach to the development of therapeutic intervention for these diseases has been to identify chemical compounds that reduce the size or number of inclusions. We have, however, identified a compound that promotes inclusion formation in cellular models of both Huntington's disease and Parkinson's disease. Of particular interest, this compound prevents huntingtin-mediated proteasome dysfunction and reduces alpha-synuclein-mediated toxicity. These results demonstrate that compounds that increase inclusion formation may actually lessen cellular pathology in both Huntington's and Parkinson's diseases, suggesting a therapeutic approach for neurodegenerative diseases caused by protein misfolding.