Background:Increasing number of people are dying with advanced dementia. Comfort and quality of life are key goals of care.Aims:To describe (1) physical and psychological symptoms, (2) health and social care service utilisation and (3) care at end of life in people with advanced dementia.Design:9-month prospective cohort study.Setting and participants:Greater London, England, people with advanced dementia (Functional Assessment Staging Scale 6e and above) from 14 nursing homes or their own homes.Main outcome measures:At study entry and monthly: prescriptions, Charlson Comorbidity Index, pressure sore risk/severity (Waterlow Scale/Stirling Scale, respectively), acute medical events, pain (Pain Assessment in Advanced Dementia), neuropsychiatric symptoms (Neuropsychiatric Inventory), quality of life (Quality of Life in Late-Stage Dementia Scale), resource use (Resource Utilization in Dementia Questionnaire and Client Services Receipt Inventory), presence/type of advance care plans, interventions, mortality, place of death and comfort (Symptom Management at End of Life in Dementia Scale).Results:Of 159 potential participants, 85 were recruited (62% alive at end of follow-up). Pain (11% at rest, 61% on movement) and significant agitation (54%) were common and persistent. Aspiration, dyspnoea, septicaemia and pneumonia were more frequent in those who died. In total, 76% had ‘do not resuscitate’ statements, less than 40% advance care plans. Most received primary care visits, there was little input from geriatrics or mental health but contact with emergency paramedics was common.Conclusion:People with advanced dementia lived with distressing symptoms. Service provision was not tailored to their needs. Longitudinal multidisciplinary input could optimise symptom control and quality of life.

The hypothesis that single low dose exposures (0.025–0.5 Gy) to low LET radiation, given at either high (about 150 mGy/min) or low (1 mGy/min) dose rate, would promote aortic atherosclerosis was tested in female C57BL/6J mice genetically predisposed to this disease (ApoE−/− ). Mice were exposed either at early stage disease (2 months of age) and examined 3 or 6 months later, or at late stage disease (8 months of age) and examined 2 or 4 months later. Changes in aortic lesion frequency, size and severity, as well as total serum cholesterol levels and the uptake of lesion lipids by lesion associated macrophages were assessed. Statistically significant changes in each of these measures were observed, depending on dose, dose rate and disease stage. In all cases, the results were distinctly non-linear with dose, with maximum effects tending to occur at 25 or 50 mGy. In general, low doses given at low dose rate at either early or late stage disease were protective, slowing the progression of the disease by one or more of these measures. Most effects appeared and persisted for months after the single exposures, but some were ultimately transitory. In contrast to exposure at low dose rate, high dose rate exposure at early stage disease produced both protective and detrimental effects, suggesting that low doses may influence this disease by more than one mechanism, and dose rate is an important parameter. These results contrast with the known, generally detrimental effects of high doses on the progression of this disease in the same mice, and in humans, suggesting that a linear extrapolation of the known increased risk from high doses to low doses is not appropriate.

Background The identification of patients with advanced liver fibrosis secondary to non-alcoholic fatty liver disease (NAFLD) remains challenging. Using non-invasive liver fibrosis tests (NILT) in primary care may permit earlier detection of patients with clinically significant disease for specialist review, and reduce unnecessary referral of patients with mild disease. We constructed an analytical model to assess the clinical and cost differentials of such strategies. Methods A probabilistic decisional model simulated a cohort of 1000 NAFLD patients over 1 year from a healthcare payer perspective. Simulations compared standard care (SC) (scenario 1) to: Scenario 2: FIB-4 for all patients followed by Enhanced Liver Fibrosis (ELF) test for patients with indeterminate FIB-4 results; Scenario 3: FIB-4 followed by fibroscan for indeterminate FIB-4; Scenario 4: ELF alone; and Scenario 5: fibroscan alone. Model estimates were derived from the published literature. The primary outcome was cost per case of advanced fibrosis detected. Results Introduction of NILT increased detection of advanced fibrosis over 1 year by 114, 118, 129 and 137% compared to SC in scenarios 2, 3, 4 and 5 respectively with reduction in unnecessary referrals by 85, 78, 71 and 42% respectively. The cost per case of advanced fibrosis (METAVIR ≥F3) detected was £25,543, £8932, £9083, £9487 and £10,351 in scenarios 1, 2, 3, 4 and 5 respectively. Total budget spend was reduced by 25.2, 22.7, 15.1 and 4.0% in Scenarios 2, 3, 4 and 5 compared to £670 K at baseline. Conclusion Our analyses suggest that the use of NILT in primary care can increases early detection of advanced liver fibrosis and reduce unnecessary referral of patients with mild disease and is cost efficient. Adopting a two-tier approach improves resource utilization.

BackgroundMany people with dementia die in nursing homes, but quality of care may be suboptimal. We developed the theory-driven ‘Compassion Intervention’ to enhance end-of-life care in advanced dementia.ObjectivesTo (1) understand how the Intervention operated in nursing homes in different health economies; (2) collect preliminary outcome data and costs of an interdisciplinary care leader (ICL) to facilitate the Intervention; (3) check the Intervention caused no harm.DesignA naturalistic feasibility study of Intervention implementation for 6 months.SettingsTwo nursing homes in northern London, UK.ParticipantsThirty residents with advanced dementia were assessed of whom nine were recruited for data collection; four of these residents’ family members were interviewed. Twenty-eight nursing home and external healthcare professionals participated in interviews at 7 (n=19), 11 (n=19) and 15 months (n=10).InterventionAn ICL led two core Intervention components: (1) integrated, interdisciplinary assessment and care; (2) education and support for paid and family carers.Data collectedProcess and outcome data were collected. Symptoms were recorded monthly for recruited residents. Semistructured interviews were conducted at 7, 11 and 15 months with nursing home staff and external healthcare professionals and at 7 months with family carers. ICL hours were costed using Department of Health and Health Education England tariffs.ResultsContextual differences were identified between sites: nursing home 2 had lower involvement with external healthcare services. Core components were implemented at both sites but multidisciplinary meetings were only established in nursing home 1. The Intervention prompted improvements in advance care planning, pain management and person-centred care; we observed no harm. Six-month ICL costs were £18 255.ConclusionsImplementation was feasible to differing degrees across sites, dependent on context. Our data inform future testing to identify the Intervention’s effectiveness in improving end-of-life care in advanced dementia.Trial registrationClinicalTrials.gov:NCT02840318: Results

Objective To understand the feasibility of recruiting people with advanced cancer into a randomised controlled trial of acceptance and commitment therapy (ACT) vs a standardised talking control (TC) and delivering ACT to this population; to explore the acceptability of outcome measures and generate normative data. Methods This was a feasibility two‐arm randomised controlled trial. Participants were attendees with advanced cancer at one of three hospice‐based day‐therapy units in London, United Kingdom, who demonstrated low scores on the Functional Assessment of Cancer Therapies—General (FACT‐G). The primary end point was 3 months. Results The recruitment target was 54 participants; 42 people were recruited and randomised to up to eight individual sessions of ACT (n = 20) or TC (n = 22). Eighteen out of 42 (43%) of participants completed the primary outcome at 3 months, and at least one follow‐up was available in 30/42 (71%) participants. An exploratory analysis revealed a non‐significant adjusted mean difference after 3 months in the main outcome FACT‐G of −3.41 (CI = −18.61‐11.79) with TC having better functioning. Over 6 months, the adjusted mean difference between trial arms was 2.25 (CI = −6.03‐10.52) in favour of ACT. Conclusions It is feasible to recruit people with advanced cancer in a trial of ACT versus TC. Future research should test the effectiveness of ACT in a fully powered trial.

BackgroundMany studies have examined the mental health of carers of people with dementia. Few have examined their experiences in the advanced stages of disease and into bereavement. We aimed to understand the experiences of carers during advanced dementia exploring the links between mental health and experiences of end of life care.MethodsMixed methods longitudinal cohort study. Thirty-five family carers of people with advanced dementia (6 at home, 29 in care homes) were recruited and assessed monthly for up to nine months or until the person with dementia died, then at two and seven months into bereavement. Assessments included: Hospital Anxiety and Depression Scale, Short Form 12 health–related quality of life, 22-item Zarit Burden Interview, Brief Coping Orientation to Problems Experienced, Inventory of Complicated Grief and Satisfaction with Care at End of Life in Dementia. Subsequently, 12 carers (34%) were bereaved and 12 undertook a qualitative interview two months after death; these data were analysed thematically. We analysed quantitative and qualitative data independently and then merged findings at the point of interpretation.ResultsAt study entry psychological distress was high; 26% reached caseness for depression and 41% for anxiety and median complicated grief scores were 27 [IQR 22–37] indicating that on average 11 of the 16 grief symptoms occurred at least monthly. Physical health reflected population norms (mean = 50) and median burden scores were 17 [IQR 9–30]. Three qualitative themes were identified: the importance of relationships with care services, understanding of the progression of dementia, and emotional responses to advanced dementia. An overarching theme tying these together was the carer’s ability to control and influence end of life care.ConclusionsWhile carers report high levels of psychological distress during advanced dementia, the experience of end of life care in dementia may be amenable to change with the provision of sensitive and timely information about the natural progression of dementia. Regular health status updates and end of life discussions can help families understand dementia progression and prepare for end of life. The extent to which our findings reflect practice across the UK or internationally warrants further investigation.

Atherosclerosis is the main cause of coronary heart disease and stroke, the two major causes of death in developed society. There is emerging evidence of excess risk of cardiovascular disease at low radiation doses in various occupationally exposed groups receiving small daily radiation doses. Assuming that they are causal, the mechanisms for effects of chronic fractionated radiation exposures on cardiovascular disease are unclear. We outline a spatial reaction-diffusion model for atherosclerosis and perform stability analysis, based wherever possible on human data. We show that a predicted consequence of multiple small radiation doses is to cause mean chemo-attractant (MCP-1) concentration to increase linearly with cumulative dose. The main driver for the increase in MCP-1 is monocyte death, and consequent reduction in MCP-1 degradation. The radiation-induced risks predicted by the model are quantitatively consistent with those observed in a number of occupationally-exposed groups. The changes in equilibrium MCP-1 concentrations with low density lipoprotein cholesterol concentration are also consistent with experimental and epidemiologic data. This proposed mechanism would be experimentally testable. If true, it also has substantive implications for radiological protection, which at present does not take cardiovascular disease into account. The Japanese A-bomb survivor data implies that cardiovascular disease and cancer mortality contribute similarly to radiogenic risk. The major uncertainty in assessing the low-dose risk of cardiovascular disease is the shape of the dose response relationship, which is unclear in the Japanese data. The analysis of the present paper suggests that linear extrapolation would be appropriate for this endpoint.

Background:The prevalence of dementia is rising worldwide and many people will die with the disease. Symptoms towards the end of life may be inadequately managed and informal and professional carers poorly supported. There are few evidence-based interventions to improve end-of-life care in advanced dementia.Aim:To develop an integrated, whole systems, evidence-based intervention that is pragmatic and feasible to improve end-of-life care for people with advanced dementia and support those close to them.Design:A realist-based approach in which qualitative and quantitative data assisted the development of statements. These were incorporated into the RAND/UCLA appropriateness method to achieve consensus on intervention components. Components were mapped to underlying theory of whole systems change and the intervention described in a detailed manual.Setting/participants:Data were collected from people with dementia, carers and health and social care professionals in England, from expert opinion and existing literature. Professional stakeholders in all four countries of the United Kingdom contributed to the RAND/UCLA appropriateness method process.Results:A total of 29 statements were agreed and mapped to individual, group, organisational and economic/political levels of healthcare systems. The resulting main intervention components are as follows: (1) influencing local service organisation through facilitation of integrated multi-disciplinary care, (2) providing training and support for formal and informal carers and (3) influencing local healthcare commissioning and priorities of service providers.Conclusion:Use of in-depth data, consensus methods and theoretical understanding of the intervention components produced an evidence-based intervention for further testing in end-of-life care in advanced dementia.