Person:

Mukamal, Kenneth

Plasma fibrinogen is an acute phase protein playing an important role in the blood coagulation cascade having strong associations with smoking, alcohol consumption and body mass index (BMI). Genome-wide association studies (GWAS) have identified a variety of gene regions associated with elevated plasma fibrinogen concentrations. However, little is yet known about how associations between environmental factors and fibrinogen might be modified by genetic variation. Therefore, we conducted large-scale meta-analyses of genome-wide interaction studies to identify possible interactions of genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentration. The present study included 80,607 subjects of European ancestry from 22 studies. Genome-wide interaction analyses were performed separately in each study for about 2.6 million single nucleotide polymorphisms (SNPs) across the 22 autosomal chromosomes. For each SNP and risk factor, we performed a linear regression under an additive genetic model including an interaction term between SNP and risk factor. Interaction estimates were meta-analysed using a fixed-effects model. No genome-wide significant interaction with smoking status, alcohol consumption or BMI was observed in the meta-analyses. The most suggestive interaction was found for smoking and rs10519203, located in the LOC123688 region on chromosome 15, with a p value of 6.2×10−8. This large genome-wide interaction study including 80,607 participants found no strong evidence of interaction between genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentrations. Further studies are needed to yield deeper insight in the interplay between environmental factors and gene variants on the regulation of fibrinogen concentrations.

Background: Recent studies have found low-normal potassium (K) to be associated with increased diabetes risk. We sought to verify these associations in a multi-ethnic US cohort; and to determine if these associations extend to US Hispanics and Asian-Americans. Methods: We analyzed data from Multi-Ethnic Study of Atherosclerosis (MESA) participants who were free-of-diabetes at baseline. We examined cross-sectional associations between measures of K—serum, dietary, and urine—with fasting glucose and HOMA-IR. We examined longitudinal associations between K and diabetes risk over 8 years. Findings: In multivariable models, compared to those with higher serum K (≥4.5mmol/L), those with lower serum K (<4.0mmol/L) had significantly higher fasting glucose [1.3 mg/dL (95%CI 0.2, 2.4), P-value = 0.03]. Incident diabetes developed in 1281 of 5415 at-risk participants. In minimally-adjusted models, we found inverse associations between serum and dietary K and diabetes risk. Compared to those with higher serum K, those with lower serum K had an HR (95% CI) of incident diabetes of 1.23 (1.04, 1.47), P-value = 0.02. However, these associations were attenuated in fully-adjusted models. We found no significant interaction between potassium and ethnicity. Conclusions: In this multi-ethnic cohort, we found a significant inverse association between serum K and fasting glucose but no significant association with longer-term diabetes risk. This inverse association between potassium and glucose must be studied further to understand the physiology and its potential impact on chronic health.

Background: Spaced education is a novel method that improves medical education through online repetition of core principles often paired with multiple-choice questions. This model is a proven teaching tool for medical students, but its effect on resident learning is less established. We hypothesized that repetition of key clinical concepts in a “Clinical Pearls” format would improve knowledge retention in medical residents. Methods: This study investigated spaced education with particular emphasis on using a novel, email-based reinforcement program, and a randomized, self-matched design, in which residents were quizzed on medical knowledge that was either reinforced or not with electronically-administered spaced education. Both reinforced and non-reinforced knowledge was later tested with four quizzes. Results: Overall, respondents incorrectly answered 395 of 1008 questions (0.39; 95% CI, 0.36–0.42). Incorrect response rates varied by quiz (range 0.34–0.49; p = 0.02), but not significantly by post-graduate year (PGY1 0.44, PGY2 0.33, PGY3 0.38; p = 0.08). Although there was no evidence of benefit among residents (RR = 1.01; 95% CI, 0.83–1.22; p = 0.95), we observed a significantly lower risk of incorrect responses to reinforced material among interns (RR = 0.83, 95% CI, 0.70–0.99, p = 0.04). Conclusions: Overall, repetition of Clinical Pearls did not statistically improve test scores amongst junior and senior residents. However, among interns, repetition of the Clinical Pearls was associated with significantly higher test scores, perhaps reflecting their greater attendance at didactic sessions and engagement with Clinical Pearls. Although the study was limited by a low response rate, we employed test and control questions within the same quiz, limiting the potential for selection bias. Further work is needed to determine the optimal spacing and content load of Clinical Pearls to maximize retention amongst medical residents. This particular protocol of spaced education, however, was unique and readily reproducible suggesting its potential efficacy for intern education within a large residency program.