RESUMEN
BACKGROUND: Burnout among postgraduate medical trainees (PMTs) is increasingly being recognized as a crisis in the medical profession. We aimed to establish the prevalence of burnout among PMTs, identify risk and protective factors, and assess whether burnout varied by country of training, year of study and specialty of practice. METHODS: We systematically searched MEDLINE, Embase, PsycINFO, the Cochrane Database of Systematic Reviews, Web of Science and Education Resources Information Center from their inception to Aug. 21, 2018, for studies of burnout among PMTs. The primary objective was to identify the global prevalence of burnout among PMTs. Our secondary objective was to evaluate the association between burnout and country of training, year of study, specialty of training and other sociodemographic factors commonly thought to be related to burnout. We employed random-effects meta-analysis and meta-regression techniques to estimate a pooled prevalence and conduct secondary analyses. RESULTS: In total, 8505 published studies were screened, 196 met eligibility and 114 were included in the meta-analysis. The pooled prevalence of burnout was 47.3% (95% confidence interval 43.1% to 51.5%), based on studies published over 20 years involving 31 210 PMTs from 47 countries. The prevalence of burnout remained unchanged over the past 2 decades. Burnout varied by region, with PMTs of European countries experiencing the lowest level. Burnout rates among medical and surgical PMTs were similar. INTERPRETATION: Current wellness efforts and policies have not changed the prevalence of burnout worldwide. Future research should focus on understanding systemic factors and leveraging these findings to design interventions to combat burnout. STUDY REGISTRATION: PROSPERO no. CRD42018108774.
Asunto(s)
Agotamiento Profesional/epidemiología , Internado y Residencia , África/epidemiología , Asia/epidemiología , Australia/epidemiología , Europa (Continente)/epidemiología , Humanos , Satisfacción en el Trabajo , Medio Oriente/epidemiología , América del Norte/epidemiología , Admisión y Programación de Personal , Prevalencia , Factores Protectores , Factores de Riesgo , América del Sur/epidemiologíaRESUMEN
The adipocyte-derived adiponectin hormone bridges obesity and its cardio-metabolic complications. Genetic variants at the ADIPOQ locus, in ADIPOR1, and ADIPOR2 have been associated with adiponectin concentrations and cardio-metabolic complications in diverse ethnicities. However, no studies have examined these associations in Mexican children. We recruited 1 457 Mexican children from Mexico City. Six genetic variants in or near ADIPOQ (rs182052, rs2241766, rs266729, rs822393), ADIPOR1 (rs10920533), and ADIPOR2 (rs11061971) were genotyped. Associations between serum adiponectin, genetic variants, and cardio-metabolic traits were assessed using linear and logistic regressions adjusted for age, sex, and recruitment center. Serum adiponectin concentration was negatively associated with body mass index, waist to hip ratio, low-density lipoprotein cholesterol, total cholesterol, triglycerides, fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance, dyslipidemia and overweight/obesity status (7.76 × 10-40 ≤ p ≤ 3.00 × 10-3). No significant associations between genetic variants in ADIPOQ, ADIPOR1, and ADIPOR2 and serum adiponectin concentration were identified (all p ≥ 0.30). No significant associations between the six genetic variants and cardio-metabolic traits were observed after Bonferroni correction (all p < 6.9 × 10-4). Our study suggests strong associations between circulating adiponectin concentration and cardio-metabolic traits in Mexican children.
Asunto(s)
Adiponectina/sangre , Adiponectina/genética , Presión Sanguínea/genética , Enfermedades Metabólicas/genética , Obesidad/complicaciones , Obesidad/fisiopatología , Receptores de Adiponectina/genética , Adolescente , Glucemia , Índice de Masa Corporal , Niño , Preescolar , LDL-Colesterol/sangre , Dislipidemias/genética , Femenino , Glucosa/metabolismo , Humanos , Insulina/sangre , Resistencia a la Insulina , Masculino , México , Polimorfismo de Nucleótido Simple , Triglicéridos/sangreRESUMEN
BACKGROUND/OBJECTIVES: Mexico has one of the highest prevalence of childhood obesity in the world. Genome-wide association studies (GWAS) for obesity have identified multiple single-nucleotide polymorphisms (SNPs) in populations of European, East Asian, and African descent. The contribution of these loci to obesity in Mexican children is unclear. We assessed the transferability of 98 obesity loci in Mexican children and fine-mapped the association signals. SUBJECTS/METHODS: The study included 405 and 390 Mexican children with normal weight and obesity. Participants were genotyped with a genome-wide dense SNP array designed for Latino populations, allowing for the analysis of GWAS index SNPs as well as fine-mapping SNPs, totaling 750 SNPs covering 98 loci. Two genetic risk scores (GRS) were constructed: a "discovery GRS" and a "best-associated GRS", representing the number of effect alleles at the GWAS index SNPs and at the best-associated SNPs after fine-mapping for each subject. RESULTS: Seventeen obesity loci were significantly associated with obesity, and five had fine-mapping SNPs significantly better associated with obesity than their corresponding GWAS index SNPs in Mexican children. Six obesity-associated SNPs significantly departed from additive to dominant (N = 5) or recessive (N = 1) models, and a significant interaction was found between rs274609 (TNNI3K) and rs1010553 (ITIH4) on childhood obesity risk. The best-associated GRS was significantly more associated with childhood obesity (OR = 1.21 per additional risk allele [95%CI:1.17-1.25], P = 4.8 × 10-25) than the discovery GRS (OR = 1.05 per additional risk allele [95%CI:1.02-1.08], P = 8.0 × 10-4), and was also associated with waist-to-hip ratio, fasting glucose, fasting insulin and triglyceride levels, the association being mediated by obesity. An overall depletion of obesity risk alleles was observed in Mexican children with normal weight when compared to GWAS discovery populations. CONCLUSIONS: Our study indicates a partial transferability of GWAS obesity loci in Mexican children, and supports the pertinence of post-GWAS fine-mapping experiments in the admixed Mexican population.
Asunto(s)
Predisposición Genética a la Enfermedad/epidemiología , Estudio de Asociación del Genoma Completo , Obesidad/genética , Polimorfismo de Nucleótido Simple/genética , Adolescente , Niño , Ayuno/sangre , Femenino , Frecuencia de los Genes , Sitios Genéticos , Humanos , Estilo de Vida , Masculino , México/epidemiología , Obesidad/sangre , Obesidad/epidemiología , Factores SocioeconómicosRESUMEN
Genome wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) that are associated with fasting plasma glucose (FPG) in adult European populations. The contribution of these SNPs to FPG in non-Europeans and children is unclear. We studied the association of 15 GWAS SNPs and a genotype score (GS) with FPG and 7 metabolic traits in 1,421 Mexican children and adolescents from Mexico City. Genotyping of the 15 SNPs was performed using TaqMan Open Array. We used multivariate linear regression models adjusted for age, sex, body mass index standard deviation score, and recruitment center. We identified significant associations between 3 SNPs (G6PC2 (rs560887), GCKR (rs1260326), MTNR1B (rs10830963)), the GS and FPG level. The FPG risk alleles of 11 out of the 15 SNPs (73.3%) displayed significant or non-significant beta values for FPG directionally consistent with those reported in adult European GWAS. The risk allele frequencies for 11 of 15 (73.3%) SNPs differed significantly in Mexican children and adolescents compared to European adults from the 1000G Project, but no significant enrichment in FPG risk alleles was observed in the Mexican population. Our data support a partial transferability of European GWAS FPG association signals in children and adolescents from the admixed Mexican population.
Asunto(s)
Glucemia/genética , Etnicidad/genética , Polimorfismo de Nucleótido Simple , Proteínas Adaptadoras Transductoras de Señales/genética , Adolescente , Niño , Preescolar , Estudios Transversales , Epistasis Genética , Ayuno/sangre , Femenino , Frecuencia de los Genes , Estudio de Asociación del Genoma Completo , Glucosa-6-Fosfatasa/genética , Humanos , Masculino , México , Receptor de Melatonina MT2/genética , Población Blanca/genéticaRESUMEN
The Pro12Ala (rs1801282) polymorphism in peroxisome proliferator-activated receptor-γ2 (PPAR-γ2) has been convincingly associated with insulin resistance (IR) and type 2 diabetes (T2D) among Europeans, in interaction with a high-fat diet. Mexico is disproportionally affected by obesity and T2D however, whether the Pro12Ala polymorphism is associated with early metabolic complications in this population is unknown. We assessed the association of PPAR-γ2 Pro12Ala with metabolic traits in 1457 Mexican children using linear regression models. Interactions between PPAR-γ2 Pro12Ala and circulating lipids on metabolic traits were determined by adding an interaction term to regression models. We observed a high prevalence of overweight/obesity (49.2%), dyslipidemia (34.9%) and IR (11.1%). We detected nominally significant/significant interactions between lipids (total cholesterol, HDL-cholesterol, LDL-cholesterol), the PPAR-γ2 Pro12Ala genotype and waist-to-hip ratio, fasting insulin, HOMA-IR and IR (9.30 × 10(-4) ≤ Pinteraction ≤ 0.04). Post-hoc subgroup analyses evidenced that the association between the PPAR-γ2 Pro12Ala genotype and fasting insulin, HOMA-IR and IR was restricted to children with total cholesterol or LDL-cholesterol values higher than the median (0.02 ≤ P ≤ 0.03). Our data support an association of the Pro12Ala polymorphism with IR in Mexican children and suggest that this relationship is modified by dyslipidemia.