Consistency and quality in written accreditation protocols for pediatrician training programs: a mixed-methods analysis of a global sample, and directions for improvement.

BACKGROUND: The World Federation for Medical Education (WFME) defines accreditation as 'certification of the suitability of medical education programs, and of…competence…in the delivery of medical education.' Accreditation bodies function at national, regional and global levels. In 2015, WFME published quality standards for accreditation of postgraduate medical education (PGME). We compared accreditation of pediatric PGME programs to these standards to understand variability in accreditation and areas for improvement. METHODS: We examined 19 accreditation protocols representing all country income levels and world regions. For each, two raters assessed 36 WFME-defined accreditation sub-areas as present, partially present, or absent. When rating "partially present" or "absent", raters noted the rationale for the rating. Using an inductive approach, authors qualitatively analyzed notes, generating themes in reasons for divergence from the benchmark. RESULTS: A median of 56% (IQR 43-77%) of WFME sub-areas were present in individual protocols; 22% (IQR 15-39%) were partially present; and 8.3% (IQR 5.5-21%) were absent. Inter-rater agreement was 74% (SD 11%). Sub-areas least addressed included number of trainees, educational expertise, and performance of qualified doctors. Qualitative themes of divergence included (1) variation in protocols related to heterogeneity in program structure; (2) limited engagement with stakeholders, especially regarding educational outcomes and community/health system needs; (3) a trainee-centered approach, including equity considerations, was not universal; and (4) less emphasis on quality of education, particularly faculty development in teaching. CONCLUSIONS: Heterogeneity in accreditation can be appropriate, considering cultural or regulatory context. However, we identified broadly applicable areas for improvement: ensuring equitable access to training, taking a trainee-centered approach, emphasizing quality of teaching, and ensuring diverse stakeholder feedback.

Management and Outcomes of Children With Nursemaid's Elbow.

STUDY OBJECTIVE: We identify the incidence and predictors of missed fracture and characterize patterns of radiography performance in children with a diagnosis of radial head subluxation in the emergency department (ED) setting. METHODS: We queried the Pediatric Health Information System database for visits by children younger than 10 years and with a diagnosis of radial head subluxation at 1 of 45 pediatric EDs from 2010 to 2018. The frequency of radiography use was assessed overall and between hospitals. Multivariable logistic regression was used to evaluate associations between patient-level characteristics and the outcome of missed fracture (return visit for upper extremity fracture within 7 days of the index visit). RESULTS: We identified 88,466 eligible visits; the median patient age was 2.1 years, 59% of visits were by female patients, and in visits in which laterality was noted, 60% of cases occurred in the left arm. Radiography was performed at 28.5% of visits; hospital rates of radiography performance ranged from 19.8% to 41.7%. Missed upper extremity fractures were observed in 247 cases (0.3% of the cohort). The odds of missed fracture were higher in children older than 6 years (adjusted odds ratio 2.32; 95% confidence interval 1.12 to 4.81), children who underwent radiography at the index visit (adjusted odds ratio 2.52; 95% confidence interval 1.84 to 3.43), and children receiving acetaminophen or ibuprofen (adjusted odds ratio 1.54; 95% confidence interval 1.15 to 2.06). CONCLUSION: Radiographs were obtained for greater than one quarter of children presenting to a pediatric ED with radial head subluxation, with wide variation between hospitals. Missed fractures were rare. Future efforts should aim to reduce unnecessary radiography in this population.

Disparities and Trends in Migraine Management in Pediatric Emergency Departments, 2009-19.

OBJECTIVE: To assess the variation in migraine management over time across US children's hospitals and to identify factors associated with disparities in management. METHODS: We conducted a retrospective study of 32 hospitals in the Pediatric Health Information System from 2009 to 2019. We included children 7 to 21 years old with primary ICD-9 or ICD-10 diagnosis codes for migraine headache. We surveyed hospitals to assess for clinical guideline presence. We assessed medication use trends over time. To examine differences in medication and advanced head imaging use by patient characteristics and presence of clinical guideline, we performed multivariable logistic regression analyses reporting adjusted odds ratios (aOR) with 95% confidence intervals (CI). RESULTS: We identified 112,077 eligible visits. Opioid use decreased over time, while nonopioid analgesic, dopamine antagonist, and diphenhydramine use increased. Multivariable analysis for opioids revealed increased odds of use for those 14 to 17 (aOR 1.19; 95% CI, 1.06, 1.34) and 18 to 21 years old (aOR 1.69; CI, 1.37, 2.08), and clinical guideline presence had decreased odds (aOR 0.64; CI, 0.48, 0.84). For head computed tomography, increased odds of use were reported for Hispanic ethnicity (aOR 1.15; CI, 1.06, 1.24) and decreased odds for 14 to 17 years (aOR 0.85; CI, 0.80, 0.90), 18 to 21 years (aOR 0.87; CI, 0.77, 0.98), and female sex (aOR 0.74; CI, 0.70, 0.79). CONCLUSIONS: Opioid use decreased while other medications increased over time. Medication and imaging differed by demographic characteristics. Opioid use was less likely in hospitals with clinical guidelines. Standardization in management may decrease care disparities and variability.

A method to culture human alveolar rhabdomyosarcoma cell lines as rhabdospheres demonstrates an enrichment in stemness and Notch signaling.

The development of three-dimensional cell culture techniques has allowed cancer researchers to study the stemness properties of cancer cells in in vitro culture. However, a method to grow PAX3-FOXO1 fusion-positive rhabdomyosarcoma (FP-RMS), an aggressive soft tissue sarcoma of childhood, has to date not been reported, hampering efforts to identify the dysregulated signaling pathways that underlie FP-RMS stemness. Here, we first examine the expression of canonical stem cell markers in human RMS tumors and cell lines. We then describe a method to grow FP-RMS cell lines as rhabdospheres and demonstrate that these spheres are enriched in expression of canonical stemness factors as well as Notch signaling components. Specifically, FP-RMS rhabdospheres have increased expression of SOX2, POU5F1 (OCT4), and NANOG, and several receptors and transcriptional regulators in the Notch signaling pathway. FP-RMS rhabdospheres also exhibit functional stemness characteristics including multipotency, increased tumorigenicity in vivo, and chemoresistance. This method provides a novel practical tool to support research into FP-RMS stemness and chemoresistance signaling mechanisms.

Soft Tissue Sarcoma Cancer Stem Cells: An Overview.

Soft tissue sarcomas (STSs) are an uncommon group of solid tumors that can arise throughout the human lifespan. Despite their commonality as non-bony cancers that develop from mesenchymal cell precursors, they are heterogeneous in their genetic profiles, histology, and clinical features. This has made it difficult to identify a single target or therapy specific to STSs. And while there is no one cell of origin ascribed to all STSs, the cancer stem cell (CSC) principle-that a subpopulation of tumor cells possesses stem cell-like properties underlying tumor initiation, therapeutic resistance, disease recurrence, and metastasis-predicts that ultimately it should be possible to identify a feature common to all STSs that could function as a therapeutic Achilles' heel. Here we review the published evidence for CSCs in each of the most common STSs, then focus on the methods used to study CSCs, the developmental signaling pathways usurped by CSCs, and the epigenetic alterations critical for CSC identity that may be useful for further study of STS biology. We conclude with discussion of some challenges to the field and future directions.

The Transcriptional Coactivator TAZ Is a Potent Mediator of Alveolar Rhabdomyosarcoma Tumorigenesis.

Purpose: Alveolar rhabdomyosarcoma (aRMS) is a childhood soft tissue sarcoma driven by the signature PAX3-FOXO1 (P3F) fusion gene. Five-year survival for aRMS is <50%, with no improvement in over 4 decades. Although the transcriptional coactivator TAZ is oncogenic in carcinomas, the role of TAZ in sarcomas is poorly understood. The aim of this study was to investigate the role of TAZ in P3F-aRMS tumorigenesis.Experimental Design: After determining from publicly available datasets that TAZ is upregulated in human aRMS transcriptomes, we evaluated whether TAZ is also upregulated in our myoblast-based model of P3F-initiated tumorigenesis, and performed IHC staining of 63 human aRMS samples from tissue microarrays. Using constitutive and inducible RNAi, we examined the impact of TAZ loss of function on aRMS oncogenic phenotypes in vitro and tumorigenesis in vivo Finally, we performed pharmacologic studies in aRMS cell lines using porphyrin compounds, which interfere with TAZ-TEAD transcriptional activity.Results: TAZ is upregulated in our P3F-initiated aRMS model, and aRMS cells and tumors have high nuclear TAZ expression. In vitro, TAZ suppression inhibits aRMS cell proliferation, induces apoptosis, supports myogenic differentiation, and reduces aRMS cell stemness. TAZ-deficient aRMS cells are enriched in G2-M phase of the cell cycle. In vivo, TAZ suppression attenuates aRMS xenograft tumor growth. Preclinical studies show decreased aRMS xenograft tumor growth with porphyrin compounds alone and in combination with vincristine.Conclusions: TAZ is oncogenic in aRMS sarcomagenesis. While P3F is currently not therapeutically tractable, targeting TAZ could be a promising novel approach in aRMS. Clin Cancer Res; 24(11); 2616-30. ©2018 AACR.