NIHRDataInsights/HRCSData huggingface dataset:
Title: The effect of geography and socioeconomic status on health care costs at the end of life: implications for resource allocation and expenditure projections in
Funder: Chief Scientist Office (Scotland)

Abstract: "Aims & Objectives: To develop an extensive modelling framework to estimate current and project future economic burden of disease; in particular accounting for: TTD, age, geography and socio-economic status (SES). Design 8i Techniques: A longitudinal random sample of the Scottish population drawn from death records linked to acute inpatient care records (SMROl) will be utilised. This determines whether decedents utilised hospital care and incurred any costs. Using Multi- Level-Modelling (MLM) techniques the association between TTD, age, geography, SES and inpatient HC expenditure will be examined, while allowing the effect of covariates to vary over hierarchical levels, such as the episode, the patient and health board. Measures of uncertainty around cost estimates will be explored and issues of reverse causality (endogeneity) between TTD and costs will be addressed. Utilising this framework, the economic burden of specific diseases (CHD, cancer, diabetes and respiratory disease) will be estimated. Exploration of costs at the end of life beyond inpatient care will be undertaken utilising linkage to social care data for the NHS Highland. Measurements & Outcomes: These include a modelling framework to estimate and project HC expenditure, which can be used to inform resource allocation and help prioritising HC delivery. This programme of work will provide more accurate estimates of HC costs, which is the basis for more refined expenditure projections, taking account of the distribution of HC costs over different age groups at the end of life. In addition, expenditure estimates for the long-term care sector will be provided in a rural setting."


Research activity codes: 8.2 HEALTH AND WELFARE ECONOMICS
Health categories: RESPIRATORY;CANCER AND NEOPLASMS;METABOLIC AND ENDOCRINE;CARDIOVASCULAR
Title: Assessment of neonatal cardiac remodelling through construction of a biventricular functional atlas of the human preterm heart using 3.0T cardiac MRI
Funder: SPARKS

Abstract: Premature babies suffer health problems resulting from their heart failing to adjust to life after birth. Performing cardiac magnetic resonance (CMR) scans on preterm babies is safe; a single scan can quantify heart function but cannot show how the heart adapts over time. Project aims: 1. Create a CMR ‘atlas’ (visual representation) from multiple CMR scans to show how the preterm heart changes over time and examine whether preterm birth compromises long-term heart function. Project benefits: Creating a CMR atlas will improve understanding of how the preterm birth affects the heart, and help identify strategies to support the vulnerable heart.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: RESPIRATORY;CARDIOVASCULAR
Title: A program of research in respiratory and cardiovascular genetic epidemiology
Funder: Medical Research Council

Abstract: Aims (1) To identify sequence and structural variants in the human genome associated with respiratory function and chronic obstructive pulmonary disease (2) To identify human genomic variants associated with blood pressure and related cardiovascular traits. Main objectives 1.1. To discover common single nucleotide polymorphisms (SNPs) associated with pulmonary function 1.2. To identify rare SNPs associated with COPD and pulmonary function in existing data and from resequencing novel loci. 1.3. To study common and rare copy number variants (CNVs) associated with pulmonary function. 1.4. To assess the role of genomic variants from 1.1 to 1.3 in: development in pulmonary function, decline in pulmonary function; pulmonary function in diseased individuals; airway response to beta-2 agonists, effect modification of tobacco smoking; Mendelian randomization studies aimed at understanding potentially modifiable intermediate pathways underlying lung function. 2.1. To discover common single nucleotide polymorphisms (SNPs) associated with blood pressure. 2.2. To study common and rare copy number variants (CNVs) associated with blood pressure. 2.3. To assess the role of blood pressure associated variants from 2.1 and 2.2 in: longitudinal change in blood pressure; circadian variation in ambulatory BP; Mendelian randomization studies to assess causal pathways influencing blood pressure. Mendelian randomization studies will utilise variants from 1.1 to 1.3 to investigate the causal mechanisms for the reported association between lung function and cardiovascular disease. Design and methodology The research will utilise existing genome-wide association study (GWAS) data in very large sample sizes and will utilise new publicly available data to impute untyped variants (1.1, 2.1). I will employ novel statistical approaches for the detection of rare variant associations (1.2) and deep resequencing (1.2) for regions identified from GWAS. I will further develop methods to study CNVs genome-wide and apply these to large study populations to test CNV associations in 1.3 and 2.2. Causal pathways underlying these traits will be investigated (1.4, 2.3) using carefully phenotyped populations, longitudinal analyses employing generalised linear mixed models we have previously developed, and Mendelian randomization analyses in very large populations using methods we have developed in the group. Scientific and medical opportunities Well-designed, adequately powered and carefully analysed genetic association studies can inform understanding of the aetiological pathways underlying disease causation and progression, and may highlight potential targets for prevention and treatment. Disease-associated genetic variants can also be used in traditional epidemiological studies (Mendelian randomization) to inform understanding of intermediate pathways that may be amenable to public health intervention.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: RESPIRATORY;CARDIOVASCULAR
Title: East Midlands Breathomics Pathology Node (EMBER)
Funder: Engineering and Physical Sciences Research Council

Abstract: We will establish the East Midlands Breathomics Pathology Node (EMBER) to develop novel breath-based systems for molecular pathology. Exhaled breath contains volatile organic compounds (VOCs) that reflect biological processes occurring within the lung and, via the vena cava, more distant organs. Analysis of VOCs in breath provides rapid, at-patient and in clinic non-invasive approaches for diagnosis, phenotyping and stratifying patients. Importantly the range of clinical conditions is large and includes: respiratory infections, cancers, respiratory disease such as asthma and chronic obstructive pulmonary disease, and cardiovascular disorders such as heart failure. The East Midlands has a unique and congruent group of clinical and analytical researchers drawn from the University of Leicester (UoL), the University Hospitals of Leicester NHS Trust (UHL) and Loughborough University (LU) with strengths in clinical research, analytical chemistry, data management and mathematical modelling of complex data. EMBER focusses these combined strengths, and co-ordinates existing collaborations with industry partners to create a nationally-leading centre in "Breathomics" with the critical mass to establish world-class delivery of new technology, applications and training in molecular pathology. EMBER will deliver near-patient and remote sensing technologies to analyse breath and by consolidating the assets and expertise across the consortia build an infrastructure that will result in novel methods to analyse complex "omics" data that will be applicable ultimately to many areas of diagnostic pathology; translated from EMBER's leadership in the analysis of breath signatures.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: RESPIRATORY;CARDIOVASCULAR
Title: Resuscitating and reconditioning thoracic organs ex vivo
Funder: Department of Health and Social Care

Abstract: Evaluate the potential for normothermic ex vivo perfusion of hearts and lungs to assess the potential function of extended criteria donor lungs prior to implantation and (b) to use ex vivo perfusion as a route for introducing and evaluating novel therapeutic interventions designed to improve the quality of donor hearts and lungs Assess 24 pairs of DCD lungs that satisfy the criteria for extended agonal period (2 hours) over years 1-2. In addition to current assessment criteria for lungs on EVLP (gas exchange, lung mechanics, perfusate flow and pulmonary vascular pressures), we will investigate addition physiological variables (eg gas diffusion), measured pulmonary blood flow, biomarkers of tissue integrity, microvascular integrity, cellular energetics and release of damage associated molecular patterns (DAMPs). Cells leaving the lungs and trapped in the leukocyte filter will be collected, and characterised by multiparameter FACS analysis To increase capacity to assess novel interventions during EVLP in a cost effective manner, in year 1 we will use DBD and DCD lungs declined for transplantation and unsuitable for the DEVELOP-UK study to develop a lobar perfusion system. The DEVELOP-UK study has already collected and stored perfusate, BAL and lung tissue samples from >40 EVLP runs that will provide a derivation cohort for the soluble biomarkers and tissue based biomarkers. Undertake ex-vivo perfusion of 10-12 DBD donor hearts declined for transplantation, and will study functional indices including the effectiveness of pharmacological agents to reduce myocardial ischaemic injury and improve heart function


Research activity codes: 6.4 SURGERY
Health categories: RESPIRATORY;CARDIOVASCULAR
Title: Air Pollution Impacts on Cardiopulmonary Disease in Beijing: An integrated study of Exposure Science, Toxicogenomics and Environmental Epidemiology
Funder: Natural Environment Research Council

Abstract: Air Pollution Impacts on Cardiopulmonary Disease in Beijing: An integrated study of Exposure Science, Toxicogenomics and Environmental Epidemiology This proposal aims to do a comprehensive evaluation of air pollution health impacts on cardiopulmonary health through integration of exposure, epidemiology, and toxicology/toxicogenomic studies. We will do detailed assessments of people's exposure to air pollution, estimating exposures for long- and short-term epidemiological analyses, and linking these to epidemiological analyses of long term health impacts based on a cohort study, short-term effects (i.e. biomarkers, blood pressure, heart rhythm, peak flow) based on a panel study, and early life effects based on a birth cohort. Additionally, we test the effect of reducing exposure to fine particles, but not gases, by designing an intervention study where volunteers will wear a face mask and examining the exposure-response relationship for the same short-term effects we evaluate in the panel study. The short-term physiological measurements we conduct in the epidemiological studies will provide insight into the mechanisms by which air pollutions affects cardiopulmonary health. To complement the human based studies into mechanisms of action, our project will also conduct extensive in vivo analyses of mechanistic effects, and early life toxicogenomics/metabonomics. Finally, we will provide practical advice to stakeholders based on our study findings, by assessing the potential value of selected strategies for control of exposure to outdoor health protection in a health risk assessment.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;8.3 POLICY, ETHICS AND RESEARCH GOVERNANCE
Health categories: RESPIRATORY;CARDIOVASCULAR
Title: Development of a novel Paediatric Continuous Early Warning (PaedCEW) monitor for children at risk of respiratory and cardiovascular collapse
Funder: Medical Research Council

Abstract: There are over 17,000 children admitted to intensive care units annually in the UK with the majority requiring cardiovascular and respiratory support. Recent key reports have highlighted the need for better monitoring of children at risk of deterioration during critical illness. Although paediatric bedside early warning scores, generated via the clinical assessment of physiological observations, can identify these children early this approach is labour intensive, often incomplete, and since it is non-continuous could delay urgent treatment if not performed frequently enough. Many emergency paediatric guidelines and early warning systems use capillary refill as a clinical indicator of cardiovascular status which, although widely used in clinical practice, is known to have marked intra- and inter-observer variability so reducing its power as a clinical guide. Whilst technology exists to measure key vital signs such as heart rate, respiratory rate and oxygen saturation, no automated medical device has been developed to monitor capillary refill. Using our patented reflectance photoplethysmography technology, we aim to develop an innovative automated capillary refill device and user interface to provide a paediatric continuous early warning (PaedCEW) monitoring system. Although the focus of this proposal is capillary refill assessment, we will develop in parallel an electronic early warning score incorporating key vital signs to aid with the recognition of clinical deterioration in children thus allowing timely intervention. The device will be non-invasive, require minimal training and operate in a semi-autonomous manner providing age specific alarms and alert thresholds. The PaedCEW system would complement and support current clinical practice and aim to address difficulties of recognising ill children. We expect that this device would improve safety and outcomes in children, reduce healthcare costs via the earlier treatment and free up nursing/medical staff time.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: RESPIRATORY;CARDIOVASCULAR
Title: Real-time monitoring techniques and simplistic platelet assays to reduce and refine animal use in cardiovascular and respiratory biomedical research
Funder: National Centre for the Replacement, Refinement and Reduction of Animals in Research

Abstract: Platelets are critical participants in haemostasis, thrombosis and inflammation. We have developed technology for assessing radiolabelled platelet aggregation responses in real-time in anaesthetised mice. Our model is a refinement of thromboembolic mortality models that operates at a lower severity level and uses considerably fewer mice. Mortality models continue to be used by a number of research groups and by initiating dialogue with users we have identified a need for more simplistic alternatives and proof of principle using current test reagents to facilitate uptake. We shall therefore evaluate systemic platelet counting as an alternative to thromboembolic mortality models using conventional antithrombotics and reagents from groups currently using mortality techniques. Our approach will refine procedures currently being used to reduce pain and suffering and will also reduce animal use by participating groups by 50%. We shall also develop techniques for assessing platelet recruitment to the lung during allergic inflammation in real-time in anaesthetised mice. This will provide an alternative to killing of mice at numerous time points for histological determination of cell infiltration. We anticipate a reduction in mouse use of 70-80%. Antithrombotic drugs will be used to distinguish the inflammatory platelet response from thrombotic platelet activation. The model will ultimately be established in a laboratory that is active in the field of inflammatory lung disease to facilitate immediate application and subsequent dissemination to other research groups. We therefore propose to develop low cost and easily applied models for assessing platelet activation during cardiovascular and respiratory diseases that refine and reduce procedures involving experimental mice.


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY)
Health categories: RESPIRATORY;CARDIOVASCULAR
Title: TRAFFIC POLLUTION AND HEALTH IN LONDON
Funder: Natural Environment Research Council

Abstract: While it has been recognised for some time that small particles from vehicle exhausts and other traffic related pollutants cause a range of health effects, policy within the UK and Europe has not directly targeted these. Emissions from vehicles and ambient air itself are regulated in terms of total particles, with no specific targeting of one component or another. While this is clearly prudent in that it potentially drives reductions in all types of particles, it is also inefficient as it is likely that some particles (or particle components) are more toxic than others. This project seeks to elucidate the more toxic components of the pollution mix in London, with particular emphasis on traffic generated particles. If successful this will inform a more focussed and more efficient policy process for regulating vehicle emissions and ambient air quality. As well as regulating vehicle emissions and ambient air, policy makers - particularly at local and regional government level-can influence air pollution impacts through traffic management and wider planning decisions. Here the project will provide better information on spatial and temporal exposures and their relation to adverse impacts of air quality. This dynamic exposure information will be a major step forward in assessing the scope for more focussed traffic and infrastructure planning and management in London, with possible applications elsewhere in the UK. Even though there is a substantial literature confirming the impact of traffic pollution on health there are still substantial gaps. There is very strong evidence that exposure to traffic pollution causes asthma exacerbations in children and reasonably strong evidence that it may cause other health effects including the onset of childhood asthma, non asthma respiratory symptoms, impaired lung function, total and cardiovascular mortality and cardiovascular morbidity. In this project we will undertake a number of new investigations to examine the relationship between chronic exposure to traffic pollution and health. These will include studies of mothers in pregnancy right through to senior citizens. These innovate studies will include health outcomes rarely if ever available for investigation of air pollution effects (e.g. primary care data, child cardiovascular risk factors). The use of exposure metrics on a fine spatial scale that are in routine use for policy in London will enable exposure response relationships to be used for quantifying policy options in terms of health impact. Further this will enable us to evaluate the health impact of trends in exposure to traffic related air pollution, most specifically the Low Emission Zone for London (LEZ).


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: RESPIRATORY;CARDIOVASCULAR
Title: Microparticles during cardiac stress and their role in the diagnosis of cardiovascular disease
Funder: Department of Health (England)

Abstract: Microparticles are vesicles derived from the membrane of cells. They are involved in inflammation, clotting and blood vessel dysfunction, important processes in the development of heart disease. The impact of cardiac stress on microparticles will be examined in healthy individuals and heart disease patients. The utility of microparticle analysis in the diagnosis and prognosis of heart disease will be examined in patients undergoing stress testing to diagnose coronary artery disease. Microparticles will be measured in chronic obstructive pulmonary disease (COPD) patients to determine the impact of treatment and to investigate their role as a non-invasive marker of blood vessel function.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING;4.4 POPULATION SCREENING
Health categories: RESPIRATORY;CARDIOVASCULAR
Title: Defining neutrophil-endothelial interactions in acute lung injury.
Funder: Wellcome Trust

Abstract: Patients suffering from septicaemia or severe trauma are known to have an accumulation of activated neutrophils (a type of white blood cell) within the network of small blood vessels in their lungs. In a proportion of patients (12-15%) these cells cause damage to the pulmonary blood vessels and migrate into the lungs to cause acute lung injury (ALI), a condition with a 40-60% mortality rate. However, my research has shown that the accumulation of these activated neutrophils is reversible, and that their presence in lung blood vessels alone does not cause ALI. We have also shown that neutrophils can be reversibly activated in vitro, completing a full cycle of activation, de-activation and re-activation; these findings have led to the hypothesis that the blood vessels of the lung have a mechanism/s by which they protect themselves from neutrophil-mediated injury, and that ALI only occurs when this mechanism fails. The aim of this project is to use high fidelity in vivo microscopy t o directly image fluorescent neutrophils as they pass through the lungs of mice to define the mechanism(s) by which the pulmonary blood vessels capture, de-activate and release neutrophils, and investigate how failure of these events may lead to lung injury.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: RESPIRATORY;CARDIOVASCULAR
Title: Over two years to study diagnostic test accuracy of a modified screening questionnaire and home pulse oximetry parameters in the diagnosis of obstructive sleep apnoea in children with Down syndrome
Funder: Action Medical Research

Abstract: Background Down syndrome is the leading genetic cause of learning disability in childhood. In the UK, approximately 750 children with Down syndrome are born each year and it is estimated that over half of these children will develop a condition known as obstructive sleep apnoea (OSA). In OSA, the muscles and soft tissues in the throat relax and collapse to cause blockage of the upper airway during sleep. Breathing is interrupted for about 10 seconds, blood oxygen levels fall and this causes the child to wake briefly and start breathing again. Although children with OSA may not be aware of their condition, these episodes can happen many times a night causing severely disturbed sleep. Untreated OSA can result in daytime inattention and problems with behaviour and learning which may make the pre-existing learning difficulties of Down syndrome worse. OSA can also cause pulmonary hypertension, a dangerous condition with elevated blood pressure in the lungs. This is of particular concern in Down syndrome children who are often born with heart disease. The research project There are effective treatments for OSA so screening and early detection is important to minimise additional health and learning difficulties in this vulnerable group. Recent Royal College of Paediatrics and Child Health (RCPCH) guidelines recommend annual OSA screening in children with Down syndrome less than six years using pulse oximetry. Pulse oximeters are small external sensors which can detect some cases of sleep apnoea by measuring decreases in the levels of oxygen in the blood. However, there is no evidence to demonstrate how effective this screening method is in Down syndrome and in practice, most children are not screened. These researchers aim to recruit 180 children with Down syndrome between the ages of six months and six years and to screen for OSA using a combination of pulse oximetry and a simple sleep questionnaire. Screening will be carried out at home. If these methods are shown to be effective for the detection of obstructive sleep apnoea in children with Down syndrome, they are likely to be adopted as a national screening standard.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: RESPIRATORY;CONGENITAL DISORDERS