Background: Studies report high burnout prevalence among resident physicians, with little consensus on methods to effectively reduce it. Objective: This systematic literature review explores the efficacy of interventions in reducing resident burnout. Methods: PubMed, Embase, and Web of Science were searched using these key words: burnout and resident, intern, or residency. We excluded review articles, editorials, letters, and non–English-language articles. We abstracted data on study characteristics, population, interventions, and outcomes. When appropriate, data were pooled using random effects meta-analysis to account for between-study heterogeneity. Study quality was assessed using Newcastle-Ottawa Scale (cohort studies) and Jadad scale (randomized control trials [RCTs]). Results: Of 1294 retrieved articles, 19 (6 RCTs, 13 cohort studies) enrolling 2030 residents and examining 12 interventions met criteria, with 9 studying the 2003 and 2011 Accreditation Council for Graduate Medical Education (ACGME) duty hour restrictions. Work hour reductions were associated with score decrease (mean difference, −2.73; 95% confidence interval (CI) −4.12 to −1.34; P < .001) and lower odds ratio (OR) for residents reporting emotional exhaustion (42%; OR = 0.58; 95% CI 0.43–0.77; P < .001); a small, significant decrease in depersonalization score (−1.73; 95% CI −3.00 to −0.46; P = .008); and no effect on mean personal accomplishment score (0.93; 95% CI −0.19–2.06; P = .10) or for residents with high levels of personal accomplishment (OR = 1.01; 95% CI 0.67–1.54; P = .95). Among interventions, self-care workshops showed decreases in depersonalization scores, and a meditation intervention reduced emotional exhaustion. Conclusions: The ACGME work hour limits were associated with improvement in emotional exhaustion and burnout.

Autonomic imbalance, a feature of both diabetes and hypertension, may contribute to adverse cardiovascular outcomes. In animal models, sympathetic nerve activity contributes to renal damage but the extent to which autonomic dysfunction precedes the development of CKD and ESRD in humans is unknown. We measured resting heart rate and heart rate variability in 13,241 adults (45- to 64-years old) followed for a median of 16 years in the Atherosclerosis Risk in Communities (ARIC) Study. We examined heart rate parameters by quartiles, defining those in the lowest quartile (by time and frequency domain measures separately) as the risk group of interest. We identified 199 cases of incident ESRD and 541 patients with CKD-related hospitalizations; higher resting heart rate and lower heart rate variability associated with both outcomes. The fully adjusted hazard ratios for ESRD were 1.98 (95% confidence interval [CI] 1.45 to 2.70) among those in the highest heart rate quartile and 1.56 (95% CI 1.14 to 2.14) for high-frequency power. Other time and frequency domain measures were similarly and significantly associated with ESRD and CKD-related hospitalizations. These results suggest that autonomic dysfunction may be an important risk factor for ESRD and CKD-related hospitalizations and call for further studies to define the mechanisms that underlie these associations.

Several genetic variants associated with platelet count and mean platelet volume (MPV) were recently reported in people of European ancestry. In this meta-analysis of 7 genome-wide association studies (GWAS) enrolling African Americans, our aim was to identify novel genetic variants associated with platelet count and MPV. For all cohorts, GWAS analysis was performed using additive models after adjusting for age, sex, and population stratification. For both platelet phenotypes, meta-analyses were conducted using inverse-variance weighted fixed-effect models. Platelet aggregation assays in whole blood were performed in the participants of the GeneSTAR cohort. Genetic variants in ten independent regions were associated with platelet count (N = 16,388) with p<5×10⁻⁸ of which 5 have not been associated with platelet count in previous GWAS. The novel genetic variants associated with platelet count were in the following regions (the most significant SNP, closest gene, and p-value): 6p22 (rs12526480, LRRC16A, p = 9.1×10⁻⁹), 7q11 (rs13236689, CD36, p = 2.8×10⁻⁹), 10q21 (rs7896518, JMJD1C, p = 2.3×10⁻¹²), 11q13 (rs477895, BAD, p = 4.9×10⁻⁸), and 20q13 (rs151361, SLMO2, p = 9.4×10⁻⁹). Three of these loci (10q21, 11q13, and 20q13) were replicated in European Americans (N = 14,909) and one (11q13) in Hispanic Americans (N = 3,462). For MPV (N = 4,531), genetic variants in 3 regions were significant at p<5×10⁻⁸, two of which were also associated with platelet count. Previously reported regions that were also significant in this study were 6p21, 6q23, 7q22, 12q24, and 19p13 for platelet count and 7q22, 17q11, and 19p13 for MPV. The most significant SNP in 1 region was also associated with ADP-induced maximal platelet aggregation in whole blood (12q24). Thus through a meta-analysis of GWAS enrolling African Americans, we have identified 5 novel regions associated with platelet count of which 3 were replicated in other ethnic groups. In addition, we also found one region associated with platelet aggregation that may play a potential role in atherothrombosis. The majority of the variation in platelet count and mean platelet volume between individuals is heritable. We performed genome-wide association studies in more than 16,000 African American participants from seven population-based cohorts to identify genetic variants that correlate with variation in platelet count and mean platelet volume. We observed statistically significant evidence (p-value<5×10⁻⁸) that 10 genomic regions were associated with platelet count and 3 were associated with mean platelet volume. Of the regions that were significantly associated, we found 5 novel regions that were not reported previously in other populations. Three of these 5 regions were also associated with platelet count in European Americans and Hispanic Americans. All these regions contain genes that are either known to have or potentially may have a role in determining platelet count and/or mean platelet volume. We further found that one of these regions was also associated with agonist-induced platelet aggregation. Further studies will determine the exact role played by these genomic regions in platelet biology. The knowledge generated by this and other studies will not only help us better understand platelet biology but can also lead us to the discovery of new anti-platelet drugs.

Genetic variation is thought to contribute to variability in platelet function; however, the specific variants and mechanisms that contribute to altered platelet function are poorly defined. With the use of a combination of fine mapping and sequencing of the platelet endothelial aggregation receptor 1 (PEAR1) gene we identified a common variant (rs12041331) in intron 1 that accounts for ≤ 15% of total phenotypic variation in platelet function. Association findings were robust in 1241 persons of European ancestry (P = 2.22 × 10⁻⁸) and were replicated down to the variant and nucleotide level in 835 persons of African ancestry (P = 2.31 × 10⁻²⁷) and in an independent sample of 2755 persons of European descent (P = 1.64 × 10⁻⁵). Sequencing confirmed that variation at rs12041331 accounted most strongly (P = 2.07 × 10⁻⁶) for the relation between the PEAR1 gene and platelet function phenotype. A dose-response relation between the number of G alleles at rs12041331 and expression of PEAR1 protein in human platelets was confirmed by Western blotting and ELISA. Similarly, the G allele was associated with greater protein expression in a luciferase reporter assay. These experiments identify the precise genetic variant in PEAR1 associated with altered platelet function and provide a plausible biologic mechanism to explain the association between variation in the PEAR1 gene and platelet function phenotype.