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Background: dementia is increasingly recognised as life-limiting condition. Although the benefits of acetylcholinesterase inhibitors (AChEIs) on cognition and function are well established, their effect on survival is less clear. Objective: to investigate associations between AChEI prescription and mortality in patients with Alzheimer's dementia (AD) in a naturalistic setting, using detailed baseline data on cognition, functioning, and mental and physical wellbeing. Methods: we used a large mental healthcare database in South London, linked to Hospital Episode Statistics and Office for National Statistics mortality data, to assemble a retrospective cohort. We conducted a survival analysis adjusting for a wide range of potential confounders using propensity scores to reduce the impact of confounding by indication. Results: of 2,464 patients with AD, 1,261 were prescribed AChEIs. We detected a strong association between AChEI receipt and lower mortality (hazard ratio = 0.57; 95% CI 0.51-0.64). This remained significant after controlling for a broad range of potential confounders including psychotropic co-prescription, symptom severity, functional status and hospital admissions (hazard ratio = 0.77; 95% CI 0.67-0.87). Conclusions: in a large cohort of patients with AD, AChEI prescription was associated with reduced risk of death by more than 20% in adjusted models. This has implications for individual care planning and service development. [ABSTRACT FROM AUTHOR]

Objective: Clinical trial data and prior preliminary research indicate that fenfluramine (FFA) provides meaningful improvements in seizure-related and quality of life (QOL) outcomes for individuals with Dravet syndrome (DS), their caregivers, and their families. This study sought to replicate and extend these preliminary findings in a new sample of individuals with DS and their families who live in European countries., Methods: Study participants were European clinicians and parents caring for individuals with DS who had participated in an EU FFA Early Access Program. Participants completed one-on-one semi-structured interviews and were asked the extent to which they noticed changes in a number of the child's seizure- and non-seizure-related QOL domains after starting FFA treatment. Participants were also asked about the benefits of FFA treatment to the caregivers' lives and for the family unit., Results: 25 parent caregivers and 16 clinicians participated. The caregivers and clinicians reported improvements in both seizure-related (i.e., reductions in seizure activity, improvements in the frequency or type of seizure triggers and post-ictal recovery times, and improved post-seizure function) and non-seizure-related (e.g., cognition, focus, alertness, speech, academic performance, behavior, sleep, motor function) QOL domains after FFA treatment in individuals with DS. Caregivers also reported improved mood and more time for things they enjoyed, felt less overwhelmed, reported better sleep quality, and had less personal and family stress; clinicians corroborated most of these reports. All clinicians (100%) and most (96%) caregivers said they would "very likely" or "quite likely" recommend FFA to others with DS., Conclusions: Real-world experience in Europe with FFA treatment is associated with meaningful improvements in many QOL domains for individuals with DS and their families; replicating findings from a previous study of DS patients and their families from the USA. Caregivers and clinicians provided specific examples of the benefits of FFA for people with DS, caregivers, and their families and are very likely to recommend FFA to others with DS., Competing Interests: Declaration of Competing Interest MPJ, DA, RS, and DW have received research funding from Zogenix (now a part of UCB). AL is a current employee of Zogenix (now a part of UCB), and ARG was an employee of Zogenix at the time the current study was conducted., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

This paper considers the assessment of the impact of a community-based randomized controlled trial to reduce repeat deliberate self-harm. It considers the drawbacks in simplistic applications of conventional significance testing procedures, as well as possible failures regarding the statistical assumptions underlying such tests. Instead, the paper considers how relevant prior information might be incorporated within a fully Bayesian-model-based assessment procedure. The model includes a latent trait approach to patient morbidity; controlling for morbidity and other patient characteristics enhances the impact of the intervention (measured by a hazard rate ratio). If allowance is made for external information (e.g. ethical approval of the treatment), the weight of evidence shifts towards a positive intervention effect. [ABSTRACT FROM AUTHOR]

Objective. This study examined whether duration of treatment effect should be considered in a benefit-risk assessment using a case study of osteoarthritis medications. Study Design and Setting. A discrete choice experiment was completed by 300 residents of the United Kingdom with hip and/or knee osteoarthritis. In 16 choice tasks, participants selected their preferred option from 2 medications. Medications were described in terms of effect on pain, stiffness, and function; duration of treatment effect; and risk of heart attack and stomach ulcer bleeding. The analysis used mixed-effects logistic regression. Results. Pain, disease severity, and duration of treatment effect had the greatest influence on medication preferences, whereas stiffness did not significantly affect medication choice. Participants were willing to accept an increase in the risk of heart attack of 2.6% (95% confidence interval: 2.0% to 3.2%) to increase the duration of treatment effect from 1 month to 12 months. Reducing pain from moderate to mild was valued the same as increasing duration of effect from 1 month to 3 months; both were seen as equivalent to an absolute reduction of 1.2% in the risk of heart attack in the next year. Subgroup analysis suggested disease severity influenced patient preferences. Conclusions. Along with treatment benefits and risks, the results suggest that duration of treatment effect is an important factor in the medication choices of people with osteoarthritis. This could have implications for the design and interpretation of clinical trials, for example, incorporating longer-term surveillance of trial participants and accounting for duration of treatment effect in risk-benefit assessments. Future research is needed to assess whether these findings are generalizable to other samples, disease areas, and levels of duration of effect.