Landmark models for optimizing the use of repeated measurements of risk factors in electronic health records to predict future disease risk

The benefits of using electronic health records for disease risk screening and personalized heathcare decisions are becoming increasingly recognized. We present a computationally feasible statistical approach to address the methodological challenges in utilizing historical repeat measures of multiple risk factors recorded in electronic health records to systematically identify patients at high risk of future disease. The approach is principally based on a two-stage dynamic landmark model. The first stage estimates current risk factor values from all available historical repeat risk factor measurements by landmark-age-specific multivariate linear mixed-effects models with correlated random-intercepts, which account for sporadically recorded repeat measures, unobserved data and measurements errors. The second stage predicts future disease risk from a sex-stratified Cox proportional hazards model, with estimated current risk factor values from the first stage. Methods are exemplified by developing and validating a dynamic 10-year cardiovascular disease risk prediction model using electronic primary care records for age, diabetes status, hypertension treatment, smoking status, systolic blood pressure, total and high-density lipoprotein cholesterol from 41,373 individuals in 10 primary care practices in England and Wales contributing to The Health Improvement Network (1997-2016). Using cross-validation, the model was well-calibrated (Brier score = 0.041 [95%CI: 0.039, 0.042]) and had good discrimination (C-index = 0.768 [95%CI: 0.759, 0.777]).This work was funded by the Medical Research Council (MRC) (grant MR/K014811/1). J.B. was supported by an MRC fellowship (grant G0902100) and the MRC Unit Program (grant MC_UU_00002/5). R.H.K. was supported by an MRC Methodology Fellowship (grant MR/M014827/1)

Statin prescribing for prevention of cardiovascular disease amongst people with severe mental illness: Cohort study in UK primary care

BACKGROUND: Severe mental illness (SMI) is associated with excess cardiovascular disease (CVD) morbidity, but little is known on provision of preventative interventions. We investigated statin initiation for primary CVD prevention in individuals with and without SMI. METHODS: We used primary care data from The Health Improvement Network from 2006 to 2015 for UK patients aged 30-99years with no pre-existing CVD conditions and selected individuals with schizophrenia (n=13,252) or bipolar disorder (n=11,994). In addition, we identified samples of individuals without schizophrenia (n=66,060) and bipolar disorder (n=59,765), but with similar age and gender distribution. Missing data on CVD covariates were estimated using multiple imputation. Statin prescribing differences between individuals with and without SMI were investigated using multivariable Poisson regression models. RESULTS: Initiation of statin prescribing was between 2 and 3 fold higher in people aged 30-59years with SMI than in those without after adjusting for CVD covariates. The rates in those aged 60-74years with SMI were similar or slightly higher relative to those without SMI. The incidence rate ratio (IRR) was 1.15 (95% CI 1.03-1.28) for bipolar disorder and 1.00 (0.91-1.11) for schizophrenia. The rate of statin prescribing was lower (IRR 0.81 (0.66-0.98)) amongst the oldest (aged 75+years) with schizophrenia relative to those without schizophrenia. CONCLUSIONS: Despite higher rates of new statin prescriptions to younger individuals with SMI relative to individuals without SMI, there was evidence of lower rates of statin initiation for older individuals with schizophrenia, and this group may benefit from additional measures to prevent CVD

Statin prescribing for people with severe mental illnesses: a staggered cohort study of 'real-world' impacts

OBJECTIVES: To estimate the 'real-world effectiveness of statins for primary prevention of cardiovascular disease (CVD) and for lipid modification in people with severe mental illnesses (SMI), including schizophrenia and bipolar disorder. DESIGN: Series of staggered cohorts. We estimated the effect of statin prescribing on CVD outcomes using a multivariable Poisson regression model or linear regression for cholesterol outcomes. SETTING: 587 general practice (GP) surgeries across the UK reporting data to The Health Improvement Network. PARTICIPANTS: All permanently registered GP patients aged 40-84 years between 2002 and 2012 who had a diagnosis of SMI. Exclusion criteria were pre-existing CVD, statin-contraindicating conditions or a statin prescription within the 24 months prior to the study start. EXPOSURE: One or more statin prescriptions during a 24-month 'baseline' period (vs no statin prescription during the same period). MAIN OUTCOME MEASURES: The primary outcome was combined first myocardial infarction and stroke. All-cause mortality and total cholesterol concentration were secondary outcomes. RESULTS: We identified 2944 statin users and 42 886 statin non-users across the staggered cohorts. Statin prescribing was not associated with significant reduction in CVD events (incident rate ratio 0.89; 95% CI 0.68 to 1.15) or all-cause mortality (0.89; 95% CI 0.78 to 1.02). Statin prescribing was, however, associated with statistically significant reductions in total cholesterol of 1.2 mmol/L (95% CI 1.1 to 1.3) for up to 2 years after adjusting for differences in baseline characteristics. On average, total cholesterol decreased from 6.3 to 4.6 in statin users and 5.4 to 5.3 mmol/L in non-users. CONCLUSIONS: We found that statin prescribing to people with SMI in UK primary care was effective for lipid modification but not CVD events. The latter finding may reflect insufficient power to detect a smaller effect size than that observed in randomised controlled trials of statins in people without SMI

Health care resource use by patients before and after a diagnosis of chronic fatigue syndrome (CFS/ME):a Clinical Practice Research Datalink study

Abstract Background Our aim was to investigate patterns of health care resource use by patients before and after a diagnosis of CFS/ME, as recorded by Clinical Practice Research Datalink (CPRD) GP practices in the UK. Methods We used a case–control study design in which patients who had a first recorded diagnosis of CFS/ME during the period 01/01/2001 to 31/12/2013 were matched 1:1 with controls by age, sex, and GP practice. We compared rates of GP consultations, diagnostic tests, prescriptions, referrals, and symptoms between the two groups from 15 years (in adults) or 10 years (in children) before diagnosis to 10 years after diagnosis. Results Data were available for 6710 adult and 916 child (age <18 years) matched case–control pairs. Rates of GP consultations, diagnostic tests, prescriptions, referrals, and symptoms spiked dramatically in the year when a CFS/ME diagnosis was recorded. GP consultation rates were 50% higher in adult cases compared to controls 11–15 years before diagnosis (rate ratio (RR) 1.49 (95% CI 1.46, 1.52)) and 56% higher 6–10 years after diagnosis (RR 1.56 (1.54, 1.57)). In children, consultation rates in cases were 45% higher 6–10 years before diagnosis (RR 1.45 (1.40, 1.51)) and 62% higher 6–10 years after diagnosis (RR 1.62 (1.54, 1.70)). For adults and children, rates of tests, prescriptions, referrals, and symptoms were higher in cases compared to controls for up to 10 years before and after diagnosis. Conclusions Adults and children with CFS/ME have greater health care needs than the rest of the population for at least ten years before their diagnosis, and these higher levels of health care resource use continue for at least ten years after diagnosis

Association of common mental disorders and quality of life with the frequency of attendance in slovenian family medicine practices: longitudinal study.

Most research on frequent attendance has been cross-sectional and restricted to one year attendance rates. A few longitudinal studies suggest that frequent attendance is self-limiting. Frequent attenders are more likely to have social and psychiatric problems, medically unexplained physical symptoms, chronic somatic diseases (especially diabetes) and are prescribed more psychotropic medication and analgesics

Health care resource use by patients before and after a diagnosis of chronic fatigue syndrome (CFS/ME):a Clinical Practice Research Datalink study

BACKGROUND: Our aim was to investigate patterns of health care resource use by patients before and after a diagnosis of CFS/ME, as recorded by Clinical Practice Research Datalink (CPRD) GP practices in the UK. METHODS: We used a case–control study design in which patients who had a first recorded diagnosis of CFS/ME during the period 01/01/2001 to 31/12/2013 were matched 1:1 with controls by age, sex, and GP practice. We compared rates of GP consultations, diagnostic tests, prescriptions, referrals, and symptoms between the two groups from 15 years (in adults) or 10 years (in children) before diagnosis to 10 years after diagnosis. RESULTS: Data were available for 6710 adult and 916 child (age <18 years) matched case–control pairs. Rates of GP consultations, diagnostic tests, prescriptions, referrals, and symptoms spiked dramatically in the year when a CFS/ME diagnosis was recorded. GP consultation rates were 50% higher in adult cases compared to controls 11–15 years before diagnosis (rate ratio (RR) 1.49 (95% CI 1.46, 1.52)) and 56% higher 6–10 years after diagnosis (RR 1.56 (1.54, 1.57)). In children, consultation rates in cases were 45% higher 6–10 years before diagnosis (RR 1.45 (1.40, 1.51)) and 62% higher 6–10 years after diagnosis (RR 1.62 (1.54, 1.70)). For adults and children, rates of tests, prescriptions, referrals, and symptoms were higher in cases compared to controls for up to 10 years before and after diagnosis. CONCLUSIONS: Adults and children with CFS/ME have greater health care needs than the rest of the population for at least ten years before their diagnosis, and these higher levels of health care resource use continue for at least ten years after diagnosis