ABSTRACT
BACKGROUND AND AIMS: Alcohol use disorder (AUD) is a persistent public health concern, contributing significantly to mortality and morbidity. This study aims to evaluate the impact of in-hospital extended-release naltrexone (XR-NTX) administration on alcohol-related outcomes. METHODS: This retrospective cohort study, conducted at an academic medical centre, included 141 adult patients with AUD who received XR-NTX between December 2020 and June 2021. Primary and secondary outcomes were assessed 90 days before and after XR-NTX administration to identify number of alcohol-related hospitalisations, emergency department (ED) visits and average length of hospital stay. Subgroup analyses assessed outcomes in high hospital utilisers and marginally housed or unhoused populations. RESULTS: There was a significant decrease in ED visits and length of hospital stay post XR-NTX and no significant difference in the number of rehospitalisations. Subgroup analysis showed significant reduction in hospital readmissions and ED visits among high hospital utilisers. Our sample was a predominantly middle-aged, male and white patient population. CONCLUSIONS: In-hospital initiation of XR-NTX for AUD was associated with a significant decrease in ED visits and length of hospital stay. While no significant impact on the number of hospitalisations was observed overall, there was a substantial reduction in hospital readmissions and ED visits among high utilisers. Our findings suggest the potential benefits of in-hospital XR-NTX, emphasising the need for further research to establish causal relationships, assess cost-effectiveness and explore effectiveness across diverse patient populations. Effective in-hospital interventions, such as XR-NTX, hold promise for improving patient outcomes and reducing the healthcare burden associated with AUD.
ABSTRACT
Mucopolysaccharidosis type I (MPS I) is an inherited metabolic disorder caused by deficiency of alpha-L-iduronidase (IDUA), resulting in accumulation of heparan and dermatan sulfate glycosaminoglycans (GAGs). Individuals with the most severe form of the disease (Hurler syndrome) suffer from neurodegeneration, intellectual disability, and death by age 10. Current treatments for this disease include allogeneic hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT). However, these treatments do not address CNS manifestations of the disease. In this study we compared the ability of intravenously administered AAV serotypes 9 and rh10 (AAV9 and AAVrh10) for delivery and expression of the IDUA gene in the CNS. Adult C57BL/6 MPS I mice were infused intravenously with either AAV9 or AAVrh10 vector encoding the human IDUA gene. Treated animals demonstrated supraphysiological levels and widespread restoration of IDUA enzyme activity in the plasma and all organs including the CNS. High levels of IDUA enzyme activity were observed in the plasma, brain and spinal cord ranging from 10 to 100-fold higher than heterozygote controls, while levels in peripheral organs were also high, ranging from 1000 to 10,000-fold higher than control animals. In general, levels of IDUA expression were slightly higher in peripheral organs for AAVrh10 administered animals although these differences were not significant except for the lung. Levels of IDUA expression between AAV 9 and rh10 were roughly equivalent in the brain. Urinary and tissue GAGs were significantly reduced starting at 3 weeks after vector infusion, with restoration of normal GAG levels by the end of the study in animals treated with either AAV9 or rh10. These results demonstrate that non-invasive intravenous AAV9 or AAVrh10-mediated IDUA gene therapy is a potentially effective treatment for both systemic and CNS manifestations of MPS I, with implications for the treatment of other metabolic and neurological diseases as well.
