Weight-loss interventions generally improve lipid profiles and reduce cardiovascular disease risk, but effects are variable and may depend on genetic factors. We performed a genetic association analysis of data from 2,993 participants in the Diabetes Prevention Program to test the hypotheses that a genetic risk score (GRS) based on deleterious alleles at 32 lipid-associated single-nucleotide polymorphisms modifies the effects of lifestyle and/or metformin interventions on lipid levels and nuclear magnetic resonance (NMR) lipoprotein subfraction size and number. Twenty-three loci previously associated with fasting LDL-C, HDL-C, or triglycerides replicated (P = 0.04–1×10−17). Except for total HDL particles (r = −0.03, P = 0.26), all components of the lipid profile correlated with the GRS (partial |r| = 0.07–0.17, P = 5×10−5–1×10−19). The GRS was associated with higher baseline-adjusted 1-year LDL cholesterol levels (β = +0.87, SEE±0.22 mg/dl/allele, P = 8×10−5, P interaction = 0.02) in the lifestyle intervention group, but not in the placebo (β = +0.20, SEE±0.22 mg/dl/allele, P = 0.35) or metformin (β = −0.03, SEE±0.22 mg/dl/allele, P = 0.90; P interaction = 0.64) groups. Similarly, a higher GRS predicted a greater number of baseline-adjusted small LDL particles at 1 year in the lifestyle intervention arm (β = +0.30, SEE±0.012 ln nmol/L/allele, P = 0.01, P interaction = 0.01) but not in the placebo (β = −0.002, SEE±0.008 ln nmol/L/allele, P = 0.74) or metformin (β = +0.013, SEE±0.008 nmol/L/allele, P = 0.12; P interaction = 0.24) groups. Our findings suggest that a high genetic burden confers an adverse lipid profile and predicts attenuated response in LDL-C levels and small LDL particle number to dietary and physical activity interventions aimed at weight loss.

Determine whether the use of a metronome improves chest compression rate and depth during cardiopulmonary resuscitation (CPR) on a pediatric manikin.METHODS: A prospective, simulation-based, crossover, randomized controlled trial was conducted. Participants included pediatric residents, fellows, nurses, and medical students who were randomly assigned to perform chest compressions on a pediatric manikin with and without an audible metronome. Each participant performed 2 rounds of 2 minutes of chest compressions separated by a 15-minute break.RESULTS: A total of 155 participants performed 2 rounds of chest compressions (74 with the metronome on during the first round and 81 with the metronome on during the second round of CPR). There was a significant improvement in the mean percentage of compressions delivered within an adequate rate (90-100 compressions per minute) with the metronome on compared with off (72% vs 50%; mean difference [MD] 22%; 95% confidence interval [CI], 15% to 29%). No significant difference was noted in the mean percentage of compressions within acceptable depth (38-51 mm) (72% vs 70%; MD 2%; 95% CI, 22% to 6%). The metronome had a larger effect among medical students (73% vs 55%; MD 18%; 95% CI, 8% to 28%) and pediatric residents and fellows (84% vs 48%; MD 37%; 95% CI, 27% to 46%) but not among pediatric nurses (46% vs 48%; MD 23%; 95% CI, 219% to 14%). CONCLUSIONS:The rate of chest compressions during CPR can be optimized by the use of a metronome. These findings will help medical professionals comply with the American Heart Association guidelines. WHAT'S KNOWN ON THIS SUBJECT:The frequency of cardiac arrest is significantly lower in children than in adults, rendering the delivery of high-quality cardiopulmonary resuscitation more difficult. Metronome-based studies in adults showed improvement in adequate compression rate, with a detrimental effect on the depth of chest compressions. WHAT THIS STUDY ADDS:This is the first pediatric study to confirm that the use of a metronome during cardiopulmonary resuscitation significantly improves the delivery of adequate rate without affecting the compression depth. This effect was more prominent among medical students and pediatric residents and fellows than nurses. Dr Zimmerman conceptualized and designed the study, coordinated and supervised data collection, carried out the initial analysis, and drafted the initial manuscript; Dr Cohen coordinated and supervised data collection, carried out the initial analysis, and drafted the initial manuscript; Drs Maniaci, Pena, and Linares carried out initial analysis and reviewed and revised the manuscript; Dr Lozano provided statistical advice on the study design, carried out initial analysis, and reviewed and revised the manuscript; and all authors approved the final manuscript as submitted.This trial has been registered at www.clinicaltrials.gov (identifier NCT02511470). 4 Poor-quality cardiopulmonary resuscitation (CPR) has been cited as a contributing factor to this dismal statistic on outcomes. 4 Optim...

Across the Diabetes Prevention Program (DPP) follow-up, cumulative diabetes incidence remained lower in the lifestyle compared with the placebo and metformin randomized groups and could not be explained by weight. Collection of self-reported physical activity (PA) (yearly) with cross-sectional objective PA (in follow-up) allowed for examination of PA and its long-term impact on diabetes prevention. RESEARCH DESIGN AND METHODS Yearly self-reported PA and diabetes assessment and oral glucose tolerance test results (fasting glucose semiannually) were collected for 3,232 participants with one accelerometry assessment 11-13 years after randomization (n 5 1,793). Mixed models determined PA differences across treatment groups. The association between PA and diabetes incidence was examined using Cox proportional hazards models. RESULTS There was a 6% decrease (Cox proportional hazard ratio 0.94 [95% CI 0.92, 0.96]; P < 0.001) in diabetes incidence per 6 MET-h/week increase in time-dependent PA for the entire cohort over an average of 12 years (controlled for age, sex, baseline PA, and weight). The effect of PA was greater (12% decrease) among participants less active at baseline (<7.5 MET-h/week) (n 5 1,338) (0.88 [0.83, 0.93]; P < 0.0001), with stronger findings for lifestyle participants. Lifestyle had higher cumulative PA compared with metformin or placebo (P < 0.0001) and higher accelerometry total minutes per day measured during follow-up (P 5 0.001 and 0.047). All associations remained significant with the addition of weight in the models. CONCLUSIONS PA was inversely related to incident diabetes in the entire cohort across the study, with cross-sectional accelerometry results supporting these findings. This highlights the importance of PA within lifestyle intervention efforts designed to prevent diabetes and urges health care providers to consider both PA and weight when counseling high-risk patients.

Prior research suggests that the Type A behavior pattern, Cook and Medley Hostility (Ho) scores, and Total Serum Cholesterol (TSC) are positively associated with physiological changes to behavioral stressors. The objective of the present study was to determine whether TSC interacts with the Type A behavior pattern and hostility to affect cardiovascular and neurohormonal responses to a mental arithmetic task (MATH). For Type A individuals, elevated TSC was associated with larger catecholamine and cortisol responses to MATH. In contrast, for Type B subjects, cholesterol was negatively associated with neurohormonal responses. The interaction between Ho score and TSC predicted a similar pattern of responses whereby, in high hostile men only, TSC was positively associated with MATH-induced changes in catecholamines and heart rate. While the mechanisms responsible for the differences in the lipid-reactivity association as a function of coronary-prone behavior measures remain to be elucidated, this differential association may play a role in the heightened risk of coronary disease among hostile Type A men.