An ADH1B variant and peer drinking in progression to adolescent drinking milestones: Evidence of a gene-by-environment interaction

BACKGROUND: Adolescent drinking is an important public health concern, one that is influenced by both genetic and environmental factors. The functional variant rs1229984 in alcohol dehydrogenase 1B (ADH1B) has been associated at a genome-wide level with alcohol use disorders in diverse adult populations. However, few data are available regarding whether this variant influences early drinking behaviors and whether social context moderates this effect. This study examines the interplay between rs1229984 and peer drinking in the development of adolescent drinking milestones. METHODS: One thousand five hundred and fifty European and African American individuals who had a full drink of alcohol before age 18 were selected from a longitudinal study of youth as part of the Collaborative Study on the Genetics of Alcoholism (COGA). Cox proportional hazards regression, with G × E product terms in the final models, was used to study 2 primary outcomes during adolescence: age of first intoxication and age of first DSM-5 alcohol use disorder symptom. RESULTS: The minor A allele of rs1229984 was associated with a protective effect for first intoxication (HR = 0.56, 95% CI 0.41 to 0.76) and first DSM-5 symptom (HR = 0.45, 95% CI 0.26 to 0.77) in the final models. Reporting that most or all best friends drink was associated with a hazardous effect for first intoxication (HR = 1.81, 95% CI 1.62 to 2.01) and first DSM-5 symptom (HR = 2.17, 95% 1.88 to 2.50) in the final models. Furthermore, there was a significant G × E interaction for first intoxication (p = 0.002) and first DSM-5 symptom (p = 0.01). Among individuals reporting none or few best friends drinking, the ADH1B variant had a protective effect for adolescent drinking milestones, but for those reporting most or all best friends drinking, this effect was greatly reduced. CONCLUSIONS: Our results suggest that the risk factor of best friends drinking attenuates the protective effect of a well-established ADH1B variant for 2 adolescent drinking behaviors. These findings illustrate the interplay between genetic and environmental factors in the development of drinking milestones during adolescence

Neighborhood Socioeconomic Status and Outcomes Following the Norwood Procedure: An Analysis of the Pediatric Heart Network Single Ventricle Reconstruction Trial Public Data Set

Background: Children with single ventricle heart disease require frequent interventions and follow‐up. Low socioeconomic status (SES) may limit access to high‐quality care and place these children at risk for poor long‐term outcomes. Methods and Results: Data from the SVR (Pediatric Heart Network Single Ventricle Reconstruction Trial Public Use) data set were used to examine the relationship of US neighborhood SES with 30‐day and 1‐year mortality or cardiac transplantation and length of stay among neonates undergoing the Norwood procedure (n=525). Crude rates of death or transplantation at 1 year after Norwood were highest for patients living in neighborhoods with low SES (lowest tertile 37.0% versus middle tertile 31.0% versus highest tertile 23.6%, P=0.024). After adjustment for patient demographics, birth characteristics, and anatomy, patients in the highest SES tertile had significantly lower risk of death or transplant than patients in the lowest SES tertile (hazard ratio 0.62, 95% confidence interval, 0.40, 0.96). When SES was examined continuously, the hazard of 1‐year death or transplant decreased steadily with increasing neighborhood SES. Hazard ratios for 30‐day transplant‐free survival and 1‐year transplant‐free survival were similar in magnitude. There were no significant differences in length of stay following the Norwood procedure by SES. Conclusions: Low neighborhood SES is associated with worse 1‐year transplant‐free survival after the Norwood procedure, suggesting that socioeconomic and environmental factors may be important determinants of outcome in critical congenital heart disease. Future studies should investigate aspects of SES and environment amenable to intervention. Clinical Trial Registration URL:http://www.clinicaltrials.gov> http://www.clinicaltrials.gov. Unique identifier: NCT00115934

Underweight, Markers of Cachexia, and Mortality in Acute Myocardial Infarction: A Prospective Cohort Study of Elderly Medicare Beneficiaries

<div><p>Background</p><p>Underweight patients are at higher risk of death after acute myocardial infarction (AMI) than normal weight patients; however, it is unclear whether this relationship is explained by confounding due to cachexia or other factors associated with low body mass index (BMI). This study aimed to answer two questions: (1) does comprehensive risk adjustment for comorbid illness and frailty measures explain the higher mortality after AMI in underweight patients, and (2) is the relationship between underweight and mortality also observed in patients with AMI who are otherwise without significant chronic illness and are presumably free of cachexia?</p><p>Methods and Findings</p><p>We analyzed data from the Cooperative Cardiovascular Project, a cohort-based study of Medicare beneficiaries hospitalized for AMI between January 1994 and February 1996 with 17 y of follow-up and detailed clinical information to compare short- and long-term mortality in underweight and normal weight patients (<i>n</i> = 57,574). We used Cox proportional hazards regression to investigate the association of low BMI with 30-d, 1-y, 5-y, and 17-y mortality after AMI while adjusting for patient comorbidities, frailty measures, and laboratory markers of nutritional status. We also repeated the analyses in a subset of patients without significant comorbidity or frailty.</p><p>Of the 57,574 patients with AMI included in this cohort, 5,678 (9.8%) were underweight and 51,896 (90.2%) were normal weight at baseline. Underweight patients were older, on average, than normal weight patients and had a higher prevalence of most comorbidities and measures of frailty. Crude mortality was significantly higher for underweight patients than normal weight patients at 30 d (25.2% versus 16.4%, <i>p <</i> 0.001), 1 y (51.3% versus 33.8%, <i>p <</i> 0.001), 5 y (79.2% versus 59.4%, <i>p <</i> 0.001), and 17 y (98.3% versus 94.0%, <i>p <</i> 0.001). After adjustment, underweight patients had a 13% higher risk of 30-d death and a 26% higher risk of 17-y death than normal weight patients (30-d hazard ratio [HR] 1.13, 95% CI 1.07–1.20; 17-y HR 1.26, 95% CI 1.23–1.30). Survival curves for underweight and normal weight patients separated early and remained separate over 17 y, suggesting that underweight patients remained at a significant survival disadvantage over time. Similar findings were observed among the subset of patients without comorbidity at baseline. Underweight patients without comorbidity had a 30-d adjusted mortality similar to that of normal weight patients but a 21% higher risk of death over the long term (30-d HR 1.08, 95% CI 0.93–1.26; 17-y HR 1.21, 95% CI 1.14–1.29). The adverse effects of low BMI were greatest in patients with very low BMIs. The major limitation of this study was the use of surrogate markers of frailty and comorbid conditions to identify patients at highest risk for cachexia rather than clear diagnostic criteria for cachexia.</p><p>Conclusions</p><p>Underweight BMI is an important risk factor for mortality after AMI, independent of confounding by comorbidities, frailty measures, and laboratory markers of nutritional status. Strategies to promote weight gain in underweight patients after AMI are worthy of testing.</p></div

Life Years Gained From Smoking-Cessation Counseling After Myocardial Infarction

INTRODUCTION: Hospitalization for acute myocardial infarction (AMI) is an opportune time to counsel smokers to quit. Studies have demonstrated lower short-term mortality for counseled versus non-counseled smokers; yet, little is known about the long-term survival benefits of post-AMI smoking-cessation counseling (SCC). METHODS: Data from the Cooperative Cardiovascular Project, a prospective cohort study of elderly patients with AMI between 1994 and 1996 with \u3e17 years of follow-up, were used to evaluate the association of SCC with short- and long-term mortality in smokers with AMI. Life expectancy and years of potential life gained were used to quantify the long-term survival benefits of SCC. Cox proportional hazards models with exponential extrapolation were used to estimate life expectancy. RESULTS: The analysis included 13,815 smokers, of whom 5,695 (41.2%) received SCC. Non-counseled smokers had higher crude mortality than counseled smokers over all 17 years of follow-up. After adjustment for patient and hospital characteristics, SCC was associated with a 22.6% lower 30-day mortality and a 7.5% lower mortality over 17 years. These survival differences produced higher life expectancy estimates for counseled smokers than non-counseled smokers at all ages, which resulted in average gains in life years of 0.13 (95% CI=-0.31, 0.56) to 0.58 (95% CI=0.25, 0.91) years, with the largest gains observed in older smokers. CONCLUSIONS: SCC is associated with longer life expectancy and gains in life years in elderly smokers with AMI, supporting the importance of post-AMI counseling efforts

Adjusting for Social Risk Factors in Pediatric Quality Measures: Adding to the Evidence Base.

BackgroundOutcome and utilization quality measures are adjusted for patient case-mix including demographic characteristics and comorbid conditions to allow for comparisons between hospitals and health plans. However, controversy exists around whether and how to adjust for social risk factors.ObjectiveTo assess an approach to incorporating social risk variables into a pediatric measure of utilization from the Pediatric Quality Measures Program (PQMP).MethodsWe used data from California Medicaid claims (2015-16) and Massachusetts All Payer Claims Database (2014-2015) to calculate health plan performance using measure specifications from the Pediatric Asthma Emergency Department Use measure. Health plan performance categories were assessed using mixed effect negative binomial models with and without adjustment for social risk factors, with both models adjusting for age, gender and chronic condition category. Mixed effects linear models were then used to compare patient social risk for health plans that changed performance categories to patient social risk for health plans that did not.ResultsOf 133 health plans, serving 404,649 pediatric patients with asthma, 7% to 13% changed performance categories after social risk adjustment. Health plans that moved to higher performance categories cared for lower socioeconomic status (SES) patients whereas those that moved to lower performance categories cared for higher SES patients.ConclusionsAdjustment for social risk factors changed performance rankings on the PQMP Pediatric Asthma Emergency Department Use measure for a substantial number of health plans. Some health plans caring for higher risk patients performed more poorly when social risk factors were not included in risk adjustment models. In light of this, social risk factors are incorporated into the National Quality Forum-endorsed measure; whether to incorporate social risk factors into pediatric quality measures will differ depending on the use case

Smoking status and life expectancy after acute myocardial infarction in the elderly

OBJECTIVE: Smokers have lower short-term mortality after acute myocardial infarction (AMI) than non-smokers; however, little is known about the long-term effects of smoking on life expectancy after AMI. This study aimed to quantify the burden of smoking after AMI using life expectancy and years of life lost. METHODS: We analysed data from the Cooperative Cardiovascular Project, a medical record study of 158 349 elderly Medicare patients with AMI and over 17 years of follow-up, to evaluate the age-specific association of smoking with life expectancy and years of life lost after AMI. RESULTS: Our sample included 23 447 (14.8%) current smokers. Current smokers had lower crude mortality up to 5 years, which was largely explained by their younger age at AMI. After adjustment other patient characteristics, smoking was associated with lower 30-day (HR 0.91, 95% CI 0.87 to 0.94) but higher long-term mortality (17-year HR 1.19, 95% CI 1.17 to 1.20) after AMI. Overall, crude life expectancy estimates were lower for current smokers than non-smokers at all ages, which translated into sizeable numbers of life-years lost attributable to smoking. As age at AMI increased, the magnitude of life-years lost due to smoking decreased. After full risk adjustment, the differences in life expectancy between current smokers and non-smokers persisted at all ages. CONCLUSIONS: Current smoking is associated with lower life expectancy and large numbers of life-years lost after AMI. Our findings lend additional support to smoking cessation efforts after AMI