Desiderata for the development of next-generation electronic health record phenotype libraries.

BACKGROUND: High-quality phenotype definitions are desirable to enable the extraction of patient cohorts from large electronic health record repositories and are characterized by properties such as portability, reproducibility, and validity. Phenotype libraries, where definitions are stored, have the potential to contribute significantly to the quality of the definitions they host. In this work, we present a set of desiderata for the design of a next-generation phenotype library that is able to ensure the quality of hosted definitions by combining the functionality currently offered by disparate tooling. METHODS: A group of researchers examined work to date on phenotype models, implementation, and validation, as well as contemporary phenotype libraries developed as a part of their own phenomics communities. Existing phenotype frameworks were also examined. This work was translated and refined by all the authors into a set of best practices. RESULTS: We present 14 library desiderata that promote high-quality phenotype definitions, in the areas of modelling, logging, validation, and sharing and warehousing. CONCLUSIONS: There are a number of choices to be made when constructing phenotype libraries. Our considerations distil the best practices in the field and include pointers towards their further development to support portable, reproducible, and clinically valid phenotype design. The provision of high-quality phenotype definitions enables electronic health record data to be more effectively used in medical domains.

Cost of managing patients with venous leg ulcers.

The aim of this study was to estimate costs associated with the management of patients with venous leg ulcers (VLUs) from the perspective of the UK National Health Service (NHS). The analysis was undertaken through the Secure Anonymised Information Linkage Databank which brings together and anonymously links a wide range of person-based data from around 75% of general practitioner (GP) practices within Wales (population coverage ~2.5 million). The data covered an 11-year period from 2007 to 2017. All patients linked to the relevant codes were tracked through primary care settings, recording the number of GP practice visits (number of days with an event recorded), and wound treatment utilisation (eg, dressings, bandages, etc.) Resources were valued in monetary terms (£ sterling) and the costs were determined from national published sources of unit costs. This is the first attempt to estimate the costs of managing of VLUs using routine data sources. The direct costs to the Welsh NHS are considerable and represent 1.2% of the annual budget. Nurse visits are the main cost driver with annual estimates of £67.8 million. At a UK level, these costs amount to £1.98 billion. Dressings and compression bandages are also major cost drivers with annual Welsh estimates of £828 790. The direct cost of managing patients with VLUs is £7706 per patient per annum, which translates to an annual cost of over £2 billion, when extrapolated to the UK population. The primary cost driver is the number of district nurse visits. Initiatives to reduce healing times through improving accuracy of initial diagnosis, and improved evidence-based treatment pathways would result in major financial savings.

Primary therapy of Graves' disease and cardiovascular morbidity and mortality: a linked-record cohort study.

BACKGROUND: Graves' disease is routinely treated with antithyroid drugs, radioiodine, or surgery, but whether the choice of initial therapy influences long-term outcomes is uncertain. We evaluated cardiovascular morbidity and mortality according to the method and effectiveness of primary therapy in Graves' disease. METHODS: In this retrospective cohort study, we identified patients with hyperthyroidism, diagnosed between Jan 1, 1998, and Dec 31, 2013, from a thyroid-stimulating hormone (TSH)-receptor antibody (TRAb) test register in south Wales, UK, and imported their clinical data into the All-Wales Secure Anonymised Information Linkage (SAIL) Databank (Swansea University, Swansea, UK). Patients with Graves' disease, defined by positive TRAb tests, were selected for the study, and their clinical data were linked with outcomes in SAIL. We had no exclusion criteria. Patients were matched by age and sex to a control population (1:4) in the SAIL database. Patients were grouped by treatment within 1 year of diagnosis into the antithyroid drug group, radioiodine with resolved hyperthyroidism group (radioiodine group A), or radioiodine with unresolved hyperthyroidism group (radioiodine group B). We used landmark Kaplan-Meier and Cox regression models to analyse the association of treatment with the primary outcome of all-cause mortality and the secondary outcome of major adverse cardiovascular events (myocardial infarction, heart failure, ischaemic stroke, or death) with the landmark set at 1 year after diagnosis. We analysed the association between outcomes and concentration of TSH using Cox regression and outcomes and free thyroxine (FT4) concentration using restricted cubic-spline regression models. FINDINGS: We extracted patient-level data on 4189 patients (3414 [81·5%] females and 775 [18·5%] males) with Graves' disease and 16 756 controls (13 656 [81·5%] females and 3100 [18·5%] males). In landmark analyses, 3587 patients were in the antithyroid drug group, 250 were in radioiodine group A, 182 were in radioiodine group B. Patients had increased all-cause mortality compared with controls (hazard ratio [HR] 1·22, 95% CI 1·05-1·42). Compared with patients in the antithyroid drug group, mortality was lower among those in radioiodine group A (HR 0·50, 95% CI 0·29-0·85), but not for those in radioiodine group B (HR 1·51, 95% CI 0·96-2·37). Persistently low TSH concentrations at 1 year after diagnosis were associated with increased mortality independent of treatment method (HR 1·55, 95% CI 1·08-2·24). Spline regressions showed a positive non-linear relationship between FT4 concentrations at 1 year and all-cause mortality. INTERPRETATION: Regardless of the method of treatment, early and effective control of hyperthyroidism among patients with Graves' disease is associated with improved survival compared with less effective control. Rapid and sustained control of hyperthyroidism should be prioritised in the management of Graves' disease and early definitive treatment with radioiodine should be offered to patients who are unlikely to achieve remission with antithyroid drugs alone. FUNDING: National Institute for Social Care and Health Research, Wales.

Presentation to primary care during the prodrome of type 1 diabetes in childhood: A case-control study using record data linkage.

OBJECTIVE: To evaluate primary care presentations during the prodrome (12 months prior to onset type-1 diabetes (T1D), with or without diabetic ketoacidosis [DKA]), to identify opportunities for earlier diagnosis. METHODS: This was a case-control study, linking 16 years of data from children (≤15 years) registered at diagnosis of T1D, and routinely collected primary care records in Wales (United Kingdom). Controls (without T1D) were matched on a 3:1 ratio. Conditional logistic regression modeling was used to compare characteristics occurring in cases (children with T1D) and controls; and cases that presented with/without DKA. RESULTS: A total of 1345 children with T1D (19% DKA) and 4035 controls were identified. During the 12 months prior to diagnosis, cases were 6.5 times more likely to have at least one primary care contact (P < 0.001). One to 30 days prior to diagnosis, contacts relating to blood tests, fungal conditions, respiratory tract infections (RTIs), urinary conditions, vomiting, and weight were independently associated with T1D, as were contacts relating to blood tests, between 91 and 180 days prior to diagnosis. Children with a contact up to a month prior to diagnosis, relating to RTIs, antibiotic prescriptions, and vomiting, were more likely to present in DKA, as were boys (P = 0.047). CONCLUSION: There are opportunities in primary care for an earlier diagnosis of T1D in childhood. These data could be used to create a predictive diagnostic tool, as a potential aid for primary care health professionals, to prevent presentation in DKA.