Pediatric Resident Well-being: A Group Concept Mapping Study.

OBJECTIVE: Pediatric residency programs invest substantial resources in supporting resident well-being. However, no pediatric resident well-being conceptual model exists to guide interventions. This study aimed to understand how a diverse stakeholder sample conceptualized well-being. METHODS: We used group concept mapping methodology. We sent a brainstorming survey to pediatric residents and program leaders at 24 US residencies with the prompt, "The experience of well-being for resident physicians includes…" Participants at 4 residencies sorted well-being ideas conceptually and rated idea importance. We performed multidimensional scaling and hierarchical cluster analysis to develop cluster maps. Using participant feedback and a consensus-driven process, we determined best cluster representation. We used pattern matching to compare domain ratings between subgroups. RESULTS: In brainstorming, 136 residents and 22 program leaders from 22 residency programs generated 97 unique ideas. Ideas were sorted and rated by 33 residents, 14 program leaders. Eight domains aligning with 4 resident roles were identified. Domains were: 1) positive, safe, and diverse culture; 2) unity and connection; 3) professional fulfillment and mindset; 4) personal health and life satisfaction; 5) professional development and recognition; 6) schedule protections and downtime; 7) work systems and benefits; 8) proactive and compassionate leadership. Domains aligned with the following roles: 1) individual, 2) colleague, 3) employee, 4) emerging pediatrician. Residents placed higher value on schedule protections and downtime than program leaders, P < .05. CONCLUSIONS: Pediatric resident well-being may be conceptualized as inter-related domains corresponding with various resident roles. Participants aligned on many well-being priorities but differed regarding work schedules.

Eight Domains of Pediatrician Wellness: A Stakeholder Informed Model.

BACKGROUND: Physician wellness is important to health care systems and quality patient care. There has been limited research clarifying the physician wellness construct. We aimed to develop a stakeholder-informed model of pediatrician wellness. METHODS: We performed a group concept mapping (GCM) study to create a model of pediatrician wellness. We followed the four main steps of GCM and recruited pediatricians at multiple sites and on social media. During brainstorming, pediatricians individually responded to a prompt to generate ideas describing the concept of pediatrician wellness. Second, pediatricians sorted the list of brainstormed ideas into conceptually similar groups and rated them on importance. Sorted data were analyzed to create maps showing each idea as a point, with lines around groups of points to create clusters of wellness. Mean importance scores for each cluster were calculated and compared using pattern match. RESULTS: Pediatricians in this study identified eight clusters of wellness: 1) Experiencing belonging and support at work, 2) Alignment in my purpose, my work, and my legacy, 3) Feelings of confidence and fulfillment at work, 4) Skills and mindset for emotional well-being, 5) Harmony in personal, professional, and community life, 6) Time and resources to support holistic sense of self, 7) Work boundaries and flexibility, and 8) Organizational culture of inclusion and trust. There were no significant differences in mean cluster rating score; the highest rated cluster was Harmony in personal, professional and community life (3.62). CONCLUSION: Pediatricians identified eight domains of wellness, spanning professional and personal life, work, and individual factors.

Medical Student Well-being Outcomes After a Novel Shared Meal and Resiliency Skills Course.

INTRODUCTION: Medical student well-being is a major problem. The authors aimed to assess well-being outcomes 6-months after a novel extracurricular shared meal and resiliency course. METHODS: We implemented the course during 3 academic years (2018-2020). Participants received surveys assessing resilience, perspective-taking, self-compassion, and empathy at 4 timepoints. We used linear mixed effects models to assess changes from baseline to post-course assessments for the 3-year aggregate and pre-COVID and early-COVID time periods. RESULTS: One week and 6 months post-course, resilience, perspective-taking, and self-compassion scores improved (P < 0.01). Notably, resilience changed significantly only during early-COVID (P < 0.01), not pre-COVID (P = 0.16). For scores with evidence-based interpretation cut-offs, no clinical changes occurred. DISCUSSION: Several well-being measures statistically improved post-course but did not change clinically. Qualitative studies may better capture meaningful well-being outcome impact.

Smartphone App for In-home Uroflowmetry.

INTRODUCTION: We compared the test results obtained by a novel MenHealth® uroflowmetry app against the standard in-office uroflowmeter. MenHealth uroflowmetry is a smartphone app that analyzes the sound of urine voided into a water-filled toilet. The program calculates maximum and average flow rates as well as volume voided. METHODS: Men over 18 years old were tested. Group 1 included 47 men with symptoms suggesting overactive bladder and/or outlet obstruction. Group 2 included 15 men with no urinary complaints. Each participant conducted a minimum of 10 MenHealth uroflowmetry measurements at home and 2 standard in-office uroflowmeter tests in our office. Maximum and average flow rates and voided volume were recorded. A comparison of averaged results of MenHealth uroflowmetry and in-office uroflowmeter was performed using a Bland-Altman analysis and a Passing-Bablok nonparametric regression analysis. RESULTS: Regression data analysis indicated a very strong correlation between maximum flow rate and average flow rate when comparing MenHealth uroflowmetry to in-office uroflowmeter (Pearson's correlation coefficients of .91 and .92, respectively). Insignificant difference in mean maximum and average flow rates for Groups 1 and 2 (< 0.5 ml/second) also proves strong correlation between the 2 methods and accuracy of MenHealth uroflowmetry. CONCLUSIONS: Data obtained by a novel MenHealth uroflowmetry app is equivalent to results from a standard in-office uroflowmeter for men with and without voiding symptoms. MenHealth uroflowmetry permits repetitive measurements in a more comfortable, "at home" setting, which provides a more comprehensive analysis, a clearer, nuanced picture of the patient's pathophysiology, and a lesser chance of misdiagnosis.

Genomic microarray analysis on formalin-fixed paraffin-embedded material for uveal melanoma prognostication.

Cytogenetic alterations are strong outcome prognosticators in uveal melanoma (UVM). Monosomy 3 (-3) and MYC amplification at 8q24 are commonly tested by fluorescence in situ hybridization (FISH). Alternatively, microarray analysis provides whole genome data, detecting partial chromosome loss, loss of heterozygosity (LOH), or abnormalities unrepresented by FISH probes. Nonfixed frozen tissue is conventionally used for microarray analysis but may not always be available. We assessed the feasibility of genomic microarray analysis for high resolution interrogation of UVM using formalin-fixed paraffin-embedded tissue (FFPET) as an alternative to frozen tissue (FZT). Enucleations from 44 patients (clinical trial NCT00952939) yielded sufficient DNA from FFPET (n = 34) and/or frozen tissue (n = 41) for comparative genomic hybridization and select single nucleotide polymorphism analysis (CGH/SNP) on Roche-NimbleGen OncoChip arrays. CEP3 FISH analysis was performed on matched cytology ThinPrep material. CGH/SNP analysis was successful in 30 of 34 FFPET and 41 of 41 FZT samples. Of 27 paired FFPET/FZT samples, 26 (96.3%) were concordant for at least four of six major recurrent abnormalities (-3, +8q, -1p, +6p, -6q, -8p), and 25 of 27 (92.6%) were concordant for -3. Results of CGH/SNP were concordant with the CEP3 FISH results in 27 of 30 (90%) FFPET and 38 of 41 (92.6%) FZT cases; partial -3q was detected in two CEP3 FISH-negative cases and whole chromosome 3, 4, and 6 SNP-LOH in one case. CGH detection of -3, +8q, -8p on FFPET and FZT showed significant correlation with the clinical outcome measures (metastasis development, time to progression, survival). Results of the UVM genotyping by CGH/SNP on FFPET are highly concordant with those of the FZT analysis and with those of the CEP3 FISH analysis, and therefore CGH/SNP is a practical method for UVM prognostication. Genome-wide coverage provides additional data with potential relevance to UVM biology, diagnosis, and prognosis.

Experience using a rapid assay for aneuploidy and microdeletion/microduplication detection in over 2,900 prenatal specimens.

BACKGROUND: While microarray testing can identify chromosomal abnormalities missed by karyotyping, its prenatal use is often avoided in low-risk pregnancies due to the possible identification of variants of uncertain significance (VOUS). METHODS: We tested 2,970 prenatal samples of all referral indications using a rapid BACs-on-Beads-based assay with probes for sex chromosomes, common autosomal aneuploidies, and 20 microdeletion/microduplication syndromes, designed as an alternative to microarray in low-risk pregnancies and an alternative to rapid aneuploidy testing in pregnancies also undergoing microarray analysis. RESULTS: Interpretable results were obtained in 2,940 cases (99.0%), with 89% receiving results in 1 day. Aneuploidies were detected in 7.3% and partial chromosome abnormalities in 0.45% (n = 13), including 5 referred for maternal age, abnormal maternal serum screen, or isolated ultrasound markers. The added detection above karyotype was 1 in 745 in lower-risk cases with normal ultrasounds or isolated ultrasound markers/increased nuchal measurements and 1 in 165 for fetuses with structural/growth abnormalities. Neither false negatives nor false positives were found within test limitations. Female polyploidy could not be detected, while polyploidies with Y chromosomes were suspected and confirmed through additional analysis. CONCLUSION: When combined with karyotyping, this assay provides increased interrogation of specific chromosomal regions, while limiting VOUS identification.

Characterization of a case of follicular lymphoma transformed into B-lymphoblastic leukemia.

Follicular lymphoma (FL) is a common form of non-Hodgkin lymphoma with an ability to transform into a more aggressive disease, albeit infrequently to B-lymphoblastic leukemia/lymphoma. While t(14;18)(q32;q21) has been associated with approximately 90% cases of FL, that alteration alone is insufficient to cause FL and associated mutations are still being elucidated. The transformation of FL to B-lymphoblastic leukemia generally includes the dysregulation of MYC gene expression, typically through IGH rearrangement. Such cases of "double-hit" leukemia/lymphoma with both BCL2 and MYC translocations warrant further study as they are often not identified early, are associated with a poor prognosis, and are incompletely understood in molecular terms. Here we describe a patient with a diagnosis of FL that transformed to B-lymphoblastic leukemia. Detailed cytogenetic characterization of the transformed specimen using karyotype, fluorescence in situ hybridization, microarray and gene rearrangement analyses revealed a complex karyotype comprised principally of whole chromosome or whole arm copy number gains or losses. Smaller, single-gene copy number alterations identified by microarray were limited in number, but included amplification of a truncated EP300 gene and alterations in NEIL1 and GPHN. Analyses defined the presence of an IGH/BCL2 fusion due to a translocation as well as a MYC/IGH fusion due to an insertion, with both rearrangements involving the same IGH allele. The data illustrate the value in characterizing double-hit lymphoma cases with both traditional and novel technologies in the detailed cytogenetic workup.

Modified array-based comparative genomic hybridization detects cryptic and variant PML-RARA rearrangements in acute promyelocytic leukemia lacking classic translocations.

Acute promyelocytic leukemia (APL) is typically defined at the molecular level by a reciprocal translocation of the promyelocytic leukemia (PML) and retinoic acid receptor α (RARA) genes. An accurate diagnosis of APL is critical for appropriate choice of therapy and prognostic assessment. Cryptic and variant rearrangements in APL are discoverable by a variety of molecular methods including fluorescence in situ hybridization (FISH), reverse transcriptase polymerase chain reaction, or gene sequencing. Rare reports of FISH-negative APL harboring cryptic rearrangements of PML-RARA detected by reverse transcriptase polymerase chain reaction or sequencing have been described. Here, we describe the detection of cryptic or variant PML-RARA rearrangements by translocation-based comparative genomic hybridization (tCGH), a recently described modification of traditional CGH technology that facilitates the detection of balanced translocations by means of the linear amplification of a potential translocation breakpoint region(s), in 2 unusual cases of APL. One tumor lacked detectable t(15;17) by karyotype and FISH, and the other tumor lacked the typical morphologic and immunophenotypic features of APL and had a variant 3-way translocation involving PML and RARA. PML-RARA translocations were identified by tCGH in both cases providing confirmation of the diagnosis of APL. These data emphasize the benefit of using complementary molecular methods including tCGH for detecting cryptic and variant PML-RARA translocations in unusual cases of APL.

The use of cytogenetic microarrays in myelodysplastic syndrome characterization.

Various microarray platforms, including BAC, oligonucleotide, and SNP arrays, have been shown to -provide clinically useful diagnostic and prognostic information for patients with myelodysplastic syndromes (MDS). Clinically useful arrays are designed with specific purposes in mind and with attention to genomic content and probe density. All array types have been shown to detect genomic copy gains and losses, with SNP arrays having the added advantage of detecting copy neutral loss of heterozygosity (CNLOH). The finding of CNLOH has led to the identification of certain disease genes implicated in the initiation or progression of myeloid diseases. In addition, SNP karyotyping alone, or in conjunction with routine cytogenetics, can affect the outcome prediction and improve prognostic stratification of patients with MDS. Patients who were reclassified after array testing as having adverse-risk chromosomal findings correlated with poor survival. Results of over 25 published studies support the use of arrays in MDS testing. Because few balanced translocations are found in MDS, this disease is particularly amenable to microarray testing, and studies have shown better disease classification, identification of cryptic changes, and prognostication in this heterogeneous group of disorders. Novel genomic alterations identified by array testing may lead to better targeted therapies for treating patients with MDS.

MEF2C Haploinsufficiency features consistent hyperkinesis, variable epilepsy, and has a role in dorsal and ventral neuronal developmental pathways.

MEF2C haploinsufficiency syndrome is an emerging neurodevelopmental disorder associated with intellectual disability, autistic features, epilepsy, and abnormal movements. We report 16 new patients with MEF2C haploinsufficiency, including the oldest reported patient with MEF2C deletion at 5q14.3. We detail the neurobehavioral phenotype, epilepsy, and abnormal movements, and compare our subjects with those previously reported in the literature. We also investigate Mef2c expression in the developing mouse forebrain. A spectrum of neurofunctional deficits emerges, with hyperkinesis a consistent finding. Epilepsy varied from absent to severe, and included intractable myoclonic seizures and infantile spasms. Subjects with partial MEF2C deletion were statistically less likely to have epilepsy. Finally, we confirm that Mef2c is present both in dorsal primary neuroblasts and ventral gamma-aminobutyric acid(GABA)ergic interneurons in the forebrain of the developing mouse. Given interactions with several key neurodevelopmental genes such as ARX, FMR1, MECP2, and TBR1, it appears that MEF2C plays a role in several developmental stages of both dorsal and ventral neuronal cell types.