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Clark A.L.,Hull York Medical School | Johnson M.,University of Hull | Fairhurst C.,University of York | Torgerson D.,University of York | And 10 more authors.
Health Technology Assessment | Year: 2015

Background: Home oxygen therapy (HOT) is commonly used for patients with severe chronic heart failure (CHF) who have intractable breathlessness. There is no trial evidence to support its use. Objectives: To detect whether or not there was a quality-of-life benefit from HOT given as long-term oxygen therapy (LTOT) for at least 15 hours per day in the home, including overnight hours, compared with best medical therapy (BMT) in patients with severely symptomatic CHF. Design: A pragmatic, two-arm, randomised controlled trial recruiting patients with severe CHF. It included a linked qualitative substudy to assess the views of patients using home oxygen, and a free-standing substudy to assess the haemodynamic effects of acute oxygen administration. Setting: Heart failure outpatient clinics in hospital or the community, in a range of urban and rural settings. Participants: Patients had to have heart failure from any aetiology, New York Heart Association (NYHA) class III/IV symptoms, at least moderate left ventricular systolic dysfunction, and be receiving maximally tolerated medical management. Patients were excluded if they had had a cardiac resynchronisation therapy device implanted within the past 3 months, chronic obstructive pulmonary disease fulfilling the criteria for LTOT or malignant disease that would impair survival or were using a device or medication that would impede their ability to use LTOT. Interventions: Patients received BMT and were randomised (unblinded) to open-label LTOT, prescribed for 15 hours per day including overnight hours, or no oxygen therapy. Main outcome measures: The primary end point was quality of life as measured by the Minnesota Living with Heart Failure (MLwHF) questionnaire score at 6 months. Secondary outcomes included assessing the effect of LTOT on patient symptoms and disease severity, and assessing its acceptability to patients and carers. Results: Between April 2012 and February 2014, 114 patients were randomised to receive either LTOT or BMT. The mean age was 72.3 years [standard deviation (SD) 11.3 years] and 70% were male. Ischaemic heart disease was the cause of heart failure in 84%; 95% were in NYHA class III; the mean left ventricular ejection fraction was 27.8%; and the median N-terminal pro-B-type natriuretic hormone was 2203 ng/l. The primary analysis used a covariance pattern mixed model which included patients only if they provided data for all baseline covariates adjusted for in the model and outcome data for at least one post-randomisation time point (n = 102: intervention, n = 51; control, n = 51). There was no difference in the MLwHF questionnaire score at 6 months between the two arms [at baseline the mean score was 54.0 (SD 18.4) for LTOT and 54.0 (SD 17.9) for BMT; at 6 months the mean score was 48.1 (SD 18.5) for LTOT and 49.0 (SD 20.2) for BMT; adjusted mean difference –0.10, 95% confidence interval (CI) –6.88 to 6.69; p = 0.98]. At 3 months, the adjusted mean MLwHF questionnaire score was lower in the LTOT group (–5.47, 95% CI –10.54 to –0.41; p = 0.03) and breathlessness scores improved, although the effect did not persist to 6 months. There was no effect of LTOT on any secondary measure. There was a greater number of deaths in the BMT arm (n = 12 vs. n = 6). Adherence was poor, with only 11% of patients reporting using the oxygen as prescribed. Conclusions: Although the study was significantly underpowered, HOT prescribed for 15 hours per day and subsequently used for a mean of 5.4 hours per day has no impact on quality of life as measured by the MLwHF questionnaire score at 6 months. Suggestions for future research include (1) a trial of patients with severe heart failure randomised to have emergency oxygen supply in the house, supplied by cylinders rather than an oxygen concentrator, powered to detect a reduction in admissions to hospital, and (2) a study of bed-bound patients with heart failure who are in the last few weeks of life, powered to detect changes in symptom severity. © Queen’s Printer and Controller of HMSO 2015.

Lucas G.,Institute Municipal dInvestigacio Medica IMIM | Lluis-Ganella C.,Institute Municipal dInvestigacio Medica IMIM | Subirana I.,Institute Municipal dInvestigacio Medica IMIM | Subirana I.,Research Center Biomedica En Red Of Epidemiologia lud Publica | And 12 more authors.
Circulation: Cardiovascular Genetics | Year: 2011

Background-After age, sex is the most important risk factor for coronary artery disease (CAD). The mechanism through which women are protected from CAD is still largely unknown, but the observed sex difference suggests the involvement of the reproductive steroid hormone signaling system. Genetic association studies of the gene-encoding Estrogen Receptor α (ESR1) have shown conflicting results, although only a limited range of variation in the gene has been investigated. Methods and Results-We exploited information made available by advanced new methods and resources in complex disease genetics to revisit the question of ESR1's role in risk of CAD. We performed a meta-analysis of 14 genome-wide association studies (CARDIoGRAM discovery analysis, N=≈87 000) to search for population-wide and sex-specific associations between CAD risk and common genetic variants throughout the coding, noncoding, and flanking regions of ESR1. In addition to samples from the MIGen (N=≈6000), WTCCC (N=≈7400), and Framingham (N=≈3700) studies, we extended this search to a larger number of common and uncommon variants by imputation into a panel of haplotypes constructed using data from the 1000 Genomes Project. Despite the widespread expression of ERα in vascular tissues, we found no evidence for involvement of common or low-frequency genetic variation throughout the ESR1 gene in modifying risk of CAD, either in the general population or as a function of sex. Conclusions-We suggest that future research on the genetic basis of sex-related differences in CAD risk should initially prioritize other genes in the reproductive steroid hormone biosynthesis system. © 2011 American Heart Association, Inc.

Patel N.,Royal Infirmary | Patel N.,Leicester Cardiovascular Biomedical Research Unit | Minhas J.S.,Royal Infirmary | Minhas J.S.,University of Leicester | And 3 more authors.
Journal of Cardiac Surgery | Year: 2015

Patients are commonly reported to experience postoperative cognitive decline (POCD) and new ischemic lesions following surgery, which many researchers have hypothesised to result from emboli entering the cerebral circulation during surgery. Modern magnetic resonance imaging techniques have enabled clear and accurate identification of ischemic lesions. However, difficulties in assessing subtle changes in cognitive impairment clinically remain. The purpose of this systematic review is to discuss the literature that has investigated cognitive outcome in relation to new ischaemic brain lesions after cardiac surgery. © 2015 Wiley Periodicals, Inc.

Patel N.,University of Leicester | Patel N.,Leicester Cardiovascular Biomedical Research Unit | Minhas J.S.,University of Leicester | Chung E.M.L.,University of Leicester | Chung E.M.L.,Leicester Cardiovascular Biomedical Research Unit
Cardiovascular Psychiatry and Neurology | Year: 2015

Modern day cardiac surgery evolved upon the advent of cardiopulmonary bypass machines (CPB) in the 1950s. Following this development, cardiac surgery in recent years has improved significantly. Despite such advances and the introduction of new technologies, neurological sequelae after cardiac surgery still exist. Ischaemic stroke, delirium, and cognitive impairment cause significant morbidity and mortality and unfortunately remain common complications. Postoperative cognitive decline (POCD) is believed to be associated with the presence of new ischaemic lesions originating from emboli entering the cerebral circulation during surgery. Cardiopulmonary bypass was thought to be the reason of POCD, but randomised controlled trials comparing with off-pump surgery show contradictory results. Attention has now turned to the growing evidence that perioperative risk factors, as well as patient-related risk factors, play an important role in early and late POCD. Clearly, identifying the mechanism of POCD is challenging. The purpose of this systematic review is to discuss the literature that has investigated patient and perioperative risk factors to better understand the magnitude of the risk factors associated with POCD after cardiac surgery. © 2015 Nikil Patel et al.

Shah S.,University College London | Nelson C.P.,University of Leicester | Nelson C.P.,Leicester Cardiovascular Biomedical Research Unit | Gaunt T.R.,University of Bristol | And 42 more authors.
Circulation: Cardiovascular Genetics | Year: 2011

Background-Presence of left ventricular hypertrophy on an ECG (ECG-LVH) is widely assessed clinically and provides prognostic information in some settings. There is evidence for significant heritability of ECG-LVH. We conducted a large-scale gene-centric association analysis of 4 commonly measured indices of ECG-LVH. Methods and Results-We calculated the Sokolow-Lyon index, Cornell product, 12-lead QRS voltage sum, and 12-lead QRS voltage product in 10 256 individuals from 3 population-based cohorts and typed their DNA using a customized gene array (the Illumina HumanCVD BeadChip 50K array), containing 49 094 genetic variants in≈2100 genes of cardiovascular relevance. We followed-up promising associations in 11 777 additional individuals. We identified and replicated 4 loci associated with ECG-LVH indices: 3p22.2 (SCN5A, rs6797133, P=1.22×10 -7) with Cornell product and 12q13.3 (PTGES3, rs2290893, P=3.74×10 -8), 15q25.2 (NMB, rs2292462, P=3.23×10 -9), and 15q26.3 (IGF1R, rs4966014, P=1.26×10 -7) with the 12-lead QRS voltage sum. The odds ratio of being in the top decile for the 12-lead QRS voltage sum for those carrying 6 trait-raising alleles at the 12q13.3, 15q25.2, and 15q26.3 loci versus those carrying 0 to 1 alleles was 1.60 (95% CI: 1.20 to 2.29). Lead single-nucleotide polymorphisms at the 12q13.3 and 15q25.2 loci showed significant expression quantitative trait loci effects in monocytes. Conclusions-These findings provide novel insights into the genetic determination of ECG-LVH. The findings could help to improve our understanding of the mechanisms determining this prognostically important trait. © 2011 American Heart Association, Inc.

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