Residency Exposures and Anticipated Future Involvement in Community Settings

Objective— To assess how exposures to community activities in residency impact anticipated future involvement in community child health settings. Methods— Prospective cohort study of pediatric residents from 10 programs (12 sites) who completed training between 2003 and 2009. Residents reported annual participation for ≥8 days in each of 7 community activities (eg, community settings, child health advocacy) in the prior year. At the start and end of residency, residents reported anticipated involvement in 10 years in 8 community settings (eg, school, shelter). Anticipated involvement was dichotomized: moderate/ substantial (“high”) versus none/limited (“low”). Logistic regression modeled whether residency exposures independently influenced anticipated future involvement at the end of residency. Results— A total of 683 residents completed surveys at the start and end of residency (66.8% participation). More than half of trainees reported ≥8 days’ of involvement in community settings (65.6%) or child health advocacy (53.6%) in residency. Fewer anticipated high involvement in at least 1 community setting at the end of residency than at the start (65.5% vs 85.6%, P < .001). Participation in each community activity mediated but did not moderate relations between anticipated involvement at the start and end of residency. In multivariate models, exposure to community settings in residency was associated with anticipated involvement at end of residency (adjusted odds ratio 1.5; 95% confidence interval 1.2, 2.0). No other residency exposures were associated. Conclusions— Residents who anticipate high involvement in community pediatrics at the start of residency participate in related opportunities in training. Exposure to community settings during residency may encourage community involvement after training

Aliskiren, enalapril, or aliskiren and enalapril in heart failure

BACKGROUND Among patients with chronic heart failure, angiotensin-converting–enzyme (ACE) inhibitors reduce mortality and hospitalization, but the role of a renin inhibitor in such patients is unknown. We compared the ACE inhibitor enalapril with the renin inhibitor aliskiren (to test superiority or at least noninferiority) and with the combination of the two treatments (to test superiority) in patients with heart failure and a reduced ejection fraction. METHODS After a single-blind run-in period, we assigned patients, in a double-blind fashion, to one of three groups: 2336 patients were assigned to receive enalapril at a dose of 5 or 10 mg twice daily, 2340 to receive aliskiren at a dose of 300 mg once daily, and 2340 to receive both treatments (combination therapy). The primary composite outcome was death from cardiovascular causes or hospitalization for heart failure. RESULTS After a median follow-up of 36.6 months, the primary outcome occurred in 770 patients (32.9%) in the combination-therapy group and in 808 (34.6%) in the enalapril group (hazard ratio, 0.93; 95% confidence interval [CI], 0.85 to 1.03). The primary outcome occurred in 791 patients (33.8%) in the aliskiren group (hazard ratio vs. enalapril, 0.99; 95% CI, 0.90 to 1.10); the prespecified test for noninferiority was not met. There was a higher risk of hypotensive symptoms in the combination-therapy group than in the enalapril group (13.8% vs. 11.0%, P=0.005), as well as higher risks of an elevated serum creatinine level (4.1% vs. 2.7%, P=0.009) and an elevated potassium level (17.1% vs. 12.5%, P&lt;0.001). CONCLUSIONS In patients with chronic heart failure, the addition of aliskiren to enalapril led to more adverse events without an increase in benefit. Noninferiority was not shown for aliskiren as compared with enalapri

Etoricoxib in the treatment of osteoarthritis over 52-weeks: a double-blind, active-comparator controlled trial [NCT00242489]

BACKGROUND: The aim of this study was to evaluate the long-term efficacy and tolerability of etoricoxib, a COX-2 selective inhibitor, in osteoarthritis (OA) patients. METHODS: A double-blind, randomized, multicenter study was conducted in 617 patients with OA of the knee. The base study was 14 weeks in duration and consisted of 2 parts; in Part I (6 weeks), patients were allocated to once daily oral etoricoxib 5, 10, 30, 60, 90 mg or placebo. In Part II (8 weeks); the placebo, etoricoxib 5 and 10 mg groups were reallocated to etoricoxib 30, 60, or 90 mg qd or diclofenac 50 mg t.i.d. Treatment was continued for consecutive 12 and 26 week extensions. Primary efficacy endpoints were the WOMAC VA 3.0 pain subscale and investigator global assessment of disease status. Safety and tolerability were assessed by collecting adverse events throughout the study. RESULTS: Compared with placebo, the etoricoxib groups displayed significant (p < 0.05), dose-dependent efficacy for all primary endpoints in Part I; efficacy was maintained throughout the 52 weeks of the study. During the 46-week active-comparator controlled period, the etoricoxib groups demonstrated clinical efficacy that was similar to that of diclofenac 150 mg and was generally well tolerated, with a lower incidence of gastrointestinal (GI) nuisance symptoms compared with diclofenac (13.1, 14.7, and 13.5% for etoricoxib 30, 60, and 90 mg, respectively compared with 22.5% for diclofenac). CONCLUSION: In this extension study, etoricoxib, at doses ranging from 30 to 90 mg, demonstrated a maintenance of significant clinical efficacy in patients with OA through 52 weeks of treatment. Etoricoxib displayed clinical efficacy similar to diclofenac 150 mg and was generally well tolerated

Diabetes prevalence is associated with serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in US middle-aged Caucasian men and women: a cross-sectional analysis within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

Hypovitaminosis D may be associated with diabetes, hypertension and CHD. However, because studies examining the associations of all three chronic conditions with circulating 25-hydroxyvitamin D (25(0H)D) and 1,25-dihydroxyvitamin D (1,25(0H)2D) are limited, we examined these associations in the US Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial (n 2465). Caucasian PLCO participants selected as controls in previous nested case-control studies of 25(0H)D and 1,25(0H)2D were included in this analysis. Diabetes, CHD and hypertension prevalence, risk factors for these conditions and intake of vitamin D and Ca were collected from a baseline questionnaire. Results indicated that serum levels of 25(0H)D were low (\u3c50nmol/1) in 29% and very low ( \u3c 37nmol/1) in 11% of subjects. The prevalence of diabetes, hypertension and CHD was 7, 30 and 10%, respectively. After adjustment for confounding by sex, geographical location, educational level, smoking history, BMI, physical activity, total dietary energy and vitamin D and Ca intake, only diabetes was significantly associated with lower 25(0H)D and 1,25(0H)2D levels. Caucasians who had 25(0H)D 2:80nmol/1 were half as likely to have diabetes (OR 0·5 (95% Cl 0·3, 0·9)) compared with those who had 25(0H)D /l. Those in the highest quartile of 1,25(0H)2D (/1) were less than half as likely to have diabetes (OR 0·3 (95% Cl 0·1, 0·7)) than those in the lowest quartile (\u3c 72pmol/l). In conclusion, the independent associations of 25(0H)D and 1,25(0H)2D with diabetes prevalence in a large population are new findings, and thus warrant confirmation in larger, prospective studies

Drug-gene interactions of antihypertensive medications and risk of incident cardiovascular disease: a pharmacogenomics study from the CHARGE consortium

Background Hypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals. Methods Using a genome-wide association study among 21,267 participants with pharmaceutically treated hypertension, we explored the hypothesis that genetic variants might influence or modify the effectiveness of common antihypertensive therapies on the risk of major cardiovascular outcomes. The classes of drug treatments included angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, each study performed array-based genome-wide genotyping, imputed to HapMap Phase II reference panels, and used additive genetic models in proportional hazards or logistic regression models to evaluate drug-gene interactions for each of four therapeutic drug classes. We used meta-analysis to combine study-specific interaction estimates for approximately 2 million single nucleotide polymorphisms (SNPs) in a discovery analysis among 15,375 European Ancestry participants (3,527 CVD cases) with targeted follow-up in a case-only study of 1,751 European Ancestry GenHAT participants as well as among 4,141 African-Americans (1,267 CVD cases). Results Although drug-SNP interactions were biologically plausible, exposures and outcomes were well measured, and power was sufficient to detect modest interactions, we did not identify any statistically significant interactions from the four antihypertensive therapy meta-analyses (Pinteraction &gt; 5.0×10−8). Similarly, findings were null for meta-analyses restricted to 66 SNPs with significant main effects on coronary artery disease or blood pressure from large published genome-wide association studies (Pinteraction ≥ 0.01). Our results suggest that there are no major pharmacogenetic influences of common SNPs on the relationship between blood pressure medications and the risk of incident CVD

The Lantern Vol. 34, No. 2, May 1968

• The Man Without a System • A Medal for Malcolm • On Hearing That Tonya Will Be Married • The Black Sea • Odyssey \u2767 • Second Poem to Chris • Singularity • Period 5-A Began • Long and Aching Ride • Souvenirs • My Eschatological Epitaph • Discotheque • Some Borrowed Words • False Breakthrough • Shore Morning • The Beholder • Thursday Childless • A Most Prominent Role • It Ran Out • Shades of the Living • The Dark Night of the Mind II • One Step Beyond the Doors • A Note of Thanks to My Parents and Teachers • To a Dead Hippie • A Scrap • Love • Haiku No. 30 • Rachel • There Is No Present • Winter Woods • One Hundred Per Cent Genuine • Heaven • Silence Is Like God • I Soaked Up Silence • Opened Letter From Whistler Homer, Insaned Assailant • Sol Clutch Rides Tonight • I Have Seen Destruction • Upon That Night • That\u27s Weird • Alone • Kathy\u27s Tune • On Walking Home • The Wheel • Some Excuse, at Least • Freedom to Flap • Awareness • Okay, You Guys • You Say You Dream • Bacci Miahttps://digitalcommons.ursinus.edu/lantern/1093/thumbnail.jp

Cognitive Information Processing

Contains research objectives and summary of research on fourteen research projects and reports on four research projects.Joint Services Electronics Program (Contract DAAB07-75-C-1346)National Science Foundation (Grant EPP74-12653)National Science Foundation (Grant ENG74-24344)National Institutes of Health (Grant 2 PO1 GM19428-04)Swiss National Funds for Scientific ResearchM.I.T. Health Sciences Fund (Grant 76-11)National Institutes of Health (Grant F03 GM58698)National Institutes of Health (Biomedical Sciences Support Grant)Associated Press (Grant

A planned, prospective comparison of short-term quality of life outcomes among older patients with breast cancer treated with standard chemotherapy in a randomized clinical trial vs. an observational study: CALGB #49907 and #369901

Patients ≥65 years old (“older”) are often not included in randomized clinical trials (RCT), but when they are, care in an RCT might improve quality of life (QoL). We conducted a prospective comparison of QoL among older women receiving standard chemotherapy from the same cooperative group physicians in an RCT vs. an observational study (“off-trial”)

A review of gene-drug interactions for nonsteroidal anti-inflammatory drug use in preventing colorectal neoplasia.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to be effective chemopreventive agents for colorectal neoplasia. Polymorphisms in NSAID targets or metabolizing enzymes may affect NSAID efficacy or toxicity. We conducted a literature review to summarize current evidence of gene-drug interactions between NSAID use and polymorphisms in COX1, COX2, ODC, UGT1A6 and CYP2C9 on risk of colorectal neoplasia by searching OVID and PubMed. Of 134 relevant search results, thirteen investigated an interaction. One study reported a significant interaction between NSAID use and the COX1 Pro17Leu polymorphism (P=0.03) whereby the risk reduction associated with NSAID use among homozygous wild-type genotypes was not observed among NSAID users with variant alleles. Recent pharmacodynamic data support the potential for gene-drug interactions for COX1 Pro17Leu. Statistically significant interactions have also been reported for ODC (315G>A), UGT1A6 (Thr181Ala+Arg184Ser or Arg184Ser alone), and CYP2C9 (*2/*3). No statistically significant interactions have been reported for polymorphisms in COX2; however, an interaction with COX2 -765G>C approached significance (P=0.07) in one study. Among seven remaining studies, reported interactions were not statistically significant for COX1, COX2 and ODC gene polymorphisms. Most studies were of limited sample size. Definitions of NSAID use differed substantially between studies. The literature on NSAID-gene interactions to date is limited. Reliable detection of gene-NSAID interactions will require greater sample sizes, consistent definitions of NSAID use and evaluation of clinical trial subjects of chemoprevention studies