ORCID Profile
0000-0002-8896-073X
Current Organisations
University of the West Indies
,
University of Manchester
,
University of Glasgow
,
The London School of Economics and Political Science
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Publisher: Elsevier BV
Date: 12-2021
Publisher: Massachusetts Medical Society
Date: 12-10-2006
DOI: 10.1056/NEJMOA065061
Publisher: Elsevier BV
Date: 02-2014
Publisher: BMJ
Date: 26-07-2016
Publisher: Elsevier BV
Date: 03-2022
Publisher: SAGE Publications
Date: 29-09-2016
Abstract: Diabetes, obesity and metabolic syndrome are highly prevalent in patients with severe mental illness and can impose a major physical health burden. To determine how anthropometric and metabolic features changed over time in a retrospective cohort of people with Severe Mental Illness living in Cheshire, UK. In all, 1307 in iduals on the severe mental illness Register were followed up between 2002 and 2012 in UK general practice. Subjects were identified through a pseudanonymised search of general practice registers. Baseline body mass index was 28.6 kg/m 2 increasing to 31.0 at 10-year follow-up ( r 2 = 0.84 p = 0.0002). There was a significant increase in fasting blood glucose from 5.72 to 6.79 mmol/L ( r 2 = 0.48 p = 0.026). Correspondingly, there was a strong positive univariate relation between increase in body mass index and fasting blood glucose ( r 2 = 0.54 p 0.0001) taking into account all measurements. Fasting blood glucose also increased slightly with age ( p = 0.028). With increasing use of statins, total cholesterol fell from 4.5 to 3.9 mmol/L ( r 2 = 0.88 p = 0.0001), as did low-density lipoprotein cholesterol from 3.43 to 2.35 mmol/L ( r 2 = 0.94 p = 0.0001). In multivariate models, adjusting for age, gender, smoking and blood pressure, each unit increase in body mass index (odds ratio = 1.07 [1.01, 1.13] p = 0.031) and triglycerides (odds ratio = 1.28 (1.06, 1.55) p = 0.009) was independently associated with an increased risk of having type 2 diabetes. Increasing body mass index relates to increasing rates of dysglycaemia over time. Measures to encourage weight reduction should be key strategies to reduce dysglycaemia rates in severe mental illness. Prescribing statins may have been effective in improving the lipid profile in this group.
Publisher: Cold Spring Harbor Laboratory
Date: 25-09-2019
DOI: 10.1101/781666
Abstract: Pulmonary inflammatory responses lie under circadian control however the importance of circadian mechanisms in fibrosis is not understood. Here, we identify a striking change to these mechanisms resulting in a gain of litude and lack of synchrony within pulmonary fibrotic tissue. These changes result from an infiltration of mesenchymal cells, an important cell type in the pathogenesis of pulmonary fibrosis. Mutation of the core clock protein REVERBα in these cells exacerbated the development of bleomycin-induced fibrosis, whereas mutation of REVERBα in club or myeloid cells had no effect on the bleomycin phenotype. Knockdown of REVERBα revealed regulation of the poorly described transcription factor TBPL1. Both REVERBα and TBPL1 altered integrinβ1 focal adhesion formation, resulting in increased myofibroblast activation. The translational importance of our findings was established through analysis of two human cohorts. In the UK Biobank circadian strain markers (sleep length, chronotype and shift work) are associated with pulmonary fibrosis making them novel risk factors. In a separate cohort REVERBα expression was increased in human idiopathic pulmonary fibrosis (IPF) lung tissue. Pharmacological targeting of REVERBα inhibited myofibroblast activation in IPF fibroblasts and collagen secretion in organotypic cultures from IPF patients, suggesting targeting REVERBα could be a viable therapeutic approach. The circadian clock plays an essential role in energy metabolism, and inflammation. In contrast the importance of the clock in the pathogenesis of fibrosis remains poorly explored. This study describes a striking alteration in circadian biology during pulmonary fibrosis where the relatively arrhythmic alveolar structures gain circadian but desynchronous rhythmicity due to infiltration by fibroblasts. Disruption of the clock in these cells, which are not widely implicated in circadian pathophysiology, results in a pro-fibrotic phenotype. Translation of these findings in humans revealed previously unrecognised important circadian risk factors for pulmonary fibrosis (sleep length, chronotype and shift work). In addition, targeting REVERBα repressed collagen secretion from human fibrotic lung tissue making this protein a promising therapeutic target.
Publisher: Elsevier BV
Date: 03-2016
Publisher: Elsevier BV
Date: 09-2006
Publisher: BMJ
Date: 16-08-2016
DOI: 10.1136/HEARTJNL-2016-309706
Abstract: Investigation of variations in provider performance and its determinants may help inform strategies for improving patient outcomes. We used the National Heart Failure Audit comprising 68 772 patients with heart failure with reduced left ventricular ejection fraction (HFREF), admitted to 185 hospitals in England and Wales (2007-2013). We investigated hospital adherence to three recommended key performance measures (KPMs) for inhospital care (ACE inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) on discharge, β-blockers on discharge and referral to specialist follow-up) in idually and as a composite performance score. Hierarchical regression models were used to investigate hospital-level variation. Hospital-level variation in adherence to composite KPM ranged from 50% to 97% (median 79%), but after adjustments for patient characteristics and year of admission, only 8% (95% CI 7% to 10%) of this variation was attributable to variations in hospital features. Similarly, hospital prescription rates for ACE-I/ARB and β-blocker showed low adjusted hospital-attributable variations (7% CI 6% to 9% and 6% CI 5% to 8%, for ACE-I/ARB and β-blocker, respectively). Referral to specialist follow-up, however, showed larger variations (median 81% range 20%, 100%) with 26% of this being attributable to hospital-level differences (CI 22% to 31%). Only a small proportion of hospital variation in medication prescription after discharge was attributable to hospital-level features. This suggests that differences in hospital practices are not a major determinant of observed variations in prescription of investigated medications and outcomes. Future healthcare delivery efforts should consider evaluation and improvement of more ambitious KPMs.
Publisher: American Medical Association (AMA)
Date: 2017
DOI: 10.1001/JAMAINTERNMED.2016.6821
Abstract: On the basis of observational studies, the use of thiazide diuretics for the treatment of hypertension is associated with reduced fracture risk compared with nonuse. Data from randomized clinical trials are lacking. To examine whether the use of thiazide diuretics for the treatment of hypertension is associated with reduced fracture risk compared with nonuse. Using Veterans Affairs and Medicare claims data, this study examined hip and pelvic fracture hospitalizations in Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial participants randomized to first-step therapy with a thiazide-type diuretic (chlorthalidone), a calcium channel blocker (amlodipine besylate), or an angiotensin-converting enzyme inhibitor (lisinopril). Recruitment was from February 1994 to January 1998 in-trial follow-up ended in March 2002. The mean follow-up was 4.9 years. Posttrial follow-up was conducted through the end of 2006, using passive surveillance via national databases. For this secondary analysis, which used an intention-to-treat approach, data were analyzed from February 1, 1994, through December 31, 2006. Hip and pelvic fracture hospitalizations. A total of 22 180 participants (mean [SD] age, 70.4 [6.7] years 43.0% female and 49.9% white non-Hispanic, 31.2% African American, and 19.1% other ethnic groups) were followed for up to 8 years (mean [SD], 4.9 [1.5] years) during masked therapy. After trial completion, 16 622 participants for whom claims data were available were followed for up to 5 additional years (mean [SD] total follow-up, 7.8 [3.1] years). During the trial, 338 fractures occurred. Participants randomized to receive chlorthalidone vs amlodipine or lisinopril had a lower risk of fracture on adjusted analyses (hazards ratio [HR], 0.79 95% CI, 0.63-0.98 P = .04). Risk of fracture was significantly lower in participants randomized to receive chlorthalidone vs lisinopril (HR, 0.75 95% CI, 0.58-0.98 P = .04) but not significantly different compared with those randomized to receive amlodipine (HR, 0.82 95% CI, 0.63-1.08 P = .17). During the entire trial and posttrial period of follow-up, the cumulative incidence of fractures was nonsignificantly lower in participants randomized to receive chlorthalidone vs lisinopril or amlodipine (HR, 0.87 95% CI, 0.74-1.03 P = .10) and vs each medication separately. In sensitivity analyses, when 1 year after randomization was used as the baseline (to allow for the effects of medications on bone to take effect), similar results were obtained for in-trial and in-trial plus posttrial follow-up. These findings from a large randomized clinical trial provide evidence of a beneficial effect of thiazide-type diuretic therapy in reducing hip and pelvic fracture risk compared with treatment with other antihypertensive medications. clinicaltrials.gov Identifier: NCT00000542.
Publisher: Elsevier BV
Date: 07-2015
DOI: 10.1016/J.JACC.2015.05.052
Abstract: Percutaneous coronary intervention (PCI) is increasingly being performed at centers with offsite surgical support. Strong guideline endorsement of this practice has been lacking, in part because outcome data are limited to modest-size populations with short-term follow-up. The aim of this study was to compare the outcomes of PCI performed at centers with and without surgical support in the United Kingdom between 2006 and 2012. A retrospective analysis was performed of centrally tracked outcomes from index PCI procedures entered in the British Cardiovascular Intervention Society database between 2006 and 2012, stratified according to whether procedures were performed at centers with onsite or offsite surgical support. The primary endpoint was 30-day all-cause mortality, with secondary endpoints of mortality at 1 and 5 years. Outcomes at a median of 3.4 years follow-up were available for 384,013 patients, of whom 31% (n = 119,096) were treated at offsite surgical centers. In an unadjusted analysis, crude mortality rates were lower in patients treated at centers with offsite versus onsite surgical coverage (2.0% vs. 2.2% p < 0.001). On multivariate adjustment, there were no between-group differences in survival between the naive and imputed populations at 30 days (naive population hazard ratio [HR]: 0.87 95% confidence interval [CI]: 0.71 to 1.06 p = 0.16 imputed population HR: 0.99 95% CI: 0.89 to 1.09 p = 0.82), 1 year (naive population HR: 0.92 95% CI: 0.79 to 1.07 p = 0.26 imputed population HR: 0.99 95% CI: 0.92 to 1.06 p = 0.78), or 5 years (naive population HR: 0.92 95% CI: 0.84 to 1.01 p = 0.10 imputed population HR: 0.97 95% CI: 0.92 to 1.03 p = 0.29). Results were consistent irrespective of procedural indication. No differences in mortality were seen in sensitivity analyses performed using a propensity-matched population of 74,001 patients. PCI performed at centers without onsite surgical backup is not associated with any mortality hazard.
Publisher: Springer Science and Business Media LLC
Date: 25-02-2019
Publisher: Oxford University Press (OUP)
Date: 07-06-2010
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 16-02-2016
Publisher: Elsevier BV
Date: 10-2015
Publisher: Springer Science and Business Media LLC
Date: 02-2001
DOI: 10.1038/35055536
Abstract: The origin of the ratites, large flightless birds from the Southern Hemisphere, along with their flighted sister taxa, the South American tinamous, is central to understanding the role of plate tectonics in the distributions of modern birds and mammals. Defining the dates of ratite ergences is also critical for determining the age of modern avian orders. To resolve the ratite phylogeny and provide biogeographical data to examine these issues, we have here determined the first complete mitochondrial genome sequences of any extinct taxa--two New Zealand moa genera--along with a 1,000-base-pair sequence from an extinct Madagascan elephant-bird. For comparative data, we also generated 12 kilobases of contiguous sequence from the kiwi, cassowary, emu and two tinamou genera. This large dataset allows statistically precise estimates of molecular ergence dates and these support a Late Cretaceous vicariant speciation of ratite taxa, followed by the subsequent dispersal of the kiwi to New Zealand. This first molecular view of the break-up of Gondwana provides a new temporal framework for speciation events within other Gondwanan biota and can be used to evaluate competing biogeographical hypotheses.
Publisher: BMJ
Date: 29-09-2015
DOI: 10.1136/BMJ.H4865
Abstract: To determine the subgroup specific associations between usual blood pressure and risk of peripheral arterial disease, and to examine the relation between peripheral arterial disease and a range of other types of vascular disease in a large contemporary cohort. Cohort study. Linked electronic health records from 1990 to 2013 in the United Kingdom. 4,222,459 people aged 30-90 years, registered at a primary care practice for at least one year and with a blood pressure measurement. Time to first diagnosis of new onset peripheral arterial disease and time to first diagnosis of 12 different vascular events. A 20 mm Hg higher than usual systolic blood pressure was associated with a 63% higher risk of peripheral arterial disease (hazard ratio 1.63, 95% confidence interval 1.59 to 1.66). The strength of the association declined with increasing age and body mass index (P<0.001 for interaction) but was not modified by sex or smoking status. Peripheral arterial disease was associated with an increased risk of 11 different vascular events, including ischaemic heart disease (1.68, 1.58 to 1.79), heart failure (1.63, 1.52 to 1.75), aortic aneurysm (2.10, 1.79 to 2.45), and chronic kidney disease (1.31, 1.25 to 1.38), but not haemorrhagic stroke. The most common initial vascular event among those with peripheral arterial disease was chronic kidney disease (24.4% of initial events), followed by ischaemic heart disease (18.5% of initial events), heart failure (14.7%), and atrial fibrillation (13.2%). Overall estimates from this cohort were consistent with those derived from traditional studies when we pooled the findings in two meta-analyses. Raised blood pressure is a strong risk factor for peripheral arterial disease in a range of patient subgroups. Furthermore, clinicians should be aware that those with established peripheral arterial disease are at an increased risk of a range of other vascular events, including chronic kidney disease, ischaemic heart disease, heart failure, atrial fibrillation, and stroke.
Publisher: Elsevier BV
Date: 02-2017
Publisher: Oxford University Press (OUP)
Date: 03-05-2016
DOI: 10.1093/IJE/DYW053
Publisher: Proceedings of the National Academy of Sciences
Date: 26-12-2019
Abstract: Pulmonary inflammatory responses lie under circadian control however, the importance of circadian mechanisms in the underlying fibrotic phenotype is not understood. Here, we identify a striking change to these mechanisms resulting in a gain of litude and lack of synchrony within pulmonary fibrotic tissue. These changes result from an infiltration of mesenchymal cells, an important cell type in the pathogenesis of pulmonary fibrosis. Mutation of the core clock protein REVERBα in these cells exacerbated the development of bleomycin-induced fibrosis, whereas mutation of REVERBα in club or myeloid cells had no effect on the bleomycin phenotype. Knockdown of REVERBα revealed regulation of the little-understood transcription factor TBPL1. Both REVERBα and TBPL1 altered integrinβ1 focal-adhesion formation, resulting in increased myofibroblast activation. The translational importance of our findings was established through analysis of 2 human cohorts. In the UK Biobank, circadian strain markers (sleep length, chronotype, and shift work) are associated with pulmonary fibrosis, making them risk factors. In a separate cohort, REVERBα expression was increased in human idiopathic pulmonary fibrosis (IPF) lung tissue. Pharmacological targeting of REVERBα inhibited myofibroblast activation in IPF fibroblasts and collagen secretion in organotypic cultures from IPF patients, thus suggesting that targeting of REVERBα could be a viable therapeutic approach.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2016
DOI: 10.1161/STROKEAHA.116.012658
Abstract: Vascular dementia is the second most common form of dementia but reliable evidence on age-specific associations between blood pressure (BP) and risk of vascular dementia is limited and some studies have reported negative associations at older ages. In a cohort of 4.28 million in iduals, free of known vascular disease and dementia and identified from linked electronic primary care health records in the United Kingdom (Clinical Practice Research Datalink), we related BP to time to physician-diagnosed vascular dementia. We further determined associations between BP and dementia in a prospective population-based cohort of incident transient ischemic attack and stroke (Oxford Vascular Study). For a median follow-up of 7.0 years, 11 114 initial presentations of vascular dementia were observed in the primary care cohort after exclusion of the first 4 years of follow-up. The association between usual systolic BP and risk of vascular dementia decreased with age (hazard ratio per 20 mm Hg higher systolic BP, 1.62 95% confidence interval, 1.13–2.35 at 30–50 years 1.26, 1.18–1.35 at 51–70 years 0.97, 0.92–1.03 at 71–90 years P trend=0.006). Usual systolic BP remained predictive of vascular dementia after accounting for effect mediation by stroke and transient ischemic attack. In the population-based cohort, prior systolic BP was predictive of 5-year risk of dementia with no evidence of negative association at older ages. BP is positively associated with risk of vascular dementia, irrespective of preceding transient ischemic attack or stroke. Previous reports of inverse associations in old age could not be confirmed.
Publisher: Springer Science and Business Media LLC
Date: 21-08-2004
DOI: 10.1007/S00125-004-1485-5
Abstract: Diabetes is a rapidly rising independent risk factor for atherosclerosis and serious illness. This risk can be reduced by lifestyle changes and/or various drugs. Novel therapies to prevent diabetes, as well as new risk factors for diabetes, atherosclerosis and obesity require testing and identification. People with impaired fasting glucose or impaired glucose tolerance were randomised to ramipril (15 mg/day) or placebo and rosiglitazone (8 mg/day) or placebo with a 2x2 factorial design. They are assessed semi-annually for the primary outcome (diabetes or death). Diabetes is diagnosed if two consecutive plasma glucose levels exceed diagnostic thresholds (i.e. fasting >/=7.0 mmol/l or 2-h >/=11.1 mmol/l) within a 3-month period. Assuming an annual primary outcome incidence of 5%, there is more than 90% power to detect a 22% reduction. Approximately 20% of participants are having annual carotid ultrasounds to assess the effects on atherosclerosis. Patients screened but not randomised are being followed prospectively to identify determinants of obesity, diabetes and related disorders. A total of 24,872 in iduals in 21 countries were screened over 2 years and are eligible for follow-up. Of these, 5269 were randomised: 1835 (35%) had isolated impaired glucose tolerance, 739 (14%) had isolated impaired fasting glucose, and 2692 (51%) had both disorders. Annual carotid ultrasounds are currently being performed in 1406 randomised in iduals. The DREAM trial and related studies will determine if ramipril or rosiglitazone reduces the number of cases of diabetes and atherosclerosis, and will identify novel risk factors for diabetes.
Publisher: Public Library of Science (PLoS)
Date: 03-09-2014
Publisher: American Society of Clinical Oncology (ASCO)
Date: 11-2022
DOI: 10.1200/GO.22.00154
Abstract: To describe a newly established international registry recruiting erse patients with advanced prostate cancer across academic and community practices to address unmet needs in this population. Initiated in 2017, IRONMAN (International Registry for Men with Advanced Prostate Cancer) is a prospective cohort of patients with advanced prostate cancer. The study will enroll 5,000 patients with metastatic hormone-sensitive prostate cancer (mHSPC) or castration-resistant prostate cancer (CRPC), recruited from Australia, the Bahamas, Barbados, Brazil, Canada, Ireland, Jamaica, Kenya, Nigeria, Norway, South Africa, Spain, Sweden, Switzerland, the United Kingdom, and the United States. The study is collecting datatypes to study variation in care and treatment of advanced prostate cancer across countries and across academic, community-based, and government practices with a focus on clinical outcomes, patient-reported outcomes, epidemiologic data, biologic subtypes, and clinician questionnaires. Through July 2022, 2,682 eligible patients were enrolled in 11 of 12 active countries. Sixty-six percent of patients have mHSPC, and 34% have CRPC. On the basis of self-report, 11% of patients are Black and 9% are Hispanic. Five Veterans Affairs Medical Centers are enrolling patients. Globally, 23% of patients report being veterans of military service. To our knowledge, this is the first international cohort of people newly diagnosed with advanced prostate cancer designed to describe variations in patient management, experiences, and outcomes. IRONMAN aims to identify optimal treatment sequences to improve survival, understand patient-reported outcomes, and explore novel biomarkers to understand treatment resistance mechanisms. Insights from IRONMAN will inform and guide future clinical management of people with mHSPC and CRPC. This cohort study will provide real-world evidence to facilitate a better understanding of the survivorship of people with advanced prostate cancer.
Publisher: American Diabetes Association
Date: 05-2008
DOI: 10.2337/DC07-1868
Abstract: OBJECTIVE—Impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG) are risk factors for diabetes, cardiovascular disease (CVD), and kidney disease. We determined the effects of ramipril and rosiglitazone on combined and in idual CVD and renal outcomes in people with IGT and/or IFG in the Diabetes REduction Assessment With ramipril and rosiglitazone Medication (DREAM) trial. RESEARCH DESIGN AND METHODS—A total of 5,269 people aged ≥30 years, with IGT and/or IFG without known CVD or renal insufficiency, were randomized to 15 mg/day ramipril versus placebo and 8 mg/day rosiglitazone versus placebo. A composite cardiorenal outcome and its CVD and renal components were assessed during the 3-year follow-up. RESULTS—Compared with placebo, neither ramipril (15.7% [412 of 2,623] vs. 16.0% [424 of 2,646] hazard ratio [HR] 0.98 [95% CI 0.84–1.13] P = 0.75) nor rosiglitazone (15.0% [394 of 2,635] vs. 16.8% [442 of 2,634] 0.87 [0.75–1.01] P = 0.07) reduced the risk of the cardiorenal composite outcome. Ramipril had no impact on the CVD and renal components. Rosiglitazone increased heart failure (0.53 vs. 0.08% HR 7.04 [95% CI 1.60–31.0] P = 0.01) but reduced the risk of the renal component (0.80 [0.68–0.93] P = 0.005) prevention of diabetes was independently associated with prevention of the renal component (P & 0.001). CONCLUSIONS—Ramipril did not alter the cardiorenal outcome or its components. Rosiglitazone, which reduced diabetes, also reduced the development of renal disease but not the cardiorenal outcome and increased the risk of heart failure.
Publisher: The Endocrine Society
Date: 08-2011
DOI: 10.1210/JC.2011-0046
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Simon George Anderson.