Development of an online intervention for the Rehabilitation Exercise and psycholoGical support After covid-19 InfectioN (REGAIN) trial.

Background: Up to half of people hospitalised with COVID-19 report diverse and persistent symptoms affecting quality of life for months and sometimes years after discharge (long-COVID). We describe the development of an online group exercise and behavioural support intervention for people who continue to experience such physical and/or emotional health problems more than three months after hospital discharge. Methods: Intervention development was informed by the Medical Research Council framework for complex interventions. Our multidisciplinary team of academics, clinicians, and people with long-COVID, had collective expertise in the development and testing of complex interventions. We integrated a bio-psycho-social model of care drawing on rehabilitation literature for long-term health conditions and experiences from our pre-pilot study. Multiple stakeholder meetings were held to refine the intervention which was designed to be deliverable within the UK National Health Service. We adhere to TIDieR guidance for transparent and explicit reporting of telehealth interventions. Results: The final REGAIN online exercise and behavioural support intervention consisted of an initial 1:1 consultation with a trained practitioner, followed by eight online group exercise, and six group support, sessions delivered over eight weeks. Participants could also access an online library of on-demand exercise and support videos. Conclusions: The final REGAIN intervention, combining exercise and behavioural support, is fully manualised with clear pathways to delivery and implementation. It is currently being tested in a randomised controlled trial. The intervention, developed with extensive patient and stakeholder engagement, could be incorporated into existing NHS rehabilitation programmes, should it prove to be clinically and cost-effective for people with long-COVID. Trial registration: International Standard Randomised Controlled Trial Number (ISRCTN) 11466448: Rehabilitation exercise and psychological support after COVID-19 infection: REGAIN.

Long-COVID has many debilitating symptoms, such as breathlessness, muscle weakness and fatigue, which significantly affect peoples' physical and mental health and quality of life. Rehabilitation programmes can help people improve their quality of life in other medical conditions with similar symptoms. We developed a programme of physical and mental health rehabilitation, delivered online, specifically to support people with ongoing long-COVID symptoms more than three months after hospital discharge. The programme was developed by people with long-COVID along with clinicians and researchers. The programme described in this article is now being tested in a large research trial to see if it can help people with long-COVID.

Moderators of Cognitive Outcomes from an Exercise Program in People with Mild to Moderate Dementia.

BACKGROUND/OBJECTIVES: Our aim was to estimate whether baseline participant variables were able to moderate the effect of an exercise intervention on cognition in patients with mild to moderate dementia. DESIGN: Subgroup analysis of a multicenter pragmatic randomized controlled trial. SETTING: Community-based gym/rehabilitation centers. PARTICIPANTS: A total of 494 community-dwelling participants with mild to moderate dementia. INTERVENTION: Participants were randomized to a moderate- to high-intensity aerobic and strength exercise program or a usual care control group. Experimental group participants attended twice weekly 60- to 90-minute gym sessions for 4 months. Participants were prescribed home exercises for an additional hour per week during the supervised period and 150 minutes each week after the supervised period. MEASUREMENTS: Multilevel regression model analyses were undertaken to identify individual moderators of cognitive function measured through the Alzheimer Disease Assessment Scale-Cognitive Subscale score at 12 months. RESULTS: When tested for a formal interaction effect, only cognitive function assessed by the baseline number cancellation test demonstrated a statistically significant interaction effect (-2.7 points; 95% confidence interval = -5.14 to -0.21). CONCLUSION: People with worse number cancellation test scores may experience greater progression of cognitive decline in response to a moderate- to high-intensity exercise program. Further analyses to examine whether these findings can be replicated in planned sufficiently powered analyses are indicated.

Does Structured Exercise Improve Cognitive Impairment in People with Mild to Moderate Dementia? A Cost-Effectiveness Analysis from a Confirmatory Randomised Controlled Trial: The Dementia and Physical Activity (DAPA) Trial.

BACKGROUND: Previous studies suggest that physical exercise could slow dementia progression. However, evidence for the cost effectiveness of structured exercise is conflicting and based on small trials. OBJECTIVES: The objective of this study was to compare the cost effectiveness of a tailored, structured, moderate- to high-intensity exercise programme versus usual care in people with mild to moderate dementia. METHODS: An economic evaluation was conducted from the UK National Health Service and personal social services perspective, based on data from a large randomised controlled trial. The primary clinical outcome was the participant reported ADAS-Cog (Alzheimer's Disease Assessment Scale-Cognitive Subscale) at 12 months. Costs (£; 2014-2015 prices) were collected prospectively over a 12-month follow-up period. A bivariate regression of costs and quality-adjusted life-years (QALYs), with multiple imputation of missing data, was conducted with the view to estimating the incremental cost per QALY gained and the incremental net monetary benefit (INMB) associated with the exercise programme plus usual care versus usual care. Sensitivity analyses were undertaken to assess the impact of uncertainty surrounding aspects of the economic evaluation, and pre-specified subgroup analyses explored heterogeneity in the cost-effectiveness results. RESULTS: Participants (n = 494) were randomised to exercise plus usual care or usual care only. By 12 months the mean ADAS-Cog score had worsened slightly to 25.2 (standard deviation [SD] 12.3) in the exercise arm and 23.8 (SD 10.4) in the usual care: difference - 1.4, 95% confidence interval (CI) - 2.6 to - 0.2 (p = 0.03). The mean (standard error [SE]) costs over 12 months for experimental versus control was £5945 (US$7856) versus £4597 (US$6574), respectively; (difference: £1347 [$1926]; p = 0.0426). Mean (SE) QALY estimates were 0.787 (0.012) versus 0.826 (0.019), respectively (p = 0.090). The probability that the exercise programme is cost effective was < 1% across cost-effectiveness thresholds. INMBs ranged between -£2601 (US$3719) and £2158 (US$3086) at cost-effectiveness thresholds between £15,000 (US$21,450) and £30,000 (US$42,900) per QALY. The cost-effectiveness results remained robust to several sensitivity and subgroup analyses. CONCLUSIONS: Building on the clinical results of the trial, which showed that the structured exercise programme evaluated does not slow cognitive impairment in people with mild to moderate dementia, this economic evaluation shows that the programme is not cost effective.

Aerobic and strength training exercise programme for cognitive impairment in people with mild to moderate dementia: the DAPA RCT.

BACKGROUND: Approximately 670,000 people in the UK have dementia. Previous literature suggests that physical exercise could slow dementia symptom progression. OBJECTIVES: To estimate the clinical effectiveness and cost-effectiveness of a bespoke exercise programme, in addition to usual care, on the cognitive impairment (primary outcome), function and health-related quality of life (HRQoL) of people with mild to moderate dementia (MMD) and carer burden and HRQoL. DESIGN: Intervention development, systematic review, multicentred, randomised controlled trial (RCT) with a parallel economic evaluation and qualitative study. SETTING: 15 English regions. PARTICIPANTS: People with MMD living in the community. INTERVENTION: A 4-month moderate- to high-intensity, structured exercise programme designed specifically for people with MMD, with support to continue unsupervised physical activity thereafter. Exercises were individually prescribed and progressed, and participants were supervised in groups. The comparator was usual practice. MAIN OUTCOME MEASURES: The primary outcome was the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog). The secondary outcomes were function [as measured using the Bristol Activities of Daily Living Scale (BADLS)], generic HRQoL [as measured using the EuroQol-5 Dimensions, three-level version (EQ-5D-3L)], dementia-related QoL [as measured using the Quality of Life in Alzheimer's Disease (QoL-AD) scale], behavioural symptoms [as measured using the Neuropsychiatric Inventory (NPI)], falls and fractures, physical fitness (as measured using the 6-minute walk test) and muscle strength. Carer outcomes were HRQoL (Quality of Life in Alzheimer's Disease) (as measured using the EQ-5D-3L) and carer burden (as measured using the Zarit Burden Interview). The economic evaluation was expressed in terms of incremental cost per quality-adjusted life-year (QALY) gained from a NHS and Personal Social Services perspective. We measured health and social care use with the Client Services Receipt Inventory. Participants were followed up for 12 months. RESULTS: Between February 2013 and June 2015, 494 participants were randomised with an intentional unequal allocation ratio: 165 to usual care and 329 to the intervention. The mean age of participants was 77 years [standard deviation (SD) 7.9 years], 39% (193/494) were female and the mean baseline ADAS-Cog score was 21.5 (SD 9.0). Participants in the intervention arm achieved high compliance rates, with 65% (214/329) attending between 75% and 100% of sessions. Outcome data were obtained for 85% (418/494) of participants at 12 months, at which point a small, statistically significant negative treatment effect was found in the primary outcome, ADAS-Cog (patient reported), with a mean difference of -1.4 [95% confidence interval (CI) -2.62 to -0.17]. There were no treatment effects for any of the other secondary outcome measures for participants or carers: for the BADLS there was a mean difference of -0.6 (95% CI -2.05 to 0.78), for the EQ-5D-3L a mean difference of -0.002 (95% CI -0.04 to 0.04), for the QoL-AD scale a mean difference of 0.7 (95% CI -0.21 to 1.65) and for the NPI a mean difference of -2.1 (95% CI -4.83 to 0.65). Four serious adverse events were reported. The exercise intervention was dominated in health economic terms. LIMITATIONS: In the absence of definitive guidance and rationale, we used a mixed exercise programme. Neither intervention providers nor participants could be masked to treatment allocation. CONCLUSIONS: This is a large well-conducted RCT, with good compliance to exercise and research procedures. A structured exercise programme did not produce any clinically meaningful benefit in function or HRQoL in people with dementia or on carer burden. FUTURE WORK: Future work should concentrate on approaches other than exercise to influence cognitive impairment in dementia. TRIAL REGISTRATION: Current Controlled Trials ISRCTN32612072. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full programme and will be published in full in Health Technology Assessment Vol. 22, No. 28. See the NIHR Journals Library website for further project information. Additional funding was provided by the Oxford NIHR Biomedical Research Centre and the Oxford NIHR Collaboration for Leadership in Applied Health Research and Care.

Dementia And Physical Activity (DAPA) trial of moderate to high intensity exercise training for people with dementia: randomised controlled trial.

OBJECTIVE: To estimate the effect of a moderate to high intensity aerobic and strength exercise training programme on cognitive impairment and other outcomes in people with mild to moderate dementia. DESIGN: Multicentre, pragmatic, investigator masked, randomised controlled trial. SETTING: National Health Service primary care, community and memory services, dementia research registers, and voluntary sector providers in 15 English regions. PARTICIPANTS: 494 people with dementia: 329 were assigned to an aerobic and strength exercise programme and 165 were assigned to usual care. Random allocation was 2:1 in favour of the exercise arm. INTERVENTIONS: Usual care plus four months of supervised exercise and support for ongoing physical activity, or usual care only. Interventions were delivered in community gym facilities and NHS premises. MAIN OUTCOME MEASURES: The primary outcome was score on the Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) at 12 months. Secondary outcomes included activities of daily living, neuropsychiatric symptoms, health related quality of life, and carer quality of life and burden. Physical fitness (including the six minute walk test) was measured in the exercise arm during the intervention. RESULTS: The average age of participants was 77 (SD 7.9) years and 301/494 (61%) were men. By 12 months the mean ADAS-cog score had increased to 25.2 (SD 12.3) in the exercise arm and 23.8 (SD 10.4) in the usual care arm (adjusted between group difference -1.4, 95% confidence interval -2.6 to -0.2, P=0.03). This indicates greater cognitive impairment in the exercise group, although the average difference is small and clinical relevance uncertain. No differences were found in secondary outcomes or preplanned subgroup analyses by dementia type (Alzheimer's disease or other), severity of cognitive impairment, sex, and mobility. Compliance with exercise was good. Over 65% of participants (214/329) attended more than three quarters of scheduled sessions. Six minute walking distance improved over six weeks (mean change 18.1 m, 95% confidence interval 11.6 m to 24.6 m). CONCLUSION: A moderate to high intensity aerobic and strength exercise training programme does not slow cognitive impairment in people with mild to moderate dementia. The exercise training programme improved physical fitness, but there were no noticeable improvements in other clinical outcomes. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10416500.

The Impact of the Physical Environment on Depressive Symptoms of Older Residents Living in Care Homes: A Mixed Methods Study.

Background and Objectives: Forty percent of residents living in care homes in the United Kingdom have significant depressive symptoms. Care homes can appear to be depressing places, but whether the physical environment of homes directly affects depression in care home residents is unknown. This study explores the relationship between the physical environment and depressive symptoms of older people living in care homes. Research Design and Methods: In a prospective cohort study the physical environment of 50 care homes were measured using the Sheffield Care Environment Assessment Matrix (SCEAM) and depressive symptoms of 510 residents measured using the Geriatric Depression Scale (GDS-15). The study was supplemented with semi-structured interviews with residents living in the care homes. Quantitative data were analyzed using multi-level modeling, and qualitative data analyzed using a thematic framework approach. Results: The overall physical environment of care homes (overall SCEAM score) did not predict depressive symptoms. Controlling for dependency, social engagement, and home type, having access to outdoor space was the only environmental variable to significantly predict depressive symptoms. Residents interviewed reported that access to outdoor space was restricted in many ways: locked doors, uneven foot paths, steep steps, and needing permission or assistance to go outside. Discussion and Implications: We provide new evidence to suggest that access to outdoor space predicts depressive symptoms in older people living in care home. Interventions aimed at increasing access to outdoor spaces could positively affect depressive symptoms in older people.

Challenges and opportunities in understanding dementia and delirium in the acute hospital.

In an Essay, Andrew Jackson and colleagues discuss challenges in the diagnosis and management of older people with dementia and delirium in acute hospitals.

Cost-effectiveness of donepezil and memantine in moderate to severe Alzheimer's disease (the DOMINO-AD trial).

OBJECTIVE: Most 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. METHODS: Cost-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. RESULTS: Continuing 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. CONCLUSIONS: Robust 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.

Acetylcholinesterase Activity Measurement and Clinical Features of Delirium.

AIMS: Cholinergic deficiency is commonly implicated in the pathophysiology of delirium. We aimed to investigate the relationship between directly measured serum acetylcholinesterase (AChE) activity and (1) clinical features of delirium and (2) outcomes among older hospital patients with delirium. METHODS: Hospitalised patients with delirium were recruited, and delirium motor subtype, severity and duration of delirium were measured. Serum AChE activity was measured using a colorimetric assay. RESULTS: The mean AChE activity for the whole sample was 2.46 µmol/µL/min (standard deviation 1.75). Higher AChE activity was associated with increased likelihood of hypoactive delirium rather than the hyperactive or mixed subtype (odds ratio 1.98, 95% confidence interval 1.10-3.59). CONCLUSION: Higher AChE activity was associated with hypoactive delirium but did not predict outcomes. Simple enhancement of cholinergic neurotransmission may not be sufficient to treat delirium.

Undiagnosed long-term cognitive impairment in acutely hospitalised older medical patients with delirium: a prospective cohort study.

BACKGROUND: delirium and dementia are common in the general hospital, being present in nearly 50% of older unselected admissions to hospital. Cognitive impairment is a risk factor for delirium, but the prevalence of previously undiagnosed cognitive impairment (dementia or mild cognitive impairment) in patients with delirium is unknown. METHODS: we performed a prospective cohort study of people over 70 years admitted to hospital with delirium to establish the prevalence of previously unrecognised prior cognitive impairment. Delirium was diagnosed at baseline using the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). Mild cognitive impairment and dementia were diagnosed 3 months following recruitment in survivors using the International Working Group on Mild Cognitive Impairment criteria and DSM-IV criteria, respectively. RESULTS: delirium was identified in 17.9% of older patients, and 82 participants with delirium were assessed at 3 months: 5 (6%) had persistent delirium, 14 (17%) had mild cognitive impairment and 47 (57%) had dementia. In 17 participants with prior dementia and 14 with prior mild cognitive impairment, the diagnosis had been unrecognised, amounting to 31/82 (38%) of all patients with delirium having some form of previously undiagnosed cognitive impairment. CONCLUSION: given that over 1/3 of older patients with delirium were found to have a previously undiagnosed cognitive impairment, the development and evaluation of services to follow-up and manage patients with delirium are warranted.

Diagnostic test accuracy of informant-based tools to diagnose dementia in older hospital patients with delirium: a prospective cohort study.

BACKGROUND: delirium and dementia co-exist commonly in hospital. Older people with delirium have high rates of undiagnosed dementia, but delirium affects the use of cognitive testing in dementia diagnosis. Novel methods to detect dementia in delirium are needed. The purpose of the study was to investigate the diagnostic test accuracy of informant tools to detect dementia in hospitalised older people with delirium. METHODS: the presence of dementia on admission was assessed using the short form of the Informant Questionnaire of Cognitive Decline in the Elderly (IQCODE-SF) and Alzheimer's Disease 8 (AD8) in people over 70 years old with delirium. Reference standard diagnosis was made using Diagnostic and Statistical Manual of Mental Disorders fourth edition (DSM-IV) criteria at 3 months. The main outcome measures were the diagnostic test accuracy of the IQCODE-SF and the AD8 in diagnosing DSM-IV dementia. RESULTS: dementia prevalence at 3 months was 61%. The area under the receiver operating characteristic curve (AUROC) was 0.93 (P < 0.0005) for admission IQCODE-SF and 0.91 (P < 0.0005) for admission AD8. An IQCODE-SF test result of >3.82 on admission had a sensitivity of 0.91 (0.79-0.97) and specificity of 0.93 (0.76-0.99) for detecting dementia. An AD8 of >6 had a sensitivity of 0.83 (0.69-0.92) and specificity of 0.90 (0.72-0.97) for detecting dementia. CONCLUSION: the IQCODE-SF and AD8 are sensitive and specific tools to detect prior dementia in older people with delirium. The routine use of either tool in practice could have important clinical impact, by improving the recognition and hence management of those with dementia.

An Occupational Therapy intervention for residents with stroke-related disabilities in UK Care Homes (OTCH): cluster randomised controlled trial with economic evaluation.

BACKGROUND: Care home residents with stroke-related disabilities have significant activity limitations. Phase II trial results suggested a potential benefit of occupational therapy (OT) in maintaining residents' capacity to engage in functional activity. OBJECTIVE: To evaluate the clinical effectiveness and cost-effectiveness of a targeted course of OT in maintaining functional activity and reducing further health risks from inactivity for UK care home residents living with stroke-related disabilities. DESIGN: Pragmatic, parallel-group, cluster randomised controlled trial with economic evaluation. Cluster randomisation occurred at the care-home level. Homes were stratified according to trial administrative centre and type of care provided (nursing or residential), and they were randomised 1 : 1 to either the intervention or the control arm. SETTING: The setting was 228 care homes which were local to 11 trial administrative centres across England and Wales. PARTICIPANTS: Care home residents with a history of stroke or transient ischaemic attack, including residents with communication and cognitive impairments, not receiving end-of-life care. INTERVENTION: Personalised 3-month course of OT delivered by qualified therapists. Care workers participated in training workshops to support personal activities of daily living. The control condition consisted of usual care for residents. MAIN OUTCOME MEASURES: Outcome data were collected by a blinded assessor. The primary outcome at the participant level was the Barthel Index of Activities of Daily Living (BI) score at 3 months. The secondary outcomes included BI scores at 6 and 12 months post randomisation, and the Rivermead Mobility Index, Geriatric Depression Scale-15 and European Quality of Life-5 Dimensions, three levels, questionnaire scores at all time points. Economic evaluation examined the incremental cost per quality-adjusted life-year (QALY) gain. Costs were estimated from the perspective of the NHS and Personal Social Services. RESULTS: Overall, 568 residents from 114 care homes were allocated to the intervention arm and 474 residents from another 114 care homes were allocated to the control arm, giving a total of 1042 participants. Randomisation occurred between May 2010 and March 2012. The mean age of participants was 82.9 years, and 665 (64%) were female. No adverse events attributable to the intervention were recorded. Of the 1042 participants, 870 (83%) were included in the analysis of the primary outcome (intervention, n = 479; control, n = 391). The primary outcome showed no significant differences between groups. The adjusted mean difference in the BI score between groups was 0.19 points higher in the intervention arm [95% confidence interval (CI) -0.33 to 0.70, p = 0.48; adjusted intracluster correlation coefficient 0.09]. Secondary outcome measures showed no significant differences at all time points. Mean incremental cost of the Occupational Therapy intervention for residents with stroke living in UK Care Homes intervention was £438.78 (95% CI -£3360.89 to £1238.46) and the incremental QALY gain was 0.009 (95% CI -0.030 to 0.048). LIMITATIONS: A large proportion of participants with very severe activity-based limitations and cognitive impairment may have limited capacity to engage in therapy. CONCLUSION: A 3-month individualised course of OT showed no benefit in maintaining functional activity in an older care home population with stroke-related disabilities. FUTURE WORK: There is an urgent need to reduce health-related complications caused by inactivity and to provide an enabling built environment within care homes. TRIAL REGISTRATION: Current Controlled Trials ISRCTN00757750. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 15. See the Health Technology Assessment programme website for further project information.

Dementia and Physical Activity (DAPA) - an exercise intervention to improve cognition in people with mild to moderate dementia: study protocol for a randomized controlled trial.

BACKGROUND: Dementia is more common in older than in younger people, and as a result of the ageing of the population in developed countries, it is becoming more prevalent. Drug treatments for dementia are limited, and the main support offered to people with dementia and their families is generally services to mitigate against loss of function. Physical exercise is a candidate non-pharmacological treatment for dementia. METHODS/DESIGN: DAPA is a randomised controlled trial funded by the National Institute for Health Research Health Technology Assessment programme to estimate the effect of a 4-month, moderate- to hard-intensity exercise training programme and subsequent advice to remain active, on cognition (primary outcome) at 12 months in people with mild to moderate dementia. Community-dwelling participants (with their carers where possible), who are able to walk 3 metres without human assistance, able to undertake an exercise programme and do not have any unstable or terminal illness are recruited. Participants are then randomised by an independent statistician using a computerised random number generator to usual care or exercise at a 2:1 ratio in favour of exercise. The exercise intervention comprises 29, 1-hour-long exercise classes, run twice weekly at suitable venues such as leisure centres, which include aerobic exercise (on static bikes) and resistance exercise (using weights). Goals for independent exercise are set while the classes are still running, and supported thereafter with phone calls. The primary outcome is measured using ADAS-cog. Secondary outcome measures include behavioural symptoms, functional ability, quality of life and carer burden. Primary and secondary outcomes will be measured at baseline and at 6 and 12 months after randomisation, by researchers masked to participant randomisation in the participants' own homes. An economic evaluation will be carried out in parallel to the RCT, as will a qualitative study capturing the experiences of participants, carers and staff delivering the intervention. DISCUSSION: The DAPA study will be the first large, randomised trial of the cognitive effects of exercise on people with dementia. The intervention is designed to be capable of being delivered within the constraints of NHS service provision, and the economic evaluation will allow assessment of its cost-effectiveness. TRIAL REGISTRATION: DAPA was registered with the ISRCTN database on 29 July 2011, registration number ISRCTN32612072 .

Nursing home placement in the Donepezil and Memantine in Moderate to Severe Alzheimer's Disease (DOMINO-AD) trial: secondary and post-hoc analyses.

BACKGROUND: Findings from observational studies have suggested a delay in nursing home placement with dementia drug treatment, but findings from a previous randomised trial of patients with mild-to-moderate Alzheimer's disease showed no effect. We investigated the effects of continuation or discontinuation of donepezil and starting of memantine on subsequent nursing home placement in patients with moderate-to-severe Alzheimer's disease. METHODS: In the randomised, double-blind, placebo-controlled Donepezil and Memantine in Moderate to Severe Alzheimer's Disease (DOMINO-AD) trial, community-living patients with moderate-to-severe Alzheimer's disease (who had been prescribed donepezil continuously for at least 3 months at a dose of 10 mg for at least the previous 6 weeks and had a score of between 5 and 13 on the Standardised Mini-Mental State Examination) were recruited from 15 secondary care memory centres in England and Scotland and randomly allocated to continue donepezil 10 mg per day without memantine, discontinue donepezil without memantine, discontinue donepezil and start memantine 20 mg per day, or continue donepezil 10 mg per day and start memantine 20 mg per day, for 52 weeks. After 52 weeks, choice of treatment was left to participants and their physicians. Place of residence was recorded during the first 52 weeks of the trial and then every 26 weeks for a further 3 years. A secondary outcome of the trial, reported in this study, was nursing home placement: an irreversible move from independent accommodation to a residential caring facility. Analyses restricted to risk of placement in the first year of follow-up after the patients had completed the double-blind phase of the trial were post-hoc. The DOMINO-AD trial is registered with the ISRCTN Registry, number ISRCTN49545035. FINDINGS: Between Feb 11, 2008, and March 5, 2010, 73 (25%) patients were randomly assigned to continue donepezil without memantine, 73 (25%) to discontinue donepezil without memantine, 76 (26%) to discontinue donepezil and start memantine, and 73 (25%) to continue donepezil and start memantine. 162 (55%) patients underwent nursing home placement within 4 years of randomisation, with similar numbers for all groups (36 [49%] in patients who continued donepezil without memantine, 42 [58%] who discontinued donepezil without memantine, 41 [54%] who discontinued donepezil and started memantine, and 43 [59%] who continued donepezil and started memantine). We noted significant (p=0·010) heterogeneity of treatment effect over time, with significantly more nursing home placements in the combined donepezil discontinuation groups during the first year (hazard ratio 2·09 [95% CI 1·29-3·39]) than in the combined donepezil continuation groups, and no difference during the next 3 years (0·89 [0·58-1·35]). We noted no effect of patients starting memantine compared with not starting memantine during the first year (0·92 [0·58-1·45]) or the next 3 years (1·23 [0·81-1·87]). INTERPRETATION: Withdrawal of donepezil in patients with moderate-to-severe Alzheimer's disease increased the risk of nursing home placement during 12 months of treatment, but made no difference during the following 3 years of follow-up. Decisions to stop or continue donepezil treatment should be informed by potential risks of withdrawal, even if the perceived benefits of continued treatment are not clear. FUNDING: Medical Research Council and UK Alzheimer's Society.

Development of an exercise intervention to improve cognition in people with mild to moderate dementia: Dementia And Physical Activity (DAPA) Trial, registration ISRCTN32612072.

More than 800000 people in the UK have dementia, and it is a government priority to improve dementia care. Drug treatment options are relatively limited. The Dementia And Physical Activity (DAPA) study is a randomised trial which targets cognition in people with dementia, using an exercise programme. There is evidence to suggest that both aerobic and resistance exercise may be useful in improving cognition. Hence the intervention comprises a supervised part of twice-weekly exercise classes of one hour duration for 4 months, including aerobic exercise at moderate intensity on static bicycles, and resistance (weight training) exercise using weight vests, weight belts and dumbbells. Thereafter participants progress to unsupervised, independent exercise. Aids to behaviour modification have been incorporated into the intervention. The DAPA intervention has been designed to maximise likelihood of effectiveness and cost-effectiveness, and for delivery in the UK National Health Service.

An occupational therapy intervention for residents with stroke related disabilities in UK care homes (OTCH): cluster randomised controlled trial.

OBJECTIVE: To evaluate the clinical efficacy of an established programme of occupational therapy in maintaining functional activity and reducing further health risks from inactivity in care home residents living with stroke sequelae. DESIGN: Pragmatic, parallel group, cluster randomised controlled trial. SETTING: 228 care homes (>10 beds each), both with and without the provision of nursing care, local to 11 trial administrative centres across the United Kingdom. PARTICIPANTS: 1042 care home residents with a history of stroke or transient ischaemic attack, including those with language and cognitive impairments, not receiving end of life care. 114 homes (n=568 residents, 64% from homes providing nursing care) were allocated to the intervention arm and 114 homes (n=474 residents, 65% from homes providing nursing care) to standard care (control arm). Participating care homes were randomised between May 2010 and March 2012. INTERVENTION: Targeted three month programme of occupational therapy, delivered by qualified occupational therapists and assistants, involving patient centred goal setting, education of care home staff, and adaptations to the environment. MAIN OUTCOME MEASURES: Primary outcome at the participant level: scores on the Barthel index of activities of daily living at three months post-randomisation. Secondary outcome measures at the participant level: Barthel index scores at six and 12 months post-randomisation, and scores on the Rivermead mobility index, geriatric depression scale-15, and EuroQol EQ-5D-3L questionnaire, at all time points. RESULTS: 64% of the participants were women and 93% were white, with a mean age of 82.9 years. Baseline characteristics were similar between groups for all measures, personal characteristics, and diagnostic tests. Overall, 2538 occupational therapy visits were made to 498 participants in the intervention arm (mean 5.1 visits per participant). No adverse events attributable to the intervention were recorded. 162 (11%) died before the primary outcome time point, and 313 (30%) died over the 12 months of the trial. The primary outcome measure did not differ significantly between the treatment arms. The adjusted mean difference in Barthel index score at three months was 0.19 points higher in the intervention arm (95% confidence interval -0.33 to 0.70, P=0.48). Secondary outcome measures also showed no significant differences at all time points. CONCLUSIONS: This large phase III study provided no evidence of benefit for the provision of a routine occupational therapy service, including staff training, for care home residents living with stroke related disabilities. The established three month individualised course of occupational therapy targeting stroke related disabilities did not have an impact on measures of functional activity, mobility, mood, or health related quality of life, at all observational time points. Providing and targeting ameliorative care in this clinically complex population requires alternative strategies.Trial registration Current Controlled Trials ISRCTN00757750.

A 12-month follow-up study of people with dementia referred to general hospital liaison psychiatry services.

BACKGROUND: new services for patients with dementia in general hospitals are being widely developed. Little is known of outcomes after hospital for such patients. OBJECTIVE: to establish outcomes for patients with dementia referred to general hospital psychiatric services. DESIGN: prospective cohort study. SETTING: two UK general hospitals. SUBJECTS: referrals with dementia to liaison psychiatric services. METHOD: eligible referrals (n = 112), and their carers, were assessed during admission, and at 6 and 12 months, using battery of health measurements. RESULTS: mortality at 6 months was 31% and at 12 months 40%. At baseline, 13% lived in a care home, rising to 84% by 6 months. Quality of life scores remained stable over 12 months, while carer stress fell significantly. Baseline clinical and demographic variables did not predict quality of life or carer stress at 6 and 12 months. CONCLUSIONS: dementia liaison services in general hospitals currently focus on poor outcome cases.

Screening for dementia in general hospital inpatients: a systematic review and meta-analysis of available instruments.

OBJECTIVE: Dementia is common and often undiagnosed. Improving rates of diagnosis has become a key part of current dementia guidelines. Older people admitted to hospital are a potential target population for screening for dementia. The objective was to report whether instruments advocated in screening for dementia had been validated in hospital inpatients and to make recommendations on evidence-based screening for dementia in this population. DESIGN: a systematic review was performed by an initial electronic database search using three key search criteria. Studies were then selected in a systematic fashion using specific predetermined criteria. Pooled meta-analysis was performed. Inclusion criteria were studies where the study group were inpatients in general hospitals, including a clearly defined group of older people (60 or older), they used a recognised screening instrument compared with a reference standard, and included at least 10 cases of dementia. Demographic data as well as sensitivity and specificity were recorded from the selected studies. RESULTS: in total nine studies describing validation of six discreet instruments satisfied all our criteria and we were able to perform meta-analysis with one instrument, the Abbreviated Mental Test Score (AMTS). With a cut-off of <7, pooled analysis of the AMTS showed a sensitivity of 81%, a specificity of 84% and an area under the curve (AUC) of 0.88. CONCLUSION: a small number of instruments have been validated for screening for dementia in general hospital. Understanding strengths and weaknesses of currently available instruments allows informed decisions about screening in this setting.

A systematic review of cluster randomised trials in residential facilities for older people suggests how to improve quality.

BACKGROUND: Previous reviews of cluster randomised trials have been critical of the quality of the trials reviewed, but none has explored determinants of the quality of these trials in a specific field over an extended period of time. Recent work suggests that correct conduct and reporting of these trials may require more than published guidelines. In this review, our aim was to assess the quality of cluster randomised trials conducted in residential facilities for older people, and to determine whether (1) statistician involvement in the trial and (2) strength of journal endorsement of the Consolidated Standards of Reporting Trials (CONSORT) statement influence quality. METHODS: We systematically identified trials randomising residential facilities for older people, or parts thereof, without language restrictions, up to the end of 2010, using National Library of Medicine (Medline) via PubMed and hand-searching. We based quality assessment criteria largely on the extended CONSORT statement for cluster randomised trials. We assessed statistician involvement based on statistician co-authorship, and strength of journal endorsement of the CONSORT statement from journal websites. RESULTS: 73 trials met our inclusion criteria. Of these, 20 (27%) reported accounting for clustering in sample size calculations and 54 (74%) in the analyses. In 29 trials (40%), methods used to identify/recruit participants were judged by us to have potentially caused bias or reporting was unclear to reach a conclusion. Some elements of quality improved over time but this appeared not to be related to the publication of the extended CONSORT statement for these trials. Trials with statistician/epidemiologist co-authors were more likely to account for clustering in sample size calculations (unadjusted odds ratio 5.4, 95% confidence interval 1.1 to 26.0) and analyses (unadjusted OR 3.2, 1.2 to 8.5). Journal endorsement of the CONSORT statement was not associated with trial quality. CONCLUSIONS: Despite international attempts to improve methods in cluster randomised trials, important quality limitations remain amongst these trials in residential facilities. Statistician involvement on trial teams may be more effective in promoting quality than further journal endorsement of the CONSORT statement. Funding bodies and journals should promote statistician involvement and co-authorship in addition to adherence to CONSORT guidelines.