Farr Institute of Health Informatics Research at London

London, United Kingdom

Farr Institute of Health Informatics Research at London

London, United Kingdom
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Nimptsch K.,Max Delbrück Center for Molecular Medicine | Nimptsch K.,Harvard University | Song M.,Harvard University | Aleksandrova K.,German Institute of Human Nutrition | And 60 more authors.
European Journal of Epidemiology | Year: 2017

Higher levels of circulating adiponectin have been related to lower risk of colorectal cancer in several prospective cohort studies, but it remains unclear whether this association may be causal. We aimed to improve causal inference in a Mendelian Randomization meta-analysis using nested case–control studies of the European Prospective Investigation into Cancer and Nutrition (EPIC, 623 cases, 623 matched controls), the Health Professionals Follow-up Study (HPFS, 231 cases, 230 controls) and the Nurses’ Health Study (NHS, 399 cases, 774 controls) with available data on pre-diagnostic adiponectin concentrations and selected single nucleotide polymorphisms in the ADIPOQ gene. We created an ADIPOQ allele score that explained approximately 3% of the interindividual variation in adiponectin concentrations. The ADIPOQ allele score was not associated with risk of colorectal cancer in logistic regression analyses (pooled OR per score-unit unit 0.97, 95% CI 0.91, 1.04). Genetically determined twofold higher adiponectin was not significantly associated with risk of colorectal cancer using the ADIPOQ allele score as instrumental variable (pooled OR 0.73, 95% CI 0.40, 1.34). In a summary instrumental variable analysis (based on previously published data) with higher statistical power, no association between genetically determined twofold higher adiponectin and risk of colorectal cancer was observed (0.99, 95% CI 0.93, 1.06 in women and 0.94, 95% CI 0.88, 1.01 in men). Thus, our study does not support a causal effect of circulating adiponectin on colorectal cancer risk. Due to the limited genetic determination of adiponectin, larger Mendelian Randomization studies are necessary to clarify whether adiponectin is causally related to lower risk of colorectal cancer. © 2017 Springer Science+Business Media Dordrecht


Sekhri N.,Barts Heart Center | Perel P.,London School of Hygiene and Tropical Medicine | Clayton T.,London School of Hygiene and Tropical Medicine | Feder G.S.,University of Bristol | And 5 more authors.
Heart | Year: 2016

Diagnostic models used in the management of suspected angina provide no explicit information about prognosis. We present a new prognostic model of 10-year coronary mortality in patients presenting for the first time with suspected angina to complement the Diamond-Forrester diagnostic model of disease probability. Methods and results A multicentre cohort of 8762 patients with suspected angina was followed up for a median of 10 years during which 233 coronary deaths were observed. Developmental (n=4412) and validation (n=4350) prognostic models based on clinical data available at first presentation showed good performance with close agreement and the final model utilised all 8762 patients to maximise power. The prognostic model showed strong associations with coronary mortality for age, sex, chest pain typicality, smoking status, diabetes, pulse rate, and ECG findings. Model discrimination was good (C statistic 0.83), patients in the highest risk quarter accounting for 173 coronary deaths (10-year risk of death: 8.7%) compared with a total of 60 deaths in the three lower risk quarters. When the model was simplified to incorporate only Diamond-Forrester factors (age, sex and character of symptoms) it underestimated coronary mortality risk, particularly in patients with reversible risk factors. Conclusions For the first time in patients with suspected angina, a prognostic model is presented based on simple clinical factors available at the initial cardiological assessment. The model discriminated powerfully between patients at high risk and lower risk of coronary death during 10-year follow-up. Clinical utility was reflected in the prognostic value it added to the updated Diamond-Forrester diagnostic model of disease probability.


Shah A.D.,Farr Institute of Health Informatics Research at London | Shah A.D.,University College London | Langenberg C.,University College London | Langenberg C.,University of Cambridge | And 15 more authors.
The Lancet Diabetes and Endocrinology | Year: 2015

Background: The contemporary associations of type 2 diabetes with a wide range of incident cardiovascular diseases have not been compared. We aimed to study associations between type 2 diabetes and 12 initial manifestations of cardiovascular disease. Methods: We used linked primary care, hospital admission, disease registry, and death certificate records from the CALIBER programme, which links data for people in England recorded in four electronic health data sources. We included people who were (or turned) 30 years or older between Jan 1, 1998, to March 25, 2010, who were free from cardiovascular disease at baseline. The primary endpoint was the first record of one of 12 cardiovascular presentations in any of the data sources. We compared cumulative incidence curves for the initial presentation of cardiovascular disease and used Cox models to estimate cause-specific hazard ratios (HRs). This study is registered at ClinicalTrials.gov (. NCT01804439). Findings: Our cohort consisted of 1 921 260 individuals, of whom 1 887 062 (98·2%) did not have diabetes and 34 198 (1·8%) had type 2 diabetes. We observed 113 638 first presentations of cardiovascular disease during a median follow-up of 5·5 years (IQR 2·1-10·1). Of people with type 2 diabetes, 6137 (17·9%) had a first cardiovascular presentation, the most common of which were peripheral arterial disease (reported in 992 [16·2%] of 6137 patients) and heart failure (866 [14·1%] of 6137 patients). Type 2 diabetes was positively associated with peripheral arterial disease (adjusted HR 2·98 [95% CI 2·76-3·22]), ischaemic stroke (1·72 [1·52-1·95]), stable angina (1·62 [1·49-1·77]), heart failure (1·56 [1·45-1·69]), and non-fatal myocardial infarction (1·54 [1·42-1·67]), but was inversely associated with abdominal aortic aneurysm (0·46 [0·35-0·59]) and subarachnoid haemorrhage (0·48 [0·26-0.89]), and not associated with arrhythmia or sudden cardiac death (0·95 [0·76-1·19]). Interpretation: Heart failure and peripheral arterial disease are the most common initial manifestations of cardiovascular disease in type 2 diabetes. The differences between relative risks of different cardiovascular diseases in patients with type 2 diabetes have implications for clinical risk assessment and trial design. Funding: Wellcome Trust, National Institute for Health Research, and Medical Research Council. © 2015 Shah et al. Open Access article distributed under the terms of CC BY.

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