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Reference to MCIDs is important for the full interpretation of the results of dementia trials and those conducting such trials should be open about the way in which they have determined and chosen their values for the MCIDs.

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This version available at: http://eprints.lse.ac.uk/64656/ Available in LSE Research Online: December 2015 LSE has developed LSE Research Online so that users may access research output of the School. Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Users may download and/or print one copy of any article(s) in LSE Research Online to facilitate their private study or for non-commercial research. You may not engage in further distribution of the material or use it for any profit-making activities or any commercial gain. You may freely distribute the URL (http://eprints.lse.ac.uk) of the LSE Research Online website. This document is the author's final accepted version of the journal article. There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it. 3Nursing home placement in the donepezil and memantine in moderate to severe Alzheimer's disease (DOMINO) trial: secondary and post-hoc analyses of a randomised trial Structured abstractBackground: Observational studies have suggested delay in nursing home placement (NHP) with dementia drug treatment, but an earlier randomised trial in patients with mild to moderate Alzheimer's disease (AD) showed no effect. We investigated the effects of continuing or discontinuing donepezil and starting memantine on subsequent NHP in moderate to severe AD. Methods:In the DOMINO trial (ISRCTN49545034) 295 community living patients with moderate to severe AD recruited from 15 centres in England and Scotland from February 2008 to March 2010 were randomised with double-blind placebo-control to continue donepezil (73), discontinue donepezil (73), discontinue donepezil and start memantine (76), or continue donepezil and start memantine (73) for 52 weeks. After 52 weeks choice of treatment was left to participants and their physicians. Place of residence was recorded at outcomes assessment points during the first 52 weeks of the trial and subsequently every 26 weeks for a further 3 years. Nursing home placement was an irreversible move from independent accommodation to a residential caring facility and was a secondary trial endpoint. Analyses restricted to the risk of placement in the first year of follow-up were post-hoc.Findings: 162 patients (55%) underwent NHP within 4 years of randomisation. Numbers of NHPs were similar for all arms (36 in patients who continued donepezil, 42 who discontinued donepezil, 41 who discontinued donepezil and started memantine, and 43 who continued donepezil and started memantine). There was significant (p=0.010) heterogeneity of treatment effect over time with significantly more NHPs in the donepezil discontinuation group during the first year (HR 2.09 (95% CI, 1.29 to 3.39)) and no difference later (HR 0.89 (95% CI, 0.58 to 1.35)). Subsequent analyses focussed on the first year of the trial and on donepezil only were post-hoc. 1-year NHP risk was 17% higher (95% CI 6% to 28%) in patients...

ObjectiveMost investigations of pharmacotherapy for treating Alzheimer's disease focus on patients with mild‐to‐moderate symptoms, with little evidence to guide clinical decisions when symptoms become severe. We examined whether continuing donepezil, or commencing memantine, is cost‐effective for community‐dwelling, moderate‐to‐severe Alzheimer's disease patients.MethodsCost‐effectiveness analysis was based on a 52‐week, multicentre, double‐blind, placebo‐controlled, factorial clinical trial. A total of 295 community‐dwelling patients with moderate/severe Alzheimer's disease, already treated with donepezil, were randomised to: (i) continue donepezil; (ii) discontinue donepezil; (iii) discontinue donepezil and start memantine; or (iv) continue donepezil and start memantine.ResultsContinuing donepezil for 52 weeks was more cost‐effective than discontinuation, considering cognition, activities of daily living and health‐related quality of life. Starting memantine was more cost‐effective than donepezil discontinuation. Donepezil–memantine combined is not more cost‐effective than donepezil alone.ConclusionsRobust evidence is now available to inform clinical decisions and commissioning strategies so as to improve patients' lives whilst making efficient use of available resources. Clinical guidelines for treating moderate/severe Alzheimer's disease, such as those issued by NICE in England and Wales, should be revisited. © 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.

Interventions for inappropriate vocalisation in dementia are not limited to medication. Environmental factors and behavioural approaches are considered ahead of pharmacotherapy as the concepts of Underlying Illness, Hidden Meaning and Empirical Treatments are used to structure consideration of important, and sometimes overlooked, issues including pain, depression and overall level of stimulation.

We review the potential to develop sources for neutron scattering science and propose that a merger with the rapidly developing field of inertial fusion energy could provide a major step-change in performance. In stark contrast to developments in synchrotron and laser science, the past 40 years have seen only a factor of 10 increase in neutron source brightness. With the advent of thermonuclear ignition in the laboratory, coupled to innovative approaches in how this may be achieved, we calculate that a neutron source three orders of magnitude more powerful than any existing facility can be envisaged on a 20- to 30-year time scale. Such a leap in source power would transform neutron scattering science.

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