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In this trans-ethnic multi-omic study we reinterpret the genetic architecture of blood pressure to identify genes, tissues, phenome, and medication contexts of blood pressure homeostasis. We discovered 208 novel common blood pressure SNPs and 53 rare variants in GWASs of systolic, diastolic and pulse pressure in up to 776,078 participants from the Million Veteran Program (MVP) and collaborating studies, with analysis of the blood pressure clinical phenome in MVP. Our transcriptome-wide association study detected 4,043 blood pressure associations with genetically-predicted gene expression of 840 genes in 45 tissues, and murine renal single-cell RNA sequencing identified upregulated blood pressure genes in kidney tubule cells.

Background Clinically important medication errors are common after hospital discharge. They include preventable or ameliorable adverse drug events as well as medication discrepancies or non-adherence with high potential for future harm (potential adverse drug events). Objective The Pharmacist Intervention for Low Literacy in Cardiovascular Disease (PILL-CVD) study sought to determine the effect of a tailored intervention on the occurrence of clinically important medication errors after hospital discharge. Design Randomized controlled trial with concealed allocation and blinded outcome assessors. Setting Two tertiary care academic hospitals. Patients Adults hospitalized with acute coronary syndromes or acute decompensated heart failure. Intervention Pharmacist-assisted medication reconciliation, inpatient pharmacist counseling, low-literacy adherence aids, and individualized telephone follow-up after discharge. Measurements The primary outcome was the number of clinically important medication errors per patient during the first 30 days after hospital discharge. Secondary outcomes included preventable or ameliorable adverse drug events, as well as potential adverse drug events. Results Among 851 participants, 432 (50.8%) experienced 1 or more clinically important medication errors; 23% of such errors were judged to be serious, and 2% life-threatening. Adverse drug events occurred in 258 patients (30.3%) and potential adverse drug events in 253 (29.7%). The intervention did not significantly alter the per-patient number of clinically important medication errors (IRR=0.92; 95% CI, 0.77 to 1.10) or adverse drug events (IRR=1.09; CI, 0.86 to 1.39). Intervention patients tended to have fewer potential adverse drug events (IRR=0.80; CI, 0.61 to 1.04). Limitations The characteristics of the study hospitals and participants may limit generalizability. Conclusions Clinically important medication errors were present among half of patients after hospital discharge and were not significantly reduced by a health-literacy sensitive, pharmacist-delivered intervention.

Background The comparative effectiveness of sulfonylureas and metformin on cardiovascular disease (CVD) outcomes in type 2 diabetes are not well characterized. Objective To compare the effectiveness of sulfonylureas and metformin on the outcome of CVD (acute myocardial infarction, stroke) or death Design Retrospective cohort study Setting National Veterans Health Administration (VHA) databases linked to Medicare files Patients Veterans who initiated metformin or sulfonylureas for diabetes. Patients with chronic kidney disease or serious medical illness were excluded. Measurements Composite outcome of hospitalizations for acute myocardial infarction, stroke, or death. Cox regression analyses compared the incidence of the composite outcome between groups, adjusting for baseline demographics, medications, cholesterol, glycated hemoglobin, creatinine, blood pressure, body mass index, healthcare utilization and co-morbidities. Results Among 253,690 patients (98,665 sulfonylurea and 155,025 metformin initiators) the crude outcome rates were 18.2 and 10.4 per 1000 person-years in sulfonylurea and metformin users, respectively (adjusted hazard ratio [aHR] 1.21, 95% Confidence Intervals [CI] 1.13, 1.30). Results were consistent for both glyburide (aHR 1.26, 95% CI 1.16, 1.37) and glipizide (aHR 1.15, 95% CI 1.06, 1.26) as well as for those with prior history of CVD (aHR 1.25, 95% CI 1.13, 1.55) and without history of CVD (aHR: 1.16, 95% CI: 1.06, 1.29). Results were also consistent in a propensity score-matched analysis. For patients initiating sulfonylureas rather than metformin, we estimated an excess of 1 and 4 CVD events per 1000 person-years for those without and with a CVD history, respectively. Limitations Data on women and minorities is limited but reflective of the VHA population. Conclusions Use of sulfonylureas compared to metformin for initial treatment of diabetes was associated with an increased hazard of CVD events or death.

A multifactorial intervention including patient education improved blood pressure control compared with provider education alone.

Importance Preferred second line medication for diabetes treatment after metformin failure remains uncertain. Objective We compared time to acute myocardial infarction [AMI], stroke, or death in a cohort of metformin initiators who added insulin or a sulfonylurea. Design Retrospective cohort constructed using national Veterans Health Administration, Medicare, and National Death Index databases. Participants Veterans initially treated with metformin from 2001 through 2008 who subsequently added either insulin or sulfonylurea. Each insulin intensifier was propensity score matched by characteristics to five sulfonylurea intensifiers. Patients were followed through September, 2011 for primary analyses or September, 2009 for cause of death analyses. Main Outcome Measures Risk of a composite outcome of AMI, stroke hospitalization or all-cause death was compared between therapies using marginal structural Cox proportional hazard models to adjust for baseline and time-varying demographics, medications, cholesterol, hemoglobin A1c, creatinine, blood pressure, body mass index, and co-morbidities. Results Among 178,341 metformin monotherapy patients, 2,948 and 39,990 added insulin or sulfonylurea, respectively. Propensity score matching yielded 2,436 metformin+insulin and 12,180 metformin+sulfonylurea patients. At intensification, the median (interquartile range) time on metformin was 14 months (5, 30) and HbA1c was 8.1% (7.2, 9.9). There were 172 versus 634 events for the primary outcome among those who added insulin versus sulfonylureas respectively (42 versus 33 events per 1000 person-years, adjusted hazard ratio [aHR] 1.30, 95% confidence interval [CI] 1.07, 1.58, p=0.009). AMI and stroke rates were statistically similar 41 versus 229 (10.2 and 11.9 per 1000 person years, aHR 0.88,95% CI 0.59, 1.30, p=0.52), while all-cause death rates were137 versus 444, respectively (33.7 and 22.7 per 1000 person-years, aHR 1.44, 95% CI,1.15, 1.79, p=0.001). There were 54 versus 258 secondary outcomes: AMI, stroke hospitalizations or cardiovascular deaths (22.8 vs. 22.5 events per 1000 person years aHR 0.98, 95% CI 0.71, 1.34. p=0.87). Conclusions Among patients with diabetes using metformin, the addition of insulin versus sulfonylurea was associated with an increased risk of a composite of nonfatal cardiovascular outcomes and all-cause mortality. These findings require further investigation to understand risks associated with insulin use in these patients.

The PPV of incident strokes was 80% using our strategy of primary discharge diagnosis and excluding prior outpatient diagnoses of stroke. Although an unknown percentage of incident strokes are missed, this group of proven incident stroke patients can be used for etiologic studies of medication exposures.

Background Patients with inadequate health literacy often have poorer health outcomes and increased utilization and costs, compared to those with adequate health literacy skills. The Institute of Medicine has recommended that health literacy assessment be incorporated into health care information systems, which would facilitate large-scale studies of the effects of health literacy, as well as evaluation of system interventions to improve care by addressing health literacy. As part of the Health Literacy Screening (HEALS) study, a brief health literacy screen (BHLS) was incorporated into the electronic health record (EHR) at a large academic medical center. Methods Changes were implemented to the nursing intake documentation across all adult hospital units, the emergency department, and three primary care practices. The change involved replacing previous education screening items with the BHLS. Implementation was based on a quality improvement framework, with a focus on acceptability, adoption, appropriateness, feasibility, fidelity and sustainability. Support was gained from nursing leadership, education and training was provided, a documentation change was rolled out, feedback was obtained, and uptake of the new health literacy screening items was monitored. Results Between November 2010 and April 2012, there were 55,611 adult inpatient admissions, and from November 2010 to September 2011, 23,186 adult patients made 39,595 clinic visits to the three primary care practices. The completion (uptake) rate in the hospital for November 2010 through April 2012 was 91.8%. For outpatient clinics, the completion rate between November 2010 and October 2011 was 66.6%. Conclusions Although challenges exist, it is feasible to incorporate health literacy screening into clinical assessment and EHR documentation. Next steps are to evaluate the association of health literacy with processes and outcomes of care across inpatient and outpatient populations.