Physician health and wellness is a critical issue gaining national attention because of the high prevalence of physician burnout. Pediatricians and pediatric trainees experience burnout at levels equivalent to other medical specialties, highlighting a need for more effective efforts to promote health and well-being in the pediatric community. This report will provide an overview of physician burnout, an update on work in the field of preventive physician health and wellness, and a discussion of emerging initiatives that have potential to promote health at all levels of pediatric training.Pediatricians are uniquely positioned to lead this movement nationally, in part because of the emphasis placed on wellness in the Pediatric Milestone Project, a joint collaboration between the Accreditation Council for Graduate Medical Education and the American Board of Pediatrics. Updated core competencies calling for a balanced approach to health, including focus on nutrition, exercise, mindfulness, and effective stress management, signal a paradigm shift and send the message that it is time for pediatricians to cultivate a culture of wellness better aligned with their responsibilities as role models and congruent with advances in pediatric training.Rather than reviewing programs in place to address substance abuse and other serious conditions in distressed physicians, this article focuses on forward progress in the field, with an emphasis on the need for prevention and anticipation of predictable stressors related to burnout in medical training and practice. Examples of positive progress and several programs designed to promote physician health and wellness are reviewed. Areas where more research is needed are highlighted. Pediatrics 2014;134:830-835 INTRODUCTIONPhysician health and wellness is an issue garnering national interest because of the high prevalence of burnout in medical practitioners and trainees. Burnout takes a steep toll on physicians and has negative effects on patients and health care systems. 1 Research advances detailing the detrimental effects of chronic stress, including impaired immune function, inflammation, elevation of cardiovascular risk factors, and depression, 2-9 are directly relevant to pediatric practitioners and create a need for organized efforts to address physician health and well-being in the pediatric community. The purpose of this report is to provide an update on the issue of physician health and wellness with regard to how they relate to pediatricians. Rather than reviewing programs already in place to address substance abuse and other serious conditions in distressed physicians, this report focuses on forward progress in the field, with an emphasis on the need for prevention and anticipation of predictable stressors related to burnout in medical training and practice. Although specific recommendations are beyond the parameters of this report, examples of positive progress and national programs to promote physician health and wellness will be reviewed. BURNOUT: THE ANTITHESIS ...

Alpha-2-Macroglobulin (A2M) is a highly plausible candidate gene for Alzheimer's disease (AD) in a region of chromosome 12 that has numerous independent reports of genetic linkage. We previously reported that a 5 bp deletion in A2M was associated with AD in a subset of the National Institute of Health (NIMH) Genetics Initiative AD family sample. Efforts to replicate this association finding in case - control samples have been largely negative, while those in family samples have been more positive. We hypothesized that variable findings regarding this deletion, along with variable reports of association with V1000I, another polymorphism in the gene, result from linkage disequilibrium in the area as well as ascertainment differences between family-based and case-control studies. Thus, we resequenced the A2M locus to identify novel polymorphisms to test for genetic association with AD. We identified seven novel polymorphisms and tested them in the full NIMH sample of 1439 individuals in 437 families. We found significant genetic association of the 5 bp deletion and two novel polymorphisms with AD. Substantial linkage disequilibrium was detected across the gene as a whole, and haplotype analysis also showed significant association between AD and groups of A2M polymorphisms. Several of these polymorphisms and haplotypes remain significantly associated with AD even after correction for multiple testing. Taken together, these findings, and the positive reports in other family-based studies, continue to support a potential role for A2M or a nearby gene in AD. However, the negative case - control studies suggest that any underlying pathogenic polymorphisms have a modest effect, and may operate primarily among individuals with a family history of AD.

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For genome-wide association studies in family-based designs, a new, universally applicable approach is proposed. Using a modified Liptak’s method, we combine the p-value of the family-based association test (FBAT) statistic with the p-value for the Van Steen-statistic. The Van Steen-statistic is independent of the FBAT-statistic and utilizes information that is ignored by traditional FBAT-approaches. The new test statistic takes advantages of all available information about the genetic association, while, by virtue of its design, it achieves complete robustness against confounding due to population stratification. The approach is suitable for the analysis of almost any trait type for which FBATs are available, e.g. binary, continuous, time to-onset, multivariate, etc. The efficiency and the validity of the new approach depend on the specification of a nuisance/tuning parameter and the weight parameters in the modified Liptak’s method. For different trait types and ascertainment conditions, we discuss general guidelines for the optimal specification of the tuning parameter and the weight parameters. Our simulation experiments and an application to an Alzheimer study show the validity and the efficiency of the new method, which achieves power levels that are comparable to those of population-based approaches.

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