SummaryBackgroundOesophageal adenocarcinoma is the sixth most common cause of cancer death worldwide and Barrett's oesophagus is the biggest risk factor. We aimed to evaluate the efficacy of high-dose esomeprazole proton-pump inhibitor (PPI) and aspirin for improving outcomes in patients with Barrett's oesophagus.MethodsThe Aspirin and Esomeprazole Chemoprevention in Barrett's metaplasia Trial had a 2 × 2 factorial design and was done at 84 centres in the UK and one in Canada. Patients with Barrett's oesophagus of 1 cm or more were randomised 1:1:1:1 using a computer-generated schedule held in a central trials unit to receive high-dose (40 mg twice-daily) or low-dose (20 mg once-daily) PPI, with or without aspirin (300 mg per day in the UK, 325 mg per day in Canada) for at least 8 years, in an unblinded manner. Reporting pathologists were masked to treatment allocation. The primary composite endpoint was time to all-cause mortality, oesophageal adenocarcinoma, or high-grade dysplasia, which was analysed with accelerated failure time modelling adjusted for minimisation factors (age, Barrett's oesophagus length, intestinal metaplasia) in all patients in the intention-to-treat population. This trial is registered with EudraCT, number 2004-003836-77.FindingsBetween March 10, 2005, and March 1, 2009, 2557 patients were recruited. 705 patients were assigned to low-dose PPI and no aspirin, 704 to high-dose PPI and no aspirin, 571 to low-dose PPI and aspirin, and 577 to high-dose PPI and aspirin. Median follow-up and treatment duration was 8·9 years (IQR 8·2–9·8), and we collected 20 095 follow-up years and 99·9% of planned data. 313 primary events occurred. High-dose PPI (139 events in 1270 patients) was superior to low-dose PPI (174 events in 1265 patients; time ratio [TR] 1·27, 95% CI 1·01–1·58, p=0·038). Aspirin (127 events in 1138 patients) was not significantly better than no aspirin (154 events in 1142 patients; TR 1·24, 0·98–1·57, p=0·068). If patients using non-steroidal anti-inflammatory drugs were censored at the time of first use, aspirin was significantly better than no aspirin (TR 1·29, 1·01–1·66, p=0·043; n=2236). Combining high-dose PPI with aspirin had the strongest effect compared with low-dose PPI without aspirin (TR 1·59, 1·14–2·23, p=0·0068). The numbers needed to treat were 34 for PPI and 43 for aspirin. Only 28 (1%) participants reported study-treatment-related serious adverse events.InterpretationHigh-dose PPI and aspirin chemoprevention therapy, especially in combination, significantly and safely improved outcomes in patients with Barrett's oesophagus.FundingCancer Research UK, AstraZeneca, Wellcome Trust, and Health Technology Assessment.

Background and Objectives Multidisciplinary rehabilitation is not incorporated into the usual care pathway for dementia despite increasing demand from key advocates. Clinician views regarding the relevance of rehabilitation in dementia care are not well known. This qualitative study explored the perspectives of health professionals regarding barriers to provision of multidisciplinary rehabilitation programs for people with dementia. Research Design and Methods Sixteen health professionals from a variety of settings and professional backgrounds were purposively sampled using maximum variation sampling. Semi-structured interviews were conducted to explore attitudes toward the care of people with dementia and beliefs about the feasibility and value of multidisciplinary rehabilitation in this population. Thematic analysis was used to identify themes. Results Participating clinicians acknowledged problems with existing dementia care pathways in Australia but rarely conceptualized rehabilitation as relevant to this pathway. Analyses yielded two main and related themes: (i) difficulty defining worthwhile outcomes of a rehabilitation program for people with dementia and (ii) perceived barriers to participation in this population. Clinicians felt that achievable outcomes for people with dementia were not sufficiently worthwhile for investment. Discussion and Implications Broader acceptance of multidisciplinary rehabilitation as relevant to dementia care will require a reframing of practice that both educates emerging health professionals regarding the outcomes that may be achievable for people with dementia and persuades staff to appreciate that the investment is worthwhile.

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Background:The aims of this study were 1) to examine postural sway in the eyes open (EO) and eyes closed (EC) conditions in people with multiple sclerosis (MS) with moderate levels of disability compared with controls and 2) to examine relationships between postural sway and total Expanded Disability Status Scale (EDSS) scores, functional system subscores, and clinical measures of strength and spasticity in the MS group.