Child Health Needs and the Pediatric Gastroenterology Workforce: 2020-2040.

This article is part of an American Board of Pediatrics Foundation-sponsored effort to analyze and forecast the pediatric subspecialty workforce between 2020 and 2040. Herein, an overview of the current pediatric gastroenterology workforce is provided, including demographics, work characteristics, and geographic distribution of practitioners. Brief context is provided on the changing nature of current practice models and the increasing prevalence of some commonly seen disorders. On the basis of a rigorous microsimulation workforce projection model, projected changes from 2020 to 2040 in the number of pediatric gastroenterologists and clinical workforce equivalents in the United States are presented. The article closes with a brief discussion of training, clinical practice, policy, and future workforce research implications of the data presented. This data-driven analysis suggests that the field of pediatric gastroenterology will continue to grow in scope and complexity, propelled by scientific advances and the increasing prevalence of many disorders relevant to the discipline. The workforce is projected to double by 2040, a growth rate faster than most other pediatric subspecialties. Disparities in care related to geography, race, and ethnicity are among the most significant challenges for the years ahead. Changes to training and education, incentives to meet the needs of underserved populations, and new multidisciplinary models for health care delivery will be necessary to optimally meet the volume, diversity, and complexity of children with gastroenterological diseases in the years ahead.

Academic Careers in Advocacy: Aligning Institutional Values Through Use of an Advocacy Portfolio.

Academic children's hospitals must embrace advocacy as a central component of their missions to discover new knowledge and improve the health of the communities and patients they serve. To do so, they must ensure faculty have both the tools and the opportunities to develop and articulate the work of advocacy as an academic endeavor. This can be accomplished by integrating the work of advocacy at the community and policy-change levels into the traditional value systems of academic medicine, especially the promotions process, to establish its legitimacy. Academic pediatric institutions can support this transformation through robust training and professional development programs and establishing opportunities, resources, and leadership positions in advocacy. The adoption of an advocacy portfolio can be used to align these activities and accomplishments to institutional values and promotion. This alignment is crucial to supporting the advocacy work of pediatricians at a time in which community engagement and systems and policy change must be added to professional activities to ensure optimal outcomes for all children.

Characterization of Electronic Health Record Use Outside Scheduled Clinic Hours Among Primary Care Pediatricians: Retrospective Descriptive Task Analysis of Electronic Health Record Access Log Data.

BACKGROUND: Many of the benefits of electronic health records (EHRs) have not been achieved at expected levels because of a variety of unintended negative consequences such as documentation burden. Previous studies have characterized EHR use during and outside work hours, with many reporting that physicians spend considerable time on documentation-related tasks. These studies characterized EHR use during and outside work hours using clock time versus actual physician clinic schedules to define the outside work time. OBJECTIVE: This study aimed to characterize EHR work outside scheduled clinic hours among primary care pediatricians using a retrospective descriptive task analysis of EHR access log data and actual physician clinic schedules to define work time. METHODS: We conducted a retrospective, exploratory, descriptive task analysis of EHR access log data from primary care pediatricians in September 2019 at a large Midwestern pediatric health center to quantify and identify actions completed outside scheduled clinic hours. Mixed-effects statistical modeling was used to investigate the effects of age, sex, clinical full-time equivalent status, and EHR work during scheduled clinic hours on the use of EHRs outside scheduled clinic hours. RESULTS: Primary care pediatricians (n=56) in this study generated 1,523,872 access log data points (across 1069 physician workdays) and spent an average of 4.4 (SD 2.0) hours and 0.8 (SD 0.8) hours per physician per workday engaged in EHRs during and outside scheduled clinic hours, respectively. Approximately three-quarters of the time working in EHR during or outside scheduled clinic hours was spent reviewing data and reports. Mixed-effects regression revealed no associations of age, sex, or clinical full-time equivalent status with EHR use during or outside scheduled clinic hours. CONCLUSIONS: For every hour primary care pediatricians spent engaged with the EHR during scheduled clinic hours, they spent approximately 10 minutes interacting with the EHR outside scheduled clinic hours. Most of their time (during and outside scheduled clinic hours) was spent reviewing data, records, and other information in EHR.

An Initiative to Increase Residency Program Diversity.

A physician workforce that reflects the patient population is associated with improved patient outcomes and promotes health equity. Notwithstanding, racial and ethnic disparities persist within US medical schools, making some individuals underrepresented in medicine (URM). We sought to increase the percentage of URM residents who matched into our pediatric residency programs from a baseline of 5% to 35% to achieve demographic parity with our patients. We developed a multifaceted approach using multiple iterative tests of change, with the primary strategy being increased visibility of URM trainees and faculty to residency applicants. Strategies included applicant interviews with URM faculty, interview dinners with URM residents, visibility at academic conferences for URM trainees, development of targeted marketing materials, and a visiting student program supported by networking with URM residents. The primary outcome measure was the percentage of matched residents in the categorical pediatrics, child neurology, and medical genetics training programs who identified as URM. The percentage of URM residents increased to 16% (6 of 37) in 2018, 26% (11 of 43) in 2019, 19% (8 of 43) in 2020, and 21% (9 of 43) in 2021 (a four-year average of 22% URM residents; P = .0002). This progress toward a more representative residency program was met by challenges, such as pipeline concerns, the minority tax, and recruitment during a pandemic. We were able to implement small, low-resource strategies that had a large cumulative impact and could be implemented in other residency programs. Specific tactics and challenges encountered are discussed in this special article.

Comorbidities in Childhood Celiac Disease: A Phenome Wide Association Study Using the Electronic Health Record.

OBJECTIVES: Celiac disease (CD) is associated with a variety of extraintestinal autoimmune and inflammatory findings that manifest clinically as symptoms and comorbidities. Understanding these comorbidities may improve identification of the disease and prevent sequelae. In this study, we use an unbiased electronic health record (EHR)-based Phenome Wide Association Study (PheWAS) method to confirm known comorbidities, discover novel associations and enhance characterization of the clinical presentation of CD in children. METHODS: Data were extracted from the Nationwide Children's Hospital EHR. Confirmed CD cases (n = 433) were matched with 4330 randomly selected controls. Utilizing an EHR-based PheWAS method to analyze associations of phenotypes with CD, we conducted an unbiased screening of all International Classification of Diseases, 10th revision diagnostic codes and examined significance by performing Fisher's Exact tests. We further tested for the association between CD and 14 previously identified comorbidities in an a priori fashion. RESULTS: We found 45 International Classification of Diseases, 10th revision codes significantly associated with CD. Thirteen are known comorbidities and nine are expected symptoms of CD, thus validating our study methods. Further investigation found symptoms that characterized CD clinically and discovered a significant association between eosinophilic disorders of the esophagus and CD. Of 14 previously identified comorbidities, 8 were significantly associated with CD. CONCLUSIONS: An EHR-based PheWAS method is a powerful, efficient, and cost-effective method to screen for possible CD comorbidities and validate associations at the population level. Ours is the first PheWAS of CD to confirm a significant association of eosinophilic disorders of the esophagus with CD in a controlled study.

Pattern recognition for identification of lysozyme droplet solution chemistry.

Pattern formation during evaporation of a colloidal sessile droplet is a phenomenon relevant to a wide variety of scientific disciplines. The patterns remaining on the substrate are indicative of the transport mechanisms and phase transitions occurring during evaporation and may reflect the solution chemistry of the fluid [1-18]. Pattern formation during evaporation of droplets of biofluids has also been examined and these complex patterns may reflect the health of the patient [23-31]. Automatic detection of variations in the fluid composition based on these deposit patterns could lead to rapid screening for diagnostic or quality control purposes. In this study, a pattern recognition algorithm is presented to differentiate between deposits containing various solution compositions. The deposits studied are from droplets of simplified, model biological fluids of aqueous lysozyme and NaCl solutions. For the solution concentrations examined here, the deposit patterns are dependent upon the initial solution composition. Deposit images are represented by extracting features using the Gabor wavelet, similar to the method used for iris recognition. Two popular pattern recognition algorithms are used to classify the deposits. The k-means clustering algorithm is used to test if incremental changes in solution concentration result in reproducible and statistically interpretable variations in the deposit patterns. The k-nearest neighbor algorithm is also used to classify the deposit images by solution concentration based on a set of training images for each class. Here, we demonstrate that the deposit patterns may act as a "fingerprint" for identification of solution chemistry. The results of this study are very promising, with classification accuracies of 90-97.5%.

Recent advances in pediatric gastroenterology, hepatology and nutrition.

Pediatric gastroenterology, hepatology and nutrition are rapidly evolving, exciting and diverse disciplines. Because the field is so expansive, this commentary highlights important trends, rather than narrowly focusing on specific advances. Examples of advances in the highest impact and rapidly moving areas of pediatric gastroenterology are reviewed, including the intestinal microbiome, biomedical genomics, the biology of unique gastrointestinal cell types, and microRNAs (miRNAs).

Salt-induced pattern formation in evaporating droplets of lysozyme solutions.

Solute self-organization during evaporation of colloidal sessile droplets has attracted the attention of researchers over the past few decades due to a variety of technological applications. Recently, pattern formation during evaporation of various biofluids has been studied due to potential applications in screening and diagnosis. The complex morphological patterns in the deposit are unique to various disorders and are influenced by various physical mechanisms occurring during evaporation. These complex patterns can be better understood by studying evaporation of model solutions of biological relevance. Here, we examine the general features of pattern formation during sessile droplet evaporation of aqueous lysozyme solutions with varying concentrations of NaCl. Lysozyme is a globular protein found in biological fluids such as tears and saliva. The morphological evolution of the droplet is studied by time-lapse video during evaporation via reflection optical microscopy. The final deposits exhibit an amorphous peripheral ring and interior regions containing crystallites and dendritic forms, dependent on NaCl concentration. Scanning electron microscopy (SEM) images demonstrate the multi-scale hierarchical nature of these structures.

Characteristic size for onset of coffee-ring effect in evaporating lysozyme-water solution droplets.

Liquid droplets containing suspended particles deposited on a solid surface often form a ring-like structure due to the redistribution of solute during evaporation, a phenomenon known as the "coffee ring effect". The complex patterns left on the substrate after evaporation are characteristic of the nature of the solute and the particle transport mechanisms. In this study, the morphological evolution and conditions for coffee ring formation for simplified model biological solutions of DI water and lysozyme are examined by AFM and optical microscopy. Lysozyme is a globular protein found in high concentration, for example, in human tears and saliva. The drop diameters studied are very small, ranging from 1 to 50 µm. In this size range, protein motion and the resulting dried residue morphology are highly influenced by the decreased evaporation time of the drop. In this work, we consider the effect of droplet size and concentration on the morphology of the deposited drop as well as the minimal conditions for coffee ring formation in this system. Two distinct deposit types are observed: a simple cap-shaped deposit for drops with small diameters and a ring-like deposit at larger diameters. Ring formation occurs at a critical diameter, which depends systematically on initial lysozyme concentration.

Knockout of Mkp-1 exacerbates colitis in Il-10-deficient mice.

Il-10-deficient mice develop colitis associated with exaggerated Th1/Th17 responses and are a valuable model of inflammatory bowel disease. Mkp-1 is a major negative regulator of MAPKs, and its expression is enhanced by IL-10. To understand the role of Mkp-1 in the regulation of intestinal mucosal immune responses, we studied the effect of Mkp-1 deletion on the pathogenesis of colitis in Il-10(-/-) mice. We found that knockout of Mkp-1 on an Il-10(-/-) background accelerated the development of colitis. Compared with Il-10(-/-) mice, colitis not only appeared earlier but also was more severe in Il-10(-/-)/Mkp-1(-/-) mice. Il-10(-/-) mice exhibited a mild intestinal inflammation in the specific pathogen-free environment, and rectal prolapse rarely appeared before 6 mo of age. In contrast, the majority of Il-10(-/-)/Mkp-1(-/-) mice developed severe colitis rapidly and presented with rectal prolapse after only 2-3 mo. The colon of Il-10(-/-)/Mkp-1(-/-) mice showed diffuse transmural chronic inflammation and mucosal hyperplasia, with significantly more proliferating crypt epithelial cells than those of Il-10(-/-) mice. In addition to the severe colitis, Il-10(-/-)/Mkp-1(-/-) mice also developed conjunctivitis and blepharitis. The colon of Il-10(-/-)/Mkp-1(-/-) mice contained significantly higher levels of proinflammatory cytokines and exhibited greater MAPK activities than did the colon of Il-10(-/-) mice. Splenocytes and lymphocytes from Il-10(-/-)/Mkp-1(-/-) mice produced higher levels of Th1 cytokines ex vivo upon activation than did cells from Il-10(-/-) mice. Our studies support a pivotal role of Mkp-1 as a negative regulator of mucosal immune responses and highlight its protective function against inflammatory bowel disease.

Lysozyme pattern formation in evaporating drops.

Liquid droplets containing suspended particles deposited on a solid, flat surface generally form ringlike structures due to the redistribution of solute during evaporation (the "coffee ring effect"). The forms of the deposited patterns depend on interactions between solute(s), solvent, and substrate. In this study, deposition patterns from droplets of a simplified model biological fluid (DI water + lysozyme) are examined by scanning probe and optical microscopy. The overall lysozyme residue morphology is complex (with both a perimeter "rim" and undulating interior) but varies little with concentration. However, the final packing of lysozyme molecules is strongly dependent on initial concentration.

Safety of pediatric percutaneous liver biopsy performed by interventional radiologists.

OBJECTIVE: National data suggest that pediatric percutaneous liver biopsy is increasingly being performed by interventional radiologists rather than pediatric gastroenterologists. The objective of the present report is to describe the safety and effectiveness of percutaneous liver biopsy performed by interventional radiologists in a large cohort of children and to compare the results with the existing literature on biopsies performed by pediatric gastroenterologists. PATIENTS AND METHODS: The medical records of 249 children undergoing ultrasound-guided percutaneous liver biopsy by interventional radiologists were reviewed for adverse events and success of obtaining tissue. Two hundred ninety-four biopsies were reviewed. RESULTS: There were no deaths. There were 2 instances of a 2-g or greater drop in hemoglobin following biopsy, neither of which was associated with clinical signs of hemorrhage. A small, asymptomatic pneumothorax quickly resolved without treatment. One patient developed Klebsiella sepsis 48  hours after biopsy. In all but 1 case, an adequate sample size was obtained. This low incidence of adverse events compares favorably with existing published reports of morbidity and mortality following percutaneous liver biopsy performed by pediatric gastroenterologists. CONCLUSIONS: Ultrasound-guided percutaneous liver biopsy performed by experienced pediatric interventional radiologists in a children's hospital setting is as safe and effective as biopsy performed by pediatric gastroenterologists.

ZAS3 accentuates transforming growth factor ß signaling in epithelial cells.

In mammals, the ZAS family of transcription factors activates or represses transcription depending on the cellular context. In the current study, we explored the interaction between ZAS3 and TGFß1 signaling in epithelial cells using HEK293 cells and the intestinal epithelial cell line, RIE-1. Endogenous ZAS3 expression was detected in each cell line and the small intestine of mice. Additionally, endogenous ZAS3 expression was increased in both whole cell and nuclear lysates by TGFß1 and in vivo in TGFß-overexpressing mice, indicating a potential interaction between ZAS3 and TGFß. ZAS3 transfection enhanced TGFß1 activation of a luciferase reporter in both HEK293 and RIE-1 cells. Analysis of truncated ZAS3 constructs revealed a 155 amino acid, N-terminal sequence between amino acids 106 and 261 that was required for enhancement of TGFß1-mediated transcription. Co-immunoprecipitation experiments with nuclear extracts from TGFß1-stimulated HEK293 cells revealed an association between ZAS3 and the Smad complex. Additionally, transfected ZAS3 decreased the association between the Smad complex and the TGFß transcriptional repressors Ski and SnoN, indicating a possible mechanism for the enhancement of transcription by exogenous ZAS3. These observations were confirmed by site-directed mutagenesis of ZAS domains homologous with Smad-interacting domains in Ski and SnoN. Finally, ZAS3 transfection enhanced the TGFß1-mediated induction of α-smooth muscle actin in HEK293 cells, indicating that ZAS3 plays a functional role in TGFß signaling. In conclusion, we have identified an interaction between ZAS3 and Smad proteins that enhances TGFß signaling. Since TGFß signaling is primarily known as a negatively regulated pathway, the enhancement of signaling by ZAS3 has novel implications for understanding TGFß biology.

Vectorial TGFbeta signaling in polarized intestinal epithelial cells.

Polarized gastrointestinal epithelial cells form tight junctions that spatially separate apical and basolateral cell membrane domains. These domains harbor functionally distinct proteins that contribute to cellular homeostasis and morphogenesis. Transforming growth factor beta (TGFbeta) is a critical regulator of gastrointestinal epithelial cell growth and differentiation. Functional assays of vectorial TGFbeta signaling and immunofluorescence techniques were used to determine the localization of TGFbeta receptors and ligand secretion in polarizing Caco-2 cells, a colon cancer cell line. Results were compared to the nontransformed MDCK cell line. In both Caco-2 and MDCK cells, addition of TGFbeta1 to the basolateral medium resulted in phosphorylation of Smad2. No phosphorylation was observed when TGFbeta1 was added to the apical chamber, indicating that receptor signaling is localized at the basolateral membrane. In support of this, immunofluorescence and biotinylation assays show receptor localization along the basolateral membrane. Secretion of TGFbeta1 from MDCK and Caco-2 cells into the apical or basolateral medium was measured by ELISA. Interestingly, secretion was exclusively apical in the nontransformed MDCK line and basolateral in transformed Caco-2 cells. Collectively, these results show basolateral domain specificity in localization of the TGFbeta receptor signaling apparatus. These observations have important implications for understanding the biology of TGFbeta in polarized epithelia, including elements of communication between epithelial and mesenchymal layers, and will prove useful in the design of therapeutics that target TGFbeta function.