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BACKGROUND: This study used data from different sources to identify the extent of the unmet need for postprandial glycemic control in patients with type 2 diabetes mellitus (T2DM) after the initiation of basal insulin therapy in Europe, Asia Pacific, the United States, and Latin America. METHODS: Different levels of evidence were used as available for each country/region, with data extracted from seven randomized controlled trials (RCTs), three clinical trial registries (CTRs), and three electronic medical record (EMR) databases. Glycemic status was categorized as "well controlled" (glycated hemoglobin [HbA ] at target [<7%]), "residual hyperglycemia" (fasting plasma glucose [FPG] but not HbA at target [FPG <7.2/7.8 mmol/L, <130/140 mg/dL, depending on country-specific recommendations]), or "uncontrolled" (both FPG and HbA above target). Predictor factors were identified from the RCT data set using logistic regression analysis. RESULTS: RCT data showed that 16.9% to 28.0%, 42.7% to 54.4%, and 16.9% to 38.1% of patients with T2DM had well-controlled glycemia, residual hyperglycemia, and uncontrolled hyperglycemia, respectively. In CTRs, respective ranges were 21.8% to 33.6%, 31.5% to 35.6%, and 30.7% to 46.8%, and in EMR databases were 4.4% to 21.0%, 23.9% to 31.8%, and 53.6% to 63.8%. Significant predictor factors of residual hyperglycemia identified from RCT data included high baseline HbA (all countries/regions except Brazil), high baseline FPG (United Kingdom/Japan), longer duration of diabetes (Brazil), and female sex (Europe/Latin America). CONCLUSIONS: Irrespective of intrinsic differences between data sources, 24% to 54% of patients with T2DM globally had residual hyperglycemia with HbA not at target, despite achieving FPG control, indicating a significant unmet need for postprandial glycemic control.

BACKGROUND & AIMS: Approximately 50% of all patients with pancreatic ductal adenocarcinoma (PDA) develop diabetes mellitus before their cancer diagnosis. Screening individuals with new-onset diabetes might allow earlier diagnosis of PDA. We sought to develop and validate a PDA risk prediction model to identify high-risk individuals among those with new-onset diabetes. METHODS: We conducted a retrospective cohort study in a population representative database from the United Kingdom. Individuals with incident diabetes after the age of 35 years and 3 or more years of follow-up after diagnosis of diabetes were eligible for inclusion. Candidate predictors consisted of epidemiologic and clinical characteristics available at the time of diabetes diagnosis. Variables with P values <.25 in the univariable analyses were evaluated using backward stepwise approach. Model discrimination was assessed using receiver operating characteristic curve analysis. Calibration was evaluated using the Hosmer-Lemeshow test. Results were internally validated using a bootstrapping procedure. RESULTS: We analyzed data from 109,385 patients with new-onset diabetes. Among them, 390 (0.4%) were diagnosed with PDA within 3 years. The final model (area under the curve, 0.82; 95% confidence interval, 0.75-0.89) included age, body mass index, change in body mass index, smoking, use of proton pump inhibitors, and anti-diabetic medications, as well as levels of hemoglobin A1C, cholesterol, hemoglobin, creatinine, and alkaline phosphatase. Bootstrapping validation showed negligible optimism. If the predicted risk threshold for definitive PDA screening was set at 1% over 3 years, only 6.19% of the new-onset diabetes population would undergo definitive screening, which would identify patients with PDA with 44.7% sensitivity, 94.0% specificity, and a positive predictive value of 2.6%. CONCLUSIONS: We developed a risk model based on widely available clinical parameters to help identify patients with new-onset diabetes who might benefit from PDA screening.

OBJECTIVES: To evaluate the risk of psoriatic arthritis (PsA) among patients with psoriasis exposed to physical trauma. METHODS: A matched cohort study was performed using data from The Health Improvement Network (THIN). Patients with psoriasis exposed to trauma were randomly matched to up to five unexposed psoriasis controls based on gender, age, duration of psoriasis and the date of entry into THIN. Trauma exposure was stratified into subgroups of joint, bone, nerve and skin trauma. Cox proportional hazard models were used to estimate the HRs for developing PsA. For comparison, an identical analysis was performed in the entire THIN population evaluating rheumatoid arthritis (RA) risk following physical trauma. RESULTS: Patients with psoriasis exposed to trauma (N=15 416) and matched unexposed patients (N=55 230) were followed for a total of 425 120 person-years during which 1010 incident PsA cases were recorded. Adjusting for potential confounders, patients with psoriasis exposed to trauma had an increased risk of PsA compared with controls, with a multivariate HR of 1.32 (95% CI 1.13 to 1.54). In our subset analysis, bone and joint trauma were associated with multivariate HRs of 1.46 (95% CI 1.04 to 2.04) and 1.50 (95% CI 1.19 to 1.90), respectively; while nerve and skin trauma were not associated with a statistically significant increase in risk compared with controls. Patients exposed to trauma in the entire THIN population did not have an increased risk of developing RA: HR 1.04 (95% CI 0.99 to 1.10). CONCLUSIONS: Patients with psoriasis exposed to physical trauma are at an increased risk of developing PsA.

AIMS/HYPOTHESIS: The aim of this research was to explore the relationship between incident epilepsy and type 1 diabetes in British participants. METHODS: Using The Health Improvement Network database, we conducted a retrospective, open-cohort study. Patients who were newly diagnosed with type 1 diabetes mellitus at the age of ≤40 years were identified and followed-up from 1 January 1990 to 15 September 2015. These patients, identified as not suffering from epilepsy at the time of diagnosis, were randomly matched with up to four individuals without type 1 diabetes mellitus, based on age, sex and participating general practice. A Cox regression analysis was subsequently performed using Townsend deprivation index, cerebral palsy, head injury and learning disabilities as model covariates. RESULTS: The study population consisted of a total of 24,610 individuals (4922 with type 1 diabetes and 19,688 controls). These individuals were followed up for a mean of 5.4 years (approximately 132,000 person-years of follow up). Patients with type 1 diabetes were significantly more likely to be diagnosed with epilepsy during the observation period compared with controls (crude HR [95% CI]: 3.02 [1.95, 4.69]). The incidence rate was estimated to be 132 and 44 per 100,000 person-years in patients and controls, respectively. This finding persisted after adjusting for model covariates (adjusted HR [95% CI]: 3.01 [1.93, 4.68]) and was also robust to sensitivity analysis, excluding adult-onset type 1 diabetes mellitus. CONCLUSIONS/INTERPRETATION: Patients with type 1 diabetes are at approximately three-times greater risk of developing epilepsy compared with matched controls without type 1 diabetes. This should be considered when investigating seizure-related disorders in patients with type 1 diabetes mellitus.

BACKGROUND: In 2014, guidelines from the National Institute for Health and Care Excellence (NICE) provided updated recommendations on lipid-modifying therapy (LMT). We assessed clinical practice contemporaneous to release of these guidelines in a UK general practice setting for secondary and high-risk primary-prevention populations, and extrapolated the findings to UK nation level. METHODS: Patients from The Health Improvement Network database with the following criteria were included: lipid profile in 2014 (index date); ≥20 years of age; ≥2 years representation in database prior to index; ≥1 statin indication either for atherosclerotic cardiovascular disease (ASCVD) or the non-ASCVD conditions high-risk diabetes mellitus and/or chronic kidney disease. RESULTS: Overall, 183 565 patients met the inclusion criteria (n=91 479 for ASCVD, 92 086 for non-ASCVD). In those with ASCVD, 79% received statin treatment and 31% received high-intensity statin. In the non-ASCVD group, 62% were on a statin and 57% received medium-intensity or high-intensity statin. In the ASCVD and non-ASCVD cohorts, 6% and 15%, respectively, were already treated according to dosing recommendations as per updated NICE guidelines. Extrapolation to the 2014 UK population indicated that, of the 3.3 million individuals with ASCVD, 2.4 million would require statin uptitration and 680 000 would require statin initiation (31% de novo initiation, 60% reinitiation, 9% addition to non-statin LMT) to achieve full concordance with updated guidelines. Of the 3.5 million high-risk non-ASCVD individuals, 1.6 million would require statin uptitration and 1.4 million would require statin initiation (59% de novo initiation, 36% reinitiation, 5% addition to non-statin LMT). CONCLUSIONS: A large proportion of UK individuals with ASCVD and high-risk non-ASCVD received statin treatment (79% and 62%, respectively) during the year of NICE 2014 guidelines release. Up to 94% of patients with ASCVD and 85% of high-risk non-ASCVD individuals, representing ∼3 million individuals in each group, would require statin uptitration or initiation to achieve full concordance with updated guidelines.

Antipsychotics may confer long term benefits and risks, including cardiovascular disease (CVD) risk. Several studies using routine clinical data have reported associations between antipsychotics and CVD but potential confounding factors and unclear classification of drug exposure limits their interpretation. METHOD: We used data from The Health Improvement Network, a large UK primary care database to determine relative risks of (CVD) comparing similar groups of people only prescribed olanzapine versus either risperidone or quetiapine. We included participants over 18 between 1995 and 2011. To assess confounding factors we created propensity scores for being prescribed each antipsychotic. We used propensity score matching and Poisson regression to calculate the CVD incidence rate ratios for olanzapine versus the other two drugs. RESULTS: We identified 18,319 people who received a single antipsychotic during follow-up (n=5090 risperidone, 7797 olanzapine and 4613 quetiapine). In unmatched analyses, the CVD incidence rate ratio (IRR) for olanzapine versus risperidone was 0.63 (0.51-0.77) but the propensity score matched IRR was 0.78 (0.61-1.02). In the unmatched olanzapine versus quetiapine analysis the IRR adjusted for age and sex for olanzapine was 1.52 (1.16-1.98) but the propensity score matched analysis gave an IRR of 1.08 (0.79-1.46). CONCLUSIONS: After propensity score matching, we found no statistical differences in CVD incidence between olanzapine and either risperidone or quetiapine. Analyses which did not account for confounding factors produced very different results. Researchers must address confounding factors when designing observational studies to assess adverse outcomes of drugs, including antipsychotics.

BACKGROUND: Hypergastrinemia may promote the development and progression of pancreatic cancer. Proton pump inhibitor (PPI) therapy is known to cause hypergastrinemia. We sought to determine the association between PPI therapy and the risk of developing pancreatic cancer as well as survival following pancreatic cancer diagnosis. METHODS: We conducted a nested case-control study and a retrospective cohort study in The Health Improvement Network (THIN), a medical records database representative of the UK population. In the case-control study, each patient with incident pancreatic cancer was matched with up to four controls based on age, sex, practice site and both duration and calendar time of follow-up using incidence density sampling. The odds ratios (ORs) and 95% confidence intervals (CIs) for pancreatic cancer risk associated with PPI use were estimated using multivariable conditional logistic regression. The retrospective cohort study compared the survival of pancreatic cancer patients according to their PPI exposure at the time of diagnosis. The effect of PPI use on pancreatic cancer survival was assessed using a multivariable Cox regression analysis. RESULTS: The case-control study included 4113 cases and 16,072 matched controls. PPI use was more prevalent in cases than controls (53% vs. 26% active users). Adjusting for diabetes, smoking, alcohol use and BMI, PPI users including both former users and active users with longer cumulative PPI use had a higher risk of pancreatic cancer compared to non-users. When assessing survival following pancreatic cancer diagnosis, only short-term, active users had a modest decrease in survival. CONCLUSIONS: Long-term PPI therapy may be associated with pancreatic cancer risk. While PPI users recently started on treatment had a slightly worse survival, this result likely is from reverse causation.

PURPOSE: Discontinuing low-dose acetylsalicylic acid (ASA) therapy after upper gastrointestinal bleeding (UGIB) may increase the risk of cardiovascular-related death. Our aim was to compare mortality in UK primary care patients who discontinue ASA after UGIB with that in patients who continue therapy. METHODS: ASA users at the time of UGIB and who were alive 30 days after were selected using The Health Improvement Network. Predictors of survival were assessed using adjusted Cox proportional hazards regression models. RESULTS: Of 547 ASA users, half did not re-initiate ASA during a mean follow-up of 4.1 years. Increasing age (a 10% increased risk for each yearly increase in age; hazard ratio [HR]: 1.10; 95% confidence interval [CI]: 1.07-1.14), female sex (HR: 1.61; 95%CI: 1.09-2.38), current smoking (HR: 2.11; 95%CI: 1.23-3.63), heavy alcohol use (HR: 3.31; 95%CI: 1.50-7.31), diabetes mellitus (HR: 1.93; 95%CI: 1.25-3.00), and chronic obstructive pulmonary disease (HR: 1.75; 95%CI: 1.03-2.99) were significantly associated with increased mortality. Most deaths (115/139) occurred in patients taking ASA for secondary prevention. In these patients, mortality tended to be lower among ASA continuer periods (HR: 0.74; 95%CI: 0.34-1.62) and higher among discontinuer periods (HR: 1.37; 95%CI: 0.81-2.30) than among non-users. Current use of clopidogrel was associated with decreased mortality in this population (HR: 0.49; 95%CI: 0.28-0.86). CONCLUSIONS: ASA therapy for secondary prevention should continue after UGIB because the risk of death tends to increase when ASA is stopped. However, a significantly increased risk was not found in these patients, likely owing to the relatively small number of ASA users and deaths that occurred during follow-up. Further studies with larger samples sizes are needed to confirm these findings among UGIB survivors taking ASA at the time of UGIB. Copyright © 2016 John Wiley & Sons, Ltd.

PURPOSE: Nitrates, commonly used antianginal medications, also have a beneficial effect on bone remodeling and bone density, particularly with intermittent use. However, their effect on fracture risk is not clear. We examined the relation of short-acting nitrate use (proxy for intermittent use) with the risk of hip fracture in a large cohort of older adults with ischemic heart disease. METHODS: Participants aged 60 years or more with ischemic heart disease and without a history of hip fracture from The Health Improvement Network, an electronic medical records database in the United Kingdom, were included. The association of incident (new) use of short-acting nitrate formulations (nitroglycerin sublingual/spray/ointment or isosorbide dinitrate injection/sprays) with incident (new-onset) hip fracture risk was examined by plotting Kaplan-Maier curves and calculating hazard ratios using Cox proportional hazards regression models. Competing risk by death was analyzed in separate analyses. RESULTS: Among 14,451 pairs of matched nitrate users and nonusers (mean age, 72 ± 7.6 years, 41% women for each cohort), 573 fractures occurred during follow-up (257 nitrate users; 316 nonusers). Hip fracture risk was 33% lower among short-acting nitrate users compared with nonusers (hazard ratio, 0.67; 95% confidence interval, 0.53-0.85; P = .0008). Competing risk analysis by death did not change effect estimates. CONCLUSIONS: In this large population-based cohort of older adults with ischemic heart disease, we found a significant reduction in hip fracture risk with the use of short-acting nitrates (intermittent use). Future studies are warranted given the potential for nitrates to be potent, inexpensive, and readily available antiosteoporotic agents.

OBJECTIVE: Mortality trends of rheumatoid arthritis (RA) are largely unknown over the past decade when new drugs and management strategies have been adopted to effectively treat RA. METHODS: Using The Health Improvement Network, an electronic medical record database representative of the UK general population, we identified patients with incident RA and up to five individuals without RA matched for age, sex and year of diagnosis between 1999 and 2014. The RA cohort was divided in two sub-cohorts based on the year of RA diagnosis: the early cohort (1999-2006) and the late cohort (2007-2014). We compared mortality rates, HRs (using a Cox proportional hazard model) and rate differences (using an additive hazard model) between RA and non-RA cohorts adjusting for potential confounders. RESULTS: Patients with RA diagnosed between 1999 and 2006 had a considerably higher mortality rate than their comparison cohort (ie, 29.1 vs 18.0 deaths/1000 person-years), as compared with a moderate difference in patients with RA diagnosed between 2007 and 2014 and their comparison cohort (17.0 vs 12.9 deaths/1000 years). The corresponding absolute mortality rate differences were 9.5 deaths/1000 person-years (95% CIs 7.5 to 11.6) and 3.1 deaths/1000 person-years (95% CI 1.5 to 4.6) and the mortality HRs were 1.56 (95% CI 1.44 to 1.69) and 1.29 (95% CI 1.17 to 1.42), respectively (both p values for interaction <0.01). CONCLUSION: This general population-based cohort study indicates that the survival of patients with RA has improved over the past decade to a greater degree than in the general population. Improved management of RA and its associated comorbidities over recent years may be providing a survival benefit.

OBJECTIVE: The aim of this study was to examine the prevalence of major congenital malformations associated with antiepileptic drug (AED) treatment in pregnancy. PATIENTS AND METHODS: Using data from The Health Improvement Network, we identified women who have given live birth and their offspring. Four subgroups were selected based on the AED treatment in early pregnancy, valproate, carbamazepine, lamotrigine and women not receiving AED treatment. We compared the prevalence of major congenital malformations within children of these four groups and estimated prevalence ratios (PRs) using Poisson regression adjusted for maternal age, sex of child, quintiles of Townsend deprivation score and indication for treatment. RESULTS: In total, 240,071 women were included in the study. A total of 229 women were prescribed valproate in pregnancy, 357 were prescribed lamotrigine and 334 were prescribed carbamazepine and 239,151 women were not prescribed AEDs. Fifteen out of 229 (6.6%) women prescribed valproate gave birth to a child with a major congenital malformation. The figures for lamotrigine, carbamazepine and women not prescribed AEDs were 2.7%, 3.3% and 2.2%, respectively. The prevalence of major congenital malformation was similar for women prescribed lamotrigine or carbamazepine compared to women with no AED treatment in pregnancy. For women prescribed valproate in polytherapy, the prevalence was fourfold higher. After adjustments, the effect of estimates attenuated, but the prevalence remained two- to threefold higher in women prescribed valproate. CONCLUSION: The results of our study suggest that lamotrigine and carbamazepine are safer treatment options than valproate in pregnancy and should be considered as alternative treatment options for women of childbearing potential and in pregnancy.

INTRODUCTION: The Informatics for Health congress, 24-26 April 2017, in Manchester, UK, brought together the Medical Informatics Europe (MIE) conference and the Farr Institute International Conference. This special issue of the Journal of Innovation in Health Informatics contains 113 presentation abstracts and 149 poster abstracts from the congress. DISCUSSION: The twin programmes of "Big Data" and "Digital Health" are not always joined up by coherent policy and investment priorities. Substantial global investment in health IT and data science has led to sound progress but highly variable outcomes. Society needs an approach that brings together the science and the practice of health informatics. The goal is multi-level Learning Health Systems that consume and intelligently act upon both patient data and organizational intervention outcomes. CONCLUSION: Informatics for Health demonstrated the art of the possible, seen in the breadth and depth of our contributions. We call upon policy makers, research funders and programme leaders to learn from this joined-up approach.

OBJECTIVES: Estimate survival after acute myocardial infarction (AMI) in the general population aged 60 and over and the effect of recommended treatments. DESIGN: Cohort study in the UK with routinely collected data between January 1987 and March 2011. SETTING: 310 general practices that contributed to The Health Improvement Network (THIN) database. PARTICIPANTS: 4 cohorts who reached the age of 60, 65, 70, or 75 years between 1987 and 2011 included 16 744, 43 528, 73 728, and 76 392 participants, respectively. Participants with a history of AMI were matched on sex, year of birth, and general practice to 3 controls each. OUTCOME MEASURES: The hazard of all-cause mortality associated with AMI was calculated by a multilevel Cox's proportional hazards regression, adjusted for sex, year of birth, socioeconomic status, angina, heart failure, other cardiovascular conditions, chronic kidney disease, diabetes, hypertension, hypercholesterolaemia, alcohol consumption, body mass index, smoking status, coronary revascularisation, prescription of β-blockers, ACE inhibitors, calcium-channel blockers, aspirin, or statins, and general practice. RESULTS: Compared with no history of AMI by age 60, 65, 70, or 75, having had 1 AMI was associated with an adjusted hazard of mortality of 1.80 (95% CI 1.60 to 2.02), 1.71 (1.59 to 1.84), 1.50 (1.42 to 1.59), or 1.45 (1.38 to 1.53), respectively, and having had multiple AMIs with a hazard of 1.92 (1.60 to 2.29), 1.87 (1.68 to 2.07), 1.66 (1.53 to 1.80), or 1.63 (1.51 to 1.76), respectively. Survival was better after statins (HR range across the 4 cohorts 0.74-0.81), β-blockers (0.79-0.85), or coronary revascularisation (in first 5 years) (0.72-0.80); unchanged after calcium-channel blockers (1.00-1.07); and worse after aspirin (1.05-1.10) or ACE inhibitors (1.10-1.25). CONCLUSIONS: The hazard of death after AMI is less than reported by previous studies, and standard treatments of aspirin or ACE inhibitors prescription may be of little benefit or even cause harm.

OBJECTIVE: To examine the prevalence and incidence of cardiovascular (CV) risk factors, including hypertension, hyperlipidemia, diabetes mellitus (DM), and obesity among patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA) compared to the general population, and to examine the treatment of incident CV risk factors in PsA and RA compared to controls. METHODS: A cohort study was conducted within The Health Improvement Network, a medical record database in the UK, using data from 1994 to 2014. Patients ages 18-89 years with PsA or RA were matched to controls on practice and start date. The prevalence and incidence of CV risk factors identified by diagnostic codes were calculated. Cox proportional hazards models were used to examine the relative incidence of these CV risk factors. Finally, pharmacologic therapies for incident CV risk factors were examined. RESULTS: Study subjects included patients with PsA (n = 12,548), RA (n = 53,215), and controls (n = 389,269). The prevalence of all CV risk factors was significantly elevated in PsA. Only the prevalence of DM and obesity was increased in RA. Incidence of hypertension, hyperlipidemia, and DM was elevated in PsA and RA. Receipt of therapy within 1 year following incident diagnosis of CV risk factors was not substantially different between the groups; approximately 85%, 65%, and 45% of patients received prescriptions for hypertension, hyperlipidemia, and DM, respectively. CONCLUSION: Patients with PsA have an increased prevalence of CV risk factors, and both patients with PsA and patients with RA have increased incidence of a new diagnosis of CV risk factors. Pharmacologic treatment of CV risk factors in patients with PsA and RA was similar to controls in the UK.

PURPOSE: The extent to which days' supply data are missing in pharmacoepidemiologic databases and effective methods for estimation is unknown. We determined the percentage of missing days' supply on prescription and patient levels for oral anti-diabetic drugs (OADs) and evaluated three methods for estimating days' supply within the Clinical Practice Research Datalink (CPRD) and The Health Improvement Network (THIN). METHODS: We estimated the percentage of OAD prescriptions and patients with missing days' supply in each database from 2009 to 2013. Within a random sample of prescriptions with known days' supply, we measured the accuracy of three methods to estimate missing days' supply by imputing the following: (1) 28 days' supply, (2) mode number of tablets/day by drug strength and number of tablets/prescription, and (3) number of tablets/day via a machine learning algorithm. We determined incidence rates (IRs) of acute myocardial infarction (AMI) using each method to evaluate the impact on ascertainment of exposure time and outcomes. RESULTS: Days' supply was missing for 24 % of OAD prescriptions in CPRD and 33 % in THIN (affecting 48 and 57 % of patients, respectively). Methods 2 and 3 were very accurate in estimating days' supply for OADs prescribed at a consistent number of tablets/day. Method 3 was more accurate for OADs prescribed at varying number of tablets/day. IRs of AMI were similar across methods for most OADs. CONCLUSIONS: Missing days' supply is a substantial problem in both databases. Method 2 is easy and very accurate for most OADs and results in IRs comparable to those from method 3.

BACKGROUND: The relation of knee replacement (KR) surgery to all-cause mortality has not been well established owing to potential biases in previous studies. Thus, we aimed to examine the relation of KR to mortality risk among patients with knee osteoarthritis (OA) focusing on identifying biases that may threaten the validity of prior studies. METHODS: We included knee OA subjects (ages 50-89 years) from The Health Improvement Network, an electronic medical records database in the UK. Risk of mortality among KR subjects was compared with propensity score-matched non-KR subjects. To explore residual confounding bias, subgroup analyses stratified by age and propensity scores were performed. RESULTS: Subjects with KR had 28% lower risk of mortality than non-KR subjects (HR 0.72, 95% CI 0.66 to 0.78). However, when stratified by age, protective effect was noted only in older age groups (>63 years) but not in younger subjects (≤63 years). Further, the mortality rate among KR subjects decreased as candidacy (propensity score) for KR increased among subjects with KR, but no such consistent trend was noted among non-KR subjects. CONCLUSIONS: While a protective effect of KR on mortality cannot be ruled out, findings of lower mortality among older KR subjects and those with higher propensity scores suggest that prognosis-based selection for KR may lead to intractable confounding by indication; hence, the protective effect of KR on all-cause mortality may be overestimated.

BACKGROUND: Policies of active case finding for cardiovascular disease (CVD) prevention in healthy adults are common, but economic evaluation has not investigated targeting such strategies at those who are most likely to benefit. AIM: To assess the cost effectiveness of targeted case finding for CVD prevention. DESIGN AND SETTING: Cost-effectiveness modelling in an English primary care population. METHOD: A cohort of 10 000 individuals aged 30-74 years and without existing CVD or diabetes was sampled from The Health Improvement Network database, a large primary care database. A discrete-event simulation was used to model the process of inviting people for assessment, assessing cardiovascular risk, and initiation and persistence with drug treatment. Risk factors and drug cessation rates were obtained from primary care data. Published sources provided estimates of uptake of assessment, treatment initiation, and treatment effects. The researchers determined the lifetime costs and quality-adjusted life years (QALYs) with opportunistic case finding, and strategies prioritising and targeting patients by age or prior estimate of cardiovascular risk. This study reports on the optimum strategy if a QALY is valued at £20 000. RESULTS: Compared with no case finding, inviting all adults aged 30-74 years in a population of 10 000 yields 30.32 QALYs at a total cost of £705 732. The optimum strategy is to rank patients by prior risk estimate and invite 8% of those who are assessed as being at highest risk (those at ≥12.76% predicted 10-year CVD risk), yielding 17.53 QALYs at a cost of £162 280. There is an 89.4% probability that the optimum strategy is to invite <35% of patients for assessment. CONCLUSION: Across all age ranges, targeted case finding using a prior estimate of CVD risk is more efficient than universal case finding in healthy adults.

Propensity scores (PS) are an increasingly popular method to adjust for confounding in observational studies. Propensity score methods have theoretical advantages over conventional covariate adjustment, but their relative performance in real-word scenarios is poorly characterized. We used datasets from 4 large-scale cardiovascular observational studies (PROMETHEUS, ADAPT-DES [the Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents], THIN [The Health Improvement Network], and CHARM [Candesartan in Heart Failure-Assessment of Reduction in Mortality and Morbidity]) to compare the performance of conventional covariate adjustment with 4 common PS methods: matching, stratification, inverse probability weighting, and use of PS as a covariate. We found that stratification performed poorly with few outcome events, and inverse probability weighting gave imprecise estimates of treatment effect and undue influence to a small number of observations when substantial confounding was present. Covariate adjustment and matching performed well in all of our examples, although matching tended to give less precise estimates in some cases. PS methods are not necessarily superior to conventional covariate adjustment, and care should be taken to select the most suitable method.