Stroke Prevention with Hydroxyurea Enabled through Research and Education: A Phase 2 Primary Stroke Prevention Trial in Sub-Saharan Africa.

INTRODUCTION: Stroke is a severe complication of sickle cell anemia (SCA), with devastating sequelae. Transcranial Doppler (TCD) ultrasonography predicts stroke risk, but implementing TCD screening with suitable treatment for primary stroke prevention in low-resource environments remains challenging. SPHERE (NCT03948867) is a prospective phase 2 open-label hydroxyurea trial for SCA in Tanzania. METHODS: After formal training and certification, local personnel screened children 2-16 years old; those with conditional (170-199 cm/s) or abnormal (≥200 cm/s) time-averaged mean velocities (TAMVs) received hydroxyurea at 20 mg/kg/day with dose escalation to maximum tolerated dose (MTD). The primary study endpoint is change in TAMV after 12 months of hydroxyurea; secondary endpoints include SCA-related clinical events, splenic volume and function, renal function, infections, hydroxyurea pharmacokinetics, and genetic modifiers. RESULTS: Between April 2019 and April 2020, 202 children (average 6.8 ± 3.5 years, 53% female) enrolled and underwent TCD screening; 196 were deemed eligible by DNA testing. Most had numerous previous hospitalizations and transfusions, with low baseline hemoglobin (7.7 ± 1.1 g/dL) and %HbF (9.3 ± 5.4%). Palpable splenomegaly was present at enrollment in 49 (25%); average sonographic splenic volume was 103 mL (range 8-1,045 mL). TCD screening identified 22% conditional and 2% abnormal velocities, with hydroxyurea treatment initiated in 96% (45/47) eligible children. CONCLUSION: SPHERE has built local capacity with high-quality research infrastructure and TCD screening for SCA in Tanzania. Fully enrolled participants have a high prevalence of elevated baseline TCD velocities and splenomegaly. SPHERE will prospectively determine the benefits of hydroxyurea at MTD for primary stroke prevention, anticipating expanded access to hydroxyurea treatment across Tanzania.

Primary resistance against integrase strand transfer inhibitors in integrase strand transfer inhibitor-naive patients failing first- and second-line ART in Tanzania.

INTRODUCTION: Sub-Saharan African countries are introducing integrase strand transfer inhibitors (INSTIs) in their ART programmes as the preferred first-line regimen, and dolutegravir is the INSTI of choice due to its potency, tolerability and high genetic barrier to resistance. Dolutegravir was introduced into the first-line ART regimen in Tanzania in 2019. However, there is a paucity of data on the occurrence of mutations in HIV lineages circulating in Tanzania. This study aimed to determine the prevalence of INSTI primary resistance mutations in Tanzanian patients exposed to ART but not INSTIs. METHODS: Plasma samples from 50 INSTI-naive patients failing first- or second-line ART [median (IQR) age: 40 (21.93-46.41) years; 68% women] were subjected to Sanger sequencing of the HIV integrase gene. Participants had been on ART for a median (IQR) duration of 7.32 (4.73-9.29) years, with 80% and 20% failing first- and second-line ART, respectively. RESULTS: No major INSTI mutations were found, but 2 (4%) participants had the accessory mutation T97A. Using the REGA HIV-1 subtyping tool, HIV subtype A1 (53.1%) was found to be dominant, followed by subtypes C (30.6%) and D (16.3%). CONCLUSIONS: This study found no current evidence for transmitted resistance against INSTIs among unexposed patients failing ART and supports the scale-up of INSTI-based regimens. However, the presence of accessory mutations calls for the surveillance of INSTI resistance mutations to ensure that the anticipated long-term desired outcomes are achieved.

A Cohort Analysis of Statin Treatment Patterns Among Small-Sized Primary Care Practices.

BACKGROUND: Small-sized primary care practices, defined as practices with fewer than 10 clinicians, delivered the majority of outpatient visits in the USA. Statin therapy in high-risk individuals reduces atherosclerotic cardiovascular disease (ASCVD) events, but prescribing patterns in small primary care practices are not well known. This study describes statin treatment patterns in small-sized primary care practices and examines patient- and practice-level factors associated with lack of statin treatment. METHODS: We conducted a retrospective cohort analysis of statin-eligible patients from practices that participated in Healthy Hearts in the Heartland (H3), a quality improvement initiative aimed at improving cardiovascular care measures in small primary care practices. All statin-eligible adults who received care in one of 53 H3 practices from 2013 to 2016. Statin-eligible adults include those aged at least 21 with (1) clinical ASCVD, (2) low-density lipoprotein cholesterol (LDL-C) ≥ 190 mg/dL, or (3) diabetes aged 40-75 and with LDL-C 70-189 mg/dL. Eligible patients with no record of moderate- to high-intensity statin prescription are defined by ACC/AHA guidelines. RESULTS: Among the 13,330 statin-eligible adults, the mean age was 58 years and 52% were women. Overall, there was no record of moderate- to high-intensity statin prescription among 5,780 (43%) patients. Younger age, female sex, and lower LDL-C were independently associated with a lack of appropriate intensity statin therapy. Higher proportions of patients insured by Medicaid and having only family medicine trained physicians (versus having at least one internal medicine trained physician) at the practice were also associated with lower appropriate intensity statin use. Lack of appropriate intensity statin therapy was higher in independent practices than in Federally Qualified Health Centers (FQHCs) (50% vs. 40%, p value < 0.01). CONCLUSIONS: There is an opportunity for improved ASCVD risk reduction in small primary care practices. Statin treatment patterns and factors influencing lack of treatment vary by practice setting, highlighting the importance of tailored approaches to each setting.

Effects of 2 Forms of Practice Facilitation on Cardiovascular Prevention in Primary Care: A Practice-randomized, Comparative Effectiveness Trial.

BACKGROUND: Effective quality improvement (QI) strategies are needed for small practices. OBJECTIVE: The objective of this study was to compare practice facilitation implementing point-of-care (POC) QI strategies alone versus facilitation implementing point-of-care plus population management (POC+PM) strategies on preventive cardiovascular care. DESIGN: Two arm, practice-randomized, comparative effectiveness study. PARTICIPANTS: Small and mid-sized primary care practices. INTERVENTIONS: Practices worked with facilitators on QI for 12 months to implement POC or POC+PM strategies. MEASURES: Proportion of eligible patients in a practice meeting "ABCS" measures: (Aspirin) Aspirin/antiplatelet therapy for ischemic vascular disease, (Blood pressure) Controlling High Blood Pressure, (Cholesterol) Statin Therapy for the Prevention and Treatment of Cardiovascular Disease, and (Smoking) Tobacco Use: Screening and Cessation Intervention, and the Change Process Capability Questionnaire. Measurements were performed at baseline, 12, and 18 months. RESULTS: A total of 226 practices were randomized, 179 contributed follow-up data. The mean proportion of patients meeting each performance measure was greater at 12 months compared with baseline: Aspirin 0.04 (95% confidence interval: 0.02-0.06), Blood pressure 0.04 (0.02-0.06), Cholesterol 0.05 (0.03-0.07), Smoking 0.05 (0.02-0.07); P<0.001 for each. Improvements were sustained at 18 months. At 12 months, baseline-adjusted difference-in-differences in proportions for the POC+PM arm versus POC was: Aspirin 0.02 (-0.02 to 0.05), Blood pressure -0.01 (-0.04 to 0.03), Cholesterol 0.03 (0.00-0.07), and Smoking 0.02 (-0.02 to 0.06); P>0.05 for all. Change Process Capability Questionnaire improved slightly, mean change 0.30 (0.09-0.51) but did not significantly differ across arms. CONCLUSION: Facilitator-led QI promoting population management approaches plus POC improvement strategies was not clearly superior to POC strategies alone.

Defragmenting Heart Failure Care: Medical Records Integration.

Heart failure management requires intensive care coordination. Guideline-directed medical therapies have been shown to save lives but are practically challenging to implement because of the fragmented care that heart failure patients experience. Electronic health record adoption has transformed the collection and storage of clinical data, but accessing these data often remains prohibitively difficult. Current legislation aims to increase the interoperability of software systems so that providers and patients can easily access the clinical information they desire. Novel heart failure devices and technologies leverage patient-generated data to manage heart failure patients, whereas new data standards make it possible for this information to guide clinical decision-making.

Inequalities in health? An update on the effect of social deprivation for patients with breast cancer in South East Wales.

BACKGROUND: Breast cancer, historically a disease of more affluent women, has increased in incidence for women from areas of greater social deprivation, yet prognosis is worse for these women. This study identifies differences in presentation, treatment and prognostic factors between the socioeconomic groups. METHODS: Patient data obtained from the prospectively maintained Welsh national Cancer Network Information System Cymru, for an 11-year period, were categorised according to Welsh Index of Multiple Deprivation quintiles. Quintiles were compared for differences in variables relating to patient characteristics, detection of cancer, tumour biology and treatment. RESULTS: 1570 patients were included. Analysis showed that in the more socially deprived quintiles, there are proportionally fewer women being diagnosed through the NHS breast cancer screening programme and as a consequence greater numbers of women from poorer areas being diagnosed outwith the screening age parameters. Screen detection is strongly associated with better prognosis in terms of Nottingham Prognostic Index. Similarly, increasing levels of social deprivation are associated with higher incidence of oestrogen receptor negative and triple negative tumours, both features associated with a shorter disease free and overall survival. Other variables of tumour biology, rates and type of surgical and adjuvant treatment were similar across social deprivation quintiles. CONCLUSION: There is a trend of reduced early detection of breast cancer in South East Wales in those patients living in areas of higher social deprivation. Given that there is equity in access to treatment within NHS, which is free for patients at the point of care, further study is warranted to address this existing disparity. Population cancer surveillance will need to inform both public health and NHS service responses, to continue to achieve improvements. Health trends may yet alter depending on current and future shifts in governmental health policy.

Validity of Cardiovascular Data From Electronic Sources: The Multi-Ethnic Study of Atherosclerosis and HealthLNK.

BACKGROUND: Understanding the validity of data from electronic data research networks is critical to national research initiatives and learning healthcare systems for cardiovascular care. Our goal was to evaluate the degree of agreement of electronic data research networks in comparison with data collected by standardized research approaches in a cohort study. METHODS: We linked individual-level data from MESA (Multi-Ethnic Study of Atherosclerosis), a community-based cohort, with HealthLNK, a 2006 to 2012 database of electronic health records from 6 Chicago health systems. To evaluate the correlation and agreement of blood pressure in HealthLNK in comparison with in-person MESA examinations, and body mass index in HealthLNK in comparison with MESA, we used Pearson correlation coefficients and Bland-Altman plots. Using diagnoses in MESA as the criterion standard, we calculated the performance of HealthLNK for hypertension, obesity, and diabetes mellitus diagnosis by using International Classification of Diseases, Ninth Revision codes and clinical data. We also identified potential myocardial infarctions, strokes, and heart failure events in HealthLNK and compared them with adjudicated events in MESA. RESULTS: Of the 1164 MESA participants enrolled at the Chicago Field Center, 802 (68.9%) participants had data in HealthLNK. The correlation was low for systolic blood pressure (0.39; P<0.0001). In comparison with MESA, HealthLNK overestimated systolic blood pressure by 6.5 mm Hg (95% confidence interval, 4.2-7.8). There was a high correlation between body mass index in MESA and HealthLNK (0.94; P<0.0001). HealthLNK underestimated body mass index by 0.3 kg/m2 (95% confidence interval, -0.4 to -0.1). With the use of International Classification of Diseases, Ninth Revision codes and clinical data, the sensitivity and specificity of HealthLNK queries for hypertension were 82.4% and 59.4%, for obesity were 73.0% and 89.8%, and for diabetes mellitus were 79.8% and 93.3%. In comparison with adjudicated cardiovascular events in MESA, the concordance rates for myocardial infarction, stroke, and heart failure were, respectively, 41.7% (5/12), 61.5% (8/13), and 62.5% (10/16). CONCLUSIONS: These findings illustrate the limitations and strengths of electronic data repositories in comparison with information collected by traditional standardized epidemiological approaches for the ascertainment of cardiovascular risk factors and events.

Impact of Practice Facilitation in Primary Care on Chronic Disease Care Processes and Outcomes: a Systematic Review.

BACKGROUND: More than 100 million individuals in the USA have been diagnosed with a chronic disease, yet chronic disease care has remained fragmented and of inconsistent quality. Improving chronic disease management has been challenging for primary care and internal medicine practitioners. Practice facilitation provides a comprehensive approach to chronic disease care. The objective is to evaluate the impact of practice facilitation on chronic disease outcomes in the primary care setting. METHODS: This systematic review examined North American studies from PubMed, EMBASE, and Web of Science (database inception to August 2017). Investigators independently extracted and assessed the quality of the data on chronic disease process and clinical outcome measures. Studies implemented practice facilitation and reported quantifiable care processes and patient outcomes for chronic disease. Each study and their evidence were assessed for risk of bias and quality according to the Cochrane Collaboration and the Grade Collaboration tool. RESULTS: This systematic review included 25 studies: 12 randomized control trials and 13 prospective cohort studies. Across all studies, practices and their clinicians were aware of the implementation of practice facilitation. Improvements were observed in most studies for chronic diseases including asthma, cancer (breast, cervical, and colorectal), cardiovascular disease (cerebrovascular disease, coronary artery disease, dyslipidemia, hypertension, myocardial infarction, and peripheral vascular disease), and type 2 diabetes. Mixed results were observed for chronic kidney disease and chronic illness care. DISCUSSION: Overall, the results suggest that practice facilitation may improve chronic disease care measures. Across all studies, practices were aware of practice facilitation. These findings lend support for the potential expansion of practice facilitation in primary care. Future work will need to investigate potential opportunities for practice facilitation to improve chronic disease outcomes in other health care settings (e.g., specialty and multi-specialty practices) with standardized measures.

Engaging Primary Care Practices in Studies of Improvement: Did You Budget Enough for Practice Recruitment?

PURPOSE: The methods and costs to enroll small primary care practices in large, regional quality improvement initiatives are unknown. We describe the recruitment approach, cost, and resources required to recruit and enroll 500 practices in the Northwest and Midwest regional cooperatives participating in the Agency for Healthcare Research and Quality (AHRQ)-funded initiative, EvidenceNOW: Advancing Heart Health in Primary Care. METHODS: The project management team of each cooperative tracked data on recruitment methods used for identifying and connecting with practices. We developed a cost-of-recruitment template and used it to record personnel time and associated costs of travel and communication materials. RESULTS: A total of 3,669 practices were contacted during the 14- to 18-month recruitment period, resulting in 484 enrolled practices across the 6 states served by the 2 cooperatives. The average number of interactions per enrolled practice was 7, with a total of 29,100 hours and a total cost of $2.675 million, or $5,529 per enrolled practice. Prior partnerships predicted recruiting almost 1 in 3 of these practices as contrasted to 1 in 20 practices without a previous relationship or warm hand-off. CONCLUSIONS: Recruitment of practices for large-scale practice quality improvement transformation initiatives is difficult and costly. The cost of recruiting practices without existing partnerships is expensive, costing 7 times more than reaching out to familiar practices. Investigators initiating and studying practice quality improvement initiatives should budget adequate funds to support high-touch recruitment strategies, including building trusted relationships over a long time frame, for a year or more.

Learning bundled care opportunities from electronic medical records.

OBJECTIVE: The traditional fee-for-service approach to healthcare can lead to the management of a patient's conditions in a siloed manner, inducing various negative consequences. It has been recognized that a bundled approach to healthcare - one that manages a collection of health conditions together - may enable greater efficacy and cost savings. However, it is not always evident which sets of conditions should be managed in a bundled manner. In this study, we investigate if a data-driven approach can automatically learn potential bundles. METHODS: We designed a framework to infer health condition collections (HCCs) based on the similarity of their clinical workflows, according to electronic medical record (EMR) utilization. We evaluated the framework with data from over 16,500 inpatient stays from Northwestern Memorial Hospital in Chicago, Illinois. The plausibility of the inferred HCCs for bundled care was assessed through an online survey of a panel of five experts, whose responses were analyzed via an analysis of variance (ANOVA) at a 95% confidence level. We further assessed the face validity of the HCCs using evidence in the published literature. RESULTS: The framework inferred four HCCs, indicative of (1) fetal abnormalities, (2) late pregnancies, (3) prostate problems, and (4) chronic diseases, with congestive heart failure featuring prominently. Each HCC was substantiated with evidence in the literature and was deemed plausible for bundled care by the experts at a statistically significant level. CONCLUSIONS: The findings suggest that an automated EMR data-driven framework conducted can provide a basis for discovering bundled care opportunities. Still, translating such findings into actual care management will require further refinement, implementation, and evaluation.

A computable phenotype for asthma case identification in adult and pediatric patients: External validation in the Chicago Area Patient-Outcomes Research Network (CAPriCORN).

Objective: Comprehensive, rapid, and accurate identification of patients with asthma for clinical care and engagement in research efforts is needed. The original development and validation of a computable phenotype for asthma case identification occurred at a single institution in Chicago and demonstrated excellent test characteristics. However, its application in a diverse payer mix, across different health systems and multiple electronic health record vendors, and in both children and adults was not examined. The objective of this study is to externally validate the computable phenotype across diverse Chicago institutions to accurately identify pediatric and adult patients with asthma. Methods: A cohort of 900 asthma and control patients was identified from the electronic health record between January 1, 2012 and November 30, 2014. Two physicians at each site independently reviewed the patient chart to annotate cases. Results: The inter-observer reliability between the physician reviewers had a κ-coefficient of 0.95 (95% CI 0.93-0.97). The accuracy, sensitivity, specificity, negative predictive value, and positive predictive value of the computable phenotype were all above 94% in the full cohort. Conclusions: The excellent positive and negative predictive values in this multi-center external validation study establish a useful tool to identify asthma cases in in the electronic health record for research and care. This computable phenotype could be used in large-scale comparative-effectiveness trials.

Distance from hospital impacts adverse event detection after outpatient endoscopy.

BACKGROUND AND AIMS: Monitoring adverse events (AEs) after GI endoscopy is an endorsed quality measure but is challenging to implement in practice. Patients with major AEs may seek care elsewhere after endoscopy. We aimed to determine the hospital utilization patterns of patients with AEs after ambulatory endoscopy. METHODS: We used the HealthLNK Data Repository, which uses a software application for integration of deidentified, patient-level clinical data across institutions. Data for patients undergoing outpatient endoscopy from 2010 to 2011 at 5 Chicago-area hospitals were used. Early mortality was defined as death no more than 2 months after the outpatient procedure. AEs were defined as a hospital admission for perforation, bleeding, or pancreatitis the same or following month after endoscopy. RESULTS: During the study period, 42,842 outpatient procedures were performed in 22,898 unique individuals. Early mortality occurred in 86 patients (.4%). Per-patient mortality was greatest after outpatient ERCP (2.5%, P < .0001). Of 86 patients with early mortality, 36 (42%) were not hospitalized at the index hospital after endoscopy. Patients who did not return to the index hospital lived farther from the index hospital (P = .02). In total, 8.3% of ambulatory endoscopies were associated with potential endoscopy-related AEs. The observed rate of potential AEs trended downward as patients' home zip codes moved farther from the index hospital (P = .01). CONCLUSIONS: Nearly half of patients who die soon after outpatient endoscopy are not hospitalized at their index hospital after endoscopy. The observed AE rate was higher for patients living closer to the index hospital, suggesting that patients who live farther away are less likely to return to the index hospital for emergency care. Novel methods to efficiently track outcomes after outpatient endoscopy are needed.

Performance of an electronic health record-based phenotype algorithm to identify community associated methicillin-resistant Staphylococcus aureus cases and controls for genetic association studies.

BACKGROUND: Community associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is one of the most common causes of skin and soft tissue infections in the United States, and a variety of genetic host factors are suspected to be risk factors for recurrent infection. Based on the CDC definition, we have developed and validated an electronic health record (EHR) based CA-MRSA phenotype algorithm utilizing both structured and unstructured data. METHODS: The algorithm was validated at three eMERGE consortium sites, and positive predictive value, negative predictive value and sensitivity, were calculated. The algorithm was then run and data collected across seven total sites. The resulting data was used in GWAS analysis. RESULTS: Across seven sites, the CA-MRSA phenotype algorithm identified a total of 349 cases and 7761 controls among the genotyped European and African American biobank populations. PPV ranged from 68 to 100% for cases and 96 to 100% for controls; sensitivity ranged from 94 to 100% for cases and 75 to 100% for controls. Frequency of cases in the populations varied widely by site. There were no plausible GWAS-significant (p < 5 E -8) findings. CONCLUSIONS: Differences in EHR data representation and screening patterns across sites may have affected identification of cases and controls and accounted for varying frequencies across sites. Future work identifying these patterns is necessary.

Genome- and phenome-wide analyses of cardiac conduction identifies markers of arrhythmia risk.

BACKGROUND: ECG QRS duration, a measure of cardiac intraventricular conduction, varies ≈2-fold in individuals without cardiac disease. Slow conduction may promote re-entrant arrhythmias. METHODS AND RESULTS: We performed a genome-wide association study to identify genomic markers of QRS duration in 5272 individuals without cardiac disease selected from electronic medical record algorithms at 5 sites in the Electronic Medical Records and Genomics (eMERGE) network. The most significant loci were evaluated within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium QRS genome-wide association study meta-analysis. Twenty-three single-nucleotide polymorphisms in 5 loci, previously described by CHARGE, were replicated in the eMERGE samples; 18 single-nucleotide polymorphisms were in the chromosome 3 SCN5A and SCN10A loci, where the most significant single-nucleotide polymorphisms were rs1805126 in SCN5A with P=1.2×10(-8) (eMERGE) and P=2.5×10(-20) (CHARGE) and rs6795970 in SCN10A with P=6×10(-6) (eMERGE) and P=5×10(-27) (CHARGE). The other loci were in NFIA, near CDKN1A, and near C6orf204. We then performed phenome-wide association studies on variants in these 5 loci in 13859 European Americans to search for diagnoses associated with these markers. Phenome-wide association study identified atrial fibrillation and cardiac arrhythmias as the most common associated diagnoses with SCN10A and SCN5A variants. SCN10A variants were also associated with subsequent development of atrial fibrillation and arrhythmia in the original 5272 "heart-healthy" study population. CONCLUSIONS: We conclude that DNA biobanks coupled to electronic medical records not only provide a platform for genome-wide association study but also may allow broad interrogation of the longitudinal incidence of disease associated with genetic variants. The phenome-wide association study approach implicated sodium channel variants modulating QRS duration in subjects without cardiac disease as predictors of subsequent arrhythmias.

A genome- and phenome-wide association study to identify genetic variants influencing platelet count and volume and their pleiotropic effects.

Platelets are enucleated cell fragments derived from megakaryocytes that play key roles in hemostasis and in the pathogenesis of atherothrombosis and cancer. Platelet traits are highly heritable and identification of genetic variants associated with platelet traits and assessing their pleiotropic effects may help to understand the role of underlying biological pathways. We conducted an electronic medical record (EMR)-based study to identify common variants that influence inter-individual variation in the number of circulating platelets (PLT) and mean platelet volume (MPV), by performing a genome-wide association study (GWAS). We characterized genetic variants associated with MPV and PLT using functional, pathway and disease enrichment analyses; we assessed pleiotropic effects of such variants by performing a phenome-wide association study (PheWAS) with a wide range of EMR-derived phenotypes. A total of 13,582 participants in the electronic MEdical Records and GEnomic network had data for PLT and 6,291 participants had data for MPV. We identified five chromosomal regions associated with PLT and eight associated with MPV at genome-wide significance (P < 5E-8). In addition, we replicated 20 SNPs [out of 56 SNPs (α: 0.05/56 = 9E-4)] influencing PLT and 22 SNPs [out of 29 SNPs (α: 0.05/29 = 2E-3)] influencing MPV in a published meta-analysis of GWAS of PLT and MPV. While our GWAS did not find any new associations, our functional analyses revealed that genes in these regions influence thrombopoiesis and encode kinases, membrane proteins, proteins involved in cellular trafficking, transcription factors, proteasome complex subunits, proteins of signal transduction pathways, proteins involved in megakaryocyte development, and platelet production and hemostasis. PheWAS using a single-SNP Bonferroni correction for 1,368 diagnoses (0.05/1368 = 3.6E-5) revealed that several variants in these genes have pleiotropic associations with myocardial infarction, autoimmune, and hematologic disorders. We conclude that multiple genetic loci influence interindividual variation in platelet traits and also have significant pleiotropic effects; the related genes are in multiple functional pathways including those relevant to thrombopoiesis.

Variants near FOXE1 are associated with hypothyroidism and other thyroid conditions: using electronic medical records for genome- and phenome-wide studies.

We repurposed existing genotypes in DNA biobanks across the Electronic Medical Records and Genomics network to perform a genome-wide association study for primary hypothyroidism, the most common thyroid disease. Electronic selection algorithms incorporating billing codes, laboratory values, text queries, and medication records identified 1317 cases and 5053 controls of European ancestry within five electronic medical records (EMRs); the algorithms' positive predictive values were 92.4% and 98.5% for cases and controls, respectively. Four single-nucleotide polymorphisms (SNPs) in linkage disequilibrium at 9q22 near FOXE1 were associated with hypothyroidism at genome-wide significance, the strongest being rs7850258 (odds ratio [OR] 0.74, p = 3.96 × 10(-9)). This association was replicated in a set of 263 cases and 1616 controls (OR = 0.60, p = 5.7 × 10(-6)). A phenome-wide association study (PheWAS) that was performed on this locus with 13,617 individuals and more than 200,000 patient-years of billing data identified associations with additional phenotypes: thyroiditis (OR = 0.58, p = 1.4 × 10(-5)), nodular (OR = 0.76, p = 3.1 × 10(-5)) and multinodular (OR = 0.69, p = 3.9 × 10(-5)) goiters, and thyrotoxicosis (OR = 0.76, p = 1.5 × 10(-3)), but not Graves disease (OR = 1.03, p = 0.82). Thyroid cancer, previously associated with this locus, was not significantly associated in the PheWAS (OR = 1.29, p = 0.09). The strongest association in the PheWAS was hypothyroidism (OR = 0.76, p = 2.7 × 10(-13)), which had an odds ratio that was nearly identical to that of the curated case-control population in the primary analysis, providing further validation of the PheWAS method. Our findings indicate that EMR-linked genomic data could allow discovery of genes associated with many diseases without additional genotyping cost.

Anatomic and advanced adenoma detection rates as quality metrics determined via natural language processing.

OBJECTIVES: The objectives of this study were to use an open-source natural language-processing tool (NLP) to accurately assess total, anatomic (left and right colon), and advanced adenoma detection rates (ADRs) and to determine how these metrics differ between high- and low-performing endoscopists. METHODS: An NLP tool was developed using the Apache Unstructured Information Management Architecture and queried all procedure records for screening colonoscopies performed in patients aged 50-75 years at a single institution from April 1998 to December 2013. Validation was performed on 200 procedures and associated pathology reports. The total, left colon, right colon, and advanced ADRs were calculated and physicians were stratified by total ADR (<20% and ≥20%). Comparisons of colonoscopy characteristics and ADR comparisons (advanced, left, right, and right/left ratio) were determined by t-tests and Wilcoxon rank-sum tests. RESULTS: The total ADR for 34,998 screening colonoscopies from 1998 to 2013 was 20.3%, as determined via NLP. The institutional left and right colon ADRs were 10.1% and 12.5%, respectively. The overall advanced ADR was 4.4%. Endoscopists with total ADRs ≥20% had higher left (12.4%) and right colon (16.4%) ADRs than endoscopists with ADRs <20% (left ADR=5.6%, right ADR=5.8%). Endoscopists with ADRs ≥20% had higher individual right/left ADR ratios than those with low ADRs (1.4 (interquartile range (IQR) 0.4) vs. 1.0 (IQR 0.4), P=0.02). There was a moderate positive correlation between advanced ADR detection and both right (Spearman's rho=0.5, P=0.05) and left colon (Spearman's rho=0.4, P=0.03) ADRs. CONCLUSIONS: Institutions should consider the use of anatomic and advanced ADRs determined via natural language processing as a refined measure of colonoscopy quality. The ability to continuously monitor and provide feedback on colonoscopy quality metrics may encourage endoscopists to refine technique, resulting in overall improvements in adenoma detection.