Alex Dregan

Chronic Inflammatory Disorders and Risk of Type 2 Diabetes Mellitus, Coronary Heart Disease, and Stroke: A Population-Based Cohort Study

Background— This study sought to evaluate whether risks of diabetes mellitus and cardiovascular disease are elevated across a range of organ-specific and multisystem chronic inflammatory disorders. Methods and Results— A matched cohort study was implemented in the UK Clinical Practice Research Datalink including participants with severe psoriasis (5648), mild psoriasis (85 232), bullous skin diseases (4284), ulcerative colitis (12 203), Crohn’s disease (7628), inflammatory arthritis (27 358), systemic autoimmune disorders (7472), and systemic vasculitis (6283) and in 373 851 matched controls. The main outcome measures were new diagnoses of type 2 diabetes mellitus, stroke, or coronary heart disease. The outcomes were evaluated for each condition in a multiple outcomes model, with adjustment for conventional cardiovascular risk factors. Estimates for different inflammatory conditions were pooled in a random-effects meta-analysis. There were 4695 new diagnoses of type 2 diabetes mellitus, 3266 of coronary heart disease, and 1715 of stroke. The hazard ratio for pooled multiple failure estimate was 1.20 (95% confidence interval [CI], 1.15–1.26). The highest relative hazards were observed in systemic autoimmune disorders (1.32; 95% CI, 1.16–1.50) and systemic vasculitis (1.29; 95% CI, 1.16–1.44). Hazards were increased in organ-specific disorders, including severe psoriasis (1.29; 95% CI, 1.12–1.47) and ulcerative colitis (1.26; 95% CI, 1.14–1.40). Participants in the highest tertile of C-reactive protein had greater risk of multiple outcomes (1.52; 95% CI, 1.37–1.68). Conclusions— The risk of cardiovascular diseases and type 2 diabetes mellitus is increased across a range of organ-specific and multisystem chronic inflammatory disorders with evidence that risk is associated with severity of inflammation. Clinical management of patients with chronic inflammatory disorders should seek to reduce cardiovascular risk.

Cardiovascular risk factors and cognitive decline in adults aged 50 and over: a population-based cohort study

OBJECTIVES the objective of the present study was to explore the association between cardiovascular risk and cognitive decline in adults aged 50 and over. METHODS participants were older adults who participated in the English Longitudinal Study of Ageing. Outcome measures included standardised z-scores for global cognition, memory and executive functioning. Associations between cardiovascular risk factors and 10-year Framingham risk scores with cognitive outcomes at 4-year and 8-year follow-ups were estimated. RESULTS the mean age of participants (n = 8,780) at 2004-05 survey was 66.93 and 55% were females. Participants in the highest quartile of Framingham stroke risk score (FSR) had lower global cognition (b = -0.73,CI: -1.37, -0.10), memory (b = -0.56, CI: -0.99, -0.12) and executive (b = -0.37, CI: -0.74, -0.01) scores at 4-year follow-up compared with those in the lower quartile. Systolic blood pressure ≥160 mmHg at 1998-2001 survey was associated with lower global cognitive (b = -1.26, CI: -2.52, -0.01) and specific memory (b = -1.16, CI: -1.94, -0.37) scores at 8-year follow-up. Smoking was consistently associated with lower performance on all three cognitive outcomes. CONCLUSION elevated cardiovascular risk may be associated with accelerated decline in cognitive functioning in the elderly. Future intervention studies may be better focused on overall risk rather than individual risk factor levels.

Continued high rates of antibiotic prescribing to adults with respiratory tract infection: survey of 568 UK general practices

Objectives Overutilisation of antibiotics may contribute to the emergence of antimicrobial drug resistance, a growing international concern. This study aimed to analyse the performance of UK general practices with respect to antibiotic prescribing for respiratory tract infections (RTIs) among young and middle-aged adults. Setting Data are reported for 568 UK general practices contributing to the Clinical Practice Research Datalink. Participants Participants were adults aged 18–59 years. Consultations were identified for acute upper RTIs including colds, cough, otitis-media, rhino-sinusitis and sore throat. Primary and secondary outcome measures For each consultation, we identified whether an antibiotic was prescribed. The proportion of RTI consultations with antibiotics prescribed was estimated. Results There were 568 general practices analysed. The median general practice prescribed antibiotics at 54% of RTI consultations. At the highest prescribing 10% of practices, antibiotics were prescribed at 69% of RTI consultations. At the lowest prescribing 10% of practices, antibiotics were prescribed at 39% RTI consultations. The median practice prescribed antibiotics at 38% of consultations for ‘colds and upper RTIs’, 48% for ‘cough and bronchitis’, 60% for ‘sore throat’, 60% for ‘otitis-media’ and 91% for ‘rhino-sinusitis’. The highest prescribing 10% of practices issued antibiotic prescriptions at 72% of consultations for ‘colds’, 67% for ‘cough’, 78% for ‘sore throat’, 90% for ‘otitis-media’ and 100% for ‘rhino-sinusitis’. Conclusions Most UK general practices prescribe antibiotics to young and middle-aged adults with respiratory infections at rates that are considerably in excess of what is clinically justified. This will fuel antibiotic resistance.

Incidence of type 2 diabetes after bariatric surgery: population-based matched cohort study

BACKGROUND The effect of currently used bariatric surgical procedures on the development of diabetes in obese people is not well defined. We aimed to assess the effect of bariatric surgery on development of type 2 diabetes in a large population of obese individuals. METHODS We did a matched cohort study of adults (age 20–100 years) identified from a UK-wide database of family practices, who were obese (BMI ≥30 kg/m2) and did not have diabetes. We enrolled 2167 patients who had undergone bariatric surgery between Jan 1, 2002, and April 30, 2014, and matched them--according to BMI, age, sex, index year, and HbA1c--with 2167 controls who had not had surgery. Procedures included laparoscopic gastric banding (n=1053), gastric bypass (795), and sleeve gastrectomy (317), with two procedures undefined. The primary outcome was development of clinical diabetes, which we extracted from electronic health records. Analyses were adjusted for matching variables, comorbidity, cardiovascular risk factors, and use of antihypertensive and lipid-lowering drugs. FINDINGS During a maximum of 7 years of follow-up (median 2·8 years [IQR 1·3–4·5]), 38 new diagnoses of diabetes were made in bariatric surgery patients and 177 were made in controls. By the end of 7 years of follow-up, 4·3% (95% CI 2·9–6·5) of bariatric surgery patients and 16·2% (13·3–19·6) of matched controls had developed diabetes. The incidence of diabetes diagnosis was 28·2 (95% CI 24·4–32·7) per 1000 person-years in controls and 5·7 (4·2–7·8) per 1000 person-years in bariatric surgery patients; the adjusted hazard ratio was 0·20 (95% CI 0·13–0·30, p<0·0001). This estimate was robust after varying the comparison group in sensitivity analyses, excluding gestational diabetes, or allowing for competing mortality risk. INTERPRETATION Bariatric surgery is associated with reduced incidence of clinical diabetes in obese participants without diabetes at baseline for up to 7 years after the procedure. FUNDING UK National Institute for Health Research.

Is Sodium Valproate, an HDAC inhibitor, associated with reduced risk of stroke and myocardial infarction? A nested case–control study

This study aimed to evaluate whether treatment with sodium valproate (SV) was associated with reduced risk of stroke or myocardial infarction (MI).

Estimating the yield of NHS Health Checks in England: a population-based cohort study

BACKGROUND This study aimed to evaluate the yield of the NHS Health Checks programme. METHODS A cohort study, conducted in the Clinical Practice Research Datalink in England. Electronic health records were analysed for patients aged 40-74 receiving an NHS Health Check between 2010 and 2013. RESULTS There were 65 324 men and 75 032 women receiving a health check. For every 1000 men assessed, there were 205 smokers (95% confidence interval 195-215), 355 (340-369) with hypertension (≥140/90 mmHg) and 633 (607-658) with elevated cholesterol (≥5 mmol/l). Among 1000 women, there were 161 (151-171) smokers, 247 (238-257) with hypertension and 668 (646-689) with elevated cholesterol. In the 12 months following the check, statins were prescribed to 18% of men and 21% of women with ≥20% cardiovascular risk and antihypertensive drugs to 11% of men and 16% of women with ≥20% cardiovascular risk. Slight reductions in risk factor values were observed in the minority of participants with follow-up values recorded in the 15 months following the check. CONCLUSIONS A universal primary prevention programme identifies substantial risk factor burden in a population without known cardiovascular disease. Research is needed to monitor interventions, and intermediate- and long-term outcomes, in those identified at high risk.

Systolic Blood Pressure Trajectory, Frailty, and All-Cause Mortality >80 Years of Age

Background: Clinical trials show benefit from lowering systolic blood pressure (SBP) in people ≥80 years of age, but nonrandomized epidemiological studies suggest lower SBP may be associated with higher mortality. This study aimed to evaluate associations of SBP with all-cause mortality by frailty category >80 years of age and to evaluate SBP trajectories before death. Methods: A population-based cohort study was conducted using electronic health records of 144 403 participants ≥80 years of age registered with family practices in the United Kingdom from 2001 to 2014. Participants were followed for ⩽5 years. Clinical records of SBP were analyzed. Frailty status was classified using the e-Frailty Index into the categories of fit, mild, moderate, and severe. All-cause mortality was evaluated by frailty status and mean SBP in Cox proportional-hazards models. SBP trajectories were evaluated using person months as observations, with mean SBP and antihypertensive treatment status estimated for each person month. Fractional polynomial models were used to estimate SBP trajectories over 5 years before death. Results: During follow-up, 51 808 deaths occurred. Mortality rates increased with frailty level and were greatest at SBP <110 mm Hg. In fit women, mortality was 7.7 per 100 person years at SBP 120 to 139 mm Hg, 15.2 at SBP 110 to 119 mm Hg, and 22.7 at SBP <110 mm Hg. For women with severe frailty, rates were 16.8, 25.2, and 39.6, respectively. SBP trajectories showed an accelerated decline in the last 2 years of life. The relative odds of SBP <120 mm Hg were higher in the last 3 months of life than 5 years previously in both treated (odds ratio, 6.06; 95% confidence interval, 5.40–6.81) and untreated (odds ratio, 6.31; 95% confidence interval, 5.30–7.52) patients. There was no evidence of intensification of antihypertensive therapy in the final 2 years of life. Conclusions: A terminal decline of SBP in the final 2 years of life suggests that nonrandomized epidemiological associations of low SBP with higher mortality may be accounted for by reverse causation if participants with lower blood pressure values are closer, on average, to the end of life.

Point-of-Care Cluster Randomized Trial in Stroke Secondary Prevention Using Electronic Health Records

Background and Purpose— The aim of this study was to evaluate whether the remote introduction of electronic decision support tools into family practices improves risk factor control after first stroke. This study also aimed to develop methods to implement cluster randomized trials in stroke using electronic health records. Methods— Family practices were recruited from the UK Clinical Practice Research Datalink and allocated to intervention and control trial arms by minimization. Remotely installed, electronic decision support tools promoted intensified secondary prevention for 12 months with last measure of systolic blood pressure as the primary outcome. Outcome data from electronic health records were analyzed using marginal models. Results— There were 106 Clinical Practice Research Datalink family practices allocated (intervention, 53; control, 53), with 11 391 (control, 5516; intervention, 5875) participants with acute stroke ever diagnosed. Participants at trial practices had similar characteristics as 47 887 patients with stroke at nontrial practices. During the intervention period, blood pressure values were recorded in the electronic health records for 90% and cholesterol values for 84% of participants. After intervention, the latest mean systolic blood pressure was 131.7 (SD, 16.8) mm Hg in the control trial arm and 131.4 (16.7) mm Hg in the intervention trial arm, and adjusted mean difference was −0.56 mm Hg (95% confidence interval, −1.38 to 0.26; P=0.183). The financial cost of the trial was approximately US

Longitudinal Trends in Hypertension Management and Mortality Among Octogenarians: Prospective Cohort Study

22 per participant, or US

Cluster randomized trial in the general practice research database: 2. Secondary prevention after first stroke (eCRT study): study protocol for a randomized controlled trial

2400 per family practice allocated. Conclusions— Large pragmatic intervention studies may be implemented at low cost by using electronic health records. The intervention used in this trial was not found to be effective, and further research is needed to develop more effective intervention strategies. Clinical Trial Registration— URL: http://www.controlled-trials.com. Current Controlled Trials identifier: ISRCTN35701810.