NIHRDataInsights/HRCSData huggingface dataset:
Title: Reconstructing sentence processing in aphasia
Funder: Stroke Association

Abstract: Aims: We address two questions: (1) Is a new intervention for sentence processing problems in aphasia more effective than usual care; (2) Does non-invasive transcranial direct current stimulation (tDCS) enhance outcomes. Background: Everyday verbal communication requires that speakers and listeners process not just single words but multiword utterances. The neurocognitive mechanisms underpinning these processes are disrupted in aphasia. While there has been substantial progress in understanding the neural basis of single word processing and development of therapies for lexical disorders, progress in understanding and treating disorders of sentence-level processing has been slower. We apply a new theoretical framework – Construction Grammar – to understand and treat aphasic sentence processing impairments. Methods: We will recruit three groups of participants with aphasia and test a novel computerised multi-stage therapy for sentence comprehension and production deficits, determining its effectiveness in combination with tDCS. Post-intervention maintenance assessment will determine longer-term impact of interventions. Expected outcomes: (1) Sentence therapy is more effective than usual care; (2) Outcomes of sentence therapy are enhanced by tDCS; (3) Improvements are evident in functional use of language; (4) Treatment effects are maintained after an 8-week maintenance period. Overall aim: inform and innovate therapies for sentence processing in aphasia.

Lay abstract: Aims: We address two questions: (1) Is a new intervention for sentence processing problems in aphasia more effective than usual care; (2) Does non-invasive transcranial direct current stimulation (tDCS) enhance outcomes. Background: Everyday verbal communication requires that speakers and listeners process not just single words but multiword utterances. The neurocognitive mechanisms underpinning these processes are disrupted in aphasia. While there has been substantial progress in understanding the neural basis of single word processing and development of therapies for lexical disorders, progress in understanding and treating disorders of sentence-level processing has been slower. We apply a new theoretical framework – Construction Grammar – to understand and treat aphasic sentence processing impairments. Methods: We will recruit three groups of participants with aphasia and test a novel computerised multi-stage therapy for sentence comprehension and production deficits, determining its effectiveness in combination with tDCS. Post-intervention maintenance assessment will determine longer-term impact of interventions. Expected outcomes: (1) Sentence therapy is more effective than usual care; (2) Outcomes of sentence therapy are enhanced by tDCS; (3) Improvements are evident in functional use of language; (4) Treatment effects are maintained after an 8-week maintenance period. Overall aim: inform and innovate therapies for sentence processing in aphasia.

Research activity codes: 6.6 PSYCHOLOGICAL AND BEHAVIOURAL;6.3 MEDICAL DEVICES
Health categories: STROKE
Title: Developing and evaluating pre-hospital interventions to improve emergency stroke care.
Funder: Stroke Association

Abstract: Background Paramedics are usually the first healthcare contact for stroke patients. Reducing the time to definitive treatment improves patient outcomes but UK paramedics spend longer with stroke patients than international peers. Telephone pre-notification reduces treatment delays in hospital. Remote specialist evaluation by telemedicine has the potential to further enhance acute care. Aims Aim one: To understand pre-hospital stroke timelines and develop an intervention to minimise pre-hospital times. Aim two: To demonstrate feasibility of a telemedicine pathway with understanding of barriers and facilitators. Methods Work package one will report pre-hospital times, identify interventions to reduce on scene times (OST) for stroke patients from the literature and survey and interview paramedics to explore pre-hospital timelines and to collect views on telemedicine. A target OST will be established using the Delphi method. An intervention to reduce OST will be developed. Work package two will collect views during focus groups with service providers and clinicians to define an emergency stroke telemedicine pathway, implementation toolkit and user training. This will be evaluated for feasibility and acceptability. Outcomes The outcomes of this study will be greater understanding of influences upon pre-hospital stroke care, an intervention to reduce OST and a telemedicine intervention for further evaluation.

Lay abstract: Background Paramedics are usually the first healthcare contact for stroke patients. Reducing the time to definitive treatment improves patient outcomes but UK paramedics spend longer with stroke patients than international peers. Telephone pre-notification reduces treatment delays in hospital. Remote specialist evaluation by telemedicine has the potential to further enhance acute care. Aims Aim one: To understand pre-hospital stroke timelines and develop an intervention to minimise pre-hospital times. Aim two: To demonstrate feasibility of a telemedicine pathway with understanding of barriers and facilitators. Methods Work package one will report pre-hospital times, identify interventions to reduce on scene times (OST) for stroke patients from the literature and survey and interview paramedics to explore pre-hospital timelines and to collect views on telemedicine. A target OST will be established using the Delphi method. An intervention to reduce OST will be developed. Work package two will collect views during focus groups with service providers and clinicians to define an emergency stroke telemedicine pathway, implementation toolkit and user training. This will be evaluated for feasibility and acceptability. Outcomes The outcomes of this study will be greater understanding of influences upon pre-hospital stroke care, an intervention to reduce OST and a telemedicine intervention for further evaluation.

Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: STROKE
Title: Increasing the experimental validity and utility of preclinical stroke research
Funder: Stroke Association

Abstract: Preclinical stroke research has not been as effective as it may be in delivering therapies for patients. Meta-analyses have suggested that most in vivo ischaemic stroke studies are at risk of bias and this is associated with overstatements in treatment effects. This evidence has focused on threats to internal validity, for which recent analyses suggest substantial improvements, and publication bias. I hypothesise that threats to other aspects of experimental validity are impeding successful translation. My aim is to use machine learning and text mining, and meta-research approaches to increase the validity of preclinical ischaemic stroke research. I will develop a living systematic review to comprehensively describe in vivo studies, to support ongoing improvements of reporting risk of bias items, and to facilitate ongoing assessments. I will investigate the limits of experimental validity more broadly, including the outcome measures used. I propose to facilitate and design multicentre studies to test hypotheses to improve experimental validity. I will also apply meta-research approaches to in vitro models of stroke, to enhance the validity of the entire spectrum of preclinical stroke. By trialling research improvement activities I will assess how to best effect positive change in preclinical stroke research based on up-to-date meta-research evidence.

Lay abstract: Preclinical stroke research has not been as effective as it may be in delivering therapies for patients. Meta-analyses have suggested that most in vivo ischaemic stroke studies are at risk of bias and this is associated with overstatements in treatment effects. This evidence has focused on threats to internal validity, for which recent analyses suggest substantial improvements, and publication bias. I hypothesise that threats to other aspects of experimental validity are impeding successful translation. My aim is to use machine learning and text mining, and meta-research approaches to increase the validity of preclinical ischaemic stroke research. I will develop a living systematic review to comprehensively describe in vivo studies, to support ongoing improvements of reporting risk of bias items, and to facilitate ongoing assessments. I will investigate the limits of experimental validity more broadly, including the outcome measures used. I propose to facilitate and design multicentre studies to test hypotheses to improve experimental validity. I will also apply meta-research approaches to in vitro models of stroke, to enhance the validity of the entire spectrum of preclinical stroke. By trialling research improvement activities I will assess how to best effect positive change in preclinical stroke research based on up-to-date meta-research evidence.

Research activity codes: 2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY)
Health categories: STROKE
Title: Repurposing existing compounds for the hyperacute treatment of ischaemic stroke
Funder: Stroke Association

Abstract: Stroke happens in the brain, and most often, it’s caused by a blood clot that blocks blood supply. This causes damage to the brain as it no longer gets the vital oxygen and nutrients that it needs to function and survive. There are medications to remove the blockage so that normal blood supply can return to the brain. But unfortunately, sometimes they don’t work and not all stroke patients can be treated with these medications. For example, the clot-busting medications currently used must be given to stroke patients in the first few hours after their stroke and sometimes people can’t get to a hospital quick enough. Early research has shown that a new medication could save brain cells and reduce damage to the brain by giving it vital supplies of energy. The medications are already used to treat other conditions in humans, so we know they are safe. They can also be given easily in an emergency, before a stroke patient even arrives at the hospital. But we need research to understand how this medication could help save the brain. This research will test if the new medication can save the brain, and reduce the effects of stroke.

Lay abstract: Stroke happens in the brain, and most often, it’s caused by a blood clot that blocks blood supply. This causes damage to the brain as it no longer gets the vital oxygen and nutrients that it needs to function and survive. There are medications to remove the blockage so that normal blood supply can return to the brain. But unfortunately, sometimes they don’t work and not all stroke patients can be treated with these medications. For example, the clot-busting medications currently used must be given to stroke patients in the first few hours after their stroke and sometimes people can’t get to a hospital quick enough. Early research has shown that a new medication could save brain cells and reduce damage to the brain by giving it vital supplies of energy. The medications are already used to treat other conditions in humans, so we know they are safe. They can also be given easily in an emergency, before a stroke patient even arrives at the hospital. But we need research to understand how this medication could help save the brain. This research will test if the new medication can save the brain, and reduce the effects of stroke.

Research activity codes: 5.1 PHARMACEUTICALS
Health categories: STROKE
Title: Bridging translational gaps to improve outcome from intracerebral haemorrhage
Funder: Stroke Association

Abstract: Haemorrhagic stroke accounts for around half of all deaths and disability due to stroke worldwide. Pessimism pervades current practice but there are interventions that improve outcome. New treatments are also needed and interleukin-1 receptor antagonist (IL-1Ra) is a promising anti-inflammatory treatment. The overarching aim of this programme is to improve outcomes for ICH patients by developing new anti-inflammatory treatments and optimising delivery of standard care. A phase II proof of concept trial of IL-1Ra will test whether it reduces cerebral oedema. A further small trial will test whether IL-1Ra enters the brain and alters the brain immune profile in patients undergoing minimally invasive haematoma evacuation. The clinical effectiveness of IL-1Ra will be tested in a large phase III clinical trial. The ABC care bundle reduced 30-day case fatality by a third at Salford and will be adopted nationally by NHS England. We will evaluate the clinical and cost effectiveness of implementing the ‘ABC’ hyperacute ICH care bundle. We will then investigate adaptations required for effective implementation of the ABC bundle in low- and middle-income countries, where much of the burden of ICH resides. An international roll-out of the ABC bundle will then be performed as a stepped wedge cluster trial.

Lay abstract: Haemorrhagic stroke accounts for around half of all deaths and disability due to stroke worldwide. Pessimism pervades current practice but there are interventions that improve outcome. New treatments are also needed and interleukin-1 receptor antagonist (IL-1Ra) is a promising anti-inflammatory treatment. The overarching aim of this programme is to improve outcomes for ICH patients by developing new anti-inflammatory treatments and optimising delivery of standard care. A phase II proof of concept trial of IL-1Ra will test whether it reduces cerebral oedema. A further small trial will test whether IL-1Ra enters the brain and alters the brain immune profile in patients undergoing minimally invasive haematoma evacuation. The clinical effectiveness of IL-1Ra will be tested in a large phase III clinical trial. The ABC care bundle reduced 30-day case fatality by a third at Salford and will be adopted nationally by NHS England. We will evaluate the clinical and cost effectiveness of implementing the ‘ABC’ hyperacute ICH care bundle. We will then investigate adaptations required for effective implementation of the ABC bundle in low- and middle-income countries, where much of the burden of ICH resides. An international roll-out of the ABC bundle will then be performed as a stepped wedge cluster trial.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: STROKE
Title: Neuro-Inflammation after Cerebral Haemorrhage in Edinburgh (NICHE)
Funder: Stroke Association

Abstract: SCIENTIFIC: Background – In animals with intracerebral haemorrhage (ICH), neuro-inflammation worsens peri-haematomal oedema (PHO) and outcome, and can be treated. However, in humans with ICH the activity, time course, and clinical significance of many neuro-inflammatory pathways are unknown. Aims – (1) Quantify a molecular pathway (Nrf2) and a cellular response (monocytes/microglia) that influence PHO and outcome in animals, are treatable with licensed drugs, but have not been studied in human brain tissue after ICH. (2) Describe the time course of PHO over two weeks after ICH in humans. (3) Design a randomised trial to treat neuro-inflammation after ICH. Methods – We will quantify and phenotype the time course and distribution of Nrf2 and monocytes/microglia, using unique existing banks of brain tissue donated by 76 patients who died within two weeks of ICH and 31 stroke-free controls who died suddenly. We will quantify the volume and growth of PHO on repeated computed tomography over two weeks and its association with candidate neuro-inflammatory pathways in a new study of 120 patients with incident ICH. Expected outcomes – Knowing which neuro-inflammatory processes are affected and the time course of PHO in humans will inform the design of a randomised trial of a licensed drug targeted at these processes.

Lay abstract: SCIENTIFIC: Background – In animals with intracerebral haemorrhage (ICH), neuro-inflammation worsens peri-haematomal oedema (PHO) and outcome, and can be treated. However, in humans with ICH the activity, time course, and clinical significance of many neuro-inflammatory pathways are unknown. Aims – (1) Quantify a molecular pathway (Nrf2) and a cellular response (monocytes/microglia) that influence PHO and outcome in animals, are treatable with licensed drugs, but have not been studied in human brain tissue after ICH. (2) Describe the time course of PHO over two weeks after ICH in humans. (3) Design a randomised trial to treat neuro-inflammation after ICH. Methods – We will quantify and phenotype the time course and distribution of Nrf2 and monocytes/microglia, using unique existing banks of brain tissue donated by 76 patients who died within two weeks of ICH and 31 stroke-free controls who died suddenly. We will quantify the volume and growth of PHO on repeated computed tomography over two weeks and its association with candidate neuro-inflammatory pathways in a new study of 120 patients with incident ICH. Expected outcomes – Knowing which neuro-inflammatory processes are affected and the time course of PHO in humans will inform the design of a randomised trial of a licensed drug targeted at these processes.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: STROKE
Title: NeuRestore: A NEW WAY OF ASSESSING POST-STROKE RECOVERY
Funder: Innovate UK

Abstract: **Public description** _NeuRestore_ complements, supplements and enhances existing stroke pathway knowledge with novel scientific techniques, to provide a clinical portal which is has a cloud-based database where clinical history, rehabilitation goals, and physiological assessments are collated, actioned and stored. This innovative system is centred around the needs of patients (who need speedy, certain and science-based determinations of their conditions) whilst clinicians require, standardisation (a gold-standard), objectivity and the ability (with confidence) to allocate what are becoming scarce financial resources, as the NHS gears up to deal/respond to Long COVID crisis.


Research activity codes: 8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: STROKE
Title: A Time-Saving Medical Device that Provides Automated Visualisation for interventional radiologists to Save Lives and Reduce Disabilities in Stroke Patient
Funder: Innovate UK

Abstract: Strokes in the UK incur annual costs of £26B and in the US $103B. Medical iSight (UK) Limited (MiS) is solving a significant, unmet, global need that could save lives and reduce disability for tens of thousands of UK patients each year, while generating a year-5 post- project revenue of £36M. The core project team from MiS includes Dr Christopher Johnson, Dr Philip Pratt, Dr Robert Merrifield and Ms Anna Schaffgotsch, a technology programme director, a medical software engineer, a medtech software CTO and a serial entrepreneur. MiS aims to simplify Mechanical Thrombectomy (MT), a relatively new and highly effective treatment for large vessel occlusive ischaemic Stroke. MT is a highly skilled and challenging procedure with some lasting 4-5 hours. In its Long Term Plan the NHS identified Stroke as a clinical priority and aims to make MT accessible to every suitable Stroke patient throughout the UK, developing up to 30 Stroke centres capable of delivering MT, nationally. Unlike the technology used by many competitors, this project aims to provide automated 3D to 2D image registration and catheter tip tracking within an extended reality environment (Microsoft HoloLens), making the procedure simpler and shorter (c30%), using established metrics to measure success.


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: STROKE
Title: Creativity in Stroke Aphasia
Funder: The British Academy

Abstract: Deficits of cognitive control are thought to contribute to chronic comprehension problems following stroke (in stroke aphasia, SA). This deficit is associated with difficulties focusing on relevant information and excluding distracting thoughts and behaviours during cognitive tasks. Our recent neuroimaging meta-analysis has found an association between cognitive control and creativity (such as thinking of alternative uses for everyday items). This is thought to aid our ability to dampen down pre-potent responses and switch between less common alternatives. However, there is evidence from patient literature that damage to these processes can enhance creativity, reportedly due to a release from the constraints which guide habitual behaviour. SA patients provide a unique opportunity to critically test the necessity of cognitive control in creativity. We hypothesise that involvement of cognitive control depends on task demands:- SA patients will perform well on tasks with limited demands, but show impairments where task demands are increased.


Research activity codes: 2.3 PSYCHOLOGICAL, SOCIAL AND ECONOMIC FACTORS
Health categories: STROKE
Title: Functional recovery from stroke during rehabilitation in the Cardiff Stroke Unit and home environment
Funder: Division for Social Care and Health Research (Wales)

Abstract: An important aim in rehabilitation is to restore walking activity to regain independence. To understand the stroke rehabilitation process thoroughly, better measurement tools are required that provide information about functional activities from the early stages to full recovery. Although various methods exist, direct continuous measurement of functional activity has been a difficulty. We developed a system using small wearable sensors and bespoke software to continuously detect physical activity and location and did successful pilot studies with healthy people. This study now aims to measure functional activity in patients recovering from stroke in a Regional Stroke Unit (RSU) and in the home environment. In a number of steps the system will be tested on patients for reliability and validity to optimise computerised determination of functional activities and interactions with others, particularly with healthcare staff. Fifty patients are then measured continuously throughout the rehabilitation period and until 6 months after their stroke as well as activities of the RSU healthcare staff. Changes in activity will be related to other factors measured at intervals until six months after the stroke. Based on this work, further studies are planned to compare different therapy approaches, rehabilitation environments and services to optimise stroke rehabilitation.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: STROKE