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35 articles scientifiques publiés — un praticien à la pointe de la recherche
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Movement disorders : official journal of the Movement Disorder Society · 2025
AbstractBackgroundGlial cell line–derived neurotrophic factor (GDNF) is required for development and survival of dopaminergic neurons. A previous trial evaluating lower‐dose adeno‐associated virus serotype 2–GDNF (AAV2‐GDNF) bilateral intraputaminal infusion in participants with advanced Parkinson's disease (PD) achieved 26% mean putaminal coverage and was associated with stable motor features with no unexpected adverse events (AEs) over 60 months.ObjectiveWe assessed safety and preliminary clinical outcomes of optimized bilateral intraputaminal infusion of a single, higher dose of AAV2‐GDNF (product code AB‐1005) for PD after 18 months.MethodsThis phase 1b single‐arm, open‐label clinical trial enrolled participants with mild (Movement Disorder Society–revised Unified Parkinson's Disease Rating Scale [MDS‐UPDRS] Part III off score ≤ 32) and moderate (MDS‐UPDRS Part III off score of 33–60) PD. The primary outcome was safety. Clinical outcomes were assessed using PD‐specific clinical measures.ResultsEleven participants were enrolled (n = 6 mild; n = 5 moderate). Mean (±SE) putaminal coverage of AAV2‐GDNF was 63% (±2%). All participants experienced treatment‐emergent AEs (63 events); most were transient and perioperative. Six serious AEs in three participants were unrelated to AAV2‐GDNF. At 18 months posttreatment, the mild cohort exhibited numerically stable MDS‐UPDRS, motor diary, Unified Dyskinesia Rating Scale (UDysRS) scores, and levodopa equivalent daily dose (LEDD). The moderate cohort demonstrated numerical improvements in mean (±SE) MDS‐UPDRS Part III off scores (−20.4 [±4.5]), motor diary off time (−1.7 [±1.1] hours), and UDysRS scores (−2.2 [±1.9]) and reduced LEDD (−257.6 [±162.2] mg).ConclusionsBilateral intraputaminal AAV2‐GDNF gene therapy was well tolerated and associated with numerical stability (mild cohort) and improvement (moderate cohort) in clinical assessments at 18 months posttreatment. © 2025 AskBio Inc and The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Drug and alcohol dependence · 2025
Journal of addiction medicine · 2024
Background Benzodiazepine-involved overdose deaths are rising, driven by increasing use of nonprescribed benzodiazepine pills. For patients who wish to stop nonprescribed benzodiazepine use, rapid inpatient tapers are typically the only option to treat benzodiazepine withdrawal. Substance use disorder bridge clinics can provide the high-touch care needed to manage outpatient benzodiazepine tapers in patients at high risk due to other substance use disorders. Objective Describe the implementation and short-term outcomes of an outpatient benzodiazepine taper protocol to treat benzodiazepine withdrawal in a substance use disorder bridge clinic. Methods The clinical team developed a 4- to 6-week intensive outpatient taper protocol using diazepam. Patients with benzodiazepine use disorder were eligible if they had benzodiazepine withdrawal, lacked a prescriber, wanted to stop benzodiazepines completely, and agreed to daily visits. For patients who initiated a taper between April 2021 and December 2022, we evaluated the proportion of patients who completed a taper (i.e., tapered to a last prescribed dose of diazepam 10 mg/d or less); likelihood of remaining on the taper over time; and seizure, overdose, or death documented at the study institution during or within 1 month of taper completion or discontinuation. Other secondary outcomes included HIV testing and prevention, hepatitis C testing, and referrals to recovery coaching or psychiatry. Results Fifty-four patients initiated a total of 60 benzodiazepine tapers. The population was mostly male (61%) and non-Hispanic White (85%). Nearly all patients had opioid use disorder (96%), and most (80%) were taking methadone or buprenorphine for opioid use disorder before starting the taper. Patients reported using multiple substances in addition to benzodiazepines, most commonly fentanyl (75%), followed by cocaine (41%) and methamphetamine (21%). Fourteen patients (23%) completed a taper with a median duration of 34 days (IQR 27.8–43.5). Most tapers were stopped when the patient was lost to follow-up (57%), or the team recommended inpatient care (18%). Two patients had a seizure, and 4 had a presumed opioid-involved overdose during or within 1 month after the last taper visit, all individuals who did not complete a taper. No deaths occurred during or within 1 month of taper completion or discontinuation. Challenges included frequent loss to follow-up in the setting of other unstable substance use. Patients received other high-priority care during the taper including HIV testing (32%), PrEP initiation (6.7%), hepatitis C testing (30%), and referrals to recovery coaches (18%) and psychiatry (6.7%). Conclusions Managing benzodiazepine withdrawal with a 4- to 6-week intensive outpatient taper in patients with benzodiazepine and opioid use disorders is challenging. More work is needed to refine patient selection, balance safety risks with feasibility, and study long-term, patient-centered outcomes.
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