Publications

INTRODUCTION: Trainee burnout has reached epidemic proportions and is increasing among physicians compared to non-health care professionals. Burnout is associated with depression and lower empathy, poor patient adherence to medical plans, and early physician retirement. Mindfulness is the quality of being nonjudgmental and present and has been shown to decrease physician burnout. Implementation of mindfulness curricula may decrease trainee burnout.

METHODS: Using Kern's six-step approach, we developed an easy-to-implement, facilitator-friendly mindfulness curriculum for pediatric interns. Curricular sessions were held monthly during preexisting 1-hour didactics over 6 months, facilitated by individuals without mindfulness experience. Learners were assessed on knowledge, attitudes, and behavior with postintervention surveys during a pilot in 2016. Qualitative data were used for curricular improvement resulting in the published curriculum.

RESULTS: Postcurriculum surveys from our pilot revealed that 69% of interns reported a more positive attitude toward mindfulness, while 62% reported having (1) greater knowledge about evidence supporting mindfulness, (2) improved knowledge on how to apply mindfulness techniques, and (3) the belief that techniques they had learned positively impacted their lives. Thirty-three percent endorsed using mindfulness techniques more frequently than they had prior to the start of the mindfulness curriculum.

DISCUSSION: Our novel curriculum provided longitudinal mindfulness training that meaningfully impacted trainee knowledge, behaviors, and attitudes. The curricular structure overcame the need for local topic experts and was feasible to implement within the confines of our complex program structure. Ongoing work will determine the impact of our curriculum on objective measures of burnout, empathy, and mindfulness.

Paroxysmal nocturnal hemoglobinuria (PNH), a disease characterized by intravascular hemolysis, thrombosis, and bone marrow failure, is associated with mutations in the PIG-A gene, resulting in a deficiency of glycosylphosphatidylinositol-anchored proteins. Many hypotheses have been posed as to whether PNH and PIG-A mutations result in an intrinsic survival benefit of CD55(-)/CD59(-) cells or an extrinsic permissive environment that allows for their clonal expansion within the bone marrow compartment. Recent data have identified the concurrence of PIG-A mutations with additional genetic mutations associated with myeloproliferative disorders, suggesting that some presentations of PNH are the result of a stepwise progression of genetic mutations similar to other myelodysplastic or myeloproliferative syndromes. We report for the first time in the literature the development of clinically significant PNH in a patient with JAK2V617F-negative, CALR-positive essential thrombocythemia, providing further support to the hypothesis that the development of PNH is associated with the accumulation of multiple genetic mutations that create an intrinsic survival benefit for clonal expansion. This case study additionally highlights the utility of genomic testing in diagnosis and the understanding of disease progression in the clinical setting.

PURPOSE: Cell-based approaches were used to identify genetic markers predictive of patients' risk for poor response prior to chemotherapy.

EXPERIMENTAL DESIGN: We conducted genome-wide association studies (GWAS) to identify single-nucleotide polymorphisms (SNP) associated with cellular sensitivity to carboplatin through their effects on mRNA expression using International HapMap lymphoblastoid cell lines (LCL) and replicated them in additional LCLs. SNPs passing both stages of the cell-based study were tested for association with progression-free survival (PFS) in patients. Phase 1 validation was based on 377 ovarian cancer patients receiving at least four cycles of carboplatin and paclitaxel from the Australian Ovarian Cancer Study (AOCS). Positive associations were then assessed in phase 2 validation analysis of 1,326 patients from the Ovarian Cancer Association Consortium and The Cancer Genome Atlas.

RESULTS: In the initial GWAS, 342 SNPs were associated with carboplatin-induced cytotoxicity, of which 18 unique SNPs were retained after assessing their association with gene expression. One SNP (rs1649942) was replicated in an independent LCL set (Bonferroni adjusted P < 0.05). It was found to be significantly associated with decreased PFS in phase 1 AOCS patients (P(per-allele) = 2 × 10(-2)), with a stronger effect in the subset of women with optimally debulked tumors (P(per-allele) = 4 × 10(-3)). rs1649942 was also associated with poorer overall survival in women with optimally debulked tumors (P(per-allele) = 9 × 10(-3)). However, this SNP was not significant in phase 2 validation analysis with patients from numerous cohorts.

CONCLUSION: This study shows the potential of cell-based, genome-wide approaches to identify germline predictors of treatment outcome and highlights the need for extensive validation in patients to assess their clinical effect.