NIHRDataInsights/HRCSData huggingface dataset:
Title: Comorbidity and changing prognosis in heart failure patients: transitions from primary care to specialist care
Funder: Department of Health (England)

Abstract: This PhD will investigate patients with heart failure and the influence of other diseases on their health status, likelihood of hospital admission and death. Key questions addressed are (i) which comorbidities are important in influencing outcomes and (ii) how does change in comorbidity status influence the prediction of health and healthcare? These questions will be answered in three phases; systematic review, general practice database studies and a new cohort study. Prognostic evidence in HF patients will provide a better basis for clinical decision making and in improving patient care and outcomes by targeting the comorbidity.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: CARDIOVASCULAR
Title: Mixed methods analysis of the clinical pathway for patients diagnosed with heart failure in primary care
Funder: Department of Health (England)

Abstract: Heart failure (HF) has a lower survival rate than most cancers but diagnosis can be difficult and delayed. There is little research which examines the whole diagnostic process in general practice. Qualitative methods will be used to elucidate the patient experience and quantitative methods will be used to examine the diagnostic pathway from initial presenting symptom to diagnosis and subsequent survival. If GPs have a better understanding of how patients with HF present they can make a more accurate and timely diagnosis and initiate treatment earlier resulting in patients with HF having both improved quality of life and increased survival.


Research activity codes: 4.4 POPULATION SCREENING
Health categories: CARDIOVASCULAR
Title: The Role of Diffuse Myocardial Fibrosis in Aortic Stenosis: Translation of Non-Invasive Quantification into Clinical Practice
Funder: Department of Health (England)

Abstract: Diffuse scarring is important in every organ in the body: it predicts outcome and is the target of therapy. We have developed scans to measure diffuse scarring in heart muscle using MRI and CT. In this project, we will investigate 150 patients with severe narrowing of the aortic valve before and one year after valve replacement. We predict the new techniques will help doctors to improve timing of valve surgery. Our ambition is a simpler, cheaper, more accurate test, accessible in any hospital. Ultimately we hope to learn more about the sick heart muscle and guide improved use of treatments.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CARDIOVASCULAR
Title: Improving Adherence to medication in older heart failure patients - a mixed methods study
Funder: Chief Scientist Office (Scotland)

Abstract: Heart Failure (HF) is a major cause of disability, hospitalisation and death, particularly amongst older people. Prognosis remains poor despite the improvements in prevention and treatment achieved through the prescribing of effective medications. Evidence suggests that adherence to medication is sub-optimal but there is a lack of current data identifying which modifiable factors are associated with poor adherence in older HF patients. The body of work proposed for this PhD therefore aims to address these issues, culminating in the development of a tailored intervention to enhance medication adherence in older HF patients. Work will combine both qualitative and quantitative research techniques commencing with a collation of the most up to date reviews prior to a purposive sampling of older HF patients. A semi-structured interview format will explore understanding of heart failure and medication, along with the perceived drivers and barriers to adherence. An observational study phase recruiting 90 community dwelling HF patients aged >70 years via the Scottish Primary Care Research Network (SPCRN) will follow. Outcome measures will be adherence as measured by Serum ACEi measurement, urinary furosemide level, evidence of prescription refill and self-reported adherence. Determinants of adherence will be measured using various tools as guided by the results of the qualitative phase. Finally the intervention will be developed, using a concept mapping approach based on the results of the literature search, qualitative work and observational study; this will be refined and fed back to patients and their carers, the process being overseen by an expert development panel.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: CARDIOVASCULAR
Title: 2012 Doctoral Fellowship: Reducing radiation dose in paediatric cardiology: An investigation into the effects on image quality and DNA integrity
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: Advancements in technology and expertise have lead to a significant increase in paediatric interventional cardiology (PIC) procedures. PIC provides an attractive alternative to cardiac surgery in children with life threatening congenital heart abnormalities. PIC relies upon radiological guidance of catheterisation equipment and imaging of cardiac anatomy for a successful procedure. Patients receiving radiation exposures during PIC are of particular concern because children have a significantly higher risk than adults of developing a radiation induced cancer. Many patients with congenital heart defects receive numerous radiation exposures from several PIC procedures in their lifetime. The radiography profession has yet to adjust to the increase in frequency of PIC fluorography. There is a lack of consensus for best practice and a wide variation in techniques performed in the United Kingdom and Ireland. Overall aim: To determine a fluorography technique which will provide adequate image quality for PIC whilst limiting radiation exposure to children to as low as reasonably achievable. Study 1: An experimental study using cardiac phantoms in the cardiac unit to conduct a factorial replicated investigation. The technique which provides the lowest radiation dose along with adequate image quality will determine the optimised fluorography technique Study 2: A clinical implementation study using the optimised fluorography technique for comparison with the routine technique currently used at RVH. Research Output: Publication (e.g British Journal of Radiology/Cardiology, Radiography). Presentation (e.g UKRC, RSNA, ECR). New knowledge will identify best clinical practice for PIC fluorography, provide further assessment of DNA integrity from PIC exposures and prevent cancer.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CARDIOVASCULAR
Title: 2012 Doctoral Fellowship: Deactivation of Implantable Cardioverter Defibrillators at end of life: An exploratory study of heart failure patients', carers' and healthcare Prof.essionals' perspectives
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: Ireland is the 2nd highest implanter of Implantable Cardioverter Defibrillators (ICD) in Europe. The ICD can effectively treat life threatening arrhythmias in the rapidly expanding heart failure population, but their use at end of life lacks evidence. When patients reach end of life the device may emit frequent shocks and cause distress. Evidence suggests Prof.essionals and patients rarely discuss deactivation, presenting difficulties in achieving optimum care. Aim: To explore the perspectives of patients’, carers’ & Prof.essionals’ regarding ICD deactivation and examine the impact these have on clinical judgement. A mixed methods approach will include qualitative data from case studies and a systematic review of the literature to inform the development of a factorial survey. For the case studies, a purposive sample of 5-8 patients, their significant family member and key members of clinical team will be interviewed. These will be taped and transcribed verbatim, before thematic analysis. Simultaneously a systematic review of the literature will be conducted, and data from both sources integrated to inform vignette development. In the factorial survey all Prof.essionals across Ireland involved in ICD management will be sent a postal vignette-based survey. Quantitative data analysis using multiple regression analysis and ANOVA to test associations will provide evidence on what factors influence clinical judgement in this group of patients at end of life. Accurately identifying the issues impacting on ICD deactivation is an essential pre-requisite to the development of a much needed care pathway for these heart failure patients and their families at end of life.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: CARDIOVASCULAR
Title: The Randomised Complete v Lesion Only Primary PCI Trial- Cardiovascular MRI substudy. (CvLPRIT CMR)
Funder: Department of Health (England)

Abstract: DESIGN: CVLPRI-t: Multi-centre open pilot randomized controlled clinical trial. CVLPRI-t-CMR: + blinded endpoint analysisPOPULATION: 250 patients with ST elevation myocardial infarction(MI) undergoing primary percutaneous angioplasty (P-PCI) with multi-vessel coronary artery disease.INTERVENTION: Complete in-hospital revascularisation with PCI (infarct-related artery and major coronary vessels (> 2.0mm) with severe stenosis) and optimal medical therapy (OMT).COMPARATOR: Infarct related P-PCI only with OMT. Further revascularisation for refractory angina despite OMT or ischaemic burden >20% of total myocardium on non-invasive imaging.OUTCOME MEASURES: Main CULPRIT study: Major adverse cardiac events: all-cause death recurrent MI heart failure need for revascularization (PCI or CABG) at 12 monthsCMR substudy (BLINDED ENDPOINTS) Primary: 1. MI size (% of LV mass) on pre-discharge CMR. Secondary: 1. Myocardial salvage index extent of microvascular obstruction ejection fraction (EF) and left ventricular(LV) end diastolic(EDV) and systolic volumes(ESV) pre-discharge CMR. 2. LVEDV ESV EF and ischaemic burden on CMR at 9 months. ASSESSMENT AND FOLLOW-UP: CMR will be performed pre-discharge (1-4 days) post MI and at 9 months. Clinical assessments for MACE at 36 9 and 12 months (endpoints). PROPOSED SAMPLE SIZE: It is anticipated the main study will recruit in total 250 patients. For the CMR study it is likely not all will be eligible/consent to CMR. 100 patients in each arm has 80% power to detect an absolute 4% difference in infarct size assuming infarct size 20 (10)% of LV mass in culprit-only revascularisation alpha=0.05 and 2-tailed.STATISTICAL ANALYSIS: Analysis will be performed by a statistician from the CTEU at the Royal Brompton Hospital (supported by Imperial CTEU). Groups will be compared by 2 sample t-tests/Fishers exact test and Chi-square as appropriate and will be by intention to treat. Event free survival will be assessed by Kaplan-Meier curves. Univariate predictors of outcome will be assessed by logistic regression analysis and independent predictors by multivariate analysis. The trial will be overseen by a trial steering committee and an independent data and safety monitoring board with planned sub group analysis when 60 patients in each arm have been recruited.PROJECT TIMETABLES AND RECRUITMENT RATE: The main CULPRIt clinical study without CMR has funding from the BHF. Ethics submission August 2010 recruitment starting in October 2010. It is anticipated that 6 patients per week (1.5/centre) will be recruited and completed within 9 months (June 2011) with a further follow-up of 12 months (June 2012) and 3 months for analysis/writing up (Sept. 2012).


Research activity codes: 6.4 SURGERY
Health categories: CARDIOVASCULAR
Title: Magnetic Resonance Imaging Using Ultrasmall Superparamagnetic Particles of Iron Oxide to Predict Clinical Outcome in Patients Under Surveillance for Abdominal Aortic Aneurysms
Funder: Chief Scientist Office (Scotland)

Abstract: Background: Ruptured aortic aneurysms are the thirteenth commonest cause of death in the United Kingdom. Surgical intervention to prevent rupture is considered when the risk of rupture outweighs the risk of procedural complications. There is a major unmet clinical need to develop a better method of identifying patients at risk of rupture and death that goes beyond simple ultrasound measurement of aneurysm. In a preliminary proof-of-concept study we have recently demonstrated that magnetic resonance detection of mural uptake of ultrasmall superparamagnetic particles of iron oxide (USPIOs) identifies abdominal aortic aneurysms with a 3-fold higher growth rate. Research Design: Prospective observational cohort study. Study Population: Patients with abdominal aortic aneurysms with anteroposterior diameter >40 mm. Planned Interventions: 3T magnetic resonance scan before and after administration of 4.0 mg/kg of USPIOs. Outcome Measures: The abdominal aortic aneurysm of each subject will be imaged with an ultrasound scanner and a 320-multidetector computed tomography scanner with contrast enhancement. Subjects will be followed up every 6 months with clinical and ultrasound scanning as part of the clinical surveillance programme. At 2 years a repeat computed tomography scan will be performed to assess three-dimensional growth of the aneurysm. Biomechanical stresses of the aneurysm will be assessed by finite element analysis and computational modeling. Assessment and Follow-up: The primary end-point of the study will be the composite of aneurysm rupture or need for surgical repair. Secondary end-points will include aneurysm growth rate as well as the individual rates of aneurysm rupture aortic aneurysm repair and aneurysm-related mortality. Growth rate will be assessed by both ultrasound and computed tomography. Reproducibility will be assessed in a subgroup of randomly selected patients (n=40). Sample Size: At 80% power and 2-sided P<0.05 228 patients with abdominal aortic aneurysms will be needed to detect a 20% absolute difference in the primary end-point assuming a 2-year event rate of 50% in those with mural USPIO uptake and 30% in those without. Statistical Analysis: Differences in event rates will be assessed using a binomial test for proportions. Growth rates will be compared using 2-sample t-test or non-parametric equivalent as appropriate. Using an appropriate regression model we will investigate whether mural uptake of USPIOs is an independent predictor of aneurysm growth. Project Timetables: Following the initial 6-month set up phase patients will be recruited from our ongoing surveillance programme (>500 suitable patients) over an 18-month period and followed up for up to 36 months. Data analysis presentation and publication will be undertaken in the final 6 months.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CARDIOVASCULAR
Title: Beating Hearts at High Resolution: Adaptive High Resolution Selective Plane Illumination Microscopy
Funder: Engineering and Physical Sciences Research Council

Abstract: In this project we will film life as it develops in the heart by exploiting developments in optical microscopy, high speed imaging, and adaptive optics. The hearts will be in live, developing zebrafish and mouse embryos. This is extremely challenging as the living heart is large (on a microscopic scale), is embedded in the body of the animal (meaning it must be imaged at depth) and is beating, and therefore moving, at a rate of around 300 beats per minute. As well as providing a challenge to demonstrate the advanced methods we will develop the study of cardiac development is important both for investigating the development of the healthy heart and for determining the causes of heart problems


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: CARDIOVASCULAR
Title: Finite element-immersed boundary method and its application to mitral valves
Funder: Engineering and Physical Sciences Research Council

Abstract: Each year, about 225,000 valve replacements in the heart are performed worldwide. In particular, mitral valve (MV) diseases such as mitral regurgitation (leakage) may lead to left ventricle (LV) dilation, decreased LV function, and increased rates of atrial fibrillation. Mathematical modelling can help us to understand MV diseases and their relationship with LV functions. However, compared to the aortic valves, the MV has been significantly understudied due to its more complex anatomical structure. We will deliver Magnetic Resonance Image based dynamic MV models which will include important features such as fluid-structure interaction and nonlinear soft tissue modelling. This will be achieved by developing novel numerical methods; i.e. a new finite element version of immersed boundary method with adaptive mesh refinement (IBAMR). The work will be carried out through an interdisciplinary collaboration between Mathematics at Glasgow, the Institute of Cardiovascular and Medical Science, and the primary developer of the IBAMR software, Prof. Boyce Griffith from NYU. IBAMR represents the state of the art immersed boundary methods, and is gaining increasing popularity in the USA due to its accuracy. Prof. Luo is one of the leading developers of this software. One of the important strengths of this project is the direct involvement of the Cardiovascular Research centre, which has the most advanced MRI facilities in the UK, and is linked to Golden Jubilee National Hospital and Western Infirmary. Thus we will have access to valve geometries from healthy and diseased patients. Most importantly, we will obtain 3D temporal displacement and strain vector field of the MV in vivo using the state of the art imaging techniques. This will tie the computational simulations with clinical applications together and allow us to identify key elements and parameters in our models.Modelling the dynamics of the MV to understand its mechanical performance in health and disease offers exciting new opportunities. Apart from addressing important physiological and pathological questions about the MV functions, our findings will serve as springboard for further research on other valvular heart disease. Improved understanding of the basic mechanisms of heart valve function will result in improved clinical therapies and therefore has clear social benefit. Ultimately, our aim is to delay or prevent progression of valvular disease, for example, by modulating transvalvular blood flow or engaging pharmacological approaches to modify cardiac output and valve elasticity. The framework to be developed from this project will also be used immediately to multi-scale models of the whole heart aiming at understanding acute myocardial infarction.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CARDIOVASCULAR
Title: Optimal Design of Drug Eluting Stents
Funder: Engineering and Physical Sciences Research Council

Abstract: Coronary artery disease is the most common type of heart disease and the number one leading cause of death in Europe and North America. It is estimated to cost the public purse over £3.5 billion per annum in the UK alone. The disease arises from atherosclerosis, in which fatty deposits build up on the walls of the blood vessels (arteries) that supply the heart itself. These deposits can narrow the artery and reduce blood flow to the heart. This may lead to angina or a heart attack. Severely narrowed arteries are often treated by insertion of a stent which is an expandable metal meshwork tube that opens up the blocked artery. The performance of these stents is improved by covering them with a layer that gradually releases a drug to moderate the wound-healing reaction of the artery wall. Without the drug coating, many patients experience a growth of tissue around the stent that can narrow the artery again. The timing and extent of release of the drug from the stent into the artery wall is critical. If drug release is inadequate then tissue growth occurs and the artery becomes blocked; however if drug release is excessive then there is a problem for the repair of the important inner lining of the artery, called the endothelium. If there is endothelial damage this increases the risk of late thrombosis. Failure of endothelial regrowth is especially critical over the metal struts of the stent, where drug concentration is highest. Thus correct performance of the drug-eluting stent depends on accurate delivery of an effective, but non-toxic, drug profile. Drug-release profiles of currently available drug-eluting stents have been derived empirically; however the use of mathematical modelling principles will enable the design of improved release profiles and should lead to improved performance and fewer adverse effects. In this project we will develop a mathematical model that will be more realistic than previous models. It will be based more closely on the structure and coposition of a diseased artery such as would be present in patients who are receiving a drug-eluting stent. Moreover our mathematical model will be more sophisticated than previous models because it will incorporate information about the errors associated with the various measurements that need to be made. We shall make accurate determinations, using the actual drugs that are used to treat patients, to find out how they move through the artery wall. We shall show that our model works correctly by measuring the performance of a stent that we have designed. The current project will utilise the best available methods to create a much more accurate and predictive model that, for the first time, will allow a stent to be designed with the assistance of a model and not solely empirically.


Research activity codes: 5.1 PHARMACEUTICALS;5.3 MEDICAL DEVICES
Health categories: CARDIOVASCULAR
Title: Multi-scale Approaches to Mechanical Contraction and Electrical Wave Conduction in A 3D Model of Human Atria during Fibrillation
Funder: Engineering and Physical Sciences Research Council

Abstract: One of the "grand challenges" of integrative biology is to predict the behaviour of an organ that emerges from integrated actions of molecules, ions, cells and tissues operating at multi-physical scales. Cardiac electro-physiology is sufficiently well est


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CARDIOVASCULAR
Title: An Active Learning Approach to Network Inference
Funder: Engineering and Physical Sciences Research Council

Abstract: The understanding of pathway structures is crucial to our understanding of the functional organisation of genes and proteins. Abnormally functioning pathways underlie many human diseases. Given the extent of noise in biological datasets, and limited amounts of data available, unsupervised determination of network topology is a substantially under-determined inference problem. Consequently, in this project, we focus on network completion, which is a supervised learning task involving multiple types of data. Starting from a set of known links and non-links we construct a classifier which predicts and ranks further possible functionmal links for experimental validation. There will be a parallel experimental programme following an active learning approach to network inference, that is, predictions of functional links will be investigated which will, in turn, be used to improve the predictor. To provide a focus for the accompanying laboratory work, by the medical researchers associated with the project, our principal aim will be the discovery and validation of pathway structures associated with hypertension. Hypertension is the most common cause of preventable disease in the developed world.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: CARDIOVASCULAR