Using national electronic health records for pandemic preparedness:validation of a parsimonious model for predicting excess deaths among those with COVID-19-a data-driven retrospective cohort study

OBJECTIVES: To use national, pre- and post-pandemic electronic health records (EHR) to develop and validate a scenario-based model incorporating baseline mortality risk, infection rate (IR) and relative risk (RR) of death for prediction of excess deaths.DESIGN: An EHR-based, retrospective cohort study.SETTING: Linked EHR in Clinical Practice Research Datalink (CPRD); and linked EHR and COVID-19 data in England provided in NHS Digital Trusted Research Environment (TRE).PARTICIPANTS: In the development (CPRD) and validation (TRE) cohorts, we included 3.8 million and 35.1 million individuals aged ≥30 years, respectively.MAIN OUTCOME MEASURES: One-year all-cause excess deaths related to COVID-19 from March 2020 to March 2021.RESULTS: From 1 March 2020 to 1 March 2021, there were 127,020 observed excess deaths. Observed RR was 4.34% (95% CI, 4.31-4.38) and IR was 6.27% (95% CI, 6.26-6.28). In the validation cohort, predicted one-year excess deaths were 100,338 compared with the observed 127,020 deaths with a ratio of predicted to observed excess deaths of 0.79.CONCLUSIONS: We show that a simple, parsimonious model incorporating baseline mortality risk, one-year IR and RR of the pandemic can be used for scenario-based prediction of excess deaths in the early stages of a pandemic. Our analyses show that EHR could inform pandemic planning and surveillance, despite limited use in emergency preparedness to date. Although infection dynamics are important in the prediction of mortality, future models should take greater account of underlying conditions.</p

Association between apolipoprotein E genotype and carotid intima-media thickness may suggest a specific effect on large artery atherothrombotic stroke

BACKGROUND AND PURPOSE: Apolipoprotein E genotype (APOE) influences cholesterol levels and ischemic heart disease. Although there is no convincing overall association with ischemic stroke, APOE may influence large artery (atherothrombotic) stroke, for which carotid intima-media thickness (CIMT) is an informative intermediate phenotype. We therefore performed a systematic review and meta-analysis of the association between APOE and CIMT. METHODS: We sought all published studies assessing the association between APOE and CIMT. From each study, we extracted available data on study methods, subjects’ characteristics, and mean (and standard deviation) CIMT for each genotype or genotype group. We calculated study-specific and random effects pooled differences in mean CIMT between genotype groups, and assessed heterogeneity between studies and predefined subgroups using I(2) and χ(2) statistics. RESULTS: Meta-analysis of 22 published studies (30 879 subjects) showed a significant association between APOE and CIMT (pooled mean difference ε4-versus ε2-allele containing genotypes 46 μm, 95% CI 29 to 62, P<0.00001). We found evidence of small study (mainly publication) bias, with a diminished (but still highly statistically significant) association in studies of >1000 subjects (pooled mean difference 17 μm, 95% CI 12 to 23, P<0.00001). The association was larger among high vascular risk and eastern Asian populations, but this may simply reflect the smaller size of these studies. CONCLUSION: Our results show a clear association of APOE with CIMT, even though publication bias means that this is overestimated by the published literature. These findings suggest the possibility of a specific association with large artery ischemic stroke

Generation Scotland: Linking all the records we can

Objectives We started a family-based genetic epidemiology study in 2006-11 which recruited ~24,000 adult volunteers from ~7000 families across Scotland with consent for follow-up through medical record linkage and re-contact. In 2022-23 we are recruiting another 20,000, with consent extended to administrative records, with age range now 12+. Methods Original volunteers completed a demographic, health and lifestyle questionnaire, provided biological samples, and underwent detailed clinical assessment. The samples, phenotype and genotype data form a resource for research on the genetics of conditions of public health importance. This has become a longitudinal dataset by linkage to routine NHS hospital, maternity, lab test, prescriptions, dentistry, mortality, imaging, cancer screening, GP data records, Covid-19 testing and vaccinations, as well as follow-up questionnaires. The new wave of recruitment is all online and can be done on a smartphone, with DNA from saliva collected by post. Teenagers aged 12-15 can join with parental consent. Results GWAS has been done on quantitative traits and biomarkers, with DNA methylation data and proteomics available for most of the cohort. Our “CovidLife” surveys collected data on effects of the pandemic. Researchers can find prevalent and incident disease cases and controls, to test research hypotheses on a stratified population. They can also do targeted recruitment of participants to new studies, including recall by genotype. We have established and validated E-HR linkage with the NHS Scotland CHI Register,,overcoming technical and governance issues in the process. We contribute to major international consortia, with collaborators from institutions worldwide, both academic and commercial. Recruits are asked to give consent to linkage to other administrative data, and reuse of samples from routine NHS tests for medical research. Conclusion We plan to extend the linkage process to include other administrative data from national datasets as and when approvals are obtained. New types of data can also be collected by online questionnaires. The Research Tissue Bank resources are available to academic and commercial researchers through a managed access process

Improving medication adherence in stroke survivors: Mediators and moderators of treatment effects

OBJECTIVE: The purpose of the current study was to test theory-based predictions of mediators and moderators of treatment effects of a pilot randomized controlled trial, which aimed to increase adherence to preventive medication in stroke survivors via addressing both automatic (i.e., habitual responses) and reflective (i.e., beliefs and value systems) aspects of medication-taking behavior. METHOD: Sixty-two stroke survivors were randomly allocated to either an intervention or control group. Intervention participants received a brief 2-session intervention aimed at increasing adherence via (a) helping patients establish better medication-taking routines using implementation intentions plans (automatic), and (b) eliciting and modifying any mistaken patient beliefs regarding medication and/or stroke (reflective). The control group received similar levels of non-medication-related contact. Primary outcome was adherence to antihypertensive medicine measured objectively over 3 months using an electronic pill bottle. Secondary outcome measures included self-reported adherence (including forgetting) and beliefs about medication. RESULTS Intervention participants had 10% greater adherence on doses taken on schedule (intervention, 97%; control, 87%; 95% CI [0.2, 16.2], p = .048), as well as significantly greater increases in self-reported adherence and reductions in concerns about medication. Treatment effects were mediated by reductions in both forgetting and concerns about medication, and moderated by the presence of preexisting medication-taking routines. CONCLUSIONS: Addressing both automatic and reflective aspects of behavior via helping stroke survivors develop planned regular routines for medication-taking, and addressing any concerns or misconceptions about their medication, can improve adherence and thus potentially patient outcomes

Raised cardiovascular disease mortality after central nervous system tumour diagnosis:Analysis of 171 926 patients from UK and USA

BACKGROUND: Patients with central nervous system (CNS) tumors may be at risk of dying from cardiovascular disease (CVD). We examined CVD mortality risk in patients with different histological subtypes of CNS tumors. METHODS: We analyzed UK(Wales)-based Secure Anonymized Information Linkage (SAIL) for 8743 CNS tumors patients diagnosed in 2000-2015, and US-based National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) for 163,183 patients in 2005-2015. We calculated age-, sex-, and calendar-year-adjusted standardized mortality ratios (SMRs) for CVD comparing CNS tumor patients to Wales and US residents. We used Cox regression models to examine factors associated with CVD mortality among CNS tumor patients. RESULTS: CVD was the second leading cause of death for CNS tumor patients in SAIL (UK) and SEER (US). Patients with CNS tumors had higher CVD mortality than the general population (SAIL SMR = 2.64, 95% CI = 2.39-2.90, SEER SMR = 1.38, 95% CI = 1.35-1.42). Malignant CNS tumor patients had over 2-fold higher mortality risk in US and UK cohorts. SMRs for nonmalignant tumors were almost 2-fold higher in SAIL than in SEER. CVD mortality risk particularly cerebrovascular disease was substantially greater in patients diagnosed at age younger than 50 years, and within the first year after their cancer diagnosis (SAIL SMR = 2.98, 95% CI = 2.39-3.66, SEER SMR = 2.14, 95% CI = 2.03-2.25). Age, sex, race/ethnicity in USA, deprivation in UK and no surgery were associated with CVD mortality. CONCLUSIONS: Patients with CNS tumors had higher risk for CVD mortality, particularly from cerebrovascular disease compared to the general population, supporting further research to improve mortality outcomes