Randomized double-blind placebo-controlled trial of the effects of oral trehalose in spinocerebellar ataxia type 3: An interim analysis.

INTRODUCTION: Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disease characterized by increasingly worsening ataxia and non-ataxia features, negatively impacting patients' quality of life. This study was designed to test formally evaluate whether oral trehalose was effective in SCA3 patients. METHODS: In this double-blind, randomized controlled trial, SCA3 patients received either 100 g oral trehalose or 30 g maltose to improve ataxia severity over six months. We also measured other clinical (non-ataxia), patient-reported (quality of life, motivations), and safety endpoints. An unscheduled interim analysis was conducted using two-way ANOVAs to analyze the interaction between time (baseline, 3-months, 6-months) and intervention (Trehalose vs. Placebo). RESULTS: Fifteen participants (Trehalose = 7 vs. Placebo = 8) completed the study at the time of interim analysis. There was no interaction effect on the ataxia severity, and available data suggested an estimated sample size of 132 (66 per arm) SCA3 patients required to demonstrate changes in a 6-month trial. There were significant interaction effects for executive function (ƞ2 = 0.28-0.43). Safety data indicated that 100 g oral trehalose was well-tolerated. CONCLUSION: We performed an unplanned interim analysis due to a slow recruitment rate. The new estimated sample size was deemed unfeasible, leading to premature termination of the clinical trial. In this small, current sample of SCA3 patients, 100 g oral trehalose did not differentially impact on ataxia severity compared to placebo. Interestingly, our findings may suggest an improvement in executive function. Future efforts will require a large multi-country, multi-center study to investigate the potential effect of trehalose.

Plethora of Antibiotics Usage and Evaluation of Carbapenem Prescribing Pattern in Intensive Care Units: A Single-Center Experience of Malaysian Academic Hospital.

Excessive antibiotic consumption is still common among critically ill patients admitted to intensive care units (ICU), especially during the coronavirus disease 2019 (COVID-19) period. Moreover, information regarding antimicrobial consumption among ICUs in South-East Asia remains scarce and limited. This study aims to determine antibiotics utilization in ICUs by measuring antibiotics consumption over the past six years (2016−2021) and specifically evaluating carbapenems prescribed in a COVID-19 ICU and a general intensive care unit (GICU) during the second year of the COVID-19 pandemic. (2) Methods: This is a retrospective cross-sectional observational analysis of antibiotics consumption and carbapenems prescriptions. Antibiotic utilization data were estimated using the WHO Defined Daily Doses (DDD). Carbapenems prescription information was extracted from the audits conducted by ward pharmacists. Patients who were prescribed carbapenems during their admission to COVID-19 ICU and GICU were included. Patients who passed away before being reviewed by the pharmacists were excluded. (3) Results: In general, antibiotics consumption increased markedly in the year 2021 when compared to previous years. Majority of carbapenems were prescribed empirically (86.8%). Comparing COVID-19 ICU and GICU, the reasons for empirical carbapenems therapy in COVID-19 ICU was predominantly for therapy escalation (64.7% COVID-19 ICU vs. 34% GICU, p < 0.001), whereas empirical prescription in GICU was for coverage of extended-spectrum beta-lactamases (ESBL) gram-negative bacteria (GNB) (45.3% GICU vs. 22.4% COVID-19 ICU, p = 0.005). Despite microbiological evidence, the empirical carbapenems were continued for a median (interquartile range (IQR)) of seven (5−8) days. This implies the need for a rapid diagnostic assay on direct specimens, together with comprehensive antimicrobial stewardship (AMS) discourse with intensivists to address this issue.