Economic evaluation of the Very Early Rehabilitation in SpEech (VERSE) intervention.

INTRODUCTION: There is limited evidence on the costs and outcomes of patients with aphasia after stroke. The aim of this study was to estimate costs in patients with aphasia after stroke according to the aphasia therapies provided. METHODS: A three-arm, prospective, randomized, parallel group, open-label, blinded endpoint assessment trial conducted in Australia and New Zealand. Usual ward-based care (Usual Care) was compared to additional usual ward-based therapy (Usual Care Plus) and a prescribed and structured aphasia therapy program in addition to Usual Care (the VERSE intervention). Information about healthcare utilization and productivity were collected to estimate costs in Australian dollars for 2017-18. Multivariable regression models with bootstrapping were used to estimate differences in costs and outcomes (clinically meaningful change in aphasia severity measured by the WAB-R-AQ). RESULTS: Overall, 202/246 (82%) participants completed follow-up at 26 weeks. Median costs per person were $23,322 (Q1 5,367, Q3 52,669, n = 63) for Usual Care, $26,923 (Q1 7,303, Q3 76,174, n = 70) for Usual Care Plus and $31,143 (Q1 7,001. Q3 62,390, n = 69) for VERSE. No differences in costs and outcomes were detected between groups. Usual Care Plus was inferior (i.e. more costly and less effective) in 64% of iterations, and in 18% was less costly and less effective compared to Usual Care. VERSE was inferior in 65% of samples and less costly and less effective in 12% compared to Usual Care. CONCLUSION: There was limited evidence that additional intensively delivered aphasia therapy within the context of usual acute care provided was worthwhile in terms of costs for the outcomes gained.

Exploring dimensions of quality-of-life in survivors of stroke with communication disabilities - a brief report.

BACKGROUND: People with communication disabilities post-stroke have poor quality-of-life. OBJECTIVES: We aimed to explore the association of self-reported communication disabilities with different dimensions of quality-of-life between 90 and 180 days post-stroke. METHODS: Cross-sectional survey data were obtained between 90 and 180 days post-stroke from registrants in the Australian Stroke Clinical Registry recruited from three hospitals in Queensland. The usual follow-up survey included the EQ5D-3L. Responses to the Hospital Anxiety and Depression Scale, and extra questions (e.g. communication disabilities) were also collected. We used χ2 statistics to determine differences. RESULTS: Overall, 244/647 survivors completed the survey. Respondents with communication disabilities (n = 72) more often reported moderate to extreme problems in all EQ5D-3L dimensions, than those without communication disabilities (n = 172): anxiety or depression (74% vs 40%, p < .001), pain or discomfort (58% vs 39%, p = .006), self-care (46% vs 18%, p < .001), usual activities (77% vs 49%, p < .001), and mobility (68% vs 35%, p < .001). Respondents with communication disabilities reported less fatigue (66% vs 89%, p < .001), poorer cognitive skills (thinking) (16% vs 1%, p < .001) and lower social participation (31% vs 6%, p < .001) than those without communication disabilities. CONCLUSIONS: Survivors of stroke with communication disabilities are more negatively impacted across different dimensions of quality-of-life (as reported between 90 and 180 days post-stroke) compared to those without communication disabilities. This highlights the need for timely and on-going comprehensive multidisciplinary person-centered support.

Novel Benzothiazole-based Ureas as 17ß-HSD10 Inhibitors, A Potential Alzheimer's Disease Treatment.

: It has long been established that mitochondrial dysfunction in Alzheimer's disease (AD) patients can trigger pathological changes in cell metabolism by altering metabolic enzymes such as the mitochondrial 17ß-hydroxysteroid dehydrogenase type 10 (17ß-HSD10), also known as amyloid-binding alcohol dehydrogenase (ABAD). We and others have shown that frentizole and riluzole derivatives can inhibit 17ß-HSD10 and that this inhibition is beneficial and holds therapeutic merit for the treatment of AD. Here we evaluate several novel series based on benzothiazolylurea scaffold evaluating key structural and activity relationships required for the inhibition of 17ß-HSD10. Results show that the most promising of these compounds have markedly increased potency on our previously published inhibitors, with the most promising exhibiting advantageous features like low cytotoxicity and target engagement in living cells.

Effects of dopamine on reinforcement learning and consolidation in Parkinson's disease.

Emerging evidence suggests that dopamine may modulate learning and memory with important implications for understanding the neurobiology of memory and future therapeutic targeting. An influential hypothesis posits that dopamine biases reinforcement learning. More recent data also suggest an influence during both consolidation and retrieval. Eighteen Parkinson's disease patients learned through feedback ON or OFF medication, with memory tested 24 hr later ON or OFF medication (4 conditions, within-subjects design with matched healthy control group). Patients OFF medication during learning decreased in memory accuracy over the following 24 hr. In contrast to previous studies, however, dopaminergic medication during learning and testing did not affect expression of positive or negative reinforcement. Two further experiments were run without the 24 hr delay, but they too failed to reproduce effects of dopaminergic medication on reinforcement learning. While supportive of a dopaminergic role in consolidation, this study failed to replicate previous findings on reinforcement learning.