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  • Empirical bioethics: Theoretical and practical perspectives

    12 September 2018

    © Cambridge University Press 2017. All rights reserved. Bioethics has long been accepted as an interdisciplinary field. The recent 'empirical turn' in bioethics is, however, creating challenges that move beyond those of simple interdisciplinary collaboration, as researchers grapple with the methodological, empirical and meta-ethical challenges of combining the normative and the empirical, as well as navigating the difficulties that can arise from attempts to transcend traditional disciplinary boundaries. Empirical Bioethics: Theoretical and Practical Perspectives brings together contributions from leading experts in the field which speak to these challenges, providing insight into how they can be understood and suggestions for how they might be overcome. Combining discussions of meta-ethical challenges, examples of different methodologies for integrating empirical and normative research, and reflection on the challenges of conducting and publishing such work, this book will both introduce the novice to the field and challenge the expert.

  • Childhood cancer research in oxford III: The work of CCRG on ionising radiation.

    12 September 2018

    BACKGROUND: High doses of ionising radiation are a known cause of childhood cancer and great public and professional interest attaches to possible links between childhood cancer and lower doses, particularly of man-made radiation. This paper describes work done by the Childhood Cancer Research Group (CCRG) on this topic METHODS: Most UK investigations have made use of the National Registry of Childhood Tumours and associated controls. Epidemiological investigations have included national incidence and mortality analyses, geographical investigations, record linkage and case-control studies. Dosimetric studies use biokinetic and dosimetric modelling. RESULTS: This paper reviews the work of the CCRG on the association between exposure to ionising radiation and childhood cancer, 1975-2014. CONCLUSION: The work of CCRG has been influential in developing understanding of the causes of 'clusters' of childhood cancer and the risks arising from exposure to ionising radiation both natural and man-made. Some clusters around nuclear installations have certainly been observed, but ionising radiation does not seem to be a plausible cause. The group's work has also been instrumental in discounting the hypothesis that paternal preconception irradiation was a cause of childhood cancers and has demonstrated an increased leukaemia risk for children exposed to higher levels of natural gamma-ray radiation.

  • Childhood cancer research in Oxford II: The Childhood Cancer Research Group.

    12 September 2018

    BACKGROUND: We summarise the work of the Childhood Cancer Research Group, particularly in relation to the UK National Registry of Childhood Tumours (NRCT). METHODS: The Group was responsible for setting up and maintaining the NRCT. This registry was based on notifications from regional cancer registries, specialist children's tumour registries, paediatric oncologists and clinical trials organisers. For a large sample of cases, data on controls matched by date and place of birth were also collected. RESULTS: Significant achievements of the Group include: studies of aetiology and of genetic epidemiology; proposals for, and participation in, international comparative studies of these diseases and on a classification system specifically for childhood cancer; the initial development of, and major contributions to, follow-up studies of the health of long-term survivors; the enhancement of cancer registration records by the addition of clinical data and of birth records. The Group made substantial contributions to the UK government's Committee on Medical Aspects of Radiation in the Environment. CONCLUSION: An important part of the ethos of the Group was to work in collaboration with many other organisations and individuals, both nationally and internationally: many of the Group's achievements described here were the result of such collaborations.

  • Cardiac Structure Injury After Radiotherapy for Breast Cancer: Cross-Sectional Study With Individual Patient Data.

    12 September 2018

    Purpose Incidental cardiac irradiation can cause cardiac injury, but little is known about the effect of radiation on specific cardiac segments. Methods For 456 women who received breast cancer radiotherapy between 1958 and 2001 and then later experienced a major coronary event, information was obtained on the radiotherapy regimen they received and on the location of their cardiac injury. For 414 women, all with documented location of left ventricular (LV) injury, doses to five LV segments were estimated. For 133 women, all with documented location of coronary artery disease with ≥ 70% stenosis, doses to six coronary artery segments were estimated. For each segment, numbers of women with left-sided and right-sided breast cancer were compared. Results Of women with LV injury, 243 had left-sided breast cancer and 171 had right-sided breast cancer (ratio of left v right, 1.42; 95% CI, 1.17 to 1.73), reflecting the higher typical LV radiation doses in left-sided cancer (average dose left-sided, 8.3 Gy; average dose right-sided, 0.6 Gy; left minus right dose difference, 7.7 Gy). For individual LV segments, the ratios of women with left- versus right-sided radiotherapy were as follows: inferior, 0.94 (95% CI, 0.70 to 1.25); lateral, 1.42 (95% CI, 1.04 to 1.95); septal, 2.09 (95% CI, 1.37 to 3.19); anterior, 1.85 (95% CI, 1.39 to 2.46); and apex, 4.64 (95% CI, 2.42 to 8.90); corresponding left-minus-right dose differences for these segments were 2.7, 4.9, 7.2, 10.4, and 21.6 Gy, respectively ( Ptrend < .001). For women with coronary artery disease, the ratios of women with left- versus right-radiotherapy for individual coronary artery segments were as follows: right coronary artery proximal, 0.48 (95% CI, 0.26 to 0.91); right coronary artery mid or distal, 1.69 (95% CI, 0.85 to 3.36); circumflex proximal, 1.46 (95% CI, 0.72 to 2.96); circumflex distal, 1.11 (95% CI, 0.45 to 2.73); left anterior descending proximal, 1.89 (95% CI, 1.07 to 3.34); and left anterior descending mid or distal, 2.33 (95% CI, 1.19 to 4.59); corresponding left-minus-right dose differences for these segements were -5.0, -2.5, 1.6, 3.5, 9.5, and 38.8 Gy ( Ptrend = .002). Conclusion For individual LV and coronary artery segments, higher radiation doses were strongly associated with more frequent injury, suggesting that all segments are sensitive to radiation and that doses to all segments should be minimized.

  • PCSK9 inhibition: ready for prime time in CKD?

    12 September 2018

    Lowering LDL cholesterol reduces the risk of atherosclerotic vascular disease in a wide range of patients with chronic kidney disease, with no evidence of a threshold below which further reductions no longer reduce risk. Statins safely lower LDL cholesterol, but novel inhibitors of proprotein convertase subtilisin kexin 9 (PCSK9) provide additional reductions which may reduce atherosclerotic vascular disease yet further in this high risk population.

  • Gestational age at birth and wheezing trajectories at 3-11 years.

    12 September 2018

    OBJECTIVE: Children born preterm have an increased risk of asthma in early childhood. We examined whether this persists at 7 and 11 years, and whether wheezing trajectories across childhood are associated with preterm birth. DESIGN: Data were from the UK Millennium Cohort Study, which recruited children at 9 months, with follow-up at 3, 5, 7 and 11 years. OUTCOMES: Adjusted ORs (aOR) were estimated for recent wheeze and asthma medication use for children born <32, 32-33, 34-36 and 37-38 weeks' gestation, compared with children born at full term (39-41 weeks) at 7 (n=12 198) and 11 years (n=11 690). aORs were also calculated for having 'early-remittent' (wheezing at ages 3 and/or 5 years but not after), 'late' (wheezing at ages 7 and/or 11 years but not before) or 'persistent/relapsing' (wheezing at ages 3 and/or 5 and 7 and/or 11 years) wheeze. RESULTS: Birth <32 weeks, and to a lesser extent at 32-33 weeks, were associated with an increased risk of wheeze and asthma medication use at ages 7 and 11, and all three wheezing trajectories. The aOR for 'persistent/relapsing wheeze' at <32 weeks was 4.30 (95% CI 2.33 to 7.91) and was 2.06 (95% CI 1.16 to 2.69) at 32-33 weeks. Birth at 34-36 weeks was not associated with asthma medication use at 7 or 11, nor late wheeze, but was associated with the other wheezing trajectories. Birth at 37-38 weeks was not associated with wheeze nor asthma medication use. CONCLUSIONS: Birth <37 weeks is a risk factor for wheezing characterised as 'early-remittent' or 'persistent/relapsing' wheeze.

  • Effect of Vitamin D Supplementation on Markers of Vascular Function: A Systematic Review and Individual Participant Meta-Analysis.

    12 September 2018

    BACKGROUND: Low 25-hydroxyvitamin D levels are associated with an increased risk of cardiovascular events, but the effect of vitamin D supplementation on markers of vascular function associated with major adverse cardiovascular events is unclear. METHODS AND RESULTS: We conducted a systematic review and individual participant meta-analysis to examine the effect of vitamin D supplementation on flow-mediated dilatation of the brachial artery, pulse wave velocity, augmentation index, central blood pressure, microvascular function, and reactive hyperemia index. MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.gov were searched until the end of 2016 without language restrictions. Placebo-controlled randomized trials of at least 4 weeks duration were included. Individual participant data were sought from investigators on included trials. Trial-level meta-analysis was performed using random-effects models; individual participant meta-analyses used a 2-stage analytic strategy, examining effects in prespecified subgroups. 31 trials (2751 participants) were included; 29 trials (2641 participants) contributed data to trial-level meta-analysis, and 24 trials (2051 participants) contributed to individual-participant analyses. Vitamin D3 daily dose equivalents ranged from 900 to 5000 IU; duration was 4 weeks to 12 months. Trial-level meta-analysis showed no significant effect of supplementation on macrovascular measures (flow-mediated dilatation, 0.37% [95% confidence interval, -0.23 to 0.97]; carotid-femoral pulse wave velocity, 0.00 m/s [95% confidence interval, -0.36 to 0.37]); similar results were obtained from individual participant data. Microvascular function showed a modest improvement in trial-level data only. No consistent benefit was observed in subgroup analyses or between different vitamin D analogues. CONCLUSIONS: Vitamin D supplementation had no significant effect on most markers of vascular function in this analysis.

  • Cardiovascular risk factors and frailty in a cross-sectional study of older people: implications for prevention.

    12 September 2018

    Objective: to examine the associations of cardiovascular disease (CVD) and cardiovascular risk factors with frailty. Design: a cross-sectional study. Setting: the Irish Longitudinal Study on Ageing (TILDA). Participants: frailty measures were obtained on 5,618 participants and a subset of 4,330 participants with no prior history of CVD. Exposures for observational study: cardiovascular risk factors were combined in three composite CVD risk scores (Systematic Coronary Risk Evaluation [SCORE], Ideal Cardiovascular Health [ICH] and Cardiovascular Health Metrics [CHM]). Main outcome measures: a frailty index (40-items) was used to screen for frailty. Methods: the associations of CVD risk factors with frailty were examined using logistic regression. Results: overall, 16.4% of participants had frailty (7.6% at 50-59 years to 42.5% at 80+ years), and the prevalence was higher in those with versus those without prior CVD (43.0% vs. 10.7%). Among those without prior CVD, mean levels of CVD risk factors were closely correlated with higher frailty index scores. Combined CVD risk factors, assessed using SCORE, were linearly and positively associated with frailty. Compared to low-to-moderate SCOREs, the odds ratio (OR) (95% confidence interval, CI) of frailty for those with very high risk was 3.18 (2.38-4.25). Conversely, ICH was linearly and inversely associated with frailty, with an OR for optimal health of 0.29 (0.21-0.40) compared with inadequate health. Conclusions: the concordant positive associations of SCORE and inverse associations of ICH and CHM with frailty highlight the potential importance of optimum levels of CVD risk factors for prevention of disability in frail older people.

  • 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.