Glaucoma, a common cause of blindness, is currently treated by intraocular pressure (IOP)-lowering interventions. However, this approach is insufficient to completely prevent vision loss. Here, we evaluate an IOP-independent gene therapy strategy using a modified erythropoietin, EPO-R76E, which has reduced erythropoietic function. We used two models of glaucoma, the murine microbead occlusion model and the DBA/2J mouse. Systemic recombinant adeno-associated virus-mediated gene delivery of EpoR76E (rAAV.EpoR76E) was performed concurrent with elevation of IOP. Axon structure and active anterograde transport were preserved in both models. Vision, as determined by the flash visual evoked potential, was preserved in the DBA/2J. These results show that systemic EpoR76E gene therapy protects retinal ganglion cells from glaucomatous degeneration in two different models. This suggests that EPO targets a component of the neurodegenerative pathway that is common to both models. The efficacy of rAAV.EpoR76E delivered at onset of IOP elevation supports clinical relevance of this treatment.
Background Psychosis is common in Parkinson’s disease-related disorders and is associated with significant morbidity. Pimavanserin is a newly approved treatment for Parkinson’s disease psychosis, but real-world experience with pimavanserin has been limited by small sample sizes and limited assessment of longitudinal outcomes. Objective The aim was to summarize the clinical experience with pimavanserin in a large cohort of patients with Parkinson’s disease-related psychosis. Methods We conducted a retrospective chart review of patients who were prescribed pimavanserin at Vanderbilt University Medical Center in the southeast United States between May 2016 and July 2018. We used Chi-squared analyses to compare efficacy and tolerability of pimavanserin, considering patient diagnosis, presence of dementia or delusions, use of deep brain stimulation, and prior antipsychotic failure. Additionally, we compared the clinical characteristics of patients who started treatment and those who did not, to evaluate safety outcomes. Results We identified 107 patients prescribed pimavanserin, and 91 began treatment. Clinical improvement in psychosis was documented in 76% of patients (69/91) and did not differ based on diagnosis, presence of dementia, delusions, use of deep brain stimulation, or prior antipsychotic failure. Adverse effects were reported in 20 patients (22%), the most common of which was worsening gait instability (5/91, 5%). Side effects led to cessation of therapy in 11 of the 91 patients (12%). At current follow-up, 50 (65%) of 77 living patients remain on treatment, with a mean treatment duration of 14.6 months. Although most of these patients are on pimavanserin monotherapy (33/50, 66%), 17 patients (34%) are on a dual-antipsychotic regimen. The living patients no longer on treatment stopped pimavanserin primarily because of a lack of perceived benefit (11/77, 14%), side effects (9/77, 12%), or both (1/77, 1%), though six patients (8%) stopped for reasons unrelated to medication effects, including the desire to reduce overall medication burden and negative media reporting on pimavanserin. Conclusions Study results emphasize long-term efficacy and tolerability of pimavanserin for psychosis in Parkinson’s disease-related disorders, including patients with dementia, delusions, deep brain stimulation use, or prior antipsychotic failure.
Purpose: Values clarification workshops on abortion have been shown to increase support for abortion among healthcare workers. However, few studies have examined the impact of values clarification workshops on abortion among medical trainees. This study aimed to understand medical student and obstetrics and gynecology (ObGyn) residents' experiences with a virtual values clarification workshop on abortion. Methods: Clerkship year medical students and ObGyn residents at four midwestern teaching hospitals were invited to be interviewed about their experiences in a virtual values clarification workshop on abortion from January 2021 through December 2021. A single interviewer conducted interviews via Zoom using a standardized interview guide. Participants were asked to provide feedback and discuss their experiences in the workshop. Four qualitatively trained evaluators coded the interview transcripts in NVivo, using an inductive approach to establish consensus codes then themes. Results: This study interviewed 37 trainees, including 24 medical students and 13 ObGyn residents, as well as five facilitators, between November 2021 and February 2022. Three themes emerged in both trainee groups. First, participants found the workshops helped trainees clarify and understand their own views on abortion through thought exploration, peer validation, and reflection on their views' potential societal impacts. Second, through the workshop, participants reflected on others' opinions on abortion and better understood the spectrum of beliefs their peers held. Finally, participants found the workshops helped them explore and develop their professional identity as physicians-in-training, through practicing communication skills and building trust and mutual respect among peers. Conclusions: Medical trainees found values clarification workshops on abortion to be valuable, helping them establish their own beliefs about abortion, contextualize these beliefs among their peers', and practice professionalism. These findings indicate that values clarification workshops can play a key role in helping medical trainees discuss abortion and prepare for their professional future.
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