Oral vancomycin is associated with improved inflammatory bowel disease clinical outcomes in primary sclerosing cholangitis-associated inflammatory bowel disease (PSC-IBD): A matched analysis from the Paediatric PSC Consortium.

BACKGROUND: Data on oral vancomycin for primary sclerosing cholangitis (PSC)-associated inflammatory bowel disease (IBD) are limited. AIMS: Using data from the Paediatric PSC Consortium, to examine the effect of vancomycin on IBD activity. METHODS: In this retrospective multi-centre cohort study, we matched vancomycin-treated and untreated patients (1:3) based on IBD duration at the time of primary outcome assessment. The primary outcome was Physician Global Assessment (PGA) of IBD clinical activity after 1 year (±6 months) of vancomycin. We used generalised estimating equations (GEE) to examine the association between vancomycin and PGA remission, adjusting for IBD type, severity and medication exposures. Secondary outcomes included serum labs and endoscopic remission (global rating of no activity) among those with available data and also analysed with GEE. RESULTS: 113 PSC-IBD patients received vancomycin (median age 12.7 years, 63% male). The matched cohort included 70 vancomycin-treated and 210 untreated patients. Vancomycin was associated with greater odds of IBD clinical remission (odds ratio [OR] 3.52, 95% CI 1.97-6.31; adjusted OR [aOR] 5.24, 95% CI 2.68-10.22). Benefit was maintained in sensitivity analyses restricted to non-transplanted patients and those with baseline moderate-severe PGA. Vancomycin was associated with increased odds of endoscopic remission (aOR 2.76, 95% CI 1.002-7.62; N = 101 with data), and with lower CRP (p = 0.03) and higher haemoglobin and albumin (both p < 0.01). CONCLUSION: Vancomycin was associated with greater odds of IBD clinical and endoscopic remission. Additional, preferably randomised, controlled studies are needed to characterise efficacy using objective markers of mucosal inflammation, and to examine safety and define optimal dosing.

Pediatric primary care clinicians' views on needs and challenges in caring for infants with intrauterine opioid exposure and their families.

Opioid use disorder (OUD) during pregnancy has risen in the U.S. over the past two decades, resulting in a growing number of children with intrauterine opioid exposure (IOE). Limited research exists supporting best practices to optimize primary care for these children and their families, particularly mothers with OUD. Using a modified Delphi method, we surveyed pediatric primary care clinicians from a single children's health care system regarding their experiences in caring for this population. In Phase 1, open-ended survey questions inquired about needs and challenges facing these infants, their families, and clinicians and resources within primary care. After thematic analysis, the most frequent responses were presented as a Phase 2 survey for clinicians to select their top five. Percentages for the most commonly selected top five themes were tabulated. Survey response rates were 58/139 (42%) for Phase 1 and 45/137 (33%) for Phase 2. For infants with IOE and their families, respondents identified parenting knowledge and family issues related to maternal OUD as top challenges, with limited resources to address them in primary care. Clinicians identified time constraints and follow-up issues as top challenges. Future intervention in pediatric primary care could include addressing parenting education, resource gaps, and best practice recommendations in caring for children with IOE.

Disparities in Vision Screening in Primary Care for Young Children With Autism Spectrum Disorder.

OBJECTIVES: To determine the rate of vision screening among children with and without autism spectrum disorder (ASD), the rate of photoscreening compared with visual acuity screening, and the effect of demographic factors on vision screening for children with ASD. METHODS: Data from well visits for 3- to 5-year-olds between January 2016 and December 2019 were collected via PEDSnet. Billing codes for vision screening were a proxy for the completion of vision screening. χ2 analysis examined the relationship of age, sex, race, ethnicity, region, and socioeconomic status to vision screening rate and rate of photoscreening versus visual acuity screening. Multivariate logistic regression assessed factors that impacted the odds of vision screening. RESULTS: We analyzed 63 829 well-child visits. Children with ASD were less likely to have a vision screening (36.5%) compared with children without ASD (59.9%). The lowest rates of screening occurred during the 3-year visit. Of those with ASD, Black children had a lower screening rate (27.6%) than white (39.7%) and other/multiracial children (39.8%). The use of photoscreening was higher in Hispanic children, increasing the overall rate of vision screening greater than non-Hispanic children. Practice region influenced the rates of vision screening for children with ASD because of more photoscreening. CONCLUSIONS: Children with ASD are less likely to receive vision screening at well visits compared with typically developing children. This disparity was greatest among younger children and Black children. One practice region used more photoscreening and had higher rates of screening. Photoscreening is a useful tool to decrease disparity, especially among high-risk patient groups.

The Intestinal Tract Brush Border in Young Children Uniformly Expresses Guanylate Cyclase C.

The present study examined staining of guanylate cyclase C (GCC/GUCY2C) in the small and large intestines of children younger than age 7 years. Normal intestinal tissue from children aged 0 to 7 years was stained using GCC, uroguanylin, and villin antibodies and scored for staining intensity. A subset underwent quantitative real-time polymerase chain reaction. Data were analyzed using t test of independent means, descriptive statistics, and logistic regression. Four hundred sixty-four specimens underwent immunohistochemistry; 291 specimens underwent real-time polymerase chain reaction. GCC, villin, and uroguanylin were detected across age groups and anatomic sites. No significant differences were identifiable across age groups. GUCY2C and uroguanylin mRNA was detected in all samples, with no variability of statistical significance of either target-to-villin normalization between any age cohorts. A gradient of expression of GCC across age groups does not seem to exist.

Impact of Early Feeding: Metagenomics Analysis of the Infant Gut Microbiome.

Background: Different feeding regimens in infancy alter the gastrointestinal (gut) microbial environment. The fecal microbiota in turn influences gastrointestinal homeostasis including metabolism, immune function, and extra-/intra-intestinal signaling. Advances in next generation sequencing (NGS) have enhanced our ability to study the gut microbiome of breast-fed (BF) and formula-fed (FF) infants with a data-driven hypothesis approach. Methods: Next generation sequencing libraries were constructed from fecal samples of BF (n=24) and FF (n=10) infants and sequenced on an Illumina HiSeq 2500. Taxonomic classification of the NGS data was performed using the Sunbeam/Kraken pipeline and a functional analysis at the gene level was performed using publicly available algorithms, including BLAST, and custom scripts. Differentially represented genera, genes, and NCBI Clusters of Orthologous Genes (COG) were determined between cohorts using count data and R (statistical packages edgeR and DESeq2). Results: Thirty-nine genera were found to be differentially represented between the BF and FF cohorts (FDR ≤ 0.01) including Parabacteroides, Enterococcus, Haemophilus, Gardnerella, and Staphylococcus. A Welch t-test of the Shannon diversity index for BF and FF samples approached significance (p=0.061). Bray-Curtis and Jaccard distance analyses demonstrated clustering and overlap in each analysis. Sixty COGs were significantly overrepresented and those most significantly represented in BF vs. FF samples showed dichotomy of categories representing gene functions. Over 1,700 genes were found to be differentially represented (abundance) between the BF and FF cohorts. Conclusions: Fecal samples analyzed from BF and FF infants demonstrated differences in microbiota genera. The BF cohort includes greater presence of beneficial genus Bifidobacterium. Several genes were identified as present at different abundances between cohorts indicating differences in functional pathways such as cellular defense mechanisms and carbohydrate metabolism influenced by feeding. Confirmation of gene level NGS data via PCR and electrophoresis analysis revealed distinct differences in gene abundances associated with important biologic pathways.

Association of Positional Plagiocephaly and Developmental Delay Within a Primary Care Network.

OBJECTIVE: Previous research has suggested an association between plagiocephaly and developmental delay. However, study samples drawn from children seen in subspecialty clinics increase the potential for selection and referral bias. Our study evaluates the association between plagiocephaly and developmental delay and the timing of these diagnoses in a primary care setting, where plagiocephaly is commonly diagnosed and managed. METHODS: Our retrospective analysis used electronic medical record data from 45 primary care sites within a children's health system from 1999 to 2017, including children aged 0 to 5 years with diagnoses determined by physician diagnosis codes at primary care visits. Children were classified in the plagiocephaly group if diagnosis occurred by 12 months of age. Primary outcome was any developmental delay. Pearson χ2 test, Fisher exact test, and logistic regression analyses were conducted, with multivariable models adjusted for sex, race, ethnicity, insurance, prematurity status (22-36 weeks' gestation), primary care sites, birth year, and diagnoses of abnormal tone and torticollis. RESULTS: Of 77,108 patients seen by 12 months, 2315 (3.0%) were diagnosed with plagiocephaly, with an increase in diagnosis prevalence over the study time frame. Plagiocephaly was independently associated with an increased odds of any developmental delay diagnosis (adjusted odds ratio 1.50, 95% confidence interval 1.32-1.70). The diagnosis of plagiocephaly was recorded before the diagnosis of developmental delay in most cases when both diagnoses were present (374 of 404, 92.6%). CONCLUSION: Data from a large primary care cohort demonstrate an association between plagiocephaly and developmental delay, affirming findings in previous subspecialty literature.

Whole genome metagenomic analysis of the gut microbiome of differently fed infants identifies differences in microbial composition and functional genes, including an absent CRISPR/Cas9 gene in the formula-fed cohort.

BACKGROUND: Advancements in sequencing capabilities have enhanced the study of the human microbiome. There are limited studies focused on the gastro-intestinal (gut) microbiome of infants, particularly the impact of diet between breast-fed (BF) versus formula-fed (FF). It is unclear what effect, if any, early feeding has on short-term or long-term composition and function of the gut microbiome. RESULTS: Using a shotgun metagenomics approach, differences in the gut microbiome between BF (n = 10) and FF (n = 5) infants were detected. A Jaccard distance principle coordinate analysis was able to cluster BF versus FF infants based on the presence or absence of species identified in their gut microbiome. Thirty-two genera were identified as statistically different in the gut microbiome sequenced between BF and FF infants. Furthermore, the computational workflow identified 371 bacterial genes that were statistically different between the BF and FF cohorts in abundance. Only seven genes were lower in abundance (or absent) in the FF cohort compared to the BF cohort, including CRISPR/Cas9; whereas, the remaining candidates, including autotransporter adhesins, were higher in abundance in the FF cohort compared to BF cohort. CONCLUSIONS: These studies demonstrated that FF infants have, at an early age, a significantly different gut microbiome with potential implications for function of the fecal microbiota. Interactions between the fecal microbiota and host hinted at here have been linked to numerous diseases. Determining whether these non-abundant or more abundant genes have biological consequence related to infant feeding may aid in understanding the adult gut microbiome, and the pathogenesis of obesity.

Immunohistochemical Staining for Uroguanylin, a Satiety Hormone, is Decreased in Intestinal Tissue Specimens From Female Adolescents With Obesity.

Gastrointestinal tract-secreted satiety hormones play a significant role in one of the largest health-care challenges for children and adults, obesity. Recent studies in mice identified a novel role for uroguanylin, the endogenous intestinal hormone that binds guanylyl cyclase C (GUCY2C), in regulating satiety via a gut-brain signaling pathway. Mice bred without GUCY2C receptors over-ate and developed obesity. We hypothesized that intestinal uroguanylin expression in pediatric patients with obesity would be lower than patients without obesity, and we attempted to examine the difference with immunohistochemistry. Retrospective chart review of gastrointestinal endoscopic procedures at an academic children's hospital identified patients with normal pathology findings on biopsy. Children aged 8-17 were included in the review; we analyzed biopsy samples from 20 matched pairs that differed only by body mass index (BMI)-for-age (average: 25%-75% vs. high: >95%). Biopsies of the duodenum, terminal ileum, ascending colon, and descending colon were subjected to immunohistochemistry for GUCY2C, uroguanylin, and the endogenous colonic hormone, guanylin. Intensity staining of all specimens was scored by a blinded pathologist. The overall staining intensity for females with high BMI-for-age was less for uroguanylin and guanylin as compared to average BMI-for-age females while GUCY2C staining was equal. Males did not exhibit different staining intensities for uroguanylin or guanylin. More matched female pairs had greater uroguanylin and guanylin staining in the average BMI-for-age cohort. The intestinal expression of uroguanylin, a key satiety hormone, appears to be diminished in female pediatric patients in the setting of obesity.

Pilot Study Measuring the Novel Satiety Hormone, Pro-Uroguanylin, in Adolescents With and Without Obesity.

OBJECTIVE: Disruption of satiety signaling may lead to increased caloric intake and obesity. Uroguanylin, the intestinal hormone, travels as a precursor to the central nervous system where it activates guanylyl cyclase C and stimulates pro-satiety neurons. Rodent studies have demonstrated that guanylyl cyclase C-knockout mice overeat and have increased weight gain versus wild-type mice and hyper-caloric obesity diminishes uroguanylin expression. We measured circulating plasma pro-uroguanylin, along with other gastrointestinal peptides and inflammatory markers, in human adolescents with and without obesity, as a pilot study. We hypothesized that adolescents with obesity would have less circulating pro-uroguanylin than adolescents without obesity have. METHODS: We recruited 24 adolescents (age 14-17 years) with and without obesity (body mass index >95% or body mass index <95%) and measured plasma pro-uroguanylin at fasting and successive time points after a meal. We measured 3 other satiety hormones and 2 inflammatory markers to characterize overall satiety signaling and highlight any link between uroguanylin and inflammation. RESULTS: Female adolescents with obesity had lower circulating pro-uroguanylin levels than female adolescents without obesity; we observed no difference in males. Other measured gastrointestinal peptides varied in their differences between cohorts. Inflammatory markers were higher in female participants with obesity. CONCLUSIONS: In adolescents with and without obesity, we can measure circulating pro-uroguanylin levels. In female adolescents without obesity, levels are particularly higher. Pro-uroguanylin secretion patterns differ from other circulating gastrointestinal peptides. In female adolescents with obesity, inflammation correlates with decreased pro-uroguanylin levels.

General Pediatrician-Staffed Behavioral/Developmental Access Clinic Decreases Time to Evaluation of Early Childhood Developmental Disorders.

OBJECTIVE: To describe and evaluate the effectiveness of a quality improvement project to decrease wait time to evaluation for children referred to Developmental Behavioral Pediatricians (DBPs). METHODS: The authors created a Behavioral/Developmental Access Clinic (BDAC) staffed by a general pediatrician (GP) and pediatric psychologist. Clinicians in the BDAC provided comprehensive developmental evaluations for children in a discrete age range (<5 yr old). We describe the establishment of the BDAC along with referrals, diagnoses, and recommended follow-up for patients seen by the GP. We used 2-tailed t tests to compare the mean time with initial evaluation for patients seen in BDAC versus a DBP. RESULTS: Sixty-three children were seen in BDAC over 6 months. Referrals from the BDAC included: physical/occupational/speech therapy (71%), psychology (35%), audiology (25%), genetics (14%), and neurology (8%). Five patients (8%) were diagnosed with autism spectrum disorder (ASD). Compared with time to appointment with a DBP (327 d), mean time to developmental assessment was shorter for the 45 patients who accepted earlier appointments in the BDAC (159 d), and for the 18 children seen in the BDAC as new referrals (11 d), p < .001. Follow-up with a DBP was recommended for 9 (50%) of the new patient referrals evaluated in BDAC. CONCLUSION: The BDAC allowed for earlier developmental assessment of young children, with potential for earlier diagnosis and treatment of developmental disorders, including ASD. Opportunity for initial evaluation in BDAC decreased the number of patients requiring evaluation by DBPs, improving access to this subspecialty in our institution.

Pediatrician preferences, local resources, and economic factors influence referral to a subspecialty access clinic.

BACKGROUND: Pediatric patients seek timely access to subspecialty care within a complex delivery system while facing barriers: distance, economics, and clinician shortages. Aim We examined stakeholder perceptions about solutions to the access challenge. We engaged over 300 referring primary care pediatricians in the evaluation of Access Clinics at an academic children's hospital. METHODS: Using an anonymous online survey, we asked pediatricians about their and their patients' experiences and analyzed factors that may influence referrals. Findings Referring pediatricians reported satisfaction; they provided feedback about their patients' experiences, physician communication, and referral influences. Distance from the Access Clinic does not correlate with differences in referral volume; living in areas with higher child populations and higher median income is associated with more referrals. Referring pediatricians have strong opinions about referrals, are attuned to patient experiences, and desire bi-directional communication. Multiple factors influence referral to and acceptance of Access Clinics, but external influences have less impact than expected.

A new model to decrease time-to-appointment wait for gastroenterology evaluation.

OBJECTIVE: To describe the implementation and evaluation of a quality improvement intervention to increase new-patient access and decrease time-to-appointment wait for gastroenterology care. METHODS: We used a new model of care for gastroenterology evaluation. For specified clinical complaints, we offered new-patient appointments that were scheduled with a general pediatrician as an alternative to a subspecialist. A nurse navigator assisted in triaging patients. We analyzed all patient encounters over an 8-month period. To verify decreased time-to-appointment wait, mystery shoppers made semimonthly calls to centralized scheduling. We surveyed parents/families after visits with the pediatrician or subspecialists regarding satisfaction. RESULTS: The "access" pediatrician evaluated and treated ∼40% of all new patients presenting to the division during the study period. Approximately 10% of new patients evaluated by the pediatrician (4% overall) were referred on to the subspecialist; fewer patients were reevaluated by the pediatrician in follow-up. The pediatrician ordered a minimal number of procedures. Semimonthly sampling revealed that overall new-patient access improved from an average time-to-appointment wait of 25 days to <1 day. Parent/family satisfaction was high for the patients evaluated by the pediatrician. CONCLUSIONS: Embedding a general pediatrician within a subspecialty division, and navigating patients to this provider, can increase access to treatment of new low- to moderate-complexity patients. The access pediatrician can maintain patient satisfaction, provide high-quality care, and decrease need for subspecialist evaluation. The model, in the setting of a large academic medical center, may provide a solution for barriers to patient care such as lengthy time-to-appointment wait.

Aortic pseudoaneurysm in a child with a left mainstem bronchial stent.

OBJECTIVE: To report a case of aortic pseudoaneurysm in a child with a metallic bronchial stent. DESIGN: Case report and literature review. SETTING: Pediatric intensive care unit at a freestanding tertiary children's hospital. PATIENT: A 12-yr-old boy with a left mainstem bronchomalacia managed with a metallic stent presenting with bleeding from his tracheostomy. INTERVENTIONS: Emergent flexible tracheobronchoscopy, computed tomography angiogram. MEASUREMENTS AND MAIN RESULTS: Discovery of a pseudoaneurysm of the descending thoracic aorta adjacent to the bronchial stent. CONCLUSIONS: We report the first case of an aortic pseudoaneurysm in association with a bronchial stent in a child.