NIHRDataInsights/HRCSData huggingface dataset:
Title: MEasurement of Dementia DIsease progression in Primary care: the MEDDIP study
Funder: Dunhill Medical Trust

Abstract: Given evidence of the continued rise in prevalence of dementia aligned to increased longevity, the UK government has prioritised early recognition and treatment of dementia, with specific goals to; prolong independence, delay nursing home and hospital admissions, and reduce mortality. It is recognised that this strategy necessitates the need for, and growth of, primary care involvement in diagnosis and management of dementia. Whilst there is established research on case finding and diagnostics in dementia within primary care, there is a marked lack of research on the course and prognosis of dementia (post diagnosis). Such information, and what markers alter or change the course of the disease, is essential for patient management. One major resource for studying these issues in primary care is Electronic Health Record (EHR) databases. 12 EHR databases have been used in health research to investigate disease epidemiology, comorbidity, prognosis, process and delivery of care, and evaluate outcome sof care in a wide spectrum of diseases and illnesses, and EHR databases are well established in the UK. For example, over 1700 research papers have used the national Clinical Practice Research Datalink (CPRD). However, the challenge in using EHR for research on dementia is the need to identify, within records, discrete markers of disease progression for patients with dementia. Evidence already exists on what some of these markers are in dementia patients, but wht is not known currently is whether any of these markers can be reliably detcted using EHR. This proposal plans to test in two phases the feasibility of establishing markers of disease progression using EHR datasets among patients with dementia. Phase 1 will test the feasbility of applying a list of markers of disease progression (identified from literature and expert consensus by current developmental work) within a regional EHR database, describe the epidemiology of those markers, and validate them in comparsion to in-depth clinic-based assessments. The second phase will establish an incident cohort of dementia patients within a UK national database (CPRD), group patients based on their trajectories of progression over time using these markers, and investigate prognostic factors for poor trajectories and relationship of trajectories to hard endpoints such as mortality. The novel outputs from this study (validated disease progression markers, mapping of dementia course, defined prognostic factors) will have direct and indirect benefits for people with dementia (e.g. identification of patients at risk of progression, ability to develop EHR research in dementia).


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: NEUROLOGICAL
Title: A Programme for ALS Care in Europe (ALS-CarE)
Funder: Economic and Social Research Council

Abstract: Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that strikes in the prime of life. There are currently no effective disease modifying therapies for ALS and death usually occurs within 3 years of symptom onset. Management is palliative and is aimed at maximising quality of life and minimising the burden of disease. The complexity and rapidly progressive nature of ALS requires a responsive multidisciplinary care system that that is built on reliable disease staging and evidence based symptom management. The purpose of ALS-CarE is to incorporate detailed clinical information drawn from population based sources into a responsive care programme. A standardised staging system will be validated, and quality of life and patient experiences will be measured and management optimised across disease stages from diagnosis to end of life. Health economic analysis will identify key differences in resource utilisation and will be useful for pharmaco-economic analyses of new therapeutics. The completed project will provide a user-friendly best practice framework for ALS that can be modified for management of other neurodegenerative diseases.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;8.2 HEALTH AND WELFARE ECONOMICS
Health categories: NEUROLOGICAL
Title: Care for Late Stage Parkinsonism
Funder: Economic and Social Research Council

Abstract: The aim of this project is to evaluate the needs and provision of care for patients in the late stages of Parkinsonism and their carers in several European countries, to compare the effectiveness of different health and social care systems, and to lay the foundation for improved outcomes in this population. We will undertake an in-depth assessment of patients and their care arrangements in a population recruited through networks in six European countries. The systems and procedures that are used in the provision of care will be reviewed through a systematic literature review, interviews and assessments of patients, carers and health care providers, and through a trial comparing assessment by a specialist with management suggestions, guidance and access to telephone advice to that of usual care. Through interviews, questionnaire assessment and review of current health-care and social care arrangement, we will assess the needs, provision of care and use of health-care resources, and their impact on patient and carer outcomes in different countries. National and regional databases will also be interrogated to identify current practice and use of health-care resources and drug usage. A systematic literature review of the evidence for effective management strategies, analysis of the study data, and evaluation of change in outcomes following specialist review will provide the basis for recommendations in the management of late stage Parkinsonism. We will also evaluate potentially useful outcome measures for use in this patient group. In addition to charting the needs and current care provision for late stage Parkinsonism in different European countries, its cost and effectiveness, and an analysis of health-care and social care predictors of improved outcome, the project will produce a platform for the assessment of patients with late stage Parkinsonism, their current treatment and care provision, as well as guidelines on the management of this late disease phase.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: NEUROLOGICAL
Title: PET Markers of Oligomeric Misfolded Proteins in Neurodegenerative Disorders
Funder: Engineering and Physical Sciences Research Council

Abstract: A common feature of all dementias e.g. Alzheimer's, Parkinson's and Huntington's diseases are the presence of specific proteins in the brain, which due to having abnormal structures, accumulate into increasingly large assemblies and fibrils. These structures, which are present in many regions of the brain, are considered to be toxic and damage brain cells, leading to the symptoms of dementia. Using the clinical brain imaging technique of Positron Emission Tomography (PET) combined with injecting into patients chemical probes which selectively bind to these assembles we can now visualize the presence and distribution of some of these toxic proteins. However, with the present range of these chemical probes we can only image the late stages of these assemblies when most of the brain damage has occurred and so too late for effective drugs therapies. Therefore our aim is to develop next generation chemical probes that can image the earlier stages and structures of these abnormal proteins when they are considered most toxic and hence cause the most damage to brains cells. This would then create a powerful means for earlier more accurate diagnosis of dementia and a means of evaluating the new types of drugs that are been developed that target these assemblies. To discover and develop these new chemical probes, will apply chemical screening methods, medicinal chemistry, radiochemistry and biological assessments. The chemical probes with appropriate properties arising from this project we would then take forward with additional funding for human imaging studies.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: NEUROLOGICAL
Title: Building multi-site clinical research capacity in Magnetoencephalography (MEG)
Funder: Engineering and Physical Sciences Research Council

Abstract: The partnership proposal brings together all eight UK MEG research groups and includes a five-year programme of activities: - We will arrange regular collaboration and management meetings between the eight sites. - Every year we will arrange training courses addressing a specific MEG research topic. - We will offer 8 PhD studentships, recruited and starting as a single cohort but working on joint research programmes between at least two partner sites. Note that all of these studentships will be working on projects that address one or more of the MRC's priority areas for studentships (e.g. biomedical imaging, stratified medicine, systems medicine and interdisciplinary strategic skills) - Each site will collect data using a set of standardised protocols over the course of one year. We propose to collect MEG data (and associated MR anatomicals for source localisation) from 80 individuals at each site. Note the intention is not to fully establish normative databases in each area, rather to act as a proof of principle that multiple sites, using different MEG scanners, can collect data using standardised protocols, assess the test-retest reliability of our measures and implement common analysis approaches. - We will purchase a shared storage system, mirrored across four sites, for the data collected as part of this partnership. - A bioinformatics research assistant will be appointed, for two years of the project, to implement the joint database and common approaches to data mining. Note that our ultimate goal is to establish a freely available 'virtual brain bank' of MEG responses to standardised protocols that any patient group across the world could be compared to. This partnership will allow us to take the initial steps towards this goal. - We will instigate a MEG international travel awards scheme. - We will offer travel/accommodation bursaries and invite international speakers to an annual "MEG UK" conference.


Research activity codes: 1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING)
Health categories: NEUROLOGICAL
Title: Examining the role of glutamate in glioma related seizures
Funder: Epilepsy Research UK

Abstract: Gliomas commonly present with seizures, which are refractory to standard anticonvulsant medication and associated with significant morbidity. Variable success is seen with standard and electro-corticography guided surgical resection for seizure control. There is a clear need for a marker that will guide resection of the ictogenic areas during surgery, to improve seizure control, limit morbidity and achieve better tumour clearance. Regions with excess glutamate seen on magnetic resonance spectroscopy (MRS) may act as such a marker. Animal glioma models suggest that increased extracellular glutamate from over expression of System XC (SXC) (cysteine/glutamate transporter) in the peri-tumoural region accelerates peri-tumoural cell death, and facilitates epileptogeneis. However, it is unknown whether areas of excess glutamate seen on MRS, correspond to regions of the brain which are epileptic from overexpression of SXC in patients with gliomas. This novel study will test whether regions with excess glutamate seen on MRS generates seizures from over expression of SXC. We aim to sample cortex with high to normal peri-tumoural glutamate on MRS intra-operatively, using a neuro-navigation system and study their seizure generating potential using ex vivo electrophysiology. This will define the role of MRS in identifying the peri-tumoural epileptogenic zone with clear immediate clinical utility.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: NEUROLOGICAL
Title: Creative Conversations': An exploratory study of an ‘arts in health’ approach to embedding person-centred care and improving communication between care staff and people living with dementia
Funder: Health and Care Research Wales (Welsh Government)

Abstract: Background Nearly two decades ago, Kitwood (1997) urged people to see the ‘PERSON with dementia’, rather than focussing on the disease and introduced the concepts of personhood and person-centred care in dementia care. Unfortunately, this is not always implemented into practice as basic training for care home staff has been found to concentrate on manual handling, fire safety and health and safety rather than understanding the needs of older people, including those with dementia. However, researchers have found that arts in health interventions aimed at people living with dementia also impacted staff and family carers and enabled them to learn new skills and gain a deeper understanding of residents. Aims This project aims to develop and test a ‘Creative Conversations’ training intervention which uses an arts in health approach to improve the knowledge and skills of the dementia care workforce and quality of interaction between carers and people living with dementia. Plan of investigation This exploratory study will examine the feasibility and impact of the ‘Creative Conversations’ training intervention in two settings: the care home (Phase 1) and community care (Phase 2) setting. Throughout the study, a collaborative approach will ensure that those thought to benefit from the training (care staff, older people, family carers and Social Services) are involved in the design and implementation. An advisory group will be held before and after each phase to discuss the feasibility and make any refinements to the intervention. An exploratory stepped-wedge cluster randomised trial in Phase 1 and a repeated measures (pre and post) approach in Phase 2 will explore whether there is a change in the knowledge and skills of care staff, and quality of interaction between carers and people living with dementia following the intervention. Benefits to Social care service users, carers In the short term, it is expected that there will be an improvement in the skills and knowledge of frontline dementia workforce in participating homes, which will lead to an improvement of the well-being of people living with dementia. This in turn will lead to improvements in the social care of people living with dementia. The project supports the Social Services and Well-being (Wales) Act by improving the quality of care and well-being of people living with dementia in care homes and the community setting as well as supporting those who care for them by increasing their knowledge and understanding.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: NEUROLOGICAL
Title: Social exclusion and use of care services in Wales: experiences of people with cognitive impairment and dementia
Funder: Health and Care Research Wales (Welsh Government)

Abstract: Current forecasts suggest that the number of people with dementia in Wales is increasing, resulting in greater need for health and social care support for people with dementia and their carers. A key challenge for service providers and planners is how to manage this increasing demand on services, particularly community based services, whilst continuing to provide the support and assistance people with dementia and their carers need to ensure a good quality of life. In order to effectively plan service provision it is important to understand current need and use of services. This research aims to gain a greater understanding of the current health and social care service needs of people with dementia, those with cognitive impairment, and carers in Wales, and how these groups currently use and access services. Using secondary data analysis of a large population based survey of people aged 65 years and over, this work will examine how health and social care services are currently being used by people with cognitive impairment in North and South Wales, how accessible services are, and whether or not people’s everyday needs are being met. The research will also examine possible factors that mediate the relationship between cognitive impairment and service use, including factors of environment, social support and personality. New primary qualitative data will be collected, supplementing existing data, to explore how people with dementia, their carers, and people with mild cognitive impairment define and act on their needs, how supported they feel by existing networks (professional, community and social), and whether these differ from those without a cognitive impairment. This work will draw out detail about why people are/ are not using or accessing services, and what support or information they may be missing. These findings will be used to inform a series of recommendations for service commissioners and providers’ regarding possible strengths, weaknesses and gaps in current service provision, as well as possible future service needs. The ultimate aim of this research is to assist in the planning and improvement of care and support services for people with dementia and their carers, and consequently improve user well-being.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: NEUROLOGICAL
Title: Improving the housing stock of Anglesey and Gwynedd: a health economics and behavioural psychology evaluation
Funder: Health and Care Research Wales (Welsh Government)

Abstract: Cold homes (particularly those below 16oC) substantially increase risk of respiratory and cardiovascular conditions. Approximately 40,000 more deaths occur in the UK during the coldest months of the year (December to March) compared to warmer months (June to September). It is estimated that at least £600 million is spent each year by the UK NHS treating ill health related directly to poor housing. A 2008 report by the Chartered Institute of Environmental Health estimated on average it costs £4,993 to remedy excess cold issues per household.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;3.4 VACCINES
Health categories: NEUROLOGICAL
Title: Acute and chronic spinal cord injury: novel studies of synaptogenesis, plasticity and mechanisms of repair
Funder: Medical Research Council

Abstract: There have been rapid and significant advances in the area of neurorestoration over the last decade or so, much of which has focussed on neuroprotection, neuroregeneration and adaptive plasticity. There is now a considerable optimism about translating this work into effective clinical therapies, particularly in the area of spinal cord injury where no restorative treatments are available. However, this drive towards therapy cannot proceed before some critical questions are addressed. These are: which of the strategies identified from basic neurobiological studies will be the most effective in the clinic? What mechanism can promote the greatest functional repair? How can a therapy best be applied in a clinical context? This proposal seeks to undertake a series of linked and mutually interdependent studies in the field of spinal cord injury which will: 1) Characterise processes underlying spontaneous changes in conduction, recovery and remyelination in a clinically relevant chronic spinal cord injury. 2) Optimise delivery of one of the leading experimental strategies, the use of chondroitinase ABC, by developing novel lentriviral vectors. 3) Develop novel techniques to assess structural and functional remodelling of synapses after spinal cord injury. I will use these to quantitatively examine synaptic rearrangements that occur spontaneously after spnal cord injury and driven by interventions targeting chondroitin sulphate proteoglycans. I believe these techniques will find widespread application in this field. 4) Identify molecular mechanisms involved in chondroitinase ABC-mediated repair.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;5.2 CELLULAR AND GENE THERAPIES
Health categories: NEUROLOGICAL
Title: Hypoxia/ischaemia and patterns of neuropathology associated with memory impairment: From infancy through adolescence
Funder: Medical Research Council

Abstract: Memory is a fundamental aspect of cognitive development, allowing children to gain a knowledge base about the world and form a store of personal memories that are essential for establishing a sense of identity. Our prior research showed that selected aspects of memory development are at risk in children with medical conditions exposing them to hypoxic-ischaemic injury to the hippocampus. The research programme we now propose aims to investigate how such memory impairments evolve by studying young infants prospectively as well as investigate in more detail both the spared and impaired memory skills and their neural correlates in older children who had sustained hippocampal injury earlier in life, often neonatally. In the first part of our programme, infants with cardiorespiratory disease requiring extracorporeal membrane oxygenation, those with transposition of the great arteries requiring open heart surgery, and those with hypoplastic left heart, will be studied from the first weeks of life until two years of age using neuroimaging, neurophysiological methods, and cognitive behavioural testing to identify the presence of hippocampal atrophy, its effects on the development of brain connectivity patterns, and its impact on memory function. In the second part of our programme, we will build on our prior work using a retrospective design to study children who experienced cardiac arrest as infants. We will examine the incidence of memory impairment in this group, the degree and selectivity of any hippocampal injury, and the long-term impacts on brain connectivity. We will also assess the sensitivity of several tests of hippocampal-dependent memory, the relation of memory performance to degree of hippocampal injury, and the neural mechanisms that enable affected children to acquire a semantic knowledge base in spite of their severe learning deficits. This research programme will provide information relevant to theories of the neurocognitive organisation of memory as well as how the brain reorganises following early injury to this critical memory structure. An important goal is the earliest possible identification of hippocampal injury in infants who have suffered hypoxia/ischaemia, as these are the cases who will be at risk for memory impairment; this will allow the earliest possible remediation efforts, including how preserved memory skills can be exploited to improve overall level of function, as well as provide key information about the trajectory of memory impairments once they appear.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL