NIHRDataInsights/HRCSData huggingface dataset:
Title: A Cochrane Overview of interventions to improve upper limb function after stroke.
Funder: Chief Scientist Office (Scotland)

Abstract: Background: Identifying effective upper limb stroke rehabilitation interventions is a recognised research priority. Current research evidence is overwhelming for decision makers and difficult to translate into clinical practice. At least 11 Cochrane reviews address upper limb rehabilitation. Aims: carry-out a Cochrane Overview, comparing effectiveness of interventions; provide a succinct, accessible overview of evidence, aiding translation of evidence into practice. Methods: The overview will follow Cochrane methods. Inclusion criteria: Studies: Cochrane systematic reviews of randomised controlled trials. Participants: stroke. Interventions: upper limb rehabilitation. Outcomes: Functional movement of the upper limb, activities of daily living, motor impairment, extended activities of daily living, quality of life, adverse events. Two independent reviewers will identify relevant reviews, assess methodological quality, assess quality of evidence (using the GRADE approach), extract and synthesise relevant data. Indirect comparisons of interventions will be computed. Output: an accessible, comprehensive synthesis of high quality evidence for upper limb stroke rehabilitation interventions.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;7.3 MANAGEMENT AND DECISION MAKING
Health categories: STROKE
Title: ReaDySpeech for people with dysarthria after stroke: a feasibility study.
Funder: Department of Health (England)

Abstract: Dysarthria, or slurred speech, is caused by muscle weakness and is common after stroke. It leads to people feeling isolated, unconfident and uncomfortable in social situations. Speech therapy can offer support and reduce symptoms but is not always provided in the NHS. So we want to develop technologies, to enable more patients to access speech rehabilitation. This study will try the technology out with clinicians and patients to see what they think of it. If clinicians and patients think using technology is acceptable we will try it out with more people so we can fully test the technology.


Research activity codes: 5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: STROKE
Title: Goal setting in community based stroke rehabilitation: A feasibility and acceptability study of implementing a goal setting and action planning practice framework.
Funder: Chief Scientist Office (Scotland)

Abstract: Background: Goal setting creates an ideal opportunity for person-centred care in stroke rehabilitation. I have developed and tested a goal setting and action planning (G-AP) framework for use in community rehabilitation teams (CRTs) with promising results. This research will examine the acceptability and feasibility of implementing G-AP in other CRT’s, and gather information to inform the design of a future effectiveness study. Project Aims: 1. To investigate current goal setting practice in CRTs providing services to people recovering from stroke across the UK. 2. To investigate the implementation of the G-AP framework with people recovering from stroke, in three different CRTs. Methods: A mixed methods study in two phases. Phase 1: A national survey of CRTs to investigate (i) the structure and organisation of CRTs providing stroke rehabilitation services in the UK, and (ii) current goal setting practice used within them. Phase 2: Implementation of G-AP in three CRTs to identify patient, carer and therapists’ views about the acceptability, feasibility and impact of G-AP in practice. Case note analysis to investigate the fidelity with which G-AP has been implemented. Outcomes: Data analysis will determine: the variation in current goal setting practice in CRTs; the acceptability of G-AP to staff, patients and carers; the feasibility of implementing G-AP, according to protocol, in diverse CRTs; what outcomes (if any) implementation of G-AP is likely to impact on. This study will benefit the NHS and patients through enhancing patient centred care and advancing clinical excellence through evidence based practice.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: STROKE
Title: Long term consequences and recovery from stroke: what is important to stroke survivors and health professionals?
Funder: Chief Scientist Office (Scotland)

Abstract: Objective: To explore the long term* consequences of, and recovery from, stroke and what is important to stroke survivors in terms of measurement of long term outcome. •greater than 18 months. Design and methods: Meaningful stroke survivor involvement will be central to this proposed programme of work: • Study 1: Documentation of current evidence with regard to the nature, importance and frequency of long term consequences of stroke. Methods will include systematic review and meta-analyses of observational studies and clinical datasets. • Study 2: Exploration of stroke survivors' and health professionals' perceptions and priorities of the long term consequences of stroke. Methods will include focus groups, thematic analysis and Q-methodology. • Study 3: Exploration of whether current outcome scales adequately assess what is important to stroke survivors and health professionals in terms of long term recovery after stroke. Methods will include rating of common outcome measures by stroke survivors and health professionals, and use of a resource of video recorded stroke survivor interviews to compare stroke survivor ratings of the most important domains with scores from the most commonly used functional assessment in stroke trials (the modified Rankin Scale). Outcome: This research will: Enable progression ofthe identified research priority relating to coming to terms with the long term consequences of stroke towards a research question which could be answered by high quality research. Lead to clear recommendations relating to relevant outcome measures, both for assessing long term clinical recovery and for use within future research trials.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: STROKE
Title: Does Levodopa (34-dihydroxy-L-phenylalanine) drug treatment in combination with routine NHS occupational and physical therapy delivered early after stroke within a stroke service improve functional recovery including walking and arm function
Funder: Department of Health (England)

Abstract: - Design: A multicentre prospective randomised double blinded placebo controlled trial. 572 people with new stroke admitted to acute stroke services will be recruited. - Setting: At least 8 UK stroke services within Stroke Local Research Networks(LRN)


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: STROKE
Title: Penumbra and Recanalisation Acute Computed Tomography in Ischaemic Stroke Evaluation (PRACTISE)
Funder: Chief Scientist Office (Scotland)

Abstract: Intravenous (IV) recombinant tissue plasminogen activator (rtPA) is highly effective for acute ischaemic stroke but is underutilised particularly in patients with minor or improving symptoms despite a high probability of poor outcome in these patients. We hypothesise that poor sensitivity (23-66%) of standard brain imaging (non-contrast CT NCCT) and risk of iatrogenic intracerebral haemorrhage lead to underuse and that multimodal imaging that includes CT angiography and CT perfusion (CTA and CTP) to stratify patient selection will lead to higher treatment rates. Design: randomised controlled trialStudy population: adult patients with acute ischaemic stroke otherwise eligible for IV rtPAPlanned Interventions: Control - routine NCCT; experimental group - multimodal CT (CT+CTA+CTP)Outcome Measures: Primary endpoint: proportion of patients treated with rtPA. This is expected to increase as a result of improved diagnostic sensitivity and identification of significant ischaemia or arterial occlusion in patients with minor neurological symptoms at presentation. Secondary end-points: assessment of disability (modified Rankin Scale mRS); Assessment & Follow-up: Acute treatment decision. Assessments of neurological status pre-randomisation 24h 72h days 7 30 and 90; adverse events to day 90; disability (mRS score) days 30 and 90. Renal function 24h and 72h.Sample Size: 200 patients per group (total 400) from 6-8 centres. We hypothesise an increase in the proportion treated from 25% to 40% requiring 152 subjects per group for 80% power at p=0.05. Literature identifies 27% of ischaemic stroke patients <3h after onset given IV rtPA and 31% excluded primarily because of a mild or improving clinical deficit. 200 subjects per group allows for a diagnosis of non-ischaemic stroke pathology in 15% of patients and for uninterpretable imaging in 10% of the multimodal imaging group.Statistical Analysis: Primary analysis will be the proportion treated with IV rtPA compared with logistic regression adjusted for randomised group and stratification variables (severity lateralisation) to generate odds ratios and 95% confidence intervals. Secondary analyses include disability outcomes using Cochran-Mantel-Haenszel comparison of mRS distribution by group and comparison of imaging interpretation by paired categorical variable analyses.Timetable: Stage 1 (months 0-6) set-up and approvals. Go/No-go: MREC approval. Stage 2 (months 6-30): clinical trial. Go/No-go: safety reviews (month 3 and 12) and feasibility/recruitment reviews (months 3 and 12). Expected recruitment rate 2-3 patients/centre/month. Stage 3 (months 30-36): analysis reporting.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: STROKE
Title: Metabolic MRI in Acute Stroke; Development and Validation of the 'Oxygen Challenge' Technique
Funder: Chief Scientist Office (Scotland)

Abstract: We propose the development of a novel imaging technique which we have termed ‘Oxygen Challenge MRI’. The aim is to image a surrogate measure of metabolic activity within the brain using the transient application of hyperoxia during continuous deoxyhaemoglobin sensitive T2*-weighted imaging. This proposal aims to continue successful pilot studies previously performed in rodents and human stroke. The first part aims to use healthy volunteers to determine the optimal oxygen concentration, MR scanner strength, and pattern of oxygen administration. The second part will use the optimised Oxygen Challenge protocol and investigate the influence of impaired autoregulation on the results from Oxygen Challenge; any influence on results will then be modelled. Carotid artery steno-occlusive disease will be used as a ‘model system’ for this part. Finally, we will image a homogeneous cohort of patients with hyperacute acute ischaemic stroke in order to validate the identification of potentially salvageable tissue.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: STROKE
Title: Supporting the ischaemic brain with oxygen-carrying perfluorocarbons
Funder: Chief Scientist Office (Scotland)

Abstract: The research proposal will investigate whether perfluorocarbon oxygen carriers (PFCs), combined with normobaric hyperoxia can support ischaemic brain, are compatible with rt-PA therapy, and have any influence on oxidative stress in rodent stroke models: specifically, their ability to improve oxygen delivery to ischaemic brain, limit brain damage, extend lifespan of potentially salvageable penumbra and therapeutic time window for thrombolysis. Pilot data are presented from a related project using PFC+hyperoxia for MRI penumbra detection. It is planned to use a PFC already being tested clinically, to facilitate rapid translation to clinical trials. Studies will investigate the ability of PFC+hyperoxia to influence stroke-induced brain injury progression and final infarct (using multi-sequence MRI), functional outcome in permanent and transient focal ischaemia and embolic stroke with and without rt-PA-induced thrombolysis. Following final scans, tissue will be analysed for malondialdehyde levels to determine any influence of PFC+hyperoxia on reperfusion or oxidative injury.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: STROKE
Title: Non-invasive measurement of cerebrovascular reactivity and compliance in cerebral small vessel disease: feasibility and estimation of sample size for translational research and clinical trials
Funder: Chief Scientist Office (Scotland)

Abstract: "Cerebral small vessel disease is the commonest vascular cause of dementia, causes a fifth of strokes and considerable physical disability in older people. The cause is unknown. Failing blood-brain barrier function, cerebral arteriolar wall thickening and impaired vasoreactivity are seen experimentally or pathologically. In vivo imaging shows blood-brain barrier malfunction and can measure cerebral microvascular reactivity, which is an important potential therapeutic target in small vessel disease. This project will test new magnetic resonance imaging methods to measure regional cerebral vasoreactivity and compliance in patients with small vessel stroke to determine if these methods are sensitive and practical enough to use as intermediary outcomes in early phase clinical trials of interventions to prevent progressive small vessel disease. Lack of patient data mean that this development is required to compare cerebral, retinal and peripheral vasoreactivity, provide proof of principle and determine sample size prior to phase 2 trials and mechanistic studies."


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: STROKE
Title: Resilience after Stroke: An Intervention to Promote Mental Health and Quality of Life among Older Stroke Survivors
Funder: Medical Research Council

Abstract: Stroke is a long term condition affecting a significant proportion of adults in the UK, with the risk of stroke increasing with age and in black ethnic groups (Heuschmann et al 2008). It is the leading cause of adult disability (WHO 2009) and associated with substantially raised risk of depression (Hackett et al 2005). Resilience among older adults, defined as an ability to adapt positively, thrive or ?bounce back? from adversity such as loss and illness (Netuveli et al 2008) is associated with improved mental health and quality of life (Nygren et al 2005, Hildon et al 2009). However, it is currently not known what resilience resources, strategies and contexts may promote or hinder older stroke survivors? ability to cope with the adverse consequences of stroke. This study aims to investigate the meaning and role of resilience after stroke among older stroke survivors and their carers from white and black ethnic groups. The study uses qualitative interviews and focus group discussions to identify user and service providers? understandings of resilience and its relationship to recovery and adaptation after stroke. Using the Medical Research Council?s (MRC) guidance framework for complex interventions (MRC 2008), this information will then be used to develop a culturally appropriate intervention fostering resilience and thereby mental health and quality of life after stroke. We anticipate that this pilot work will lead in the future to the development of a larger randomised controlled trial to promote resilience after stroke for older stroke survivors and their carers.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: STROKE
Title: Investigating the impact of early brain injury on outcomes after subarachnoid haemorrhage using MRI
Funder: Medical Research Council

Abstract: Background: Delayed cerebral ischaemia (DCI) is the most important cause of mortality and morbidity following aneurysmal subarachnoid haemorrhage (SAH). Despite extensive research, the exact pathophysiology is still unclear and predicting, diagnosing and treating the condition remains difficult. Recent studies have highlighted the importance of the ischaemic damage caused by the initial bleed - so called early brain injury (EBI). This may result in a number of processes including cortical spreading depression, that damage resting state connectivity in the brain and result in neurocognitive deficits after SAH. The majority of current data following SAH has been obtained from animal studies with little in-vivo research and there is no current clinical method for assessing, treating or preventing either EBI or cortical spreading depression. Many patients may remain clinically asymptomatic despite significant cerebral injury and the impact of this on functional outcome is unknown. Aims and Objectives: 1. To use magnetic resonance imaging (MRI) scanning techniques to assess and quantify the changes in cerebral perfusion, structure and function that occur due to EBI 2. To assess whether EBI causes damage to resting state cortical connectivity 3. To assess whether long term clinical and neuro-cognitive outcomes are linked to EBI 4. To assess the potential of MRI evidence of EBI to act as a tissue biomarker in predicting the risk of DCI after SAH Study Design: The proposed project will have 3 component studies: 1) A healthy volunteer study into the effects of nimodipine on cerebral perfusion. 2) A prospective comparison study of MRI and clinical data from patients taken post-SAH with healthy controls. 3) A follow-up study of patients at 2 months post-SAH to correlate ischaemic damage at the time of the bleed with functional and neurocognitive outcomes. Methodology: The MRI brain imaging protocol planned includes arterial spin labeling (ASL), vascular space occupancy (VASO) and blood oxygenation level dependent (BOLD) sequences, as well as structural imaging (T1,T2). Analysis of MRI data will include standard general linear modelling, perfusion analysis and independent component analysis. This will link multi-modal MRI data obtained acutely following SAH with long-term clinical and neurocognitive outcomes. Opportunities: This research will investigate the role of functional MRI in the assessment of EBI after SAH and inform on the pathological processes in-vivo that remain unclear. It will also assess the impact of EBI on functional and neurocognitive outcomes following SAH and whether MRI can identify tissue biomarkers that predict risk of DCI.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: STROKE
Title: Modulation of microRNA as a therapeutic strategy for stroke
Funder: Medical Research Council

Abstract: This project aims to determine the effect of microRNA (miRNA) modulation as a novel intervention strategy in a robust pre-clinical model of stroke. Given that one miRNA can alter the expression of many both divergent and converging genes in multiple pathways, through a single modulation a significant effect on those pathways implicated in lesion progression or the promotion of endogenous repair will be achieved. Initially, the expression of miRNA which have been previously published to be altered following cerebral ischaemia will be validated in our experimental model of transient middle cerebral artery occlusion (tMCAO) in the spontaneously hypertensive stroke prone rat (SHRSP) and an in vitro model of hypoxia/reoxygenation. The in vitro model will allow the effect of specific miRNA modulation by lentivirus infection (over-expression or knockdown) to be determined through a number of functional assays prior to translation to the in vivo model. On identification of the most promising therapeutic miRNA candidates for modulation from the in vitro characterisation studies a canine adenovirus-2 (CAV-2) vector will be generated. CAV-2 has been shown to be highly neurotrophic in the SHRSP and other animal models of neurodegenerative diseases. Its marked efficiency of neuronal transduction, retrograde transport from the injection site resulting in a significant area of transduction and lack of immune response due to a lack of existing immunity make it an ideal and novel vector for study in the current proposal. CAV-2 will be administered by stereotaxic injection 24 hours post-tMCAO in the SHRSP and the effect of miRNA modulation (up to 4 therapeutic groups vs control tMCAO and sham controls) determined. To fully characterise the effect of such intervention animals will be taken out to 21 days post-tMCAO to monitor neurological recovery (using the tapered beam test and assessment of neurological score through a battery of 10 tests), infarct volume (by H&E staining) and functional assays (IHC for specific proteins, western blotting, biochemical assays, pressure myography). This will provide a comprehensive follow-up to ascertain the effect of specific miRNA in the setting of experimental stroke. Through the studies outlined here, I aim to demonstrate the therapeutic potential of miRNAs for stroke using a novel gene delivery vector in a robust and clinically relevant experimental model at a timepoint which would be clinically significant.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;5.2 CELLULAR AND GENE THERAPIES
Health categories: STROKE
Title: Limbs Alive Monitoring of Upper Limb Rehabilitation and Recovery after Stroke Through Gaming.
Funder: Department of Health (England)

Abstract: a) The unmet healthcare need Stroke frequently damages the area of the brain controlling movement; as a consequence there are thousands of people with weakness down one side of their body. This has a major impact on their lives because everyday activities require two hands. The brain can relearn control of the weak arm, but this needs frequent therapy over many months. There are not enough therapists to provide this on a one-to-one basis and fewer than 20% of patients regain independence after a stroke. b) The technology to be developed We have developed a library of video-games to be played at home, which provide highly motivating therapy for relearning arm and hand movements. We plan to analyse information about patients' performance of arm and hand movements during the video games in order to provide feedback to the patient and their therapist via the internet. c) The key goals and deliverables This will enable effective rehabilitation of arm and hand movements to be delivered at home at times and places to suit patients, whilst still maintaining expert supervision from a therapist. d) The healthcare impact The need for hospital visits will be greatly reduced, patients will have the opportunity to undertake more frequent therapy sessions, therapists will be able to supervise more patients and patients should regain greater independence.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: STROKE
Title: Developing a stepped care model for treating anxiety disorders after stroke
Funder: Chief Scientist Office, Scotland

Abstract: There are 1.2 million stroke survivors in the UK. About a quarter of them are affected by anxiety disorders. This is when anxiety or fears become excessive or out-of-proportion, affecting the person’s ability to carry on with their life normally. Anxiety can become persistent and lead to a poorer quality of life. The proposed research Using existing research, patient interviews and questionnaires, I will develop methods to identify, characterise and treat anxiety after stroke, in a way that is practical for the National Health Service in Scotland. These methods will be tested first in stroke survivors to determine if they are acceptable or practical to deliver. Outcomes and expected benefits Following this project, I will test if this new way of identifying, characterising and treating anxiety after stroke leads to better health in a large group of stroke survivors in Scotland, before rolling it out within the NHS.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: STROKE