NIHRDataInsights/HRCSData huggingface dataset:
Title: Elucidating torpor's effects on brain activity and behaviour and investigating its neuroprotective properties against acute ischaemic stroke
Funder: Medical Research Council

Abstract: BACKGROUND Stroke is a leading cause of adult disability and mortality globally. Hypothermia is the most potent experimental neuroprotective therapy for stroke. However, the thermogenic response to hypothermia has limited its progress in clinical trials. Thermogenesis is suppressed in torpor - a state of regulated hypothermia occurring naturally in some animals in response to food shortage. Recent studies show torpor can be pharmacologically-induced via activation of A1 adenosine receptors (A1AR) in the central nervous system, even in animals incapable of natural torpor. Consequently, there is growing promise that neuroprotective properties of torpor can be harnessed to develop novel therapies for acute stroke. However, key aspects of torpor are not well-understood and require further investigation as per below. OBJECTIVES To investigate in mice: 1) The precise temporal dynamics of brain activity during torpor, and whether single neurons are less excitable and more resistant to excitotoxic damage; 2) Torpor's effect on subsequent behavioural performance; 3) The neuroprotective properties of pharmacologically-induced torpor in stroke models, comparing these with adenosine's hypothermia-independent neuroprotective effects. METHODS 1) Electrically-evoked local field potentials will be measured during torpor in mice; spike-sorting algorithms will be used to distil individual neurons' activity profiles. 2) Performance of mice in a battery of behavioural tests will be measured before, during and after torpor. 3) Stroke will be induced via insertion of a carotid intraluminal suture under anaesthesia (a minimally-invasive and reproducible method well-established in mice). Torpor will subsequently be induced by intracerebroventricular-infusion of A1AR agonist cyclohexyladenosine. Infarct size and behavioural performance of mice will be quantified. Experiments will be repeated in mice artificially-maintained at normal body temperature.


Research activity codes: 6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: STROKE
Title: Developing methods for identifying clinical phenotypes from routinely collected health data with applications to stroke genetics.
Funder: Medical Research Council

Abstract: For objective (1) I will start by using data from the UK Biobank participants, building on the pilot work undertaken in the UK Biobank to date, which has generated "case vignettes" composed of relevant medical record free text. Following validation in UK Biobank, the developed algorithms and methods can then be applied to and further validated in other consented cohorts (e.g., Generation Scotland). For objective (2), I will build on an ongoing systematic review that will lead to a set of phenotypes that will form the hypothesis for a phenome-wide association study using data from the UK Biobank. For objective (3) I will use my existing network of collaborations within the International Stroke Genetics Consortium (ISGC) to access relevant datasets to test the proposed methods. I will also collaborate with other researchers from the University of Edinburgh and across the UK, as well as with other HDR UK fellows, to build the skills and capacity to undertake and further develop these proposed directions. This project aligns with HDR UK priorities, as it will develop national leadership, partnerships, and interdisciplinary skills and capacity through the development of novel analytical methods and tools, which can in the future be applied and taken up for research of health conditions beyond stroke.


Research activity codes: 7.4 RESOURCES AND INFRASTRUCTURE (DISEASE MANAGEMENT)
Health categories: STROKE
Title: Interventions for dysphagia in acute and subacute stroke
Funder: Department of Health and Social Care

Abstract: Stroke affects 140,000 people each year in the UK. Dysphagia (swallowing problems) is common after stroke and affects up to 50% of patients [1]; although two-thirds of patients improve spontaneous, many need feeding acutely via a nasogastric tube and then chronically with a percutaneous endoscopic feeding tube. Patients with post-stroke dysphagia have a poor outcome with increased pneumonia and malnutrition, increased death, increased death and dependency, prolonged stay in hospital, and are more likely to be discharged to an institution after hospital [2]. As such, dysphagia is expensive financially to society and the NHS, leads to long-term occupation of hospital and institutional beds, and is distressing to patients and their carers and family. In our last Cochrane review of interventions for dysphagia and nutritional support in acute and subacute stroke (published in 2012 [3]), we identified no treatments that reduce dysphagia. However, many new studies have been reported (e.g. [4]) and the review needs updating to identify potential interventions that might be beneficial and change clinical practice. Due to the extent and complexity of dysphagia management, we are removing the nutritional support content from the planned review update.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: STROKE
Title: Staff-led interventions for improving oral hygiene in patients following stroke
Funder: Department of Health and Social Care

Abstract: Stroke-Associated Pneumonia (SAP) is a leading cause of hospital-acquired infection affecting a fifth of stroke survivors annually (estimated 232,000 worldwide; 33,000 in the UK). SAP is associated with triple the risk of death at 30 days, poorer rehabilitation outcomes, prolonged hospital stays and dependency at discharge 1-4. The annual cost of SAP in the United States is estimated at $495 million 5. Admissions to stroke care settings are expected to increase by 30% over the next 20 years 6. The possibility of a relationship between SAP and patients’ oral health is receiving increasing attention 7. Pneumonia and Oral health care: Recent non-Cochrane review evidence suggested that the incidence of pneumonia and chest infection (and associated mortality risk) amongst elderly nursing home residents is reduced with the provision of professional OHC (absolute risk reduction ranging from 6.6% to 11.7% and numbers needed to treat from 8.6 to 15.3) 7. There are good theoretical reasons to believe that benefits may extend to hospitalised stroke populations. Current Cochrane review evidence is considered severely outdated 8. Recent national stroke clinical guidelines 9 considered evidence from eight relevant RCTs completed since our review update 8. References: 1. Langhorne P, Stott DJ et al Medical complications after stroke. Stroke 2000:31;1223-9. 2. Hilker R, Poetter C, et al. Nosocomial pneumonia after acute stroke – implications for neurological intensive care medicine. Stroke 2003;34:975-81 3. Katzan IL, Cebul RD et al The effect of pneumonia on mortality among patients hospitalized for acute stroke. Neurology 2003: 60(4);620-5 4. Perry L, Love CP. Screening for Dysphagia and Aspiration in Acute Stroke: Dysphagia 2001;16:7–18. 5. Katzan IL, Dawson NV et al. The cost of pneumonia after acute stroke. Neurology 2007; 68:1938-43. 6. Lopez AD, Mathers CD et al. Global and regional burden of disease and risk factors 2001: Systematic analysis of population health data. Lancet 2006; 367:1747-57. 7. Sjögren P, Nilsson E et al. A systematic review of the preventative effect of oral hygiene on pneumonia and respiratory tract infection in elderly people in hospitals and nursing homes. Journal of the American Geriatric Society 2008:56:2124-30. 8. Brady MC, Furlanetto D, Hunter R, Lewis SC, Milne V. Staff-led interventions for improving oral hygiene in patients following stroke. Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.: CD003864. DOI: 10.1002/14651858.CD003864.pub2 (update published June 2011


Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: STROKE
Title: Reveal LINQ Insertable Cardiac Monitor with CareLink Service to detect atrial fibrillation after a cryptogenic stroke
Funder: Department of Health and Social Care

Abstract: The aim of this diagnostic assessment review is to assess whether the use of implantable cardiac monitors to assess for suspected paroxysmal atrial fibrillation in people who have had a cryptogenic stroke represents a cost-effective use of National Health Service (NHS) resources compared to no further testing after outpatient external ambulatory electrocardiogram (ECG) monitoring.

Lay abstract: Ischaemic strokes are blockages in blood vessels in the brain that lead to the death of brain tissue, resulting in clinical signs and symptoms such as weakness or loss of function in the arms or legs, slurred speech or drooping of part of the face. Cryptogenic ischaemic strokes are strokes that have no clearly identifiable cause despite standard medical investigations such as blood tests, a heart tracing (electrocardiogram [ECG]), and a scan of the heart (echocardiogram [ECHO]). Cryptogenic transient ischaemic attacks (TIAs) are like strokes only the symptoms resolve within 24 hours. Atrial fibrillation (AF) is an irregular heart rhythm that can occur intermittently or permanently and is associated with an increased risk of stroke and TIA. It is thought that undiagnosed AF may be the cause of some cryptogenic strokes and TIAs. Patients with a cryptogenic stroke or TIA may benefit from further tests to investigate for the presence of AF, as there are treatments that can be given to reduce the risk of stroke in patients diagnosed with AF. AF is diagnosed as an irregular heart rhythm seen using inpatient or outpatient ECGs, or heart rhythm monitors that are worn at home by a patient as part of a test known as “external ambulatory ECG monitoring”. External ambulatory ECG monitoring is typically done for between 24 hours and two weeks depending on the device used. However, the intermittent nature of AF in some patients can make it difficult to diagnose AF using ECG or external ambulatory ECG monitoring and so longer-term heart rhythm monitoring may be beneficial. Reveal LINQ™, Confirm RX™ and BioMonitor 2-AF™ are implantable cardiac monitors (ICMs), which can be put inside patients with cryptogenic strokes or TIAs, to monitor their heart for AF on a longerterm basis (typically for 2 to 4 years depending on the battery life of the device). ICMs may help in identifying patients with cryptogenic stroke or TIA who have AF that has not already been diagnosed using external ambulatory ECG monitoring. The aim of this project is to review the clinical scientific evidence, and to assess the costs and benefits associated with the use of ICMs to detect AF in people with cryptogenic strokes and TIAs.

Research activity codes: 6.3 MEDICAL DEVICES
Health categories: STROKE
Title: How and why does uptake of secondary prevention medication after stroke vary between general practices and between patient groups?
Funder: Department of Health and Social Care

Abstract: Recurrent stroke is a major cause of morbidity and mortality. Medications can reduce the risk of recurrent stroke but their usage is incomplete. This PhD will use a mix of quantitative and social science methods to identify first: how rates of uptake vary between patient groups and between general practices using a search of three million patient records; second: why rates of uptake in different patient groups vary between general practices, using a mix of observation of daily practice and interviews of patients and staff in approximately 12 purposively sampled general practices.

Lay abstract: Recurrent stroke is a major cause of morbidity and mortality. Medications can reduce the risk of recurrent stroke but their usage is incomplete. This PhD will use a mix of quantitative and social science methods to identify first: how rates of uptake vary between patient groups and between general practices using a search of three million patient records; second: why rates of uptake in different patient groups vary between general practices, using a mix of observation of daily practice and interviews of patients and staff in approximately 12 purposively sampled general practices.

Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: STROKE
Title: Doctoral Research Fellowship: Stroke Prevention Rehabilitation Intervention Trial of Exercise - SPRITE - A Feasibility and Pilot Study
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: Stroke, a major cause of death and disability, may be prevented by intervention following a transient ischaemic attach (TIA) or 'minor stroke' but the best approach to such prevention remains unknown. This study aims to develop a home-based intervention, using core components of cardiac rehabilitation, with or without an added pedometer intervention, began within 2 weeks of a TIA/minor stroke. Rates of recruitment, retention, adherence and completion of measurements in a 12-week pilot trial, with participant feedback, will determine the feasibility of a randomised controlled trial of its effectiveness. Potential benefits for patients include improved well-being and reduced risk of stroke. BACKGROUND: Approximately 1,700 transient ischaemic attacks (TIAs) occer annually in NI. TIA and strokes share common risk factors with cardiovascular disease. Cardiac rehabilitation post-myocardial infarction has shown significant reductions in morbidity and mortality, with home-based programmes producing better adherence and similar outcomes to hospital-and community-based programmes. However, the value of rehabilitation programmes for stroke prevention following a TIA or minor stroke is unclear. Predicted VO2max is a short-term measure of their effectiveness: it is a function of fitness, associated with mortality risk and improved by increasing physical activity. AIMS: To determine if a novel rehabilitation programme for TIA/minor stroke patients can be developed, using MRC guidelines, from an approved home-based cardiac rehabilitation programme (the 'Heart Manual') and to pilot a 12-week trial of the novel programme, with predicted VO2max as a measure of its effectiveness. METHODS: All patients attending a TIA clinic in Belfast within 2 weeks of their first TIA/mild stroke will be invited to participate. The novel home-based programme manual will be developed following systematic review of literature and qualitative exploration with the target population, using 4 focus groups. A pilot trial will recruit to 3 different treatments: (1) standard care; (2) standard care plus the manual; (3) standard care, manual plus a pedometer (to further promote physicla activity). Interviews and focus groups will be employed to assess the interventions' acceptability. CONCLUSIONS: The findings will inform the development of a novel secondary prevention programme for TIA/minor stroke patients and of a trial to test its effectiveness and longer-term potential to improve outcomes for TIA/stroke patients.


Research activity codes: 6.7 PHYSICAL;7.1 INDIVIDUAL CARE NEEDS
Health categories: STROKE
Title: A randomized controlled trial (RCT) of mirror box therapy in upper limb rehabilitation with sub-acute stroke patients
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: Background: Individuals who have sustained a stroke are often left with residual deficits of the upper limb such as impaired movement and sensation. These deficits restrict functional use of the limb in everyday activities and can result in increased dependency upon others to engage in some tasks. Regaining independence through functional use of the arm and hand is an aim of occupational therapy (OT) rehabilitation. Mirror box therapy (MBT) is a relatively new innovation being introduced into OT interventions. Some studies have reported it to be beneficial in upper limb rehabilitation, however, these studies have not involved a sub-acute stroke population. Design: This is a Randomised Controlled Trial. Sample: 180 participants from 4 healthcare organisations in both Northern and Southern Ireland who meet study criteria will be randomised to either a control (standard OT upper limb rehabilitation) or intervention (standard OT plus MBT) group. Population: Individuals who have sustained a stroke within the past 3 months and are hospital in-patients will be recruited. Inclusion Criteria: 18 years and over; newly admitted inpatient of the rehabilitation ward; first diagnosis of CVA in the last three months resulting in upper limb motor loss; able to follow two part spoken or written commands in the English language; upper limb therapy designated as a main portion of goal directed treatment programme; able to perform at least one of the upper limb movements as per Canadian Partnership of Stroke Recovery Criteria; Fatigue Severity Score of 35 or below and consent to take part in the study. Intervention: Standard upper limb rehabilitation of 3-5 sessions per week of approximately 45 minutes duration will be augmented by 2, 20 minute sessions of mirror box therapy on a daily basis for the intervention group. Comparison: Standard upper limb rehabilitation of 3-5 sessions per week of approximately 45 minutes duration Outcome Measurements: The graded Wolf Motor Function Test (primary outcome measure); the Functional Independence Measure; the EQ5D5L and the Canadian Occupational Performance Measure will be recorded at baseline, 2 weekly, at discharge and 12 weeks post-discharge. Anticipated Outcome: This study aims to provide robust evidence as to whether this type of therapy offers greater potential in functional gains in the sub-acute recovery period of stroke than standard rehabilitation of the upper limb alone. Time: We expect this trial to take 3 years to complete with a 30-month active recruitment period.


Research activity codes: 6.7 PHYSICAL
Health categories: STROKE
Title: Prevention Of Hypertensive Injury to the Brain by Intensive Treatment after IntraCerebral Haemorrhage: a pilot randomized trial of home telemetry-guided treatment
Funder: Stroke Association

Abstract: Background. About 15,000 to 23,000 of the 150,000 strokes in the UK per year are due to spontaneous (non-traumatic) intracerebral haemorrhage (ICH). Mortality is ~50%, and most survivors have physical or cognitive impairments. The main cause of ICH is cerebral small vessel disease (SVD). Sustained BP lowering is the most promising intervention to prevent SVD progression and ICH, but the optimum target is unknown, and in practice adherence and BP control remain poor. Telemetric home monitoring shows promise to optimize BP control after ICH. Methods. PROHIBIT-ICH is a pilot multi-centre randomized controlled trial comparing a strategy of intensive BP treatment (target 120/70mm Hg) guided by telemetric home monitoring, versus standard care, in 100 adult survivors of SVD-related ICH. We will establish feasibility and explore whether the intervention reduces the progression of SVD-injury on brain MRI. Outcome Measures include: feasibility (consent rate, dropout from the intervention arm, patient approval); safety (adverse events); exploratory efficacy (incidence of microbleeds, change in white matter hyperintensity volume and cognitive function, recurrent cerebrovascular events over 1 year). Expected outcomes. This pilot study will estimate the key parameters needed to design a definitive efficacy and mechanism trial of intensive BP lowering using telemetric home monitoring after ICH.


Research activity codes: 6.3 MEDICAL DEVICES
Health categories: STROKE
Title: Stroke Prevention: Cerebral Embolic Protection Device and reduction of Neurological Injury in Thoracic Aortic Stenting
Funder: Stroke Association

Abstract: Background The incidence of thoracic aortic disease is rising, and there has been a dramatic increase in the number of TEVARs (thoracic endovascular aortic repair) in the last decade. The risk of stroke during TEVAR is 2-10%, with a 70% silent cerebral infarction (SCI) rate. SCI is brain infarction detected on MRI and is a predictor of future stroke, dementia, depression and neurocognitive decline. Cerebral embolic protection devices (CEPD) are novel technologies, successfully used in other endovascular procedures to reduce brain injury. Their use in TEVAR has not been investigated. Aim A pilot study to assess the efficacy and feasibility of CEPD in patients undergoing TEVAR. Method All patients anatomically suitable CEPD (N=30) will be recruited over 18 months. Patients will undergo pre and postoperative MRI; pre, postoperative, 6 week neurocognitive assessment, and trancranial doppler monitoring (TCD). External monitoring and safety data for the device will be recorded. All embolic material captured in the filters will be sent for histopathological analysis. Expected outcome We expect a reduction in both number and volume of SCIs and an improvement in neurological and neurocognitive outcome. The study will provide evidence for an RCT to assess reduction of brain injury in patients with CEPD in TEVAR.


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: STROKE
Title: Linguistic Underpinnings of Narrative in Aphasia (LUNA): A proof-of-concept study of a novel discourse treatment for aphasia using personal narratives
Funder: Stroke Association

Abstract: How best to recover everyday discourse skills in chronic aphasia after stroke is an internationally recognised service user, clinical, and research priority. Progress is hindered by the dearth of efficacious discourse treatments and the lack of speech and language therapists’ (SLTs) clinical expertise in discourse assessment and treatment. This study will develop a theory and model of linguistic change across the word, sentence and discourse levels in narrative in aphasia (LUNA), and operationalize it through co-design with NHS SLTs and people with aphasia into a personalised treatment approach, manuals and clinical tools. It will (1) identify SLTs’ knowledge, skills, and perceived facilitators and barriers to discourse assessment and treatment; (2) develop and test a training programme to examine SLTs’ accuracy and efficiency in discourse assessment, thereby demonstrating clinical viability of methods used in the second stage; and (3) generate proof-of-concept in a small-scale mixed-methods experimental study comparing LUNA plus “usual care” to “usual care” only) and assessing: feasibility and participant acceptability; initial efficacy of LUNA on discourse and psychosocial state outcomes (clinical tests and participant self-report); and treatment fidelity. This early developmental research project will lead to a future Phase II exploratory feasibility RCT in the NHS community SLT setting.


Research activity codes: 5.6 PSYCHOLOGICAL AND BEHAVIOURAL;6.6 PSYCHOLOGICAL AND BEHAVIOURAL
Health categories: STROKE