Estimation of recurrent atherosclerotic cardiovascular event risk in patients with established cardiovascular disease: the updated SMART2 algorithm.

AIMS: The 10-year risk of recurrent atherosclerotic cardiovascular disease (ASCVD) events in patients with established ASCVD can be estimated with the Secondary Manifestations of ARTerial disease (SMART) risk score, and may help refine clinical management. To broaden generalizability across regions, we updated the existing tool (SMART2 risk score) and recalibrated it with regional incidence rates and assessed its performance in external populations. METHODS AND RESULTS: Individuals with coronary artery disease, cerebrovascular disease, peripheral artery disease, or abdominal aortic aneurysms were included from the Utrecht Cardiovascular Cohort-SMART cohort [n = 8355; 1706 ASCVD events during a median follow-up of 8.2 years (interquartile range 4.2-12.5)] to derive a 10-year risk prediction model for recurrent ASCVD events (non-fatal myocardial infarction, non-fatal stroke, or cardiovascular mortality) using a Fine and Gray competing risk-adjusted model. The model was recalibrated to four regions across Europe, and to Asia (excluding Japan), Japan, Australia, North America, and Latin America using contemporary cohort data from each target region. External validation used data from seven cohorts [Clinical Practice Research Datalink, SWEDEHEART, the international REduction of Atherothrombosis for Continued Health (REACH) Registry, Estonian Biobank, Spanish Biomarkers in Acute Coronary Syndrome and Biomarkers in Acute Myocardial Infarction (BACS/BAMI), the Norwegian COgnitive Impairment After STroke, and Bialystok PLUS/Polaspire] and included 369 044 individuals with established ASCVD of whom 62 807 experienced an ASCVD event. C-statistics ranged from 0.605 [95% confidence interval (CI) 0.547-0.664] in BACS/BAMI to 0.772 (95% CI 0.659-0.886) in REACH Europe high-risk region. The clinical utility of the model was demonstrated across a range of clinically relevant treatment thresholds for intensified treatment options. CONCLUSION: The SMART2 risk score provides an updated, validated tool for the prediction of recurrent ASCVD events in patients with established ASCVD across European and non-European populations. The use of this tool could allow for a more personalized approach to secondary prevention based upon quantitative rather than qualitative estimates of residual risk.

Associations between attainment of incentivised primary care indicators and incident diabetic retinopathy in England: a population-based historical cohort study.

BACKGROUND: The associations between England's incentivised primary care-based diabetes prevention activities and hard clinical endpoints remain unclear. We aimed to examine the associations between attainment of primary care indicators and incident diabetic retinopathy (DR) among people with type 2 diabetes. METHODS: A historical cohort (n = 60,094) of people aged ≥ 18 years with type 2 diabetes and no DR at baseline was obtained from the UK Clinical Practice Research Datalink (CPRD). Exposures included attainment of the Quality and Outcomes Framework (QOF) HbA1c (≤ 7.5% or 59 mmol/mol), blood pressure (≤ 140/80 mmHg), and cholesterol (≤ 5 mmol/L) indicators, and number of National Diabetes Audit (NDA) care processes completed (categorised as 0-3, 4-6, or 7-9), in 2010-2011. Outcomes were time to development of DR and sight-threatening diabetic retinopathy (STDR). Nearest neighbour propensity score matching was undertaken and Cox proportional hazards models then fitted using the matched samples. Concordance statistics were calculated for each model. RESULTS: 8263 DR and 832 STDR diagnoses were observed over mean follow-up periods of 3.5 (SD 2.1) and 3.8 (SD 2.0) years, respectively. HbA1c and blood pressure (BP) indicator attainment were associated with lower rates of DR (adjusted hazard ratios (aHRs) 0.94 (95% CI 0.89-0.99) and 0.87 (0.83-0.92), respectively), whereas cholesterol indicator attainment was not (aHR 1.03 (0.97-1.10)). All QOF indicators were associated with lower rates of STDR (aHRs 0.74 (0.62-0.87) for HbA1c, 0.78 (0.67-0.91) for BP, and 0.82 (0.67-0.99) for cholesterol). Completion of 7-9 vs. 0-3 NDA processes was associated with fewer STDR diagnoses (aHR 0.72 (0.55-0.94)). CONCLUSIONS: Attainment of key primary care indicators is associated with lower incidence of DR and STDR among patients with type 2 diabetes in England.

Associations between attainment of incentivized primary care indicators and incident sight-threatening diabetic retinopathy in England: A population-based historical cohort study.

AIM: To examine the impact of attainment of primary care diabetes clinical indicators on progression to sight-threatening diabetic retinopathy (STDR) among those with mild non-proliferative diabetic retinopathy (NPDR). MATERIALS AND METHODS: An historical cohort study of 18,978 adults (43.63% female) diagnosed with type 2 diabetes before 1 April 2010 and mild NPDR before 1 April 2011 was conducted. The data were obtained from the UK Clinical Practice Research Datalink during 2010-2017, provided by 330 primary care practices in England. Exposures included attainment of the Quality and Outcomes Framework HbA1c (≤59 mmol/mol [≤7.5%]), blood pressure (≤140/80 mmHg) and cholesterol (≤5 mmol/L) indicators in the financial year 2010-2011, as well as the number of National Diabetes Audit processes completed in 2010-2011. The outcome was time to incident STDR. Nearest neighbour propensity score matching was undertaken, and univariable and multivariable Cox proportional hazards models were then fitted using the matched samples. Concordance statistics were calculated for each model. RESULTS: A total of 1037 (5.5%) STDR diagnoses were observed over a mean follow-up of 3.6 (SD 2.0) years. HbA1c, blood pressure and cholesterol indicator attainment were associated with lower rates of STDR (adjusted hazard ratios [95% CI] 0.64 [0.55-0.74; p < .001], 0.83 [0.72-0.94; p = .005] and 0.80 [0.66-0.96; p = .015], respectively). CONCLUSIONS: Our findings provide support for meeting appropriate indicators for the management of type 2 diabetes in primary care to bring a range of benefits, including improved health outcomes-such as a reduction in the risk of STDR-for people with type 2 diabetes.

Associations between active travel and adiposity in rural India and Bangladesh: a cross-sectional study.

BACKGROUND: Data on use and health benefits of active travel in rural low- and middle- income country settings are sparse. We aimed to examine correlates of active travel, and its association with adiposity, in rural India and Bangladesh. METHODS: Cross sectional study of 2,122 adults (≥18 years) sampled in 2011-13 from two rural sites in India (Goa and Chennai) and one in Bangladesh (Matlab). Logistic regression was used to examine whether ≥150 min/week of active travel was associated with socio-demographic indices, smoking, oil/butter consumption, and additional physical activity. Adjusting for these same factors, associations between active travel and BMI, waist circumference and waist-to-hip ratio were examined using linear and logistic regression. RESULTS: Forty-six percent of the sample achieved recommended levels of physical activity (≥150 min/week) through active travel alone (range: 33.1 % in Matlab to 54.8 % in Goa). This was more frequent among smokers (adjusted odds ratio 1.36, 95 % confidence interval 1.07-1.72; p = 0.011) and those that spent ≥150 min/week in work-based physical activity (OR 1.71, 1.35-2.16; p < 0.001), but less frequent among females than males (OR 0.25, 0.20-0.31; p < 0.001). In fully adjusted analyses, ≥150 min/week of active travel was associated with lower BMI (adjusted coefficient -0.39 kg/m(2), -0.77 to -0.02; p = 0.037) and a lower likelihood of high waist circumference (OR 0.77, 0.63-0.96; p = 0.018) and high waist-to-hip ratio (OR 0.72, 0.58-0.89; p = 0.002). CONCLUSIONS: Use of active travel for ≥150 min/week was associated with being male, smoking, and higher levels of work-based physical activity. It was associated with lower BMI, and lower risk of a high waist circumference or high waist-to-hip ratio. Promotion of active travel is an important component of strategies to address the growing prevalence of overweight in rural low- and middle- income country settings.

Prevalence of COPD in India: a systematic review.

BACKGROUND: The increasing burden of chronic diseases is a particular risk to countries with developing health systems. Chronic obstructive pulmonary disease (COPD) is contributing to the burden of chronic diseases. Understanding the current prevalence of COPD in India is important for the production of sustainable management strategies. AIMS: To provide a systematic review of studies assessing the prevalence of COPD in India. METHODS: Database searches, journal hand searches, and scanning of reference lists were used to identify studies. Studies of general adult populations resident in India were included. Data extraction and quality assessment were carried out using pre-tested proformas. Owing to the heterogeneity of reviewed studies, meta-analysis was not appropriate. Thus, narrative methods were used. RESULTS: We did not identify any studies from which we could draw a rigorous estimate of the prevalence of COPD by standard definition. Reliable standard estimates of chronic bronchitis were only available for rural populations. We identified four studies that gave estimated prevalences between 6.5% and 7.7%, and others suggestive that prevalences in some environmentally atypical regions may lie outside this range. Sex and smoking status were relatively important predictors of COPD prevalence. Residential environs, age, and domestic smoke exposure are also important, but investigation of their effect was limited by study heterogeneity. CONCLUSIONS: Although limited by the number and heterogeneity of studies and their unsuitability for meta-analysis, we found the most rigorous existing estimates of the general prevalence of chronic bronchitis in rural areas to lie between 6.5% and 7.7%. These figures are unlikely to apply to all Indian subpopulations, so the general prevalence of chronic bronchitis in India remains unknown. Accurate estimates of the prevalence of chronic bronchitis/COPD from across the country are required to supplement existing data if optimal management strategies are to be devised.

Assessing the external validity of the SAFEHEART risk prediction model in patients with familial hypercholesterolaemia in an English routine care cohort.

BACKGROUND AND AIMS: The SAFEHEART tool has shown good discrimination in predicting cardiovascular events in a bespoke genotyped cohort with familial hypercholesterolaemia (FH). We assessed whether the tool could aid clinical decision making in an English routine care cohort with FH. METHODS: A historical (2000-2017) open cohort of 3643 participants aged 18-79 years and ≥6-months since FH diagnosis was derived from the Clinical Practice Research Datalink. Individual 10-year cardiovascular risks were predicted using the SAFEHEART model, with multiple imputation used to manage missing data. Outcomes were the first occurrence of myocardial infarction, coronary revascularisation, ischaemic stroke, carotid revascularisation, peripheral arterial revascularisation, non-traumatic lower limb amputation, or cardiovascular death. Model performance was assessed using standard measures of calibration and discrimination, and decision curve analysis. RESULTS: 147 outcome events were observed over a median 3.73 (IQR 1.59-6.48) years follow-up. While the model had some discriminatory value (Harrell's c-statistic 0.67 (95% CI 0.61-0.72)), observed outcome risks departed substantially from predicted risks. Calibration slopes for men and women by age decile were 10.09 (95% CI 7.40-12.77) and 2.85 (1.25-4.45), respectively. Recalibration-in-the-large led to closer alignment of observed and predicted risks (recalibration slopes 3.48 (2.55-4.41) and 1.14 (0.50-1.79), respectively). Decision curve analysis suggested the recalibrated model had net benefit at predicted risks of 10-30%. CONCLUSIONS: The original SAFEHEART model has limited generalisability to the routinely identifiable English primary care FH population. With recalibration it appears to have moderate utility at 10-30% predicted risk. It may have greater validity in more bespoke genetically defined FH populations.

Estimated cardiovascular benefits of bempedoic acid in patients with established cardiovascular disease.

Background and aims: Cardiovascular outcomes trials have demonstrated that lowering low-density lipoprotein cholesterol (LDL-C) reduces the risk for future cardiovascular events. We assessed the potential cardiovascular benefits of bempedoic acid through a simulation study in patients with atherosclerotic cardiovascular disease (ASCVD) and elevated LDL-C. Methods: The validated SMART prediction model was used to estimate the baseline 10-year risk of three-point major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke) in patients with ASCVD who were enrolled in four Phase 3, randomized, placebo-controlled bempedoic acid studies. The predicted change in 10-year cardiovascular risk associated with bempedoic acid was estimated for each patient based on the Cholesterol Treatment Trialists' model. Data were analyzed in two cohorts: Cohort 1 included mostly patients treated with moderate-high intensity statins, and Cohort 2 included patients who were intolerant of more than low-intensity statin. Results: A total of 2884 patients were included in Cohort 1 and 226 in Cohort 2. Weighted average baseline 10-year cardiovascular event risk was 26.1% and 31.6% for Cohorts 1 and 2, respectively. The least squares mean percent difference (95% confidence interval (CI) of the predicted absolute change in 10-year cardiovascular event risk with bempedoic acid was -3.3% (-3.7% to -2.9%) for patients in Cohort 1 and -6.0% (-7.7% to -4.3%) for patients in Cohort 2 compared with placebo (p < 0.0001 for both). Conclusions: Among patients with ASCVD who could potentially benefit from additional LDL-C lowering, our simulation predicted a lower absolute cardiovascular event risk after initiating bempedoic acid as compared with placebo.

Is the SMART risk prediction model ready for real-world implementation? A validation study in a routine care setting of approximately 380 000 individuals.

AIMS: Reliably quantifying event rates in secondary prevention could aid clinical decision-making, including quantifying potential risk reductions of novel, and sometimes expensive, add-on therapies. We aimed to assess whether the SMART risk prediction model performs well in a real-world setting. METHODS AND RESULTS: We conducted a historical open cohort study using UK primary care data from the Clinical Practice Research Datalink (2000-2017) diagnosed with coronary, cerebrovascular, peripheral, and/or aortic atherosclerotic cardiovascular disease (ASCVD). Analyses were undertaken separately for cohorts with established (≥6 months) vs. newly diagnosed ASCVD. The outcome was first post-cohort entry occurrence of myocardial infarction, stroke, or cardiovascular death. Among the cohort with established ASCVD [n = 244 578, 62.1% male, median age 67.3 years, interquartile range (IQR) 59.2-74.0], the calibration and discrimination achieved by the SMART model was not dissimilar to performance at internal validation [Harrell's c-statistic = 0.639, 95% confidence interval (CI) 0.636-0.642, compared with 0.675, 0.642-0.708]. Decision curve analysis indicated that the model outperformed treat all and treat none strategies in the clinically relevant 20-60% predicted risk range. Consistent findings were observed in sensitivity analyses, including complete case analysis (n = 182 482; c = 0.624, 95% CI 0.620-0.627). Among the cohort with newly diagnosed ASCVD (n = 136 445; 61.0% male; median age 66.0 years, IQR 57.7-73.2), model performance was weaker with more exaggerated risk under-prediction and a c-statistic of 0.559, 95% CI 0.556-0.562. CONCLUSIONS: The performance of the SMART model in this validation cohort demonstrates its potential utility in routine healthcare settings in guiding both population and individual-level decision-making for secondary prevention patients.

Associations between attainment of incentivised primary care diabetes indicators and mortality in an English cohort.

AIMS: To describe associations between incentivised primary care clinical and process indicators and mortality, among patients with type 2 diabetes in England. METHODS: A historical 2010-2017 cohort (n = 84,441 adults) was derived from the UK CPRD. Exposures included English Quality and Outcomes Framework glycated haemoglobin (HbA1c; 7.5%, 59 mmol/mol), blood pressure (140/80 mmHg), and cholesterol (5 mmol/L) indicator attainment; and number of National Diabetes Audit care processes completed, in 2010-11. The primary outcome was all-cause mortality. RESULTS: Over median 3.9 (SD 2.0) years follow-up, 10,711 deaths occurred. Adjusted hazard ratios (aHR) indicated 12% (95% CI 8-16%; p < 0.0001) and 16% (11-20%; p < 0.0001) lower mortality rates among those who attained the HbA1c and cholesterol indicators, respectively. Rates were also lower among those who completed 7-9 vs. 0-3 or 4-6 care processes (aHRs 0.76 (0.71-0.82), p < 0.0001 and 0.61 (0.53-0.71), p < 0.0001, respectively), but did not obviously vary by blood pressure indicator attainment (aHR 1.04, 1.00-1.08; p = 0.0811). CONCLUSIONS: Cholesterol, HbA1c and comprehensive process indicator attainment, was associated with enhanced survival. Review of community-based care provision could help reduce the gap between indicator standards and current outcomes, and in turn enhance life expectancy.

Associations between attainment of incentivised primary care indicators and emergency hospital admissions among type 2 diabetes patients: a population-based historical cohort study.

OBJECTIVES: England has invested considerably in diabetes care over recent years through programmes such as the Quality and Outcomes Framework and National Diabetes Audit. However, associations between specific programme indicators and key clinical endpoints, such as emergency hospital admissions, remain unclear. We aimed to examine whether attainment of Quality and Outcomes Framework and National Diabetes Audit primary care diabetes indicators is associated with diabetes-related, cardiovascular, and all-cause emergency hospital admissions. DESIGN: Historical cohort study. SETTING: A total of 330 English primary care practices, 2010-2017, using UK Clinical Practice Research Datalink. PARTICIPANTS: A total of 84,441 adults with type 2 diabetes. MAIN OUTCOME MEASURES: The primary outcome was emergency hospital admission for any cause. Secondary outcomes were (1) diabetes-related and (2) cardiovascular-related emergency admission. RESULTS: There were 130,709 all-cause emergency admissions, 115,425 diabetes-related admissions and 105,191 cardiovascular admissions, corresponding to unplanned admission rates of 402, 355 and 323 per 1000 patient-years, respectively. All-cause hospital admission rates were lower among those who met HbA1c and cholesterol indicators (incidence rate ratio = 0.91; 95% CI 0.89-0.92; p < 0.001 and 0.87; 95% CI 0.86-0.89; p < 0.001), respectively), with similar findings for diabetes and cardiovascular admissions. Patients who achieved the Quality and Outcomes Framework blood pressure target had lower cardiovascular admission rates (incidence rate ratio = 0.98; 95% CI 0.96-0.99; p = 0.001). Strong associations were found between completing 7-9 (vs. either 4-6 or 0-3) National Diabetes Audit processes and lower rates of all admission outcomes (p-values < 0.001), and meeting all nine National Diabetes Audit processes had significant associations with reductions in all types of emergency admissions by 22% to 26%. Meeting the HbA1c or cholesterol Quality and Outcomes Framework indicators, or completing 7-9 National Diabetes Audit processes, was also associated with longer time-to-unplanned all-cause, diabetes and cardiovascular admissions. CONCLUSIONS: Attaining Quality and Outcomes Framework-defined diabetes intermediate outcome thresholds, and comprehensive completion of care processes, may translate into considerable reductions in emergency hospital admissions. Out-of-hospital diabetes care optimisation is needed to improve implementation of core interventions and reduce unplanned admissions.

Associations between attainment of incentivized primary care indicators and incident lower limb amputation among those with type 2 diabetes: a population-based historical cohort study.

INTRODUCTION: England has invested considerably in diabetes care through such programs as the Quality and Outcomes Framework (QOF) and National Diabetes Audit (NDA). Associations between program indicators and clinical endpoints, such as amputation, remain unclear. We examined associations between primary care indicators and incident lower limb amputation. RESEARCH DESIGN AND METHODS: This population-based retrospective cohort study, spanning 2010-2017, was comprised of adults in England with type 2 diabetes and no history of lower limb amputation. Exposures at baseline (2010-2011) were attainment of QOF glycated hemoglobin (HbA1c), blood pressure and total cholesterol indicators, and number of NDA processes completed. Propensity score matching was performed and multivariable Cox proportional hazards models, adjusting for disease-related, comorbidity, lifestyle, and sociodemographic factors, were fitted using matched samples for each exposure. RESULTS: 83 688 individuals from 330 English primary care practices were included. Mean follow-up was 3.9 (SD 2.0) years, and 521 (0.6%) minor or major amputations were observed (1.62 per 1000 person-years). HbA1c and cholesterol indicator attainment were associated with considerably lower risks of minor or major amputation (adjusted HRs; 95% CIs) 0.61 (0.49 to 0.74; p<0.0001) and 0.67 (0.53 to 0.86; p=0.0017), respectively). No evidence of association between blood pressure indicator attainment and amputation was observed (adjusted HR 0.88 (0.73 to 1.06; p=0.1891)). Substantially lower amputation rates were observed among those completing a greater number of NDA care processes (adjusted HRs 0.45 (0.24 to 0.83; p=0.0106), 0.67 (0.47 to 0.97; p=0.0319), and 0.38 (0.20 to 0.70; p=0.0022) for comparisons of 4-6 vs 0-3, 7-9 vs 0-3, and 7-9 vs 4-6 processes, respectively). Results for major-only amputations were similar for HbA1c and blood pressure, though cholesterol indicator attainment was non-significant. CONCLUSIONS: Comprehensive primary care-based secondary prevention may offer considerable protection against diabetes-related amputation. This has important implications for diabetes management and medical decision-making for patients, as well as type 2 diabetes quality improvement programs.

Central opioid inhibition of neuroendocrine stress responses in pregnancy in the rat is induced by the neurosteroid allopregnanolone.

The hypothalamus-pituitary-adrenal (HPA) axis is the major neuroendocrine stress response system. Corticotropin-releasing hormone (CRH) neurons in the parvocellular paraventricular nucleus (pPVN) play a key role in coordinating responses of this system to stressors. The cytokine interleukin-1beta (IL-1beta), mimicking infection, robustly activates these CRH neurons via a noradrenergic input arising from the nucleus tractus solitarii (NTS). In late pregnancy, HPA axis responses to stressors, including IL-1beta, are attenuated by a central opioid mechanism that auto-inhibits noradrenaline release in the PVN. Here we show that the neuroactive progesterone metabolite allopregnanolone induces these changes in HPA responsiveness to IL-1beta in pregnancy. In late pregnancy, inhibition of 5alpha-reductase (an allopregnanolone-synthesizing enzyme) with finasteride restored HPA axis responses (rapidly increased pPVN CRH mRNA expression, ACTH, and corticosterone secretion) to IL-1beta. Conversely, allopregnanolone reduced HPA responses in virgin rats. In late pregnancy, activity of the allopregnanolone-synthesizing enzymes (5alpha-reductase and 3alpha-hydroxysteroid dehydrogenase) was increased in the hypothalamus as was mRNA expression in the NTS and PVN. Naloxone, an opioid antagonist, restores HPA axis responses to IL-1beta in pregnancy but had no additional effect after finasteride, indicating a causal connection between allopregnanolone and the endogenous opioid mechanism. Indeed, allopregnanolone induced opioid inhibition over HPA responses to IL-1beta in virgin rats. Furthermore, in virgin rats, allopregnanolone treatment increased, whereas in pregnant rats finasteride decreased proenkephalin-A mRNA expression in the NTS. Thus, in pregnancy, allopregnanolone induces opioid inhibition over HPA axis responses to immune challenge. This novel opioid-mediated mechanism of allopregnanolone action may alter regulation of other brain systems in pregnancy.

Trends in tobacco, alcohol and branded fast-food imagery in Bollywood films, 1994-2013.

BACKGROUND AND AIMS: Exposure to tobacco, alcohol and fast-food use in films is associated with initiation of these behaviours. India is the world's largest film producer, but the extent of such imagery in Bollywood (Hindi cinema) films is unclear. We therefore aimed to describe the extent of and trends in tobacco, alcohol and fast-food imagery in Bollywood films, between 1994-2013. METHODS: For the 15 top-grossing films each year between 1994-2013, the number of five-minute intervals containing product images were determined separately for tobacco, alcohol and fast-food. Both the proportion of films containing at least one image occurrence, and occurrences per film, were described overall and by year. Negative binomial regression described associations between film rating and occurrences/film, and estimated time-trends in occurrences/film, adjusted for rating. RESULTS: We analysed 93 U-rated (unrestricted), 150 U/A-rated (parental guidance for children aged <12 years) and 55 A-rated (restricted to adult audience) films, containing 9,226 five-minute intervals (mean intervals/film 30.8, SD 4.0). 70% (n = 210), 93% (n = 278) and 21% (n = 62) of films contained at least one tobacco, alcohol and fast-food occurrence, respectively. Corresponding total mean occurrences/film were 4.0 (SD 4.9), 7.0 (4.7) and 0.4 (0.9). Tobacco occurrences were more common in U/A films (incidence rate ratio 1.49, 95% confidence interval 1.06-2.09) and A films (2.95; 1.95-4.48) than U-rated films. Alcohol occurrences were also more common in A-rated films than U-rated films (1.48; 1.15-1.85). Tobacco occurrences/film became less common over the observed period (adjusted trend -4% per annum; -2 to -7%; p <0.001), while alcohol (+2%; 0-3%; p = 0.02), and fast food (+8%; 2-14%; p = 0.01) occurrences/film became more common. CONCLUSIONS: Although the extent of tobacco imagery in Bollywood films fell over 1994-2013, it is still frequently observed. Alcohol imagery is widespread, even in U-rated films, and trends in both alcohol and fast-food imagery are upwards.

Universal screening at age 1-2 years as an adjunct to cascade testing for familial hypercholesterolaemia in the UK: A cost-utility analysis.

BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) is widely underdiagnosed. Cascade testing (CT) of relatives has been shown to be feasible, acceptable and cost-effective in the UK, but requires a supply of index cases. Feasibility of universal screening (US) at age 1-2 years was recently demonstrated. We examined whether this would be a cost-effective adjunct to CT in the UK, given the current and plausible future undiagnosed FH prevalence. METHODS: Seven cholesterol and/or mutation-based US ±â€¯reverse cascade testing (RCT) alternatives were compared with no US in an incremental analysis with a healthcare perspective. A decision model was used to estimate costs and outcomes for cohorts exposed to the US component of each strategy. RCT case ascertainment was modelled using recent UK CT data, and probabilistic Markov models estimated lifetime costs and health outcomes for the cohorts screened under each alternative. 1000 Monte Carlo simulations were run for each model, and average outcomes reported. Further uncertainty was explored deterministically. Threshold analysis investigated the association between undiagnosed FH prevalence and cost-effectiveness. RESULTS: A strategy involving cholesterol screening followed by diagnostic genetic testing and RCT was the most cost-effective modelled (incremental cost-effectiveness ratio (ICER) versus no US £12,480/quality adjusted life year (QALY); probability of cost-effectiveness 96·8% at £20,000/QALY threshold). Cost-effectiveness was robust to both deterministic sensitivity analyses and threshold analyses that modelled ongoing case ascertainment at theoretical maximum levels. CONCLUSIONS: These findings support implementation of universal cholesterol screening followed by diagnostic genetic testing and RCT for FH, under a UK conventional willingness-to-pay threshold.

Junior Doctors in England Strike for the First Time in 40 Years.

The UK government recently stated its intention to impose a new junior doctor contract in England. Related negotiations between the British Medical Association and government representatives started in 2013. These have to-date failed to reassure doctors, who are concerned about risks to their welfare, patient safety, and the future of England's National Health Service. With the impending imposition of the new contract, and lack of progress, junior doctors felt the risks of striking had fallen below those of inaction. Hence, the first strike staged by the English medical workforce for 40 years occurred in January 2016.

Management of a patient at high risk of type 2 diabetes.

Rates of type 2 diabetes mellitus have risen rapidly over the past three to four decades. This article describes a typical patient presenting with intermediate hyperglycaemia in primary care. We suggest the appropriate action to reduce the risk of diabetes developing. Population-level preventive interventions, and adequate recognition and early management of those at risk of developing diabetes, could mitigate the impact of this evolving health epidemic.

Clinical impact of lifestyle interventions for the prevention of diabetes: an overview of systematic reviews.

OBJECTIVES: To review the clinical outcomes of combined diet and physical activity interventions for populations at high risk of type 2 diabetes. DESIGN: Overview of systematic reviews (search dates April-December 2015). SETTING: Any level of care; no geographical restriction. PARTICIPANTS: Adults at high risk of diabetes (as per measures of glycaemia, risk assessment or presence of risk factors). INTERVENTIONS: Combined diet and physical activity interventions including ≥2 interactions with a healthcare professional, and ≥12 months follow-up. OUTCOME MEASURES: Primary: glycaemia, diabetes incidence. Secondary: behaviour change, measures of adiposity, vascular disease and mortality. RESULTS: 19 recent reviews were identified for inclusion; 5 with AMSTAR scores <8. Most considered only randomised controlled trials (RCTs), and RCTs were the major data source in the remainder. Five trials were included in most reviews. Almost all analyses reported that interventions were associated with net reductions in diabetes incidence, measures of glycaemia and adiposity, at follow-up durations of up to 23 years (typically <6). Small effect sizes and potentially transient effect were reported in some studies, and some reviewers noted that durability of intervention impact was potentially sensitive to duration of intervention and adherence to behaviour change. Behaviour change, vascular disease and mortality outcome data were infrequently reported, and evidence of the impact of intervention on these outcomes was minimal. Evidence for age effect was mixed, and sex and ethnicity effect were little considered. CONCLUSIONS: Relatively long-duration lifestyle interventions can limit or delay progression to diabetes under trial conditions. However, outcomes from more time-limited interventions, and those applied in routine clinical settings, appear more variable, in keeping with the findings of recent pragmatic trials. There is little evidence of intervention impact on vascular outcomes or mortality end points in any context. 'Real-world' implementation of lifestyle interventions for diabetes prevention may be expected to lead to modest outcomes.

Strategies for tobacco control in India: a systematic review.

BACKGROUND: Tobacco control needs in India are large and complex. Evaluation of outcomes to date has been limited. AIM: To review the extent of tobacco control measures, and the outcomes of associated trialled interventions, in India. METHODS: Information was identified via database searches, journal hand-searches, reference and citation searching, and contact with experts. Studies of any population resident in India were included. Studies where outcomes were not yet available, not directly related to tobacco use, or not specific to India, were excluded. Pre-tested proformas were used for data extraction and quality assessment. Studies with reliability concerns were excluded from some aspects of analysis. The Framework Convention on Tobacco Control (FCTC) was use as a framework for synthesis. Heterogeneity limited meta-analysis options. Synthesis was therefore predominantly narrative. RESULTS: Additional to the Global Tobacco Surveillance System data, 80 studies were identified, 45 without reliability concerns. Most related to education (FCTC Article 12) and tobacco-use cessation (Article 14). They indicated widespread understanding of tobacco-related harm, but less knowledge about specific consequences of use. Healthcare professionals reported low confidence in cessation assistance, in keeping with low levels of training. Training for schoolteachers also appeared suboptimal. Educational and cessation assistance interventions demonstrated positive impact on tobacco use. Studies relating to smoke-free policies (Article 8), tobacco advertisements and availability (Articles 13 and 16) indicated increasingly widespread smoke-free policies, but persistence of high levels of SHS exposure, tobacco promotions and availability-including to minors. Data relating to taxation/pricing and packaging (Articles 6 and 11) were limited. We did not identify any studies of product regulation, alternative employment strategies, or illicit trade (Articles 9, 10, 15 and 17). CONCLUSIONS: Tobacco-use outcomes could be improved by school/community-based and adult education interventions, and cessation assistance, facilitated by training for health professionals and schoolteachers. Additional tobacco control measures should be assessed.

Are primary care factors associated with hospital episodes for adverse drug reactions? A national observational study.

OBJECTIVE: Identification of primary care factors associated with hospital admissions for adverse drug reactions (ADRs). DESIGN AND SETTING: Cross-sectional analysis of 2010-2012 data from all National Health Service hospitals and 7664 of 8358 general practices in England. METHOD: We identified all hospital episodes with an International Classification of Diseases (ICD) 10 code indicative of an ADR, in the 2010-2012 English Hospital Episode Statistics (HES) admissions database. These episodes were linked to contemporary data describing the associated general practice, including general practitioner (GP) and patient demographics, an estimate of overall patient population morbidity, measures of primary care supply, and Quality and Outcomes Framework (QOF) quality scores. Poisson regression models were used to examine associations between primary care factors and ADR-related episode rates. RESULTS: 212,813 ADR-related HES episodes were identified. Rates of episodes were relatively high among the very young, older and female subgroups. In fully adjusted models, the following primary care factors were associated with increased likelihood of episode: higher deprivation scores (population attributable fraction (PAF)=0.084, 95% CI 0.067 to 0.100) and relatively poor glycated haemoglobin (HbA1c) control among patients with diabetes (PAF=0.372; 0.218 to 0.496). The following were associated with reduced episode likelihood: lower GP supply (PAF=-0.016; -0.026 to -0.005), a lower proportion of GPs with UK qualifications (PAF=-0.035; -0.058 to -0.012), lower total QOF achievement rates (PAF=-0.021; -0.042 to 0.000) and relatively poor blood pressure control among patients with diabetes (PAF=-0.144; -0.280 to -0.022). CONCLUSIONS: Various aspects of primary care are associated with ADR-related hospital episodes, including achievement of particular QOF indicators. Further investigation with individual level data would help develop understanding of the associations identified. Interventions in primary care could help reduce the ADR burden. ADRs are candidates for primary care sensitive conditions.