No description available.

Introduction: Improvements in the delivery of intensive care have led to a growing number of children with chronic medical conditions at significant risk of recurrent and prolonged critical illness. These patients are increasingly described as having pediatric chronic critical illness (CCI). To date, pediatric CCI is without an accepted consensus case definition. Objective: To evaluate how pediatric CCI has been defined in the current literature, including the concept of prolonged PICU admission, and describe the methodologies used to develop any existing definitions. Secondary aims included describing patient characteristics and outcomes evaluated in included studies. Methods: We searched four electronic databases for studies evaluating children identified with “CCI.” We also searched for studies describing prolonged PICU admission, as this concept is related to pediatric CCI. We developed a hybrid crowdsourcing and machine-learning (ML) methodology to complete citation screening. Screening and data abstraction were performed by two reviewers, independently and in duplicate. We completed data abstraction including details of population definitions, demographic and clinical characteristics of children with CCI, and outcomes evaluated. Results: Twenty-eight reviewers from 11 countries performed citation screening, with a mean sensitivity of 92%. Of 24,729 unique citations assessed for eligibility, 453 full-texts were reviewed and 67 studies were included. Of these, 12 studies (18%) defined CCI, most commonly by a prolonged PICU length of stay (LOS), either in isolation or in addition related to medical complexity patient characteristics and/or readmissions rate. The concept of prolonged PICU admission was defined in an additional 55 (82%) studies by a median of 14 days (range, 1 day-6 weeks). Conclusion: To our knowledge, this scoping review provides the most comprehensive epidemiologic evidence addressing pediatric CCI. Our results suggest a uniform consensus definition is needed in order to advance this emerging and important area of pediatric critical care research. / Thesis / Master of Science (MSc)

This study examined pediatric residents’ responsiveness and experiences in the context of a new pilot program, building an on-site Behavioral Health Consultant (BHC) into their primary care training site. Fifteen pediatric residents were divided so that 9 had access to an on-site BHC and 6 did not. Over the first year of the program, research assistants observed 322 patient visits to record concerns raised, residents’ responses, and visit length. Data regarding BHC activity and residents’ subjective impressions of the program were also collected. Results showed that at least one BH concern was raised in 24% of observed visits. Residents with access to the BHC initiated 89 on-the-spot referrals, resulting in 127 BHC-to-patient interactions. On average, residents spent 10 additional min/visit when BH concerns were raised but those with access to the BHC saved 8 min/visit when BH concerns were raised. Overall, residents utilized the service, particularly first and second year residents. Those with BHC access managed BH concerns in less time than those in the control group. Residents who utilized the BHC were very satisfied, perceived a better quality of care and patient outcomes, and desired future BHC collaboration. Implications for training residents in the area of pediatric behavioral health by using an on-site provider are discussed.

Purpose: Determination of genotypic/phenotypic features of GATAD2B-associated neurodevelopmental disorder(GAND). Methods: Fifty GAND subjects were evaluated to determine consistentgenotypic/phenotypic features. Immunoprecipitation assays utilizing in vitrotranscription–translation products were used to evaluate GATAD2B missensevariants’ ability to interact with binding partners within the nucleosomeremodeling and deacetylase (NuRD) complex. Results: Subjects had clinical findings that included macrocephaly,hypotonia, intellectual disability, neonatal feeding issues, polyhydramnios,apraxia of speech, epilepsy, and bicuspid aortic valves. Forty-one novelGATAD2B variants were identified withmultiple variant types (nonsense, truncating frameshift, splice-site variants,deletions, and missense). Seven subjects were identified with missense variantsthat localized within two conserved region domains (CR1 or CR2) of the GATAD2Bprotein. Immunoprecipitation assays revealed several of these missense variantsdisrupted GATAD2B interactions with its NuRD complex binding partners. Conclusions: A consistent GAND phenotype was caused by a range of geneticvariants in GATAD2B that includeloss-of-function and missense subtypes. Missense variants were present inconserved region domains that disrupted assembly of NuRD complex proteins.GAND’s clinical phenotype had substantial clinical overlap with other disordersassociated with the NuRD complex that involve CHD3 and CHD4, with clinicalfeatures of hypotonia, intellectual disability, cardiac defects, childhoodapraxia of speech, and macrocephaly.

Purpose: A few de novo missense variants in the cytoplasmic FMRP-interacting protein 2 (CYFIP2) gene have recently been described as a novel cause of severe intellectual disability, seizures, and hypotonia in 18 individuals, with p.Arg87 substitutions in the majority. Methods: We assembled data from 19 newly identified and all 18 previously published individuals with CYFIP2 variants. By structural modeling and investigation of WAVE-regulatory complex (WRC)-mediated actin polymerization in six patient fibroblast lines we assessed the impact of CYFIP2 variants on the WRC. Results: Sixteen of 19 individuals harbor two previously described and 11 novel (likely) disease-associated missense variants. We report p.Asp724 as second mutational hotspot (4/19 cases). Genotype–phenotype correlation confirms a consistently severe phenotype in p.Arg87 patients but a more variable phenotype in p.Asp724 and other substitutions. Three individuals with milder phenotypes carry putative loss-of-function variants, which remain of unclear pathogenicity. Structural modeling predicted missense variants to disturb interactions within the WRC or impair CYFIP2 stability. Consistent with its role in WRC-mediated actin polymerization we substantiate aberrant regulation of the actin cytoskeleton in patient fibroblasts. Conclusion: Our study expands the clinical and molecular spectrum of CYFIP2-related neurodevelopmental disorder and provides evidence for aberrant WRC-mediated actin dynamics as contributing cellular pathomechanism.

Abstract available through the Journal of Investigative Medicine.

No description available.

This presentation will feature real world implementation examples from a seasoned interprofessional team working in a high needs primary care clinic. In Part 1 of our session (approx. 30 minutes), we will define implementation science and familiarize the audience with the EPIS framework (Aarons, Hurlburt, & Horwitz, 2011). We will also describe champion teams as a practical and efficient way to conduct implementation science on the clinic level. Part 2 of our session (approx. 30 min) will be dedicated to translating concepts learned in Part 1 to audience members' personal work via individual worksheets, small and large group discussion, and a question and answer period. Additionally, participants will gain access to an electronic toolkit with relevant articles, worksheets and materials to and build on ideas generated during the session and support their project implementation after the conference.

Abstract available in the Journal of Investigative Medicine.

Abstract available in the Journal of Investigative Medicine.