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  • Trans-ethnic association study of blood pressure determinants in over 750,000 individuals.

    4 January 2019

    In this trans-ethnic multi-omic study, we reinterpret the genetic architecture of blood pressure to identify genes, tissues, phenomes and medication contexts of blood pressure homeostasis. We discovered 208 novel common blood pressure SNPs and 53 rare variants in genome-wide association studies of systolic, diastolic and pulse pressure in up to 776,078 participants from the Million Veteran Program (MVP) and collaborating studies, with analysis of the blood pressure clinical phenome in MVP. Our transcriptome-wide association study detected 4,043 blood pressure associations with genetically predicted gene expression of 840 genes in 45 tissues, and mouse renal single-cell RNA sequencing identified upregulated blood pressure genes in kidney tubule cells.

  • Constructing and reconstructing 'best interests': An interpretative examination of substitute decision-making under the Mental Capacity Act 2005

    13 December 2018

    The Mental Capacity Act 2005 (MCA) authorises substitute decision-making in England and Wales, in relation to 'acts in connection with care or treatment', for a person lacking the capacity to make an autonomous decision, if it is both necessary and in his or her 'best interests' to do so. The approach adopted by the MCA is consistent with the common law, but widens both the scope and procedures of a 'best interests' determination to allow for a general model of substitute decision-making in everyday health and social care. However, by decontextualising substitute decision-making, the MCA's procedures relating to 'best interests' may prove to be problematic in three ways: first, by failing to adequately resolve certain ethical dilemmas that pervade this area; second, by reducing applied substitute decision-making to a series of compulsory generalised instructions; and, finally, by necessitating deliberation but offering little practical guidance to the process of determination. Whilst the codification of five statutory principles in the MCA is designed to foster the empowerment of vulnerable adults, the realisation of these procedural and conceptual problems may have a negative impact on the implementation of the Act.

  • Evaluation of New Technology-Based Tools for Dietary Intake Assessment-An ILSI Europe Dietary Intake and Exposure Task Force Evaluation.

    9 January 2019

    BACKGROUND: New technology-based dietary assessment tools, including Web-based programs, mobile applications, and wearable devices, may improve accuracy and reduce costs of dietary data collection and processing. The International Life Sciences Institute (ILSI) Europe Dietary Intake and Exposure Task Force launched this project to evaluate new tools in order to recommend general quality standards for future applications. METHODS: A comprehensive literature search identified technology-based dietary assessment tools, including those published in English from 01/2011 to 09/2017, and providing details on tool features, functions and uses. Each of the 43 tools identified (33 for research and 10 designed for consumer use) was rated on 25 attributes. RESULTS: Most of the tools identified (79%) relied on self-reported dietary intakes. Most (91%) used text entry and 33% used digital images to help identify foods. Only 65% had integrated databases for estimating energy or nutrients. Fewer than 50% contained any features of customization and about half generated automatic reports. Most tools reported on usability or reported validity compared with another assessment method (77%). A set of Best Practice Guidelines was developed for reporting dietary assessment tools using new technology. CONCLUSIONS: Dietary assessment methods that utilize technology offer many advantages for research and are often preferable to consumers over more traditional methods. In order to meet general quality standards, new technology tools require detailed publications describing tool development, food identification and quantification, customization, outputs, food composition tables used, and usability/validity testing.

  • Real-time analysis of nanopore-based metagenomic sequencing from orthopaedic device infection

    20 February 2019

    Prosthetic joint infections are clinically difficult to diagnose and treat. Previously, we demonstrated metagenomic sequencing on an Illumina MiSeq replicates the findings of current gold standard microbiological diagnostic techniques. Nanopore sequencing offers advantages in speed of detection over MiSeq. Here, we compare direct-from-clinical-sample metagenomic Illumina sequencing with Nanopore sequencing, and report a real-time analytical pathway for Nanopore sequence data, designed for detecting bacterial composition of prosthetic joint infections. DNA was extracted from the sonication fluids of seven explanted orthopaedic devices, and additionally from two culture negative controls, and was sequenced on the Oxford Nanopore Technologies MinION platform. A specific analysis pipeline was assembled to overcome the challenges of identifying the true infecting pathogen, given high levels of host contamination and unavoidable background lab and kit contamination. The majority of DNA classified (>90%) was host contamination and discarded. Using negative control filtering thresholds, the species identified corresponded with both routine microbiological diagnosis and MiSeq results. By analysing sequences in real time, causes of infection were robustly detected within minutes from initiation of sequencing. We demonstrate initial proof of concept that metagenomic MinION sequencing can provide rapid, accurate diagnosis for prosthetic joint infections. We demonstrate a novel, scalable pipeline for real-time analysis of MinION sequence data. The high proportion of human DNA in extracts prevents full genome analysis from complete coverage, and methods to reduce this could increase genome depth and allow antimicrobial resistance profiling.

  • Self-efficacy and health-related quality of life: a cross-sectional study of primary care patients with multi-morbidity.

    20 February 2019

    BACKGROUND: Multi-morbidity in chronic long-term conditions is a major concern for health services. Self-management in concert with clinical care forms part of the effective management of multi-morbidity. Self-efficacy is a mechanism through which self-management can be achieved. Quality of life is adversely impacted by multi-morbidity but could be improved by effective self-management. This study examines the relationship between self-efficacy and quality of life in primary care patients with multi-morbidity. METHODS: A cross-sectional survey was conducted with primary care patients in England. Potential participants were mailed a questionnaire containing quality of life measures (the EQ-5D-5L and the Long-Term Conditions Questionnaire (LTCQ)), the Disease Burden Impact Scale (DBIS) and the Self-efficacy for Managing Chronic Disease Scale. Descriptive statistics, analysis of variance and linear regression analyses were conducted to examine the relationship between quality of life (dependent variable), self-efficacy, and demographic and disease-related variables. RESULTS: The 848 participants living with multi-morbidity reported a mean of 6.46 (SD 3.49) chronic long-term conditions, with the mean number of physical conditions 5.99 (SD 3.34) and mental health conditions 0.47 (SD 0.66). The mean scores were 15.45 (SD 12.00) for disease burden, 0.69 (SD 0.28) for the EQ-5D-5L, 65.44 (SD 23.66) for the EQ-VAS, and 69.31 (SD 21.77) for the LTCQ. The mean self-efficacy score was 6.69 (SD 2.53). The regression models were all significant at p < 0.001 (adjusted R2 > 0.70). Significant factors in all models were self-efficacy, disease burden and being permanently sick or disabled. Other factors varied between models, with the most notable being the presence of a mental health condition in the LTCQ model. CONCLUSIONS: Multi-morbid primary care patients with lower self-efficacy and higher disease burden have lower quality of life. Awareness of self-efficacy levels among patients with multi-morbidity may help health professionals identify patients who are in need of enhanced self-management support. Providing self-management support for chronic disease has been hailed as a hallmark of good care. Higher self-efficacy may lead to enhanced quality of life in multi-morbidity.

  • Economic evaluation plan of a randomised controlled trial of intra-nodular injection of anti-TNF and placebo among patients with early Dupuytren's disease: Repurposing Anti-TNF for Treating Dupuytren's Disease (RIDD).

    20 February 2019

    Dupuytren's disease (DD) is a common fibroproliferative condition of the palmar and digital fascia of the hand; however, there is currently no approved treatment for early stage DD. The objective of this paper is to describe the methods applied to assess the cost-effectiveness of adalimumab injections compared to placebo for controlling the progression of early stage DD in the Repurposing Anti-TNF for Treating Dupuytren's Disease (RIDD) trial. Measure of effectiveness and resource use will be obtained from a randomised clinical trial, carried out in three healthcare centres, and recruiting a minimum of 138 patients aged 18 years and above with a diagnosis of early stage DD. Resource use and utility measures (quality-adjusted life years) will be collected at 3, 6, 9, 12 (primary outcome endpoint) and 18 months post-randomisation. A within-trial cost-utility analysis (CUA) will be conducted at 12 months and if the intervention is effective, a decision analytic model will be applied to estimate the lifetime effectiveness and costs. The analysis will be performed from a health system (National Health Service and personal social services) perspective. Sensitivity analysis will be conducted to assess the robustness of the results. RIDD is the first randomised controlled trial with an economic evaluation conducted among patients with early stage DD. The protocol described here records our intent to conduct both a within-trial CUA alongside the RIDD study and a lifetime CUA using decision-analytic modelling.

  • Aspirin and other Anti-Platelet Drugs

    7 June 2018

    Aspirin can block the aggregation of blood platelets and in the early 1980s several randomised trials assessed whether it might be able to prevent heart attacks and strokes in people at high risk of such an event. These trials were too small to provide a definitive answer, so we established the Anti-Platelet Trialists’ (APT) Collaboration to conduct a meta-analysis of all such trials.

  • Big Data

    7 June 2018

    The emergence of new digital technologies is allowing huge quantities of information on health exposures and outcomes to be captured, stored, and analysed using advanced statistical techniques. ‘Big data’ will provide new ways to conduct research and offers the potential of a dramatic increase in the scale and efficiency of clinical studies.

  • Cancer

    7 June 2018

    Despite improvements in survival in recent decades, cancer remains a major cause of death. The most common types of cancer in males are lung cancer, prostate cancer, colorectal cancer, and stomach cancer, and in females, are breast cancer, colorectal cancer, lung cancer, and cervical cancer.

  • Cardiovascular Disease

    7 June 2018

    Cardiovascular disease (CVD) includes all the diseases of the heart and circulation such as coronary heart disease, angina, heart attack, congenital heart disease and stroke. Despite improvements in the prevention and treatment of CVD, it remains the leading cause of death worldwide particularly in developed countries.

  • Cholesterol

    7 June 2018

    Blood lipids are a major cause of cardiovascular disease. It has been known for some time that higher levels of LDL ("bad") cholesterol and lower levels of HDL cholesterol are associated with higher heart disease risk, but effective treatments to substantially lower LDL cholesterol have only become available in recent decades.

  • Dementia and other Neurodegenerative Diseases

    7 June 2018

    Degenerative diseases of the brain and nervous system such as dementia, Parkinson’s disease and motor neuron disease, are common and serious health problems of middle and old age.

  • Diet, Nutrition and Obesity

    7 June 2018

    Obesity is a major factor influencing the burden of disease globally. We investigate the impact of obesity on health and on the healthcare system across a range of diseases. Our research into diet and nutrition assesses the environmental determinants of dietary behaviour and models and evaluates population based interventions, such as food labelling and so-called junk food taxes, which aim to promote healthier eating.

  • Healthcare Economics

    7 June 2018

    Health Economics research explores the economic aspects of health and disease including the determinants of health, the economic consequences of ill health, the costs and benefits of prevention and treatment, and the financing, design and evaluation of health systems.

  • Health Ethics and Law

    7 June 2018

    The translation of medical research into health care practice can present a range of ethical challenges. If ethical and social issues are not identified, analysed and appropriately addressed as research progresses, they have the potential to block the successful completion of the research and its translation into health benefits. In a time of rapid scientific advances and emerging technologies in healthcare, the exploration of the relationships between law, ethics and practice can identify how new technologies may be accommodated within existing legal frameworks and whether these frameworks need to change.

  • Kidney Disease and Diabetes

    7 June 2018

    More than half a million people worldwide have a kidney transplant and many more are waiting for one. People with kidney disease have a much higher risk of developing a number of diseases, particularly cardiovascular disease. In Diabetes Mellitus blood sugar levels are raised over a prolonged period. People with diabetes are at increased risk of cardiovascular disease, kidney disease and damage to the eyes. Rates of type-2 diabetes have increased rapidly in recent decades due to changes in diet and other lifestyle factors.