NIHRDataInsights/HRCSData huggingface dataset:
Title: Improving organ donor management and evaluating novel interventions
Funder: Department of Health and Social Care

Abstract: Increase the number and improve the quality of transplantable organs from deceased donors through improved organ donor management and novel interventions in deceased donors, in line with the NHSBT Transplantation 2020 Vision Retrospective analysis of the currently collected NHSBT UK DCD donor dataset on the events from withdrawal of life supporting treatment to organ retrieval will be performed on up to 1,500 DCD donors (collected routinely from 2012-15). The analysis will include available demographic and limited physiological data and will highlight areas where more information is required and help set future hypotheses Observational cohort study of 50 DCD donors (in Cambridge and Newcastle) to determine in detail the physiological and metabolic events that accompany the agonal period, and to identify putative biomarkers and targets for intervention to protect organs from severe injury. Evaluate Normothermic Regional Perfusion (NRP) of abdominal organs and Normothermic Antegrade Perfusion (NAP) of the heart in DCD donors. Effectiveness of pharmacological intervention during NRP to improve organ function will be evaluated. This will include a series of pilot studies of mitochondria-targeted therapies (MitoQ and MitoSNO) and other agents that may ameliorate ischaemia reperfusion injury. Within the first 2 years we will also undertake a proof of principle study of NAP of hearts in 10 DCD donors


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING
Health categories: CARDIOVASCULAR
Title: Evaluating exome sequencing as a tool for diagnostic genetic testing and disease gene discovery in the NHS: A case study using Hypertrophic Cardiomyopathy (HCM).
Funder: Health Education England

Abstract: Exome sequencing is a powerful new tool which could transform NHS genetic testing services. However, further studies are needed to ensure that it produces the high quality results required in a clinical laboratory. I aim to develop an Exome sequencing procedure suitable for use in the NHS. I will then use this procedure to look for new disease causing genes in a group of patients with Hypertrophic Cardiomyopathy (HCM), a common inherited heart condition.Through this research I aim to develop a more sensitive genetic test for HCM; this will improve diagnosis and enable more effective patient management.

Lay abstract: Exome sequencing is a powerful new tool which could transform NHS genetic testing services. However, further studies are needed to ensure that it produces the high quality results required in a clinical laboratory. I aim to develop an Exome sequencing procedure suitable for use in the NHS. I will then use this procedure to look for new disease causing genes in a group of patients with Hypertrophic Cardiomyopathy (HCM), a common inherited heart condition.Through this research I aim to develop a more sensitive genetic test for HCM; this will improve diagnosis and enable more effective patient management.

Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CARDIOVASCULAR
Title: 2017 Doctoral Fellowship: Improving engagement with Cardiac Rehabilitation using innovative approaches developed through Experience Based Co-Design
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: Background: Cardiovascular disease is the biggest killer in Europe, with 10 people every day suffering a Myocardial Infarction (Heart Attack) in Northern Ireland. The costs to the individual and society are high in terms of treatment costs, economics and human suffering. Cardiac Rehabilitation (CR) is an effective, well established programme that reduces mortality by 20% following an MI. Despite proven efficacy, uptake of CR in Northern Ireland is dismal at 32% - well below the UK average of 45%. Aim: To explore the current challenges of Cardiac Rehabilitation and using Experience Based Co-Design develop innovative approaches that maximise patient engagement. Methods: Experience Based Co-Design (EBCD) involves gathering experiences from patients and staff to co-design services together in partnership. EBCD will be used along with latest evidence to develop innovative approaches to CR. 1. Structured Literature Review - to evaluate existing approaches to CR delivery and to identify which intervention strategies are most effective and why. 2. Focus Groups – separate small group discussions using the theoretical domains framework with staff (n=25) and patients who have attended CR (n=50) to explore strengths, weaknesses and challenges of existing CR. 3. Telephone Interviews - with patients not attending CR despite being offered it (n=50) to identify barriers to attendance and conversely what would facilitate attendance. 4. Feedback and development - using the data from Phases 1-3 the Steering group will propose innovative approaches for the delivery of CR 5. Workshop (n=50) with patients and staff to “experience” the identified innovative approaches and provide feedback. Outcome: Innovative methods of delivering CR will be identified and will proceed to further testing beyond this study. The study will provide evidence of the benefit of working with patients to develop their service.


Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES;7.1 INDIVIDUAL CARE NEEDS
Health categories: CARDIOVASCULAR
Title: Interactions between fluid dynamics and biological function in microvascular disease
Funder: Royal Academy of Engineering

Abstract: The main aim of my fellowship research is to establish the role of blood flow in thepathogenesis of microvascular diseases, with a focus on diabetic retinopathy. Theendothelial cells that line all vessel walls respond to mechanical cues from blood flow, inorder to regulate blood flow and fluid and solute transport across the vessel wall. Theseprocesses become dysfunctional in microvascular diseases. However, the role of fluiddynamics in the disease progression is not well understood. To address this, my researchaims to establish greater knowledge of i) the forces that blood applies to the vessel walland the effects of changes to blood properties observed in disease, ii) the response ofmicrovascular endothelial cells to biological and mechanical cues and the relativeimportance of each.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: CARDIOVASCULAR
Title: Active Filtering Technology Transfer for Magnetocardiogram Data Sets (ATTMEDS)
Funder: Science and Technology Facilities Council

Abstract: Creavo Medical Technologies make magnetocardiographs, devices for detailed modelling of the heart of patients presenting with symptoms consistent with heart disease. We propose a collaborative research project with Creavo, that utilises existing expertise in signal processing, vibration isolation, vibration measurement, and dynamic tracking of sine wave components of data, to try and improve the filtering of background noise in the hospital environment found to affect Creavo devices. This expertise was gained whilst the Sheffield group was working on instrument science in connection with the LIGO gravitational wave detectors, and thus this project represents technology transfer from LIGO (with STFC support) to a UK owned and located SME. This project has the potential to impact heart patients worldwide, to help a strong British business, and to achieve impact from STFC-funded, nominally ' blue skies ' University research. The proposed duration of the project is two years, during which specialised noise removal techniques will be tried in Creavo units under evaluation in test facilities at Creavo's research headquarters, and also at the University of Sheffield. We will also explore the use of specialised vibration measurement hardware and explore possibilities for the implementation of the developed methods in commercial unites manufactured by Creavo.


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CARDIOVASCULAR
Title: Developing synergies between transient astronomy and early medical intervention
Funder: Science and Technology Facilities Council

Abstract: The application of artificial intelligence (AI) to healthcare will revolutionise medicine and patient care over the coming decades. The wealth of data being collected by medical professionals keeps growing and they need significant help to quickly understand this information for their key diagnostic tests. In particular, can this wealth of digital data be used to automatically detect possible problems early, and thus alert doctors for closer inspection? Astronomy is also experiencing a data revolution driven by STFC experiments like LIGO and LSST. These experiments are opening up the time domain in astronomy and in the near-future astronomers will be deluged by millions of transient events a day; LSST will produce on average hundreds of transients per second! The prioritisation of so many events will be key to our success and astrophysicists are already developing and applying AI technology to help find the most interesting events within the ocean of "ordinary" transients. This project brings these two problems together by applying the knowledge and expertise developed in transient astronomy to the early automated diagnosis of medical problems. This project is at the forefront of interdisciplinary research bring world-leading cardiologists from King's College Hospital together with the best transient astrophysicists in the UK. Together, we hope to find early diagnostic signatures in detailed time-series patient data e.g. ECGs. This pilot activity will be used to prime-pump future investigations and grow the number of scientists engaged in such impactful research.


Research activity codes: 4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: CARDIOVASCULAR
Title: How intensively should we treat blood pressure in established cerebral small vessel disease?
Funder: Stroke Association

Abstract: Cerebral small vessel disease (SVD) accounts for about 20% of all stroke and is the major cause of vascular cognitive impairment and dementia. The major risk factor is hypertension but in patients with severe disease (with radiological changes of extensive white matter damage or leukoaraiosis) we do not know how intensively we should treat blood pressure. In this clinical trial we will determine whether intensive, versus standard, treatment of blood pressure in hypertensive individuals with SVD and radiological leukoaraiosis is associated with reduced cognitive decline. In nested substudies we will investigate the underlying mechanism and determine whether any treatment effect is mediated through a reduced rate of white matter damage assessed by Diffusion Tensor MRI, and/or through an increase in cerebral blood flow assessed using arterial spin labelling MRI. In addition to answering this important clinical question we will use the MRI substudy data to compare the sensitivity of DTI MRI and brain atrophy as markers of white matter damage for therapeutic trials, compared with the conventional MRI marker of T2 white matter lesion volume, and assess their relationship to cognitive decline. This will provide novel and important data on the use of surrogate MRI markers for future clinical trials.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CARDIOVASCULAR
Title: Blood Pressure Variability - Definition, Natural History, Prognosis and Treatment Following Acute Stroke
Funder: Stroke Association

Abstract: Hypertension is a well recognised major modifiable risk factor for stroke. Recently, increased blood pressure variability (BPV) has also been reported to be associated with vascular risk independent of mean BP. In addition, commonly used antihypertensive agents have different class effects on BPV, which may, in part, explain the overall differential effects on stroke risk for similar absolute reductions in mean BP in a hypertensive population. However, there are limited data on BPV in the acute stroke period, and more research is required to understand fully the natural history of BPV following acute stroke and its prognostic significance. Therefore, as part of the proposed Research Programme, a systematic review of BPV and outcome following stroke will be undertaken, which will assess the prognostic significance of systolic, diastolic and mean BPV and pulse pressure (PP), and in particular the definitions and measurement techniques used. In addition, a prospective observational study will be undertaken to assess BPV utilising beat-to-beat, casual, 24-hour and Home BP monitoring techniques, including measurement failure rates and acceptability to patients. Patients recruited to this study will be followed-up over a 12-month period. BPV measurements will be repeated at 1 week or hospital discharge, and at 1, 3 and 12 months to determine the natural history of BPV following stroke. Outcome measures related to neurological and functional status, as well as mortality and cardiovascular events will be collected at the same time-point, to ascertain the prognostic significance of increased BPV in acute stroke. Finally, the Research Programme will conclude with a prospective, randomised, open, blinded-endpoint trial to compare the effects of a CCB versus ACEI/ ARB-based regime on BPV in first-ever TIA and minor ischaemic stroke patients at high risk of recurrent TIA/ stroke recruited within 24 hours of symptom onset. The overall objective of the proposed Research Programme being to reduce the risk of recurrent stroke and other cardiovascular events by the assessment of a novel therapeutic strategy based on the reduction of increased BPV following TIA and stroke.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CARDIOVASCULAR
Title: Xanthine oxidase Inhibition for improvement of Long-term Outcomes Following Ischaemic Stroke and Transient ischaemic attack (XILO-FIST)
Funder: Stroke Association

Abstract: Recurrent stroke and cognitive decline are common after ischaemic stroke. Allopurinol has been shown to reduce myocardial ischaemia, left ventricular hypertrophy (LVH), arterial stiffness, to improve cerebrovascular nitric oxide availability and may reduce arterial blood pressure (BP). We aim to explore whether allopurinol will reduce white matter hyper-intensity (WMH) progression, LVH and BP after stroke. These are associated with recurrent stroke risk and cognitive decline. We propose a multi-centre randomised, double-blind placebo controlled study to investigate whether two years allopurinol 300 mg twice per day (BD) improves these 3 surrogate outcomes inextricably linked to risk of recurrence and cognitive decline after ischaemic stroke. A total of 464 participants will be randomised from ~12 sites in the UK. Randomised participants will undergo brain MRI imaging at baseline and at 2 years. Our primary endpoint is WMH progression measured using the Rotterdam progression scale. The first 240 participants will also be eligible for a BP sub-study. The primary endpoint for this sub-study is change in mean day-time systolic BP at 1 month. 100 participants with evidence of LVH will be eligible for the cardiac sub-study. The primary endpoint for this sub-study will be change in measured LVM at 2 years. The study will take 5 years to complete.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CARDIOVASCULAR
Title: Alteplase-Tenecteplase Trial Evaluation for Stroke Thrombolysis (ATTEST 2)
Funder: Stroke Association

Abstract: Intravenous thrombolysis with the recombinant tissue plasminogen activator (rtPA) alteplase significantly improves the chances of recovery to independence after acute ischaemic stroke: reorganisation of acute stroke services has allowed a high proportion of patients to benefit. Newer plasminogen activators have replaced alteplase in other medical fields due to improved pharmacological characteristics. We recently completed a phase 2 trial of one of these, tenecteplase, in acute ischaemic stroke. Results from this study and two previous small trials comparing tenecteplase and alteplase suggest potentially better efficacy and safety (with a trend towards fewer significant intracranial haemorrhages). Since tenecteplase is less expensive and easier to administer it may offer important advantages over alteplase. We propose to further investigate tenecteplase in a phase 3 randomised controlled clinical trial of PROBE design, comparing it against alteplase in acute stroke patients considered eligible for IV thrombolysis within 4.5h of onset. In order to ensure generalizable results, the study will select patients on the basis of current clinical criteria and non-contrast CT brain. Sample size calculations indicate 1870 patients would allow determination of superior efficacy using 90 day modified Rankin Scale ordinal shift analysis.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CARDIOVASCULAR
Title: Towards An Integrated Self-Monitoring SolutIoN for Stroke/TIA: TASMIN5S
Funder: Stroke Association

Abstract: Background: raised blood pressure is a key risk factor for subsequent cardiovascular disease in people with stroke/TIA but is often poorly controlled. Aims: to assess the impact of an integrated primary care intervention for people with previous stroke or TIA combining self-monitoring with self-management where possible, and professional prompts for adherence and/or specialist review compared with usual care. Population: people with stroke or TIA recruited in primary care Methods: three workstreams (WS), with PPI input, comprising: intervention development and testing using “think aloud” techniques (WS1); a randomised controlled trial of the self-monitoring intervention including process evaluation (WS2); assessment of cost-effectiveness including both within-trial analysis and long-term modelling (WS3). Outcomes: WS1 will develop an integrated intervention using mobile phones (text+/-app) to transmit blood pressure readings and provide automated feedback. The primary outcome of the trial in WS2 is systolic blood pressure after a year. The cost-effectiveness analyses will ultimately provide a cost per Quality Adjusted Life Year. Impacts: this work will develop and test a novel intervention for the control of blood pressure after stroke/TIA which we hope will reduce subsequent cardiovascular events in a cost-effective manner, producing sufficient evidence to drive implementation within the NHS and inclusion in national guidelines.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CARDIOVASCULAR
Title: An open label randomised controlled trial of mycophenolate mofetil versus cyclophosphamide for the induction of remission of childhood polyarteritis nodosa (MYPAN)
Funder: Versus Arthritis

Abstract: Standard therapy for systemic polyarteritis nodosa (PAN) comprises high-dose corticosteroids and cyclophosphamide (CYC) to induce remission, despite no trial evidence in children to support its use. CYC treatment is toxic and is associated with severe adverse events in 25-50%, and late CYC toxicity includes malignancy and infertility. Open label studies in vasculitis of mycophenolate mofetil (MMF) suggest comparable efficacy and lower toxicity than CYC. The aim of MYPAN will be to compare the efficacy and safety of MMF versus CYC for the induction of remission of PAN at 6 months, based on a non-inferiority hypothesis: MMF is non-inferior for induction of remission to CYC (standard therapy) but with less or comparable short term toxicity. Since PAN is a rare disease the trial is of Bayesian design. 40 new paediatric patients with PAN will be randomised to MMF 1200 mg/m2/day (maximum 2g/day), or an intravenous cyclophosphamide regimen, with the same prednisolone dosing. Following a 3-6 month induction course patients will receive standard remission maintenance treatment. The primary end-point is remission by six months based on a standard definition. The trial will be led and conducted by the MCRN Clinical Trials Unit with international collaboration with the Pediatric Rheumatology International Trials Organization.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CARDIOVASCULAR
Title: Using mobile phone technology in the assessment of Raynaud’s phenomenon; a potential outcome measure for clinical trials?
Funder: Versus Arthritis

Abstract: Clinical trials of Raynaud’s phenomenon (RP) have been hampered by the lack of reliable outcome measures of frequency, duration and severity of RP attacks (disease burden) for use ‘in the field’ (including out-of-doors) which is where attacks commonly occur. Our goal is to develop an outcome score using a smartphone application (‘app’). This score will encompass traditional outcome measures (e.g. Raynaud’s Condition Score/paper diary), and improve on these by adding the objectivity of witnessed colour change. Our vision is that patients will monitor their disease via their mobile phone which, judging from a recent patient survey, 80-90% of patients already carry with them, suggesting feasibility of this approach. Our three specific objectives are to (a) develop appropriate methods of extracting and analysing all available data from mobile phone camera photographs of RP attacks (from images already collected from 40 patients) (b) develop an RP-monitoring ‘app’ (informed by user-group feedback) (c) test the ‘app’ in a cohort of 40 patients (who will collect RP attack data over a 2 week period), including comparison between the two data collection methods (traditional paper diary versus ‘app’). A reliable, easy-to-use ‘app’-based outcome measure will facilitate clinical trials of badly needed novel treatment strategies.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CARDIOVASCULAR
Title: Preclinical studies for gene therapy in deficiency of adenosine deaminase type 2
Funder: Versus Arthritis

Abstract: Background: Vasculitides are a group of devastating diseases leading to significant organ injury (strokes, heart attacks, kidney failure, arthritis and other disabling musculoskeletal complications), and death if not diagnosed and treated promptly. For years, these conditions were considered sporadic and the underlying cause(s) were poorly understood. This makes treatment extremely challenging, and cure impossible particularly since the therapies used have significant side effects, and are “untargeted”. Excitingly, in 2014 an inherited form of polyarteritis nodosa was discovered called deficiency of adenosine-deaminase-type-2 (DADA2), caused by loss of function mutations in the CECR1 gene. Following this discovery, we identified several cases (n=25) at GOSH with this disease. We have established that treatment with biologic agents targeting TNF-alpha is particularly effective, but has side effects, is expensive and is required to be given by injection for life. Moreover, NHS England often refuse to provide funding for this treatment leaving patients with little hope of treatment. We now have a very realistic opportunity to cure DADA2 within a relatively short period of time using gene therapy. By resolving the root cause of this form of vasculitis, gene therapy now offers a real prospect of cure, never before possible in this field.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;5.2 CELLULAR AND GENE THERAPIES
Health categories: CARDIOVASCULAR