Changing practice in dementia care in the community: developing and testing evidence-based interventions, from timely diagnosis to end of life (EVIDEM)

BACKGROUND: The needs of people with dementia and their carers are inadequately addressed at all key points in the illness trajectory, from diagnosis through to end-of-life care. The EVIDEM (Evidence-based Interventions in Dementia) research and development programme (2007–12) was designed to help change this situation within real-life settings. OBJECTIVES: The EVIDEM projects were (1) evaluation of an educational package designed to enhance general practitioners’ (GPs’) diagnostic and management skills; (2) evaluation of exercise as therapy for behavioural and psychological symptoms of dementia (BPSD); (3) development of a toolkit for managing incontinence in people with dementia living at home; (4) development of a toolkit for palliative care for people with dementia; and (5) development of practice guidance on the use of the Mental Capacity Act (MCA) 2005. DESIGN: Mixed quantitative and qualitative methods from case studies to large database analyses, including longitudinal surveys, randomised controlled trials and research register development, with patient and public involvement built into all projects. SETTING: General practices, community services, third-sector organisations and care homes in the area of the North Thames Dementia and Neurodegenerative Diseases Research Network local research network. PARTICIPANTS: People with dementia, their family and professional carers, GPs and community mental health team members, staff in local authority social services and third-sector bodies, and care home staff. MAIN OUTCOME MEASURES: Dementia management reviews and case identification in general practice; changes in behavioural and psychological symptoms measured with the Neuropsychiatric Inventory (NPI); extent and impact of incontinence in community-dwelling people with dementia; mapping of pathways to death of people with dementia in care homes, and testing of a model of collaborative working between primary care and care homes; and understandings of the MCA 2005 among practitioners working with people with dementia. RESULTS: An educational intervention in general practice did not alter management or case identification. Exercise as a therapy for BPSD did not reduce NPI scores significantly, but had a significant positive effect on carer burden. Incontinence is twice as common in community-dwelling people with dementia than their peers, and is a hidden taboo within a stigma. Distinct trajectories of dying were identified (anticipated, unexpected and uncertain), and collaboration between NHS primary care and care homes was improved, with cost savings. The MCA 2005 legislation provided a useful working framework for practitioners working with people with dementia. CONCLUSIONS: A tailored educational intervention for general practice does not change practice, even when incentives, policy pressure and consumer demand create a favourable environment for change; exercise has potential as a therapy for BPSD and deserves further investigation; incontinence is a common but unrecognised problem for people with dementia in the community; changes in relationships between care homes and general practice can be achieved, with benefits for people with dementia at the end of life and for the UK NHS; application of the MCA 2005 will continue to improve but educational reinforcements will help this. Increased research capacity in dementia in the community was achieved. This study suggests that further work is required to enhance clinical practice around dementia in general practice; investigate the apparent beneficial effect of physical activity on BPSD and carer well-being; develop case-finding methods for incontinence in people with dementia; optimise working relationships between NHS staff and care homes; and reinforce practitioner understanding of the MCA 2005. TRIAL REGISTRATION: EVIDEM: ED-NCT00866099; EVIDEM: E-ISRCTN01423159. FUNDING: This project was funded by the Programme Grants for Applied Research programme of the National Institute for Health Research

The UK experience of promoting dementia recognition and management in primary care

BACKGROUND: The early and timely recognition of dementia syndrome is a policy imperative in many countries. In the UK the achievement of earlier and timelier recognition has been pursued through educational interventions, incentivisation of general practitioners and the promotion of a network of memory clinics. OBJECTIVE: The effectiveness of education, incentivisation and memory clinic activity are unknown. This article analyses data from different sources to evaluate the impact of these interventions on the incidence and prevalence of dementia, and the diagnostic performance of memory clinics. MATERIAL AND METHODS: Three data sources were used: 1) aggregated, anonymised data from a network of general practices using the same electronic medical record software, The Health Information Network (THIN), 2) UK Health & Social Care Information Centre data reports and 3) Responses to Freedom of Information Act requests. RESULTS: Educational interventions did not appear to change the recorded incidence of dementia syndrome. There was no apparent effect of education, incentives or memory clinic activity on the reported incidence of dementia syndrome between 1997 and 2011 but there were signs of change in the documentation of consultations with people with dementia. There was no clear impact of incentivisation and memory clinic activity in prevalence data. Memory clinics are seeing more patients but fewer are being diagnosed with dementia. CONCLUSION: It is not clear why there has been no upturn in documented incidence or prevalence of dementia syndrome despite substantial efforts and this requires further investigation to guide policy changes. The performance of memory clinics also needs further study

Effects of Land Use Change on Channel Morphology in Northeastern Puerto Rico

Between 1830 and 1950 much of northeastern Puerto Rico was cleared for agriculture. Runoff increased by 50% and sediment supply to the river channels increased by more than an order of magnitude. Much of the land clearance extended to steep valley slopes, resulting in widespread gullying and landslides and a large load of coarse sediments delivered to the stream channels. A shift from agriculture to industrial and residential land uses over the past 50 yr has maintained the elevated runoff while sediment supply has decreased, allowing the rivers to begin removing coarse sediment stored within their channels. The size, abundance, and stratigraphic elevation of in-channel gravel bar deposits increases, channel depth decreases, and the frequency of overbank flooding increases downstream along these channels. This is presumed to be a transient state and continued transport will lead to degradation of the bed in downstream sections as the channel adjusts to the modern supply of water and sediment. A downstream decrease in channel size is contrary to the expected geometry of self-adjusted channels, but is consistent with the presence of partially evacuated sediment remaining from the earlier agricultural period. Reverse (downstream decreasing) channel morphology is not often cited in the literature, although consistent observations are available from areas with similar land-use history. Identification of reverse channel morphology along individual watercourses may be obscured in multiwatershed compilations in which other factors produce a consistent, but scattered downstream trend. Identification of reverse channel morphology along individual streams in areas with similar land-use history would be useful for identifying channel disequilibrium and anticipating future channel adjustments

‘It’s a real fine balancing act’: Directly employed care workers’ experiences of engaging with health services

Little is known of the experiences of directly employed care workers communicating with healthcare providers about the situations of their employers. We report findings from 30 in-depth semi-structured interviews with directly employed care workers in England undertaken in 2018–19. Findings relate to role content, communication with healthcare professionals and their own well-being. Directly employed care workers need to be flexible about the tasks they perform and the changing needs of those whom they support. Having to take on health liaison roles can be problematic, and the impact of care work on directly employed workers’ own health and well-being needs further investigation

Under the radar: General practitioners' experiences of directly employed care workers for older people

The Care Act 2014 allows eligible people with care and support needs to access funding directly from local authorities in England. Such funds may be used to employ care workers. Others may employ care workers using their own or family resources. This study explores the working relationships, views and experiences of General Practitioner (GP) about older people's directly employed care workers (DECWs). Qualitative interviews were conducted with 20 GPs in England, identified by convenience sampling of research networks and snowballing methods. Data were analysed thematically. Three overarching themes were identified: (a) anxieties about the identity of the DECW, and their relationship to their employer; (b) experiences of relationship‐based care, and; (c) tasks carried out by DECWs. Identity mattered because DECWs can appear as an unknown participant in consultations, raising questions about consent, and prompting thoughts about elder abuse. Uncertainty about identity made documentation of DECWs' details in electronic medical records and care plans problematic. Case examples of relational care illustrated the benefits of reciprocity between older person and their employee who sometimes provided continuity of care and care co‐ordination for their employer. Participants were alert to the risks of exploitation and insecurity for DECWs whose tasks were thought to span household and personal care, transport assistance and health‐related activities. The involvement of DECWs in maintaining older people's health raises questions about the support they receive from health professionals. In conclusion DECWs are well placed to monitor older people's health, provide continuity of care and undertake certain healthcare tasks. GPs envisaged such workers as potentially valuable assets in community‐based care for an ageing population. They called for skills training for this workforce and the development of protocols for delegation of health tasks and safeguarding of vulnerable older people. Older people employing care workers and those advising or supporting them should address communications with health providers in employment contracts and job descriptions

DGAT1 is a lipid metabolism oncoprotein that enables cancer cells to accumulate fatty acid while avoiding lipotoxicity [preprint]

Dysregulated cellular metabolism is a hallmark of cancer. As yet, few druggable oncoproteins directly responsible for this hallmark have been identified. Increased fatty acid acquisition allows cancer cells to meet their membrane biogenesis, ATP, and signaling needs. Excess fatty acids suppress growth factor signaling and cause oxidative stress in non-transformed cells, but surprisingly not in cancer cells. Molecules underlying this cancer adaptation may provide new drug targets. Here, we identify Diacylglycerol O-acyltransferase 1 (DGAT1), an enzyme integral to triacylglyceride synthesis and lipid droplet formation, as a frequently up-regulated oncoprotein allowing cancer cells to tolerate excess fatty acids. DGAT1 over-expression alone induced melanoma in zebrafish melanocytes, and co-operated with oncogenic BRAF or NRAS for more rapid melanoma formation. Mechanistically, DGAT1 stimulated melanoma cell growth through sustaining mTOR kinase–S6 kinase signaling and suppressed cell death by tempering fatty acid oxidation, thereby preventing accumulation of reactive oxygen species including lipid peroxides

Passive immunotherapy against Aβ in aged APP-transgenic mice reverses cognitive deficits and depletes parenchymal amyloid deposits in spite of increased vascular amyloid and microhemorrhage

BACKGROUND: Anti-Aβ immunotherapy in transgenic mice reduces both diffuse and compact amyloid deposits, improves memory function and clears early-stage phospho-tau aggregates. As most Alzheimer disease cases occur well past midlife, the current study examined adoptive transfer of anti-Aβ antibodies to 19- and 23-month old APP-transgenic mice. METHODS: We investigated the effects of weekly anti-Aβ antibody treatment on radial-arm water-maze performance, parenchymal and vascular amyloid loads, and the presence of microhemorrhage in the brain. 19-month-old mice were treated for 1, 2 or 3 months while 23-month-old mice were treated for 5 months. Only the 23-month-old mice were subject to radial-arm water-maze testing. RESULTS: After 3 months of weekly injections, this passive immunization protocol completely reversed learning and memory deficits in these mice, a benefit that was undiminished after 5 months of treatment. Dramatic reductions of diffuse Aβ immunostaining and parenchymal Congophilic amyloid deposits were observed after five months, indicating that even well-established amyloid deposits are susceptible to immunotherapy. However, cerebral amyloid angiopathy increased substantially with immunotherapy, and some deposits were associated with microhemorrhage. Reanalysis of results collected from an earlier time-course study demonstrated that these increases in vascular deposits were dependent on the duration of immunotherapy. CONCLUSIONS: The cognitive benefits of passive immunotherapy persist in spite of the presence of vascular amyloid and small hemorrhages. These data suggest that clinical trials evaluating such treatments will require precautions to minimize potential adverse events associated with microhemorrhage

Dysregulation of Na+/K+ ATPase by amyloid in APP+PS1 transgenic mice

BACKGROUND: The pathology of Alzheimer's disease (AD) is comprised of extracellular amyloid plaques, intracellular tau tangles, dystrophic neurites and neurodegeneration. The mechanisms by which these various pathological features arise are under intense investigation. Here, expanding upon pilot gene expression studies, we have further analyzed the relationship between Na+/K+ ATPase and amyloid using APP+PS1 transgenic mice, a model that develops amyloid plaques and memory deficits in the absence of tangle formation and neuronal or synaptic loss. RESULTS: We report that in addition to decreased mRNA expression, there was decreased overall Na+/K+ ATPase enzyme activity in the amyloid-containing hippocampi of the APP+PS1 mice (although not in the amyloid-free cerebellum). In addition, dual immunolabeling revealed an absence of Na+/K+ ATPase staining in a zone surrounding congophilic plaques that was occupied by dystrophic neurites. We also demonstrate that cerebral Na+/K+ ATPase activity can be directly inhibited by high concentrations of soluble Aβ. CONCLUSIONS: The data suggest that the reductions in Na+/K+ ATPase activity in Alzheimer tissue may not be purely secondary to neuronal loss, but may results from direct effects of amyloid on this enzyme. This disruption of ion homeostasis and osmotic balance may interfere with normal electrotonic properties of dendrites, blocking intraneuronal signal processing, and contribute to neuritic dystrophia. These results suggest that therapies aimed at enhancing Na+/K+ ATPase activity in AD may improve symptoms and/or delay disease progression