NIHRDataInsights/HRCSData huggingface dataset:
Title: Developing a model for improving communication and shared decision-making after severe stroke
Funder: Chief Scientist Office, Scotland

Abstract: Many people, prior to having a stroke, say that they would not want to survive with a severe disability. Many treatments after a stroke increase the likelihood of survival but with disability. Doctors are unable to accurately predict what the various outcomes after stroke are, and patients, therefore, do not make informed choices about their treatment. Knowledge of the likeliest outcome after stroke might alter decisions made by patients and families. The proposed research I will test statistical models to improve predictions of outcome after a severe stroke. Thereafter, by interviewing patients and families, I will establish what their preferences are for surviving with various outcomes, and the usefulness of providing them with predictions in how they make decisions. Outcomes and expected benefits My study will provide patients with predictions as to likely outcomes after stroke and help them make informed choices about preferred outcomes and appropriate treatments.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: STROKE
Title: We Walk: Development of a family-centred behavioural intervention to support regular outdoor walking after stroke
Funder: Chief Scientist Office, Scotland

Abstract: Stroke causes weakness, difficulty walking and disability. Many survivors have low levels of physical activity (PA) and fitness, raising risk of further stroke, cardiovascular disease, falls and poor mobility. Regular PA, including walking, reduces these risks. However even after attending PA programmes, survivors resume inactive lifestyles. Our earlier research examining barriers and facilitators to PA after stroke showed that survivors’ preferred PA is walking, and family, friends or peers and professionals, can provide supportive behavioural strategies for PA. This study extends our research to develop a family-centred and peer-support behavioural intervention to promote regular walking as part of survivors’ daily lives. We will systematically map identified behavioural barriers to a behavioural intervention development framework, to identify intervention components. We will consult participants - stroke survivors, their families, friends or peers, and appropriate health, social care and exercise professionals, to define the intervention, and appropriate delivery and training formats. Participatory Action Research will enable participants to try the intervention, providing ideas about adapting the intervention to match their needs. It will also inform us about how the intervention should be adapted for implementation in diverse contexts. We will apply for subsequent funding to test feasibility and effectiveness of this co-created intervention. Stroke causes weakness, difficulty walking and disability. Many survivors have low levels of physical activity (PA) and fitness, raising risk of further stroke, cardiovascular disease, falls and poor mobility. Regular PA, including walking, reduces these risks. However even after attending PA programmes, survivors resume inactive lifestyles. Our earlier research examining barriers and facilitators to PA after stroke showed that survivors’ preferred PA is walking, and family, friends or peers and professionals, can provide supportive behavioural strategies for PA. This study extends our research to develop a family-centred and peer-support behavioural intervention to promote regular walking as part of survivors’ daily lives. We will systematically map identified behavioural barriers to a behavioural intervention development framework, to identify intervention components. We will consult participants - stroke survivors, their families, friends or peers, and appropriate health, social care and exercise professionals, to define the intervention, and appropriate delivery and training formats. Participatory Action Research will enable participants to try the intervention, providing ideas about adapting the intervention to match their needs. It will also inform us about how the intervention should be adapted for implementation in diverse contexts. We will apply for subsequent funding to test feasibility and effectiveness of this co-created intervention.


Research activity codes: 5.7 PHYSICAL
Health categories: STROKE
Title: TRIMETHS - A novel urinary biomarker for minor stroke and transient ischaemic attack
Funder: Chief Scientist Office, Scotland

Abstract: We have identified a novel molecule ( a trimethylamine derivative, called TriMethS). It is found more commonly and at elevated levels in the urine of patients with stroke and transient ischaemic attack (TIA) compared to patients with suspected stroke who turn out to have an alternative diagnosis (called a “mimic”). About half of patients referred with suspected minor stroke or TIA have a mimic and sometimes it is hard to discriminate. It is important to make this distinction. People with minor stroke or TIA need preventative treatment to reduce the risk of a disabling stroke. We want to find out if TriMethS levels can be used to help us make the correct diagnosis of stroke/TIA. We will study levels of TriMethS in 300 people referred with suspected minor stroke and TIA. All particpants will be verified as having suffered minor stroke/TIA or a mimic. We will assess whether knowledge of TriMethS levels improves diagnostic accuracy and whether levels are related to long term outcomes. We also perform further experiments to elucidate the role of TriMethS and will begin developing simple methods for the measurement of TriMethS in the NHS.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: STROKE
Title: What is the best brain imaging strategy for patient's with suspected minor stroke or transient ischaemic attack (TIA)?
Funder: Chief Scientist Office, Scotland

Abstract: People frequently present to hospital, GPs or stroke clinics with symptoms of minor stroke or transient ischaemic attack (TIA). About half of these people are eventually diagnosed with stroke or TIA, and they are at high risk of a subsequent major stroke. However, those people with symptoms who are not diagnosed with stroke or TIA are also at risk of a major stroke in the future. More detailed brain imaging – with magnetic resonance (MR) scanning – could identify those at the highest risk, who merit treatment to prevent stroke. However, MR scans are expensive, in great demand for other conditions, and it is uncertain whether they increase the number of correctly diagnoses compared to current methods. In patients with suspected stroke or TIA, we will test whether MR brain scanning is better that CT for the diagnosis of TIA/stroke, and for the identification of those at highest risk of future stroke. This could lead to faster emergency department diagnosis and better targeting of treatment to prevent stroke.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: STROKE
Title: Whole-brain Human ischaemic stroke perfusion and extended re-canalisation (WHISPER)
Funder: Chief Scientist Office, Scotland

Abstract: Ischemic stroke is caused by a blood clot blocking an artery in the brain. “Clot-busting” treatment is effective if started within 4.5 hours after stroke onset, and clot removal (“thrombectomy”) up to 6 hours after symptoms appear. Scans of brain blood flow can distinguish irreversibly damaged brain tissue from tissue that is still rescuable. Recent studies show that clot removal may be useful for longer periods, maybe up to 24 hours, in some patients with favourable blood flow scans. However, it is not known what proportion of people have significant amounts of rescuable brain tissue, what factors predict its loss, or the speed with which tissue becomes permanently damaged. We wish to investigate people within the first 24 hours after onset of stroke symptoms with blood flow scans to investigate how many people are affected, and to extend our previous investigations into what factors determine the development of irreversible damage. In particular, we will explore the role of raised blood sugar in preventing the opening of blood vessels that maintain some flow to the tissue that is at risk.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: STROKE
Title: Timing the ischaemic stroke by quantitative 1H magnetic resonance imaging
Funder: Dunhill Medical Trust

Abstract: One in 4 ischaemic stroke patients are ineligible for recanalization due to unknown onset time. To increase the number of patients for recanalization, objective methods to quickly determine stroke duration and brain tissue status are urgently needed. We have developed and tested 1H MRI protocols based on quantitative relaxation times that provide accurate timing of stroke in preclinical models of stroke. These techniques outperform the proposed T2-FLAIR/diffusion MRI mismatch both in accuracy of timing and sensitivity to ischaemia. We are currently performing a study in Bristol to implement to the MRI protocol to evaluation of acute stroke patients. We propose to (a) translate the 1H MRI protocol to stroke patient stratification and (b) to develop automated post-processing routines to determine stroke duration and to reveal volumes of salvageable tissue from a multi-parametric MRI. The quantitative MRI protocol is expected to impact stroke patient outcome by maximising the use of recanalization therapy.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: STROKE
Title: Low-cost personalised instrumented clothing with integrated FES electrodes for upper limb rehabilitation
Funder: Medical Research Council

Abstract: Stroke is the second highest cause of disability in the UK. Stroke survivors receive rehabilitation at home, but about 60% of Persons with Stroke (PwS) fail to regain upper limb function. Clinical evidence supports the use of Functional Electrical Stimulation (FES) to restore upper limb function in PwS. However, existing commercial FES devices are not highly effective due to significant limitations: 1) Too few muscles are stimulated. 2) Their large non-selective electrodes cause imprecise movement. 3) Imprecise movement also occurs because the FES controller is not adjusted using movement sensor feedback. 4) Devices are bulky and expensive, or difficult to set-up. In previous research, we demonstrated the concept of screen printing fabric-based FES; in this project we further address the above limitations by combining recently developed technologies to implement the following advantages: 1) Electrode arrays printed directly on fabric, using bespoke inks, will provide high muscle selectivity scalable to all the appropriate limb muscles. 2) Direct write printing and 3D scanning will allow rapid fabrication of low cost personalised designs matching the users' physiology. 3) Intelligent control using movement sensors will automatically adjust the FES to enable precise functional movements (e.g. repositioning objects). Clothing is defined in this project as any fabric-based item (e.g. cuff/armband, sleeve) worn on the body. The device specification will be defined by an Expert User Group (EUG) consisting of PwS, carers, FES engineers and healthcare professionals. The FES array and control/sensor technologies will be refined to meet this specification (milestone 1). These components will be integrated into candidate clothing designs with wireless electronics and training software, and evaluated (milestone 2). This project delivers a practical, comfortable, high performance solution for cost effective rehabilitation.


Research activity codes: 5.7 PHYSICAL
Health categories: STROKE
Title: An exploration of the application of non-invasive cerebellar stimulation in the neurorehabilitation of dysphagia after stroke
Funder: Medical Research Council

Abstract: In this proposal we will explore the feasibility and effectiveness of non-invasive cerebellar stimulation to enhance motor plasticity and swallowing recovery after stroke. Such an approach has mainly been examined in animals where direct cerebellar stimulation has showed enhancement of limb motor evoked potentials and enhanced motor recovery after focal cortical ischemia. By comparison, we have shown that the human cerebellum when stimulated with single magnetic pulses can strongly facilitate corticobulbar pharyngeal projections in humans. More recently we have identified the most relevant frequency of stimulation of the cerebellum (10Hz) that can produce longer term excitation in the human swallowing motor system. Our objectives are to test the following hypotheses: Cerebellar stimulation will - i. Reverse the brain inhibition and behavioural dysfunction following a virtual lesion model of disrupted swallowing in healthy brain; ii. Reduce the degree of aspiration in acute dysphagia after brain damage (stroke). The studies will utilise transcranial magnetic stimulation (TMS), motor evoked potentials and swallowing evaluations (i.e instrumental exams) in order to answer the questions below: Question 1: Can cerebellar stimulation of either cerebellar hemisphere reverse swallowing dysruption following unilateral suppression of swallowing motor cortex? We will use a virtual lesion approach in healthy participants in a randomised study of cerebellar stimulation to determine the optimal side of stimulation. Question 2: Can cortical stimulation produce short term improvements in swallowing after acute stroke and what is the optimal stimulation regimen for longer term improvement? This part of the proposal will include a short-term feasibility RCT of a single session of cerebellar stimulation on dysphagic stroke followed by a small dose ranging phase IIa RCT of 2 different regimens of treatment (vs. sham) with changes in aspiration as the primary outcome.


Research activity codes: 5.7 PHYSICAL
Health categories: STROKE
Title: Identification of excitability profiles following acquired brain injury: A biomarker of neuronal health
Funder: Medical Research Council

Abstract: Aims: 1) To identify excitability profiles of membrane depolarisation and hyperpolarisation as a surrogate marker of neuronal health following acquired brain injury. 2) To ascertain the effect of spreading depolarisations (SD) on the viability of neurons. 3) To identify excitability profiles that predict harmful SDs 4) To characterise the excitability profiles associated with systemic variables, intracerebral variables and clinical interventions. Methods: Twenty-five brain injured adults will be recruited. Intraparenchymal and subdural platinum electrode arrays (Ad-Tech, USA) will be placed in penumbral tissue at conclusion of emergency surgery. Subdural electrodes will be used to identify spreading depolarisations and intraparenchymal electrodes to record Compound Bundle Action Potential (CBAP) responses. CBAPs will be acquired using Qtrac (Inst. of Neurology) to control delivery of stimuli via a stimulator (DS5; Digitimer, UK). Parameters will be kept within safe limits. Stimulus-response: A CBAP of target amplitude (TA) will be set by recording a stimulus-response curve. Stimulus required to evoke TA is referred to as 'absolute threshold'. Absolute Threshold will be tracked by automatically adjusting stimulus intensity up or down depending on whether a recent CBAP was lessor or greater than TA. Recovery Cycle of excitability (RC) will be obtained by comparing absolute threshold with the stimulus required to evoke TA after a sequence of afterpotentials have been set in motion by a previous stimulus given at a series of interstimulus intervals (ISI). The superexcitable and late subexcitability phase of the RC will be tracked by cyclically delivering stimuli (0.2Hz) with an ISI of 20ms and 100ms, respectively. Opportunities: Real-time detection of changing neuronal health status provides a unique opportunity to limit the amount of secondary damage that occurs after an acute brain injury, thereby greatly improving patient outcome.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: STROKE
Title: Pathomolecular mechanisms of intracerebral haemorrhage: functional analysis of collagen IV variants.
Funder: Medical Research Council

Abstract: 15% of stroke cases are due to intracerebral haemorrhage (ICH), and there is a need for specific treatments, indicating increased knowledge of its genetic and pathomolecular basis is required. Collagen IV is an extracellular matrix component that provides structural support to blood vessels and affects cell behaviour. Rare mutations in COL4A1 or COL4A2 (collagen IV alpha chain 1/2) cause familial ICH and importantly we have now established common COL4A2 variants are a risk factor for sporadic ICH, but their prevalence and disease mechanism are unknown. Here we will use sequence analysis of a large cohort of sporadic deep ICH cases to establish the identity and prevalence of novel rare mutations and common variants in COL4A1/4A2 in ICH. Functional analysis of selected identified common variants and novel rare mutations (e.g. predicted to enhance or decrease expression, alter protein composition) will be used to address our hypothesis that ER stress is a shared mechanism between sporadic and familial ICH: ER stress results from intracellular retention of secreted proteins, can be pathogenic when chronic and be modulated by FDA-approved compounds. We will address this using a combination of genome editing, molecular cell biology and complementary -omics approaches, and in so doing provide unparalleled insight into the nature of compositional matrix defects and ER stress response, and their effects on downstream cellular pathways, leading to endothelial cell dysfunction. Parallel analysis of "ER stress only" models will inform on the relative contribution of ER stress. Importantly, the relevance of identified mechanisms will be verified in brain samples of mice and patients with ICH. This will transform our knowledge of the genetic and pathomolecular basis of ICH in the general population, inform on patient stratification based on disease mechanism, and highlight future therapeutic avenues including the potential repurposing of FDA-approved compounds.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: STROKE
Title: MICA: Efficacy and safety evaluation of AZD1236 (Matrix metalloproteinase 9 & 12 inhibitor) in experimental stroke
Funder: Medical Research Council

Abstract: An urgent need exists for new acute stroke therapies. The only approved treatment for ischaemic stroke is recombinant tissue plasminogen activator (t-PA), but the benefits of t-PA are limited by a short treatment time window, low rates of reperfusion, and the potential for haemorrhagic transformation. We, and others, have shown that matrix metalloproteinases (MMPs), especially MMP-9 play a key role in the cascade of pathological processes that are activated by cerebral ischaemia. These processes include disruption of the blood brain barrier (BBB). This exacerbates brain oedema and potentiates ischaemic cell injury leading to widespread cell death. Moreover, MMP-9 increases risk of haemorrhagic transformation after thrombolysis resulting in poorer outcomes. Published data have shown that inhibition of MMP-9 is highly protective in experimental stroke. Recent studies also suggest that MMP-12 may play a deleterious role in stroke directly, and by also enhancing MMP-9 activity. Since both MMP-9 and MMP-12 play important (and potentially synergistic) roles in stroke, inhibition of both MMPs could be a powerful treatment for acute stroke. In collaboration with AstraZeneca, we advance a series of proof of concept studies to evaluate the efficacy and safety in experimental stroke of a novel MMP-9 and MMP-12 inhibitor, AZD1236 which was originally developed for the treatment of chronic obstructive pulmonary disease and is a phase 2-ready compound for an acute indication such is stroke. Using mouse middle cerebral artery occlusion (MCAO) models, we will: 1. Determine the pharmacokinetics, efficacy and safety of AZD1236 in a number of experimental models of stroke 2. Determine the effect of AZD1236 on MMP expression and activity in brain and serum 3. Determine the effect of AZD1236 on BBB integrity using histology and 7-T MRI Successful completion of these studies will establish whether further preclinical development of this compound is warranted.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: STROKE
Title: TREATS-AF:Educational intervention vs usual care on anticoagulation therapy control based on a SAMe-TT2R2 score-guided strategy
Funder: Medical Research Council

Abstract: The proposed research provides a major sustainable development in the management of patients in Thailand with atrial fibrillation (AF) who require life-long oral anticoagulation. We aim to conduct a prospective individually-randomised-controlled trial of warfarin-naïve Thai AF patients to evaluate the use of a clinical prediction score to stratify treatment modalities in relation to patient response to anticoagulation with warfarin. Outcomes would be measured by the time in therapeutic range (TTR, primary outcome) compared with usual care. Second, we aim to assess the cost-effectiveness of an educational-behavioural intervention, to perform cross-cultural adaptation of the intervention and translation, validation of the translated patient knowledge questionnaire, and subsequent analysis. Third, we intend to perform a qualitative sub-study to investigate patient satisfaction and acceptance of this practical intervention to improve anticoagulation management. Finally, we will explore the cost-effectiveness of the intervention. This study could potentially provide an inexpensive, easy and practical approach that can be readily integrated into the existing Thai health service to improve the health of those patients with AF, thus optimising anticoagulation management with warfarin, and reducing both their risk of stroke and associated death. This unique collaboration would also facilitate development of novel patient-centred tools (e.g. Thai-version of the educational intervention, Thai-language questionnaires, etc.) that can be sustainably integrated into existing Thai healthcare services. This proposal identifies a key approach to improve health and welfare by reducing the risk of complications arising from poor anticoagulation control (stroke/major bleeding) and will support capacity building in trial methodology helping develop the clinical research infrastructure beyond the proposed study.


Research activity codes: 3.1 PRIMARY PREVENTION INTERVENTIONS TO MODIFY BEHAVIOURS OR PROMOTE WELL-BEING;4.4 POPULATION SCREENING
Health categories: STROKE