CDK19-related disorder results from both loss-of-function and gain-of-function de novo missense variants.

PURPOSE: To expand the recent description of a new neurodevelopmental syndrome related to alterations in CDK19. METHODS: Individuals were identified through international collaboration. Functional studies included autophosphorylation assays for CDK19 Gly28Arg and Tyr32His variants and in vivo zebrafish assays of the CDK19G28R and CDK19Y32H. RESULTS: We describe 11 unrelated individuals (age range: 9 months to 14 years) with de novo missense variants mapped to the kinase domain of CDK19, including two recurrent changes at residues Tyr32 and Gly28. In vitro autophosphorylation and substrate phosphorylation assays revealed that kinase activity of protein was lower for p.Gly28Arg and higher for p.Tyr32His substitutions compared with that of the wild-type protein. Injection of CDK19 messenger RNA (mRNA) with either the Tyr32His or the Gly28Arg variants using in vivo zebrafish model significantly increased fraction of embryos with morphological abnormalities. Overall, the phenotype of the now 14 individuals with CDK19-related disorder includes universal developmental delay and facial dysmorphism, hypotonia (79%), seizures (64%), ophthalmologic anomalies (64%), and autism/autistic traits (56%). CONCLUSION: CDK19 de novo missense variants are responsible for a novel neurodevelopmental disorder. Both kinase assay and zebrafish experiments showed that the pathogenetic mechanism may be more diverse than previously thought.

Updates in Pediatric Hospital Medicine: Six Practical Ways to Improve the Care of Hospitalized Children.

BACKGROUND: As pediatric hospital medicine continues to grow, it is important to keep abreast of the current literature. This article provides a summary of six of the most impactful articles published in 2018. METHODS: The authors reviewed articles published between January 2018 and December 2018 for the 2019 Society of Hospital Medicine national conference presentation of Top Articles in Pediatric Hospital Medicine, where the top 10 articles of 2018 were presented. Six of the 10 articles are highlighted in this review based on article quality and their applicability to change practices in the hospital setting or prompt further research. RESULTS: Key findings from the articles include: multiple interventions aimed at providers can improve compliance with bronchiolitis guidelines; a developed calculator can improve testing for urinary tract infections in children aged 2-24 months; nonmedical costs of hospitalizations are underappreciated and disproportionately affect those with a lower socioeconomic status; a progress note template in an electronic health record can lead to higher quality and shorter notes; for febrile infants aged 60 days and younger, most blood and cerebrospinal fluid culture pathogens can be identified within 24 hours and nearly all by 36 hours; and the development of a high-value care tool can help to bring concepts of high-value care into family-centered rounds. CONCLUSION: The six selected articles highlight findings pertinent to pediatric hospital medicine.

Using Didactics and Simulation to Enhance Comfort, Knowledge, and Skills of Nonsurgical Trainees Caring for Patients With Tracheostomy and Laryngectomy.

INTRODUCTION: Management of tracheostomy and laryngectomy is an important skill for physicians who often care for patients with multiple, comorbid, chronic medical conditions. There is little published literature on training for tracheostomy and laryngectomy care during nonsurgical specialty residencies. This project was designed to assess and improve comfort with, knowledge of, proficiency in tracheostomy and laryngectomy care. METHODS: This prospective observational study comprised 122 physician trainees from internal medicine, emergency medicine, and anesthesia training programs at the University of Arkansas for Medical Sciences participating in a simulation-based curriculum from April 2016 to December 2016. The curriculum included didactic session, hands-on experience performing a tracheostomy change, and practicing emergency scenarios on interactive, high-fidelity simulation mannequins. Preintervention and postintervention assessments of self-perceived comfort, objective knowledge, and tracheostomy change proficiency were performed and results compared. RESULTS: Self-perceived comfort improved from a mean Likert score from 2.12 to 4.43 (P = 0.009). Knowledge mean scores improved from 57% to 82% (P < 0.001) on multiple-choice testing. Tracheostomy change proficiency mean scores improved from 41% to 84% (P < 0.001) of proficiencies correctly performed. Six-month follow-up assessment of comfort and knowledge showed statistically significant retention of comfort (P = 0.002) and knowledge (P = 0.026). CONCLUSIONS: Comprehensive tracheostomy and laryngectomy education, which combines enhancement of knowledge with simulation of both routine and emergent aspects of care, is an effective strategy in improving confidence with, knowledge of, proficiency in tracheostomy and laryngectomy care. Retention of confidence and knowledge was demonstrated 6 months later.