Evaluating Ethnic Variations in the Risk of Infections in People With Prediabetes and Type 2 Diabetes: A Matched Cohort Study.

OBJECTIVE: People living with type 2 diabetes (T2D) are at higher infection risk, but it is unknown how this risk varies by ethnicity or whether the risk is similarly observed in people with nondiabetic hyperglycemia ("prediabetes"). RESEARCH DESIGN AND METHODS: We included 527,151 patients in England with T2D and 273,216 with prediabetes, aged 18-90, and alive on 1 January 2015 on the Clinical Practice Research Datalink. Each was matched to two patients without diabetes or prediabetes on age, sex, and ethnic group. Infections during 2015-2019 were collated from primary care and linked hospitalization records. Infection incidence rate ratios (IRRs) for those with prediabetes or T2D were estimated, unadjusted and adjusted for confounders. RESULTS: People with T2D had increased risk for infections presenting in primary care (IRR 1.51, 95% CI 1.51-1.52) and hospitalizations (IRR 1.91, 1.90-1.93). This was broadly consistent overall within each ethnic group, although younger White T2D patients (age <50) experienced a greater relative risk. Adjustment for socioeconomic deprivation, smoking, and comorbidity attenuated associations, but IRRs remained similar by ethnicity. For prediabetes, a significant but smaller risk was observed (primary care IRR 1.35, 95% CI 1.34-1.36; hospitalization IRR 1.33, 1.31-1.35). These were similar within each ethnicity for primary care infections, but less consistent for infection-related hospitalizations. CONCLUSIONS: The elevated infection risk for people with T2D appears similar for different ethnic groups and is also seen in people with prediabetes. Infections are a substantial cause of ill-health and health service use for people with prediabetes and T2D. This has public health implications with rising prediabetes and diabetes prevalence.

Risk factors for excess all-cause mortality during the first wave of the COVID-19 pandemic in England: A retrospective cohort study of primary care data.

BACKGROUND: The COVID-19 pandemic's first wave in England during spring 2020 resulted in an approximate 50% increase in all-cause mortality. Previously, risk factors such as age and ethnicity, were identified by studying COVID-related deaths only, but these were under-recorded during this period. OBJECTIVE: To use a large electronic primary care database to estimate the impact of risk factors (RFs) on excess mortality in England during the first wave, compared with the impact on total mortality during 2015-19. METHODS: Medical history, ethnicity, area-based deprivation and vital status data were extracted for an average of 4.8 million patients aged 30-104 years, for each year between 18-March and 19-May over a 6-year period (2015-2020). We used Poisson regression to model total mortality adjusting for age and sex, with interactions between each RF and period (pandemic vs. 2015-19). Total mortality during the pandemic was partitioned into "usual" and "excess" components, assuming 2015-19 rates represented "usual" mortality. The association of each RF with the 2020 "excess" component was derived as the excess mortality ratio (EMR), and compared with the usual mortality ratio (UMR). RESULTS: RFs where excess mortality was greatest and notably higher than usual were age >80, non-white ethnicity (e.g., black vs. white EMR = 2.50, 95%CI 1.97-3.18; compared to UMR = 0.92, 95%CI 0.85-1.00), BMI>40, dementia, learning disability, severe mental illness, place of residence (London, care-home, most deprived). By contrast, EMRs were comparable to UMRs for sex. Although some co-morbidities such as cancer produced EMRs significantly below their UMRs, the EMRs were still >1. In contrast current smoking has an EMR below 1 (EMR = 0.80, 95%CI 0.65-0.98) compared to its UMR = 1.64. CONCLUSIONS: Studying risk factors for excess mortality during the pandemic highlighted differences from studying cause-specific mortality. Our approach illustrates a novel methodology for evaluating a pandemic's impact by individual risk factor without requiring cause-specific mortality data.

Prevalence and incidence of neuromuscular conditions in the UK between 2000 and 2019: A retrospective study using primary care data.

BACKGROUND: In the UK, large-scale electronic primary care datasets can provide up-to-date, accurate epidemiological information on rarer diseases, where specialist diagnoses from hospital discharges and clinic letters are generally well recorded and electronically searchable. Current estimates of the number of people living with neuromuscular disease (NMD) have largely been based on secondary care data sources and lacked direct denominators. OBJECTIVE: To estimate trends in the recording of neuromuscular disease in UK primary care between 2000-2019. METHODS: The Clinical Practice Research Datalink (CPRD) database was searched electronically to estimate incidence and prevalence rates (per 100,000) for a range of NMDs in each year. To compare trends over time, rates were age standardised to the most recent CPRD population (2019). RESULTS: Approximately 13 million patients were actively registered in each year. By 2019, 28,230 active patients had ever received a NMD diagnosis (223.6), which was higher among males (239.0) than females (208.3). The most common classifications were Guillain-Barre syndrome (40.1), myasthenia gravis (33.7), muscular dystrophy (29.5), Charcot-Marie-Tooth (29.5) and inflammatory myopathies (25.0). Since 2000, overall prevalence grew by 63%, with the largest increases seen at older ages (≥65-years). However, overall incidence remained constant, though myasthenia gravis incidence has risen steadily since 2008, while new cases of muscular dystrophy fell over the same period. CONCLUSIONS: Lifetime recording of many NMDs on primary care records exceed current estimates of people living with these conditions; these are important data for health service and care planning. Temporal trends suggest this number is steadily increasing, and while this may partially be due to better recording, it cannot be simply explained by new cases, as incidence remained constant. The increase in prevalence among older ages suggests increases in life expectancy among those living with NMDs may have occurred.

Equity-specific effects of interventions to promote physical activity among middle-aged and older adults: results from applying a novel equity-specific re-analysis strategy.

BACKGROUND: Reducing inequalities in physical activity (PA) and PA-associated health outcomes is a priority for public health. Interventions to promote PA may reduce inequalities, but may also unintentionally increase them. Thus, there is a need to analyze equity-specific intervention effects. However, the potential for analyzing equity-specific effects of PA interventions has not yet been sufficiently exploited. The aim of this study was to set out a novel equity-specific re-analysis strategy tried out in an international interdisciplinary collaboration. METHODS: The re-analysis strategy comprised harmonizing choice and definition of outcomes, exposures, socio-demographic indicators, and statistical analysis strategies across studies, as well as synthesizing results. It was applied in a collaboration of a convenience sample of eight European PA intervention studies in adults aged ≥45 years. Weekly minutes of moderate-to-vigorous PA was harmonized as outcome. Any versus no intervention was harmonized as exposure. Gender, education, income, area deprivation, and marital status were harmonized as socio-demographic indicators. Interactions between the intervention and socio-demographic indicators on moderate-to-vigorous PA were analyzed using multivariable linear regression and random-effects meta-analysis. RESULTS: The collaborative experience shows that the novel re-analysis strategy can be applied to investigate equity-specific effects of existing PA interventions. Across our convenience sample of studies, no consistent pattern of equity-specific intervention effects was found. Pooled estimates suggested that intervention effects did not differ by gender, education, income, area deprivation, and marital status. CONCLUSIONS: To exploit the potential for equity-specific effect analysis, we encourage future studies to apply the strategy to representative samples of existing study data. Ensuring sufficient representation of 'hard to reach' groups such as the most disadvantaged in study samples is of particular importance. This will help to extend the limited evidence required for the design and prioritization of future interventions that are most likely to reduce health inequalities.

The effects of step-count monitoring interventions on physical activity: systematic review and meta-analysis of community-based randomised controlled trials in adults.

BACKGROUND: Step-count monitors (pedometers, body-worn trackers and smartphone applications) can increase walking, helping to tackle physical inactivity. We aimed to assess the effect of step-count monitors on physical activity (PA) in randomised controlled trials (RCTs) amongst community-dwelling adults; including longer-term effects, differences between step-count monitors, and between intervention components. METHODS: Systematic literature searches in seven databases identified RCTs in healthy adults, or those at risk of disease, published between January 2000-April 2020. Two reviewers independently selected studies, extracted data and assessed risk of bias. Outcome was mean differences (MD) with 95% confidence intervals (CI) in steps at follow-up between treatment and control groups. Our preferred outcome measure was from studies with follow-up steps adjusted for baseline steps (change studies); but we also included studies reporting follow-up differences only (end-point studies). Multivariate-meta-analysis used random-effect estimates at different time-points for change studies only. Meta-regression compared effects of different step-count monitors and intervention components amongst all studies at ≤4 months. RESULTS: Of 12,491 records identified, 70 RCTs (at generally low risk of bias) were included, with 57 trials (16,355 participants) included in meta-analyses: 32 provided change from baseline data; 25 provided end-point only. Multivariate meta-analysis of the 32 change studies demonstrated step-counts favoured intervention groups: MD of 1126 steps/day 95%CI [787, 1466] at ≤4 months, 1050 steps/day [602, 1498] at 6 months, 464 steps/day [301, 626] at 1 year, 121 steps/day [- 64, 306] at 2 years and 434 steps/day [191, 676] at 3-4 years. Meta-regression of the 57 trials at ≤4 months demonstrated in mutually-adjusted analyses that: end-point were similar to change studies (+ 257 steps/day [- 417, 931]); body-worn trackers/smartphone applications were less effective than pedometers (- 834 steps/day [- 1542, - 126]); and interventions providing additional counselling/incentives were not better than those without (- 812 steps/day [- 1503, - 122]). CONCLUSIONS: Step-count monitoring leads to short and long-term step-count increases, with no evidence that either body-worn trackers/smartphone applications, or additional counselling/incentives offer further benefit over simpler pedometer-based interventions. Simple step-count monitoring interventions should be prioritised to address the public health physical inactivity challenge. SYSTEMATIC REVIEW REGISTRATION: PROSPERO number CRD42017075810 .

Longitudinal impact of changes in the residential built environment on physical activity: findings from the ENABLE London cohort study.

BACKGROUND: Previous research has reported associations between features of the residential built environment and physical activity but these studies have mainly been cross-sectional, limiting inference. This paper examines whether changes in a range of residential built environment features are associated with changes in measures of physical activity in adults. It also explores whether observed effects are moderated by socio-economic status. METHODS: Data from the Examining Neighbourhood Activity in Built Living Environments in London (ENABLE London) study were used. A cohort of 1278 adults seeking to move into social, intermediate, and market-rent East Village accommodation was recruited in 2013-2015, and followed up after 2 years. Accelerometer-derived steps (primary outcome), and GIS-derived measures of residential walkability, park proximity and public transport accessibility were obtained both at baseline and follow-up. Daily steps at follow-up were regressed on daily steps at baseline, change in built environment exposures and confounding variables using multilevel linear regression to assess if changes in neighbourhood walkability, park proximity and public transport accessibility were associated with changes in daily steps. We also explored whether observed effects were moderated by housing tenure as a marker of socio-economic status. RESULTS: Between baseline and follow-up, participants experienced a 1.4 unit (95%CI 1.2,1.6) increase in neighbourhood walkability; a 270 m (95%CI 232,307) decrease in distance to their nearest park; and a 0.7 point (95% CI 0.6,0.9) increase in accessibility to public transport. A 1 s.d. increase in neighbourhood walkability was associated with an increase of 302 (95%CI 110,494) daily steps. A 1 s.d. increase in accessibility to public transport was not associated with any change in steps overall, but was associated with a decrease in daily steps amongst social housing seekers (- 295 steps (95%CI - 595, 3), and an increase in daily steps for market-rent housing seekers (410 95%CI -191, 1010) (P-value for effect modification = 0.03). CONCLUSION: Targeted changes in the residential built environment may result in increases in physical activity levels. However, the effect of improved accessibility to public transport may not be equitable, showing greater benefit to the more advantaged.

Development of a structured clinical pharmacology review for specialist support for management of complex polypharmacy in primary care.

AIMS: Polypharmacy is widespread and associated with medication-related harms, including adverse drug reactions, medication errors and poor treatment adherence. General practitioners and pharmacists cite limited time and training to perform effective medication reviews for patients with complex polypharmacy, yet no specialist referral mechanism exists. To develop a structured framework for specialist review of primary care patients with complex polypharmacy. METHODS: We developed the clinical pharmacology structured review (CPSR) and stopping by indication tool (SBIT). We tested these in an age-sex stratified sample of 100 people with polypharmacy aged 65-84 years from the Clinical Practice Research Datalink, an anonymised primary care database. Simulated medication reviews based on electronic records using the CPSR and SBIT were performed. We recommended medication changes or review to optimise treatment benefits, reduce risk of harm or reduce treatment burden. RESULTS: Recommendations were made for all patients, for almost half (4.8 ± 2.4) of existing medicines (9.8 ± 3.1), most commonly stopping a drug (1.7 ± 1.3/patient) or reviewing with the patient (1.4 ± 1.2/patient). At least 1 new medicine (0.7 ± 0.9) was recommended for 51% patients. Recommendations predominantly aimed to reduce harm (44%). There was no relationship between number of recommendations made and time since last primary care medication review. We identified a core set of clinical information and investigations (polypharmacy workup) that could inform a standard screen prior to specialist review. CONCLUSION: The CPSR, SBIT and polypharmacy workup could form the basis of a specialist review for patients with complex polypharmacy. Further research is needed to test this approach in patients in general practice.

Variability in Glycated Hemoglobin and Risk of Poor Outcomes Among People With Type 2 Diabetes in a Large Primary Care Cohort Study.

OBJECTIVE: Diabetes guidelines focus on target glycated hemoglobin (HbA1c) levels. Long-term variability in HbA1c may be predictive of hospitalization or mortality, but its importance at different average levels or trajectories is unclear. RESEARCH DESIGN AND METHODS: Using English primary care data, 58,832 patients with type 2 diabetes had HbA1c average (mean of annual means), variability (coefficient of variation), and trajectory (annual regression slope) estimated during 2006-2009. Hazard ratios (HRs) for mortality and emergency hospitalization during 2010-2015, with adjustment for age, sex, smoking, BMI, duration of diabetes, and deprivation, were estimated using Cox regression. The simultaneous impact of HbA1c average, variability, and trajectory was estimated using percentiles. RESULTS: In mutually adjusted models, HbA1c variability showed a consistent dose-response relationship with all-cause mortality, while average level was only important among individuals in the highest or lowest 10% of the distribution, and trajectory had no independent effect. Individuals with the most unstable HbA1c (top 10%) were almost twice as likely to die (HR 1.93 [95% CI 1.72-2.16]) than were those with the most stable (bottom 10%)-an association attenuated but not explained by hypoglycemia. For emergency hospitalizations, similar trends were seen except for coronary artery disease (CAD) and ischemic stroke (IS), where increasing average rather than variability was predictive. CONCLUSIONS: HbA1c variability was strongly associated with overall mortality and emergency hospitalization and not explained by average HbA1c or hypoglycemic episodes. Only for CAD and IS hospitalizations was no association found, with average HbA1c strongly predictive. Targets should focus on both stability and absolute level of HbA1c.

Longitudinal exposure of English primary care patients to pharmacogenomic drugs: An analysis to inform design of pre-emptive pharmacogenomic testing.

AIMS: To investigate the longitudinal exposure of English primary care patients to pharmacogenomic drugs to inform design of pre-emptive testing. METHODS: Sixty-three drugs were identified with dosing guidelines based on variants of 19 pharmacogenes in the Pharmacogenomics Knowledgebase on 01 September 2018. Prescribing of these pharmacogenomic drugs between 1993 and 2017 was summarised for a sample of 648 141 English patients aged 50-99 years on 01 January 2013, registered with Clinical Practice Research Datalink practices during 2011-12. Exposure of patients to pharmacogenomic drugs retrospectively (2, 10, 20 y) and prospectively (5 y) was described. RESULTS: During 2011-12, 58% of patients were prescribed at least 1 pharmacogenomic drug, increasing to 80% over the previous 20 years. Multiple exposure was common, with 47% patients prescribed ≥2 pharmacogenomic drugs and 7% prescribed ≥5 pharmacogenomic drugs over the next 5 years. The likelihood of exposure to pharmacogenomic drugs increased with age, with 89% patients ≥70 years prescribed at least 1 pharmacogenomic drug over the previous 20 years. Even among those aged 50-59 years, 71% were prescribed at least 1 pharmacogenomic drug over the previous 20 years. The pharmacogenomic drugs prescribed to the most patients were for pain relief, gastroprotection, psychiatric and cardiovascular conditions. Three pharmacogenes (CYP2D6, CYP2C19 and SLCO1B1) accounted for >95% pharmacogenomic drugs prescribed. CONCLUSIONS: In primary care patients, exposure to pharmacogenomic drugs is extremely common, multiplicitous and has commenced by relatively early adulthood. A small number of pharmacogenes account for the majority of drugs prescribed. These findings could inform design of pre-emptive pharmacogenomic testing for implementation in primary care.

Measuring change in trials of physical activity interventions: a comparison of self-report questionnaire and accelerometry within the PACE-UP trial.

BACKGROUND: Few trials have compared estimates of change in physical activity (PA) levels using self-reported and objective PA measures when evaluating trial outcomes. The PACE-UP trial offered the opportunity to assess this, using the self-administered International Physical Activity Questionnaire (IPAQ) and waist-worn accelerometry. METHODS: The PACE-UP trial (N = 1023) compared usual care (n = 338) with two pedometer-based walking interventions, by post (n = 339) or with nurse support (n = 346). Participants wore an accelerometer at baseline and 12 months and completed IPAQ for the same 7-day periods. Main outcomes were weekly minutes, all in ≥10 min bouts as per UK PA guidelines of: i) accelerometer moderate-to-vigorous PA (Acc-MVPA) ii) IPAQ moderate+vigorous PA (IPAQ-MVPA) and iii) IPAQ walking (IPAQ-Walk). For each outcome, 12 month values were regressed on baseline to estimate change. RESULTS: Analyses were restricted to 655 (64%) participants who provided data on all outcomes at baseline and 12 months. Both intervention groups significantly increased their accelerometry MVPA minutes/week compared with control: postal group 42 (95% CI 22, 61), nurse group 43 (95% CI 24, 63). IPAQ-Walk minutes/week also increased: postal 57 (95% CI 2, 112), nurse 43 (95% CI -11, 97) but IPAQ-MVPA minutes/week showed non-significant decreases: postal -11 (95% CI -65, 42), nurse -34 (95% CI -87, 19). CONCLUSIONS: Our results demonstrate the necessity of using a questionnaire focussing on the activities being altered, as with IPAQ-Walk questions. Even then, the change in PA was estimated with far less precision than with accelerometry. Accelerometry is preferred to self-report measurement, minimising bias and improving precision when assessing effects of a walking intervention. TRIAL REGISTRATION: ISRCTN, ISRCTN98538934 . Registered 2 March 2012.

Are noise and air pollution related to the incidence of dementia? A cohort study in London, England.

OBJECTIVE: To investigate whether the incidence of dementia is related to residential levels of air and noise pollution in London. DESIGN: Retrospective cohort study using primary care data. SETTING: 75 Greater London practices. PARTICIPANTS: 130 978 adults aged 50-79 years registered with their general practices on 1 January 2005, with no recorded history of dementia or care home residence. PRIMARY AND SECONDARY OUTCOME MEASURES: A first recorded diagnosis of dementia and, where specified, subgroups of Alzheimer's disease and vascular dementia during 2005-2013. The average annual concentrations during 2004 of nitrogen dioxide (NO2), particulate matter with a median aerodynamic diameter ≤2.5 µm (PM2.5) and ozone (O3) were estimated at 20×20 m resolution from dispersion models. Traffic intensity, distance from major road and night-time noise levels (Lnight) were estimated at the postcode level. All exposure measures were linked anonymously to clinical data via residential postcode. HRs from Cox models were adjusted for age, sex, ethnicity, smoking and body mass index, with further adjustments explored for area deprivation and comorbidity. RESULTS: 2181 subjects (1.7%) received an incident diagnosis of dementia (39% mentioning Alzheimer's disease, 29% vascular dementia). There was a positive exposure response relationship between dementia and all measures of air pollution except O3, which was not readily explained by further adjustment. Adults living in areas with the highest fifth of NO2 concentration (>41.5 µg/m3) versus the lowest fifth (<31.9 µg/m3) were at a higher risk of dementia (HR=1.40, 95% CI 1.12 to 1.74). Increases in dementia risk were also observed with PM2.5, PM2.5 specifically from primary traffic sources only and Lnight, but only NO2 and PM2.5 remained statistically significant in multipollutant models. Associations were more consistent for Alzheimer's disease than vascular dementia. CONCLUSIONS: We have found evidence of a positive association between residential levels of air pollution across London and being diagnosed with dementia, which is unexplained by known confounding factors.

Association between depressive symptoms and objectively measured daily step count in individuals at high risk of cardiovascular disease in South London, UK: a cross-sectional study.

OBJECTIVES: Depressive symptoms are common but rarely considered a risk factor for unhealthy lifestyles associated with cardiovascular disease (CVD). This study investigates whether depressive symptoms are associated with reduced physical activity (PA) in individuals at high risk of developing CVD. DESIGN: Secondary analysis of the cross-sectional baseline data from a randomised controlled trial of an intensive lifestyle intervention. SETTING: 135 primary care practices in South London, UK. PARTICIPANTS: 1742 adults, 49-74 years, 86% male at high (≥20%) risk of developing CVD in the next 10 years as defined via QRISK2 score. OUTCOME MEASURES: The main explanatory variable was depressive symptoms measured via the Patient Health Questionnaire-9 (PHQ-9). The main outcome was daily step count measured with an accelerometer (ActiGraph GT3X) stratified by weekdays and weekend days. RESULTS: The median daily step count of the total sample was 6151 (IQR 3510) with significant differences (P<0.001) in mean daily step count between participants with low (PHQ-9 score: 0-4), mild (PHQ-9 score: 5-9) and moderate to severe depressive symptoms (PHQ-9 score: ≥10). Controlling for age, gender, ethnicity, education level, body mass index (BMI), smoking, consumption of alcohol, day of the week and season, individuals with mild depressive symptoms and those with moderate to severe depressive symptoms walked 13.3% (95% CI 18.8% to 7.9%) and 15.6% (95% CI 23.7% to 6.5%) less than non-depressed individuals, respectively. Furthermore, male gender, white ethnicity, higher education level, lower BMI, non-smoking, moderate alcohol intake, weekdays and summer season were independently associated with higher step count. CONCLUSIONS: People at high risk of CVD with depressive symptoms have lower levels of PA. TRIAL REGISTRATION: ISRCTN84864870; Pre-results.

Risk of Infection in Type 1 and Type 2 Diabetes Compared With the General Population: A Matched Cohort Study.

OBJECTIVE: We describe in detail the burden of infections in adults with diabetes within a large national population cohort. We also compare infection rates between patients with type 1 and type 2 diabetes mellitus (T1DM and T2DM). RESEARCH DESIGN AND METHODS: A retrospective cohort study compared 102,493 English primary care patients aged 40-89 years with a diabetes diagnosis by 2008 (n = 5,863 T1DM and n = 96,630 T2DM) with 203,518 age-sex-practice-matched control subjects without diabetes. Infection rates during 2008-2015, compiled from primary care and linked hospital and mortality records, were compared across 19 individual infection categories. These were further summarized as any requiring a prescription or hospitalization or as cause of death. Poisson regression was used to estimate incidence rate ratios (IRRs) between 1) people with diabetes and control subjects and 2) T1DM and T2DM adjusted for age, sex, smoking, BMI, and deprivation. RESULTS: Compared with control subjects without diabetes, patients with diabetes had higher rates for all infections, with the highest IRRs seen for bone and joint infections, sepsis, and cellulitis. IRRs for infection-related hospitalizations were 3.71 (95% CI 3.27-4.21) for T1DM and 1.88 (95% CI 1.83-1.92) for T2DM. A direct comparison of types confirmed higher adjusted risks for T1DM versus T2DM (death from infection IRR 2.19 [95% CI 1.75-2.74]). We estimate that 6% of infection-related hospitalizations and 12% of infection-related deaths were attributable to diabetes. CONCLUSIONS: People with diabetes, particularly T1DM, are at increased risk of serious infection, representing an important population burden. Strategies that reduce the risk of developing severe infections and poor treatment outcomes are under-researched and should be explored.

Preventable Emergency Hospital Admissions Among Adults With Intellectual Disability in England.

PURPOSE: Adults with intellectual disabilities experience poorer physical health and health care quality, but there is limited information on the potential for reducing emergency hospital admissions in this population. We describe overall and preventable emergency admissions for adults with vs without intellectual disabilities in England and assess differences in primary care management before admission for 2 common ambulatory care-sensitive conditions (ACSCs). METHODS: We used electronic records to study a cohort of 16,666 adults with intellectual disabilities and 113,562 age-, sex-, and practice-matched adults without intellectual disabilities from 343 English family practices. Incident rate ratios (IRRs) from conditional Poisson regression were analyzed for all emergency and preventable emergency admissions. Primary care management of lower respiratory tract infections and urinary tract infections, as exemplar ACSCs, before admission were compared in unmatched analysis between adults with and without intellectual disabilities. RESULTS: The overall rate for emergency admissions for adults with vs without intellectual disabilities was 182 vs 68 per 1,000 per year (IRR = 2.82; 95% CI, 2.66-2.98). ACSCs accounted for 33.7% of emergency admissions among the former compared with 17.3% among the latter (IRR = 5.62; 95% CI, 5.14-6.13); adjusting for comorbidity, smoking, and deprivation did not fully explain the difference (IRR = 3.60; 95% CI, 3.25-3.99). Although adults with intellectual disability were at nearly 5 times higher risk for admission for lower respiratory tract infections and urinary tract infections, they had similar primary care use, investigation, and management before admission as the general population. CONCLUSIONS: Adults with intellectual disabilities are at high risk for preventable emergency admissions. Identifying strategies for better detecting and managing ACSCs, including lower respiratory and urinary tract infections, in primary care could reduce hospitalizations.

Mortality Among Adults With Intellectual Disability in England: Comparisons With the General Population.

OBJECTIVES: To describe mortality among adults with intellectual disability in England in comparison with the general population. METHODS: We conducted a cohort study from 2009 to 2013 using data from 343 general practices. Adults with intellectual disability (n = 16 666; 656 deaths) were compared with age-, gender-, and practice-matched controls (n = 113 562; 1358 deaths). RESULTS: Adults with intellectual disability had higher mortality rates than controls (hazard ratio [HR] = 3.6; 95% confidence interval [CI] = 3.3, 3.9). This risk remained high after adjustment for comorbidity, smoking, and deprivation (HR = 3.1; 95% CI = 2.7, 3.4); it was even higher among adults with intellectual disability and Down syndrome or epilepsy. A total of 37.0% of all deaths among adults with intellectual disability were classified as being amenable to health care intervention, compared with 22.5% in the general population (HR = 5.9; 95% CI = 5.1, 6.8). CONCLUSIONS: Mortality among adults with intellectual disability is markedly elevated in comparison with the general population, with more than a third of deaths potentially amenable to health care interventions. This mortality disparity suggests the need to improve access to, and quality of, health care among people with intellectual disability.

Health characteristics and consultation patterns of people with intellectual disability: a cross-sectional database study in English general practice.

BACKGROUND: People with intellectual disability (ID) are a group with high levels of healthcare needs; however, comprehensive information on these needs and service use is very limited. AIM: To describe chronic disease, comorbidity, disability, and general practice use among people with ID compared with the general population. DESIGN AND SETTING: This study is a cross-sectional analysis of a primary care database including 408 English general practices in 2012. METHOD: A total of 14 751 adults with ID, aged 18-84 years, were compared with 86 221 age-, sex- and practice-matched controls. Depending on the outcome, prevalence (PR), risk (RR), or odds (OR) ratios comparing patients with ID with matched controls are shown. RESULTS: Patients with ID had a markedly higher prevalence of recorded epilepsy (18.5%, PR 25.33, 95% confidence interval [CI] = 23.29 to 27.57), severe mental illness (8.6%, PR 9.10, 95% CI = 8.34 to 9.92), and dementia (1.1%, PR 7.52, 95% CI = 5.95 to 9.49), as well as moderately increased rates of hypothyroidism and heart failure (PR>2.0). However, recorded prevalence of ischaemic heart disease and cancer was approximately 30% lower than the general population. The average annual number of primary care consultations was 6.29 for patients with ID, compared with 3.89 for matched controls. Patients with ID were less likely to have longer doctor consultations (OR 0.73, 95% CI = 0.69 to 0.77), and had lower continuity of care with the same doctor (OR 0.77, 95% CI = 0.73 to 0.82). CONCLUSION: Compared with the general population, people with ID have generally higher overall levels of chronic disease and greater primary care use. Ensuring access to high-quality chronic disease management, especially for epilepsy and mental illness, will help address these greater healthcare needs. Continuity of care and longer appointment times are important potential improvements in primary care.

Body mass index in early and middle adult life: prospective associations with myocardial infarction, stroke and diabetes over a 30-year period: the British Regional Heart Study.

OBJECTIVES: Adiposity in middle age is an established risk factor for cardiovascular disease and type 2 diabetes; less is known about the impact of adiposity from early adult life. We examined the effects of high body mass index (BMI) in early and middle adulthood on myocardial infarction (MI), stroke and diabetes risks. DESIGN: A prospective cohort study. PARTICIPANTS: 7735 men with BMI measured in middle age (40-59 years) and BMI ascertained at 21 years from military records or participant recall. PRIMARY AND SECONDARY OUTCOME MEASURES: 30-year follow-up data for type 2 diabetes, MI and stroke incidence; Cox proportional hazards models were used to examine the effect of BMI at both ages on these outcomes, adjusted for age and smoking status. RESULTS: Among 4846 (63%) men (with complete data), a 1 kg/m(2) higher BMI at 21 years was associated with a 6% (95% CI 4% to 9%) higher type 2 diabetes risk, compared with a 21% (95% CI 18% to 24%) higher diabetes risk for a 1 kg/m(2) higher BMI in middle age (hazard ratio (HR) 1.21, 95% CI 1.18 to 1.24). Higher BMI in middle age was associated with a 6% (95% CI 4% to 8%) increase in MI and a 4% (95% CI 1% to 7%) increase in stroke; BMI at 21 years showed no associations with MI or stroke risk. CONCLUSIONS: Higher BMI at 21 years of age is associated with later diabetes incidence but not MI or stroke, while higher BMI in middle age is strongly associated with all outcomes. Early obesity prevention may reduce later type 2 diabetes risk, more than MI and stroke.

Variation in the SLC23A1 gene does not influence cardiometabolic outcomes to the extent expected given its association with L-ascorbic acid.

BACKGROUND: Observational studies showed that circulating L-ascorbic acid (vitamin C) is inversely associated with cardiometabolic traits. However, these studies were susceptible to confounding and reverse causation. OBJECTIVES: We assessed the relation between L-ascorbic acid and 10 cardiometabolic traits by using a single nucleotide polymorphism in the solute carrier family 23 member 1 (SLC23A1) gene (rs33972313) associated with circulating L-ascorbic acid concentrations. The observed association between rs33972313 and cardiometabolic outcomes was compared with that expected given the rs33972313-L-ascorbic acid and L-ascorbic acid-outcome associations. DESIGN: A meta-analysis was performed in the following 5 independent studies: the British Women's Heart and Health Study (n = 1833), the MIDSPAN study (n = 1138), the Ten Towns study (n = 1324), the British Regional Heart Study (n = 2521), and the European Prospective Investigation into Cancer (n = 3737). RESULTS: With the use of a meta-analysis of observational estimates, inverse associations were shown between L-ascorbic acid and systolic blood pressure, triglycerides, and the waist-hip ratio [the strongest of which was the waist-hip ratio (-0.13-SD change; 95% CI: -0.20-, -0.07-SD change; P = 0.0001) per SD increase in L-ascorbic acid], and a positive association was shown with high-density lipoprotein (HDL) cholesterol. The variation at rs33972313 was associated with a 0.18-SD (95% CI: 0.10-, 0.25-SD; P = 3.34 × 10⁻6) increase in L-ascorbic acid per effect allele. There was no evidence of a relation between the variation at rs33972313 and any cardiometabolic outcome. Although observed estimates were not statistically different from expected associations between rs33972313 and cardiometabolic outcomes, estimates for low-density lipoprotein cholesterol, HDL cholesterol, triglycerides, glucose, and body mass index were in the opposite direction to those expected. CONCLUSIONS: The nature of the genetic association exploited in this study led to limited statistical application, but despite this, when all cardiometabolic traits were assessed, there was no evidence of any trend supporting a protective role of L-ascorbic acid. In the context of existing work, these results add to the suggestion that observational relations between L-ascorbic acid and cardiometabolic health may be attributable to confounding and reverse causation.

Increased risk of acute cardiovascular events after partner bereavement: a matched cohort study.

IMPORTANCE The period immediately after bereavement has been reported as a time of increased risk of cardiovascular events. However, this risk has not been well quantified, and few large population studies have examined partner bereavement. OBJECTIVE To compare the rate of cardiovascular events between older individuals whose partner dies with those of a matched control group of individuals whose partner was still alive on the same day. DESIGN, SETTING, AND PARTICIPANTS Matched cohort study using a UK primary care database containing availale data of 401 general practices from February 2005 through September 2012. In all, 30 447 individuals aged 60 to 89 years at study initiation who experienced partner bereavement during follow-up were matched by age, sex, and general practice with the nonbereaved control group (n = 83 588) at the time of bereavement. EXPOSURES Partner bereavement. MAIN OUTCOMES AND MEASURES The primary outcome was occurrence of a fatal or nonfatal myocardial infarction (MI) or stroke within 30 days of bereavement. Secondary outcomes were non-MI acute coronary syndrome and pulmonary embolism. All outcomes were compared between the groups during prespecified periods after bereavement (30, 90, and 365 days). Incidence rate ratios (IRRs) from a conditional Poisson model were adjusted for age, smoking status, deprivation, and history of cardiovascular disease. RESULTS Within 30 days of their partner's death, 50 of the bereaved group (0.16%) experienced an MI or a stroke compared with 67 of the matched nonbereaved controls (0.08%) during the same period (IRR, 2.20 [95% CI, 1.52-3.15]). The increased risk was seen in bereaved men and women and attenuated after 30 days. For individual outcomes, the increased risk was found separately for MI (IRR, 2.14 [95% CI, 1.20-3.81]) and stroke (2.40 [1.22-4.71]). Associations with rarer events were also seen after bereavement, including elevated risk of non-MI acute coronary syndrome (IRR, 2.20 [95% CI, 1.12-4.29]) and pulmonary embolism (2.37 [1.18-4.75]) in the first 90 days. CONCLUSIONS AND RELEVANCE This study provides further evidence that the death of a partner is associated with a range of major cardiovascular events in the immediate weeks and months after bereavement. Understanding psychosocial factors associated with acute cardiovascular events may provide opportunities for prevention and improved clinical care.

Mortality associations with long-term exposure to outdoor air pollution in a national English cohort.

RATIONALE: Cohort evidence linking long-term exposure to outdoor particulate air pollution and mortality has come largely from the United States. There is relatively little evidence from nationally representative cohorts in other countries. OBJECTIVES: To investigate the relationship between long-term exposure to a range of pollutants and causes of death in a national English cohort. METHODS: A total of 835,607 patients aged 40-89 years registered with 205 general practices were followed from 2003-2007. Annual average concentrations in 2002 for particulate matter with a median aerodynamic diameter less than 10 (PM(10)) and less than 2.5 µm (PM(2.5)), nitrogen dioxide (NO(2)), ozone, and sulfur dioxide (SO(2)) at 1 km(2) resolution, estimated from emission-based models, were linked to residential postcode. Deaths (n = 83,103) were ascertained from linkage to death certificates, and hazard ratios (HRs) for all- and cause-specific mortality for pollutants were estimated for interquartile pollutant changes from Cox models adjusting for age, sex, smoking, body mass index, and area-level socioeconomic status markers. MEASUREMENTS AND MAIN RESULTS: Residential concentrations of all pollutants except ozone were positively associated with all-cause mortality (HR, 1.02, 1.03, and 1.04 for PM(2.5), NO(2), and SO(2), respectively). Associations for PM(2.5), NO(2), and SO(2) were larger for respiratory deaths (HR, 1.09 each) and lung cancer (HR, 1.02, 1.06, and 1.05) but nearer unity for cardiovascular deaths (1.00, 1.00, and 1.04). CONCLUSIONS: These results strengthen the evidence linking long-term ambient air pollution exposure to increased all-cause mortality. However, the stronger associations with respiratory mortality are not consistent with most US studies in which associations with cardiovascular causes of death tend to predominate.