NIHRDataInsights/HRCSData huggingface dataset:
Title: Determining the source of variability within experimental stroke models
Funder: National Centre for the Replacement, Refinement and Reduction of Animals in Research

Abstract: Efficacy of stroke interventions are tested using rodent middle cerebral artery occlusion (MCAO) models of focal brain ischemia but these have a poor record of translating into clinically effective treatments. The majority of experimental stroke studies use lesion volume as the primary outcome measure. However, variability in MCAO lesion volume is high with significant differences generally tested using parametric analyses requiring a normal data distribution. Data from my laboratory over the last 10 years (and confirmed by others) shows that MCAO lesion volume data is not normally distributed and results in a bimodal distribution of small (purely striatal) and large (striato-cortical) lesions. We aim to determine (i) whether variability in MCAO lesion data is due to differences in cerebrovascular anatomy and, (ii) whether refinement of the surgical technique can improve outcome reproducibility. Rodents show a large variability in the Circle of Willis and studies have shown this to produce variability in lesion volume thus, requiring increased animal numbers to achieve statistical significance. However, traditional methods to assess the Circle of Willis anatomy are conducted post-mortem following the induction of MCAO. Firstly, we will assess, using MRI, whether the reported variability in outcome following MCAO is dependent upon the anatomy of the Circle of Willis and if so, can we develop a screening technique to identify 'suitable' mice to undergo MCAO and therefore reduce the number of animals undergoing MCAO. In addition, we will assess whether a refinement in the surgical approach used to permit reperfusion followng MCAO can be applied in mice. This will allow reperfusion to occur irrespective of the completeness of the Circle of Willis which is currently the main limitation in determining the effectiveness of reperfusion. This should reduce the variability in reperfusion associated experimental stroke models and reduce the number of animals used.


Research activity codes: 5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT)
Health categories: STROKE
Title: Visual Cue training to improve walking and turning after stroke: a pilot study
Funder: Department of Health (England)

Abstract: Background The walking of many stroke patients > 6 months after stroke remains impoverished and is characterized by impairments including slow gait speeds, asymmetries in step lengths, widths and stance and swing phase durations. A recent Cochrane review reported that there was inconclusive evidence as to whether therapy one year after stroke was able to improve walking ability in these patients, so further well-designed trials are needed. The use of enhanced visual cues in order to overcome somatosensory impairments and improve gait characteristics has been found effective populations other than stroke such as Parkinson’s Disease (PD). We propose that such visual cue training (VCT) will also be effective in improving the gait of people with stroke. Aims The aims of the pilot are: Determine the numbers of patients willing to be recruited into both control and VCT groups Determine the willingness of physiotherapists at each collaborating site to enrol patients to both control and VCT groups Determine the numbers of patients who do not complete the allocated treatment, thus dropping out of the study, and determine the reasons for dropping out. Use knowledge gathered about recruitment, outcomes and drop-out rates to determine sample size for a subsequent definitive trial. Measure completeness of outcome data, i.e. percentage of patients with no missing values in outcome assessments. Plan of Investigation We will: Recruit patients to the pilot trial. Randomise participants to either Visual Cue Training or Conventional Overground Walking training for a period of 8 weeks, three times per week. Measure primary outcomes (proportion of participants reaching gait speed of 0.4 m/s or 0.8 m/s and time and number of steps to complete a 90 degree turn) and secondary outcomes, at baseline, 8 weeks and 3 months post randomisation. Record number of patients enrolled at each collaborating site to both control and VCT groups; number of patients who do not complete the allocated treatment, and reasons for dropping out; measure completeness of outcome data. Potential Impact Currently there is insufficient evidence that current rehabilitation strategies improve walking in people who are more than 6 months post-stroke. We propose a novel intervention, Visual Cue Training, that builds on previous evidence both from our laboratory and from the wider literature, that potentially offers a more effective means of training walking in this group. This study lays the groundwork for a definitive trial of VCT. If the intervention is found to be more effective than conventional overground walking therapy in the future trial, it could be delivered throughout the NHS and improve community ambulation and thus independence and quality of life after stroke.


Research activity codes: 6.7 PHYSICAL
Health categories: STROKE
Title: Evaluation of Stroke Services in Anglia Stroke & Heart Clinical Network using patient-centred approach
Funder: Department of Health (England)

Abstract: Background Stroke is the third leading cause of death in developed countries and the leading cause of long-term disability worldwide. A series of national stroke audits in the UK highlighted the differences in stroke care between hospitals. Recent initiatives by the Department of Health have aimed to improving stroke care in the UK, including Stroke Clinical Networks to support NHS trusts in England. This study will examine how variations in provision of NHS stroke services in the East of England affect patient outcomes and health care costs. Aims The proposed study aims to describe variation in outcomes following stroke and to identify the characteristics of services that are associated with better outcomes, after accounting for case mix differences and individual prognostic factors. This observational study will identify areas of clinical practice which merit future randomised controlled trials (RCTs) to identify best practice in improving stroke care which will be of maximum benefit to patients, NHS and society. We also aim to obtain preliminary data to estimate sample sizes and conduct value of information analyses to design future pragmatic RCTs of innovative ways of delivering stroke care. Plan of Investigation We propose a 3 year cohort study in eight acute NHS trusts within East of England, with at least one year of follow-up after stroke. The study population will be a systematically selected random sample of patients admitted with stroke during the study period, recruited within each hospital. We will collect individual patient data on prognostic characteristics, health care received, outcomes and costs of care and we will also record relevant characteristics of each provider organisation. The determinants of one year outcome including patient reported outcome will be assessed statistically with proportional hazards regression models. Self (or proxy) completed EuroQol (EQ-5D) questionnaires will measure quality of life at baseline and follow-up for cost utility analyses. Potential Impact This study will provide observational data about health service factors associated with variations in patient outcomes and health care costs following hospital admission for acute stroke. This will form the basis for future RCTs by identifying promising health service interventions, assessing the feasibility of recruiting and following up trial patients, and provide evidence about frequency and variances in outcomes, and intra-cluster correlation of outcomes, for sample size calculations. The results will inform clinicians, public, service providers, commissioners and policy makers to drive further improvement in health services which will bring direct benefit to the patients.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: STROKE
Title: Understanding and measuring the burden of supported self-care rehabilitation (SS-CR) in stroke
Funder: Department of Health (England)

Abstract: After physiotherapy ends, rehabilitation 'work' is passed to people with stroke and their families, who often feel overwhelmed. Supported Self-Care Rehabilitation (SS-CR) interventions (telerehabilitation, assistive-technologies, exercise-prescription) are being developed but with limited consideration of the burdens they generate. Excessive burdens may reduce people’s capacity to cooperate in care and limit recovery. Understanding ‘rehabilitation burden’ is vital to providing appropriate support and developing minimally-disruptive interventions. This research will review the literature, conduct interviews, develop a model of SS-CR and design a questionnaire to measure the burden of SS-CR with the aim of minimising the burden of future stroke rehabilitation interventions.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;6.7 PHYSICAL
Health categories: STROKE
Title: vCJD Tissue Infectivity Studies
Funder: Department of Health (England)

Abstract: Background latrogenic transmission of CJD via neuronal tissue has been described both in experimental models and in a clinical setting. The risk of transmission via other tissues is less well described. Whilst variant CJD infectivity levels have been defined in tonsils and spleen (Bruce et al. 2001), those in other organs and tissues are not known. This project aims to assess the levels of infectivity in a further twenty tissues and organs identified as posing a risk for the iatrogenic transmission of variant CJD. The project will use tissue samples collected by the National CJD Surveillance Unit from patients with vCJD and evaluate their ability to generate infection in RIII mice over an extended period of incubation of 600 days (as per Bruce et al. 2001). Infection will be assessed in life by monitoring for recognised clinical signs and confirmed post mortem by histopathological examination of brain tissue sections. Animals will be housed in purpose-built accommodation on the Porton site operated by PrimaTec Ltd on behalf of the Department of Health. All breeding, husbandry, procedural work, clinical monitoring, histology and study management will be carried out by HPA staff. The project builds upon existing capabilities and programmes of work at the HPA Centre for Emergency Preparedness & Response, Porton Down employing assays and models for prion disease and in the handling of infectious agents at ACDP CL3. The NCJDSU under the direction of Professor James Ironside will provide the tissues and variant CJD expertise required, while Professor Moira Bruce, Neuropathogenesis Unit, Institute for Animal Health, Edinburgh will supply the expertise regarding the conduct and comparability of the animal studies. Aims HISTORIC PROJECT - Entire abstract transferred from the previous database into the [Scientific summary background] field of this database. Plan of Investigation HISTORIC PROJECT - Entire abstract transferred from the previous database into the [Scientific summary background] field of this database. Potential Impact HISTORIC PROJECT - Entire abstract transferred from the previous database into the [Scientific summary background] field of this database. Policy Relevance Creutzfeldt-Jakob Disease (CJD) is a fatal progressive neurodegenerative disorder for which no therapy is currently available. The exposure of a large proportion of the UK population to potential infection with the prion agent responsible for BSE and the subsequent emergence of a novel variant of the disease, variant CJD, has raised significant public health issues. The potential for istrogenic transmission of vCJD requires continuedresearch to assess the risk associated with particular tissues and surgical procedures.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: STROKE
Title: Is intermittent exercise better for vascular repair in postmenopausal women
Funder: The Dunhill Medical Trust

Abstract: Following the menopausal transition the risk of ischemic stroke doubles every 10 years in women and it appears that much of this risk is associated with decreasing oestradiol concentrations. Unfortunately, oestrogen replacement therapy has been associated with an increased risk of thromboembolytic events and breast cancer and its use thus curtailed. Endothelial progenitor cells (EPC) are known to be involved in vascular repair and have been seen to be significantly reduced in age related white matter changes and stroke. We have seen improved EPC number and function following acute intermittent exercise in 5 postmenopausal women. This exercise is deemed to be far more achievable than the normally prescribed moderate intensity continuous exercise. Thus the purpose of this research would be to evaluate the effect of 16 weeks of intermittent versus continuous exercise training upon EPC number and function in healthy postmenopausal women aged 45-60 years.


Research activity codes: 6.7 PHYSICAL
Health categories: STROKE
Title: Supporting people living with stroke
Funder: Division for Social Care and Health Research (Wales)

Abstract: In the UK, stroke is the single most common cause of severe disability. Stroke happens when the blood supply to the brain is severely reduced causing brain damage. The consequences of stroke can be devastating, and can affect every aspect of a sufferer’s life. For this reason, people often use of a wide range of services provided by health and social care organisations and charities. Families also play a key role in supporting people living with stroke, but they also need to be supported, for example through assessment of their needs. Evaluations of the experiences of people and families affected by stroke have highlighted that this support needs to be improved. The aim of this research is to develop and test a framework that outlines what all staff need to know and do to support families affected by stroke. The framework will apply across all organisations and staff that provide this support. The North Wales Stroke Forum (a network of staff from across health and social care and charities) will play an active part in guiding this research, and ensuring that the findings are used. This study is divided into three parts. Firstly, and to develop the framework, a comprehensive review of the literature will be conducted to identify good practice. People and families affected by stroke will be interviewed to identify their views. Secondly, a group of social, health and voluntary workers will be supported to agree the detail of the framework. Relate (a national charity working with families in crisis) will also be consulted. The final phase of the research will test the implementation of the framework in two settings or services which support families affected by stroke. Research findings will be widely disseminated, and links made to education, training and policy initiatives to ensure they are used.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: STROKE
Title: Implementing evidence within the Welsh Care Home sector: investigating the impact of a guideline for stroke care
Funder: Division for Social Care and Health Research (Wales)

Abstract: Stroke remains a major cause of disability in Wales. Two thirds of all strokes occur after 65 years of age and the loss of physical functioning following a stroke can be devastating. Many people who survive a stroke are discharged from hospital to care homes. People living with stroke in care home settings often do not receive the rehabilitation they should. This means they may not be as independent as they could be, and may mean they may not be able to get home. Knowing what rehabilitation should be delivered in care homes is difficult to determine. This research will use a new method of identifying evidence for stroke rehabilitation that may work in care home settings. This will be used to plan a guideline of what rehabilitation can be delivered by different members of care home staff. Getting staff to use evidence is difficult. We will use a new framework that explains how implementation works, and see if it applies to the care home sector. As there are few studies of implementation in this setting, in addition to improving stroke care, this research will help us know more about how care homes can be supported to implement evidence-based practice.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: STROKE
Title: Thrombolysis for acute ischaemic stroke
Funder: Chief Scientist Office (Scotland)

Abstract: About 150000 people have a stroke each year in the UK: a third die a third are dependent and only a third return to independent life. Most strokes are due to thromboembolic occlusion of an artery. Thrombolytic drugs dissolve the thrombus open the artery and improve longterm independent survival after stroke but with an increased risk of bleeding into the brain and death soon after treatment. Thrombolysis is the most effective treatment for stroke by a large margin of considerable interest to patients but it remains highly controversial. Concerns about its effects and which patients should be treated persist. Usage in many countries still varies widely. This review is one of the oldest continuously sustained Cochrane Reviews the highest cited Stroke Review in 2012. It is the only place where comprehensive data on all thrombolytic drugs in stroke are assessed. It was last updated in 2009. The new update would nearly double the current data (at least six new trials c4000 patients) and will increase reliable information on the effect of age time to treatment risk factors for haemorrhage and failed treatment.This update will influence thrombolysis prescribing and guidelines as it has done several times in the past.


Research activity codes: 6.2 CELLULAR AND GENE THERAPIES
Health categories: STROKE
Title: Interventions for deliberately altering blood pressure in acute stroke
Funder: Department of Health (England)

Abstract: Stroke is common (1:6 people 140000 per annum in UK) devastating in outcome (30% dead 30% dependent by 12 months) and expensive (5% of NHS spend). 75% of patients with acute stroke have high blood pressure (BP) an independent risk factor for poor outcome. Several small trials and only 3 medium sized ones (IMAGES n=2589 SCAST n=2029 INTERACT-2 n=2839) have assessed the effect of lowering BP in acute stroke giving mixed results. Variation in results may relate to stroke type; type timing and administration route of intervention; and magnitude of BP lowering. As a result UK clinical practice varies between doing nothing to intensive BP lowering; stroke physicians and the Nottingham Stroke Consumer Group rate highly the question of how to manage BP in acute stroke. The proposed update to this Cochrane review will incorporate the latest trials including SCAST INTERACT-2 and two to be presented in early 2014 (FAST-Mag n=1700 MRC/EME-funded ENOS n=4000); altogether the review will add >10 trials and >11000 patients to the existing 12 trials and 1153 patients. If lowering BP improves outcome then the intervention is easy and inexpensive to commission and administer will change guidelines and will reduce the costs of rehabilitation and institutionalisation.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: STROKE
Title: Inflammation and cerebrovascular proteolysis: potential mechanisms underlying the deleterious impact of obesity on stroke.
Funder: Wellcome Trust

Abstract: A stroke happens when the blood supply to part of the brain is stopped, usually due to a blockage in an artery that carries blood to the brain. In the UK, someone has a stroke every 5 minutes, almost a third of patients die, and many more are seriously disabled. It is therefore very important to understand why and how strokes happen in order to develop ways to prevent or treat them. Obese people are more likely to get strokes, and if they do they will probably do much worse, although we really d o not know why. We have discovered that strokes in obese mice are worse, and bleeding in the brain is more likely. This may be due to the immune system, which normally protects us from bugs and disease. In obesity the immune system does not work properly, and can disrupt the blood vessels in the brain, which makes bleeding more likely during a stroke. We will examine how the immune system and the blood vessels change after a stroke in obese mice, and try and block any changes we find in the hope of preventing the bad effects of obesity on stroke.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: STROKE
Title: Blood brain barrier dysfunction and cerebral small vessel disease
Funder: Wellcome Trust

Abstract: Cerebral small vessel disease causes 25% of all ischaemic strokes and contributes to cognitive decline and dementia. The pathogenesis is poorly understood, with debate about the roles of atherothromboembolism/ischaemia and endothelial dysfunction/blood-brain barrier leak, progress being hampered by scant, often late-stage, histology and lack of suitable experimental models. We developed validated methods for magnetic resonance imaging of cerebral microvessel abnormalities, which showed that pati ents with lacunar stroke had generalised, subtly increased blood-brain barrier permeability in white matter with increased contrast agent leakage into the CSF, compared to atherothromboembolic (i.e. cortical) stroke control patients. Our aim now is to determine whether blood-brain barrier dysfunction predates progression of clinical/imaging features of cerebral small vessel disease and therefore might be causative. We will recruit 250 patients with lacunar stroke and mild cortical stroke control s, perform careful baseline clinical characterisation and brain imaging, then follow-up at one year to assess whether recurrent stroke and progressive worsening of imaging abnormalities are associated with blood-brain barrier permeability levels at baseline. All necessary facilities are available: strong track record in clinical stroke research, highly organised stroke service, sufficient patients, research scanner within a Clinical Research Facility, well-validated image acquisition and analysi s methods.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: STROKE
Title: Improving prevention of stroke by better understanding of existing risk factors and treatments.
Funder: Wellcome Trust

Abstract: This programme brings together four projects which aim to improve prevention of stroke by better understanding of which individuals are at highest risk, more effective use of existing medical investigations, and more detailed determination of the effects of existing treatments. In terms of understanding of risk, we will study patients with symptoms of possible minor stroke to determine whether their risk of major stroke is sufficiently high to warrant preventive treatment and we will study patie nts with definite minor stroke to develop a score to reliably identify those at high risk of major stroke. In terms of improving medical investigations, we will determine whether more detailed scans of the brain and its blood vessels and prolonged monitoring of heart rate and blood pressure can improve our understanding of the cause of stroke. In terms of treatments, we will study the risk of bleeding events on aspirin and the effect of aspirin on risk of cancer, and we will determine the extent to which the reduction in stroke risk with use of drugs to lower high blood pressure is due, at least in part, reduced variability in blood pressure as well as a reduction in the average level.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING
Health categories: STROKE