Purpose: To explore the association between CYP3A4 and CYP3A5 gene polymorphisms and blood pressure response to amlodipine among participants from the African-American Study of Kidney Disease and Hypertension Trial randomized to amlodipine (n = 164). Methods: Cox proportional hazards models were used to determine the risk of reaching a target mean arterial pressure (MAP) of ≤107 mm Hg by CYP3A4 (A–392G and T16090C) and CYP3A5 (A6986G) gene polymorphisms, stratified by MAP randomization group (low or usual) and controlling for other predictors for blood pressure response. Results: Women randomized to a usual MAP goal with an A allele at CYP3A4 A–392G were more likely to reach a target MAP of 107 mm Hg. The adjusted hazard ratio (AA/AG compared to GG) with 95% confidence interval was 3.41 (1.20–9.64; p = 0.020). Among participants randomized to a lower MAP goal, those with the C allele at CYP3A4 T16090C were more likely to reach target MAP: The adjusted hazard ratio was 2.04 (1.17–3.56; p = 0.010). After adjustment for multiple testing using a threshold significance level of p = 0.016, only the CYP3A4 T16090C SNP remained significant. CYP3A5 A6986G was not associated with blood pressure response. Conclusions: Our findings suggest that blood pressure response to amlodipine among high-risk African-Americans appears to be determined by CYP3A4 genotypes, and sex specificity may be an important consideration. Clinical applications of CYP3A4 genotype testing for individualized treatment regimens warrant further study.

The variation in the association between estimated access and outcomes affects the projected reductions of severe outcomes with access improvement. Thus applying one intervention would not have the same level of improvement across geography. Interventions must be tailored to target regions with the potential to deliver the highest effect to gain maximum benefit.

The Veterans Affairs Hypertension Primary Care Longitudinal Cohort (VAHC) was initiated in 2003 as a pilot study designed to link the VA electronic medical record system with individual genetic data. Between June 2003 and December 2004, 1,527 hypertensive participants were recruited. Protected health information (PHI) was extracted from the regional VA data warehouse. Differences between the clinic and mail recruits suggested that clinic recruitment resulted in an over-sampling of African Americans. A review of medical records in a random sample of study participants confirmed that the data warehouse accurately captured most selected diagnoses. Genomic DNA was acquired non-invasively from buccal cells in mouthwash; ~ 96.5 per cent of samples contained DNA suitable for genotyping, with an average DNA yield of 5.02 ± 0.12 micrograms, enough for several thousand genotypes. The coupling of detailed medical databases with genetic information has the potential to facilitate the genetic study of hypertension and other complex diseases.

Objective:To evaluate the Orange County Clostridium difficile infection (CDI) prevention collaborative’s effect on rates of CDI in acute-care hospitals (ACHs) in Orange County, California.Design:Controlled interrupted time series.Methods:We convened a CDI prevention collaborative with healthcare facilities in Orange County to reduce CDI incidence in the region. Collaborative participants received onsite infection control and antimicrobial stewardship assessments, interactive learning and discussion sessions, and an interfacility transfer communication improvement initiative during June 2015–June 2016. We used segmented regression to evaluate changes in monthly hospital-onset (HO) and community-onset (CO) CDI rates for ACHs. The baseline period comprised 17 months (January 2014–June 2015) and the follow-up period comprised 28 months (September 2015–December 2017). All 25 Orange County ACHs were included in the CO-CDI model to account for direct and indirect effects of the collaborative. For comparison, we assessed HO-CDI and CO-CDI rates among 27 ACHs in 3 San Francisco Bay Area counties.Results:HO-CDI rates in the 15 participating Orange County ACHs decreased 4% per month (incidence rate ratio [IRR], 0.96; 95% CI, 0.95–0.97; P < .0001) during the follow-up period compared with the baseline period and 3% (IRR, 0.97; 95% CI, 0.95–0.99; P = .002) per month compared to the San Francisco Bay Area nonparticipant ACHs. Orange County CO-CDI rates declined 2% per month (IRR, 0.98; 95% CI, 0.96–1.00; P = .03) between the baseline and follow-up periods. This decline was not statistically different from the San Francisco Bay Area ACHs (IRR, 0.97; 95% CI, 0.95–1.00; P = .09).Conclusions:Our analysis of ACHs in Orange County provides evidence that coordinated, regional multifacility initiatives can reduce CDI incidence.