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BACKGROUND Specific combinations of two drug classes are recommended in a variety of clinical situations in the management of hypertension. These preferred combinations are based on complimentary blood pressure (BP) lowering mechanisms or benefit for a concomitant disease. METHODS Using electronic health records (EHRs) data from 27,579 ambulatory hypertensive patients, we investigated antihypertensive therapy prescribing patterns and associations of preferred two drug classes with BP control. RESULTS Overall, BP control, defined as BP CONCLUSIONS Prescribing of guideline-recommended antihypertensive drug classes for concomitant diseases is suboptimal and prescribing of preferred/optimized drug class combinations was moderate. We did not find a clear association between the use of optimized drug class combinations and greater BP control. Overall, using EHR data, we identified potential opportunities for re-examining prescribing practices with implications for clinical decision support and healthcare improvement at the community and health system-wide levels.

Background Evolutionary theory suggests that natural selection favors the evolution of cognitive abilities which allow humans to use facial cues to assess traits of others. The use of facial and somatic cues by humans has been studied mainly in western industrialized countries, leaving unanswered whether results are valid across cultures. Methodology/Principal Findings Our objectives were to test (i) if previous finding about raters' ability to get accurate information about an individual by looking at his facial photograph held in low-income non western rural societies and (ii) whether women and men differ in this ability. To answer the questions we did a study during July-August 2007 among the Tsimane', a native Amazonian society of foragers-farmers in Bolivia. We asked 40 females and 40 males 16–25 years of age to rate four traits in 93 facial photographs of other Tsimane' males. The four traits were based on sexual selection theory, and included health, dominance, knowledge, and sociability. The rating scale for each trait ranged from one (least) to four (most). The average rating for each trait was calculated for each individual in the photograph and regressed against objective measures of the trait from the person in the photograph. We found that (i) female Tsimane' raters were able to assess facial cues related to health, dominance, and knowledge and (ii) male Tsimane' raters were able to assess facial cues related to dominance, knowledge, and sociability. Conclusions/Significance Our results support the existence of a human ability to identify objective traits from facial cues, as suggested by evolutionary theory.

We used electronic health records (EHRs) data from 5658 ambulatory chronic kidney disease (CKD) patients with hypertension and prescribed antihypertensive therapy to examine antihypertensive drug prescribing patterns, blood pressure (BP) control, and risk factors for resistant hypertension (RHTN) in a real-world setting. Two-thirds of CKD patients and three-fourths of those with proteinuria were prescribed guideline-recommended renoprotective agents including an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB); however, one-third were not prescribed an ACEI or ARB. CKD patients, particularly those with stages 1-2 CKD, who were prescribed regimens including beta-blocker (BB) + diuretic or ACEI/ARB + BB + diuretic were more likely to have controlled BP (

Objectives This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype–guided antiplatelet therapy after percutaneous coronary intervention (PCI). Background CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI. Methods After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights. Results Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60). Conclusions These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.

Background The majority of hypertensive individuals require combination antihypertensive therapy to achieve adequate blood pressure ( BP ) control. This study aimed to identify genetic variants associated with uncontrolled BP on combination therapy with a thiazide diuretic and a β‐blocker. Methods and Results A genome‐wide association study of uncontrolled BP on combination therapy was conducted among 314 white participants of the PEAR (Pharmacogenomic Evaluation of Antihypertensive Responses) trial. Multivariable logistic regression analysis was used. Genetic variants meeting a suggestive level of significance ( P INVEST (International Verapamil‐ SR Trandolapril study). We also examined genome‐wide variant associations with systolic and diastolic BP response on combination therapy and tested for replication. We discovered a single nucleotide polymorphism, the rs261316 major allele, at chromosome 15 in the gene ALDH1A2 associated with an increased odds of having uncontrolled BP on combination therapy (odds ratio: 2.56, 95% confidence interval, 1.69–3.88, P =8.64E‐06). This single nucleotide polymorphism replicated (odds ratio: 1.86, 95% confidence interval, 1.35–2.57, P =0.001) and approached genome‐wide significance in the meta‐analysis between discovery and replication cohorts (odds ratio: 2.16, 95% confidence interval, 1.63–2.86, P =8.60E‐08). Other genes in the region surrounding rs261316 ( ALDH1A2) include AQP9 and LIPC . Conclusions A single nucleotide polymorphism in the gene ALDH1A2 may be associated with uncontrolled BP following treatment with a thiazide diuretic/β‐blocker combination. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT 00246519.

Sibling configuration, including birth order, or the number, age, and sex of siblings is associated with parental resource allocation between children and is thus associated with a person's well-being. Little is known about the association between specific types of siblings and adult health outcomes. Here we test several hypotheses about sibling composition (number of older brothers, older sisters, younger sisters, younger brothers) and adult blood pressure in a foraging-farming society of native Amazonians in Bolivia (Tsimane'). We collected data in 2007 from 374 adults (16-60years of age) from 196 households in 13 villages. Household random-effects multiple regressions were run using systolic (SBP) or diastolic blood pressure (DBP) as outcomes; covariates included the four sibling categories and control variables (e.g., sex, age, education, body mass index [BMI]). Mean SBP and DBP were 114 (SD=14) and 66 (SD=11)mmHg. The prevalence of hypertension was 5.08%. Having an additional younger brother bore a small (3.3-5.9%) positive association with both SBP and DBP, with the effect weakening as people aged. Having an additional younger sister was associated with a small (3.8%) increase in SBP among women, with the magnitude shrinking as people aged. In a large family, the number of younger brothers may exert an impact on an individual's blood pressure.

The ubiquity and consequences of childhood growth stunting (

Genome-wide association studies (GWAS) of obesity measures have identified associations with single nucleotide polymorphisms (SNPs). However, no large-scale evaluation of gene-environment interactions has been performed. We conducted a search of gene-environment (G × E) interactions in post-menopausal African-American and Hispanic women from the Women's Health Initiative SNP Health Association Resource GWAS study. Single SNP linear regression on body mass index (BMI) and waist-to-hip circumference ratio (WHR) adjusted for multidimensional-scaling-derived axes of ancestry and age was run in race-stratified data with 871,512 SNPs available from African-Americans (N = 8,203) and 786,776 SNPs from Hispanics (N = 3,484). Tests of G × E interaction at all SNPs for recreational physical activity (m h/week), dietary energy intake (kcal/day), alcohol intake (categorical), cigarette smoking years, and cigarette smoking (ever vs. never) were run in African-Americans and Hispanics adjusted for ancestry and age at interview, followed by meta-analysis of G × E interaction terms. The strongest evidence for concordant G × E interactions in African-Americans and Hispanics was for smoking and marker rs10133840 (Q statistic P = 0.70, beta = -0.01, P = 3.81 × 10(-7)) with BMI as the outcome. The strongest evidence for G × E interaction within a cohort was in African-Americans with WHR as outcome for dietary energy intake and rs9557704 (SNP × kcal = -0.04, P = 2.17 × 10(-7)). No results exceeded the Bonferroni-corrected statistical significance threshold.

Siblings compete for parental resources. Little is known about how sibling composition (older sisters, older brothers, younger sisters, younger brothers) might affect child anthropometric indicators of nutritional status.This study evaluates the associations between sibling composition and child anthropometry using panel data from a native Amazonian society (Tsimane').Anthropometry of ~168 girls and 169 boys aged 2-9 years were measured annually during 2002-2007 (2360 observations). Children's weight-for-height Z-score (WHZ), mid-upper arm circumference (MUAC), mid-upper arm muscle area (AMA) and triceps skin-fold thickness (TST) were regressed separately against all of the sibling composition variables while controlling for child's age and survey year. Multivariate panel linear regressions were used with individual, village, survey year and village-year fixed-effects, clustering by household.Among girls, an additional older brother was associated with a 1.4% decrease in MUAC (p0.01) and a 4.3% decrease in AMA (p0.01); an additional younger sister was associated with a 6.3% decrease in TST (p0.01). The association between sibling composition and arm anthropometry was robust to various model specifications.Older brothers and younger sisters were negatively associated with arm measures in girls. This finding may help improve policy interventions that aim to address children's nutritional health and long-term well-being.

The present study provides evidence to support enhanced attention to reproductive health and comprehensive measures to increase access to quality reproductive health services. We compare and contrast the financing and utilization of reproductive health services in six sub-Saharan African countries using data from National Health Accounts and Demographic and Health Surveys. Spending on reproductive health in 2006 ranged from US$4 per woman of reproductive age in Ethiopia to US$17 in Uganda. These are below the necessary level for assuring adequate services given that an internationally recommended spending level for family planning alone was US$16 for 2006. Moreover, reproductive health spending shows signs of decline in tandem with insufficient improvement in service utilization. Public providers played a predominant role in antenatal and delivery care for institutional births, but home deliveries with unqualified attendants dominated. The private sector was a major supplier of condoms, oral pills and IUDs. Private clinics, pharmacies and drug vendors were important sources of STI treatment. The findings highlight the need to commit greatly increased funding for reproductive health services as well as more policy attention to the contribution of public, private and informal providers and the role of collaboration among them to expand access to services for under-served populations.

Among adults of industrial nations, growth stunting (-2 SD height Z score) is associated with worse indicators of adult well-being (e.g., income). Does adult stunting also inflict private costs in traditional societies? Adult stunting penalties or height premiums might only emerge when traditional societies modernize. Here we estimate the association between adult stunting and indicators of adult well-being using data from a panel study in progress among the Tsimane', a foraging-farming society of native Amazonians in Bolivia. Subjects included 248 women and 255 menor=age 22 measured annually during 5 consecutive years (2002-2006). Nine outcomes (wealth, monetary income, illness, access to credit, mirth, schooling, math skills, plant knowledge, forest clearance) were regressed separately against a stunting dummy variable and a wide range of control variables. We found no significant association between any of the indicators of own well-being and adult stunting. Additional analysis showed that stunting bore an association only with poorer mid-arm muscle area. Height premiums and stunting penalties, though evident and marked in modern societies, might not be common in all traditional societies.