High Body Mass Index and Response to Anti-Tumor Necrosis Factor Therapy in Pediatric Crohn's Disease.

INTRODUCTION: Obesity is common among patients with pediatric Crohn's disease (PCD). Some adult studies suggest obese patients respond less well to anti-tumor necrosis factor (TNF) treatment. This study sought compares anti-TNF response and anti-TNF levels between pediatric patients with normal and high body mass index (BMI). METHODS: The COMBINE trial compared anti-TNF monotherapy with combination therapy with methotrexate in patients with PCD. In this secondary analysis, a comparison of time-to-treatment failure among patients with normal BMI vs BMI Z -score >1, adjusting for prescribed anti-TNF (infliximab [IFX] or adalimumab [ADA]), trial treatment assignment (combination vs monotherapy), and relevant covariates. Median anti-TNF levels across BMI category was also examined. RESULTS: Of 224 participants (162 IFX initiators and 62 ADA initiators), 111 (81%) had a normal BMI and 43 (19%) had a high BMI. High BMI was associated with treatment failure among ADA initiators (7/10 [70%] vs 12/52 [23%], hazard ratio 0.29, P = 0.007) but not IFX initiators. In addition, ADA-treated patients with a high BMI had lower ADA levels compared with those with normal BMI (median 5.8 vs 12.8 µg/mL, P = 0.02). IFX trough levels did not differ between BMI groups. DISCUSSION: Overweight and obese patients with PCD are more likely to experience ADA treatment failure than those with normal BMI. Higher BMI was associated with lower drug trough levels. Standard ADA dosing may be insufficient for overweight children with PCD. Among IFX initiators, there was no observed difference in clinical outcomes or drug levels, perhaps due to weight-based dosing and/or greater use of proactive drug monitoring.

Treatment and biologic maintenance-dosing patterns among pediatric patients with ulcerative colitis or Crohn's disease.

OBJECTIVES: To assess treatment patterns and initial and maintenance dosing of biologics over 3 years in pediatric patients with ulcerative colitis (UC) or Crohn's disease (CD), utilizing data from the ImproveCareNow registry. METHODS: Pediatric patients diagnosed with UC or CD and aged 2-17 years were included in the study. Descriptive statistics were employed to summarize baseline demographics. The proportion of patients on medication for UC or CD were analyzed at the baseline visit, 1-year, and 3-year time points (Cohort 1). Biologic maintenance dosage was calculated only for patients who had data for dose and weight at all-time points (Cohort 2). RESULTS: In Cohort 1 (UC = 1784; CD = 4720), baseline treatment in UC included corticosteroid, 5-ASA, and 6-MP/AZA; at 1-year and 3-year time points, treatment with 5-ASA and corticosteroid decreased, whereas 6-MP/AZA and anti-TNFs increased. In CD, baseline treatment included corticosteroid, anti-TNF, 6-MP/AZA, and methotrexate; use of corticosteroids decreased, whereas the use of methotrexate and anti-TNFs increased over 3 years. In Cohort 2 (UC = 350; CD = 1537), at first maintenance dose, UC patients on infliximab received a mean dose of 10.5 mg/kg/8 wk, adalimumab (weight < 40 kg and ≥40 kg) 1.3 mg/kg/2 wk and 0.8 mg/kg/2 wk, and vedolizumab 6.9 mg/kg/8 wks. At the first maintenance dose, CD patients on infliximab received a mean dose of 8.1 mg/kg/8 wk, adalimumab (weight < 40 kg) 1.1 mg/kg/2 wk, adalimumab (weight ≥ 40 kg) 0.8 mg/kg/2 wk, and vedolizumab 10.5 mg/kg/8 wks. CONCLUSION: The use of corticosteroids was common at the initial visit in patients. Anti-TNFs remain the most used class of biologics, however, reported doses in our study were substantially higher than the standard dosing guidelines.

North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Position Paper on Entrustable Professional Activities: Development of Pediatric Gastroenterology, Hepatology, and Nutrition Entrustable Professional Activities.

Quality training in pediatric gastroenterology, hepatology, and nutrition is essential for the future of our specialty from advancing the science through research to providing clinical care for children with gastrointestinal, hepatic and nutritional disorders. As educational theory has developed, both the American Board of Pediatrics (ABP) and the Accreditation Council for Graduate Medical Education (ACGME) have commissioned projects to better define training including core competencies, and milestones with the goal of competency-based assessment. Seeking to provide a clinical context for these competencies and milestones, the ABP commissioned a project for each pediatric subspecialty to develop entrustable professional activities (EPA) while at the same time developing EPAs that are common to all pediatric subspecialties. North American Society for Pediatric Gastroenterology, Hepatology, Nutrition (NASPGHAN) commissioned an EPA Task Force to develop the pediatric gastroenterology, hepatology and nutrition EPAs. This document serves as an introduction to EPAs, including their historical background, underlying educational theory, and the process used to develop the pediatric gastroenterology, hepatology and nutrition EPAs in the United States of America.

Implementing a Novel Quality Improvement-Based Approach to Data Quality Monitoring and Enhancement in a Multipurpose Clinical Registry.

OBJECTIVE: To implement a quality improvement based system to measure and improve data quality in an observational clinical registry to support a Learning Healthcare System. DATA SOURCE: ImproveCareNow Network registry, which as of September 2019 contained data from 314,250 visits of 43,305 pediatric Inflammatory Bowel Disease (IBD) patients at 109 participating care centers. STUDY DESIGN: The impact of data quality improvement support to care centers was evaluated using statistical process control methodology. Data quality measures were defined, performance feedback of those measures using statistical process control charts was implemented, and reports that identified data items not following data quality checks were developed to enable centers to monitor and improve the quality of their data. PRINCIPAL FINDINGS: There was a pattern of improvement across measures of data quality. The proportion of visits with complete critical data increased from 72 percent to 82 percent. The percent of registered patients improved from 59 percent to 83 percent. Of three additional measures of data consistency and timeliness, one improved performance from 42 percent to 63 percent. Performance declined on one measure due to changes in network documentation practices and maturation. There was variation among care centers in data quality. CONCLUSIONS: A quality improvement based approach to data quality monitoring and improvement is feasible and effective.

Proactively Optimized Infliximab Monotherapy Is as Effective as Combination Therapy in IBD.

Background: Infliximab (IFX) discontinuation is not uncommon during the first year of treatment due to inadequate drug concentrations and anti-IFX antibodies (ATI). Both combination therapy and proactive therapeutic drug monitoring (pTDM) are used to decrease ATI and increase IFX durability. We proposed that monotherapy (Mono) is as effective as combination therapy (Combo) if the first maintenance infusion is dosed based on week 10 pTDM. Methods: In a retrospective cohort of 83 patients with inflammatory bowel disease (IBD), we examined the frequency of IFX discontinuation, ATI, infusion reactions, and IFX concentrations during the first year of treatment in patients receiving week 10 pTDM-guided IFX monotherapy (Mono pTDM; n = 16) compared with patients on mono (n = 32) or combination therapy (n = 35) in whom TDM was introduced at or after week 14, per standard of care (SOC). Results: The frequency of IFX discontinuation was lower with Mono pTDM compared with Mono SOC (P = 0.04) but did not differ with Combo SOC (P = 1). At first TDM, no patient in the pTDM strategy had ATI, vs 41% in Mono SOC (P = 0.002) and 6% in Combo SOC (P = 1). Of the 13 subjects with ATI in Mono SOC, 7 (47%) had ATI already at week 14. IFX trough concentrations with Mono pTDM were higher during maintenance compared with Mono SOC (9.5 vs 6.4 µg/mL, P = 0.04) but not Combo SOC. Conclusions: Infliximab durability did not differ between patients on IFX monotherapy dosed based on p-TDM and patients receiving combination therapy. In the absence of concomitant immunosuppression, proactive TDM may improve IFX durability by maintaining higher IFX concentrations entering into maintenance. Further studies are needed to confirm our findings.

Patient-reported Anxiety: A Possible Predictor of Pediatric Inflammatory Bowel Disease Health Care Use.

BACKGROUND: Anxiety is linked with adverse health-related outcomes and increased health-seeking behaviors among patients with chronic illness. Yet, this relationship has received little attention in pediatric inflammatory bowel disease. The aim of this study was to examine whether anxiety symptoms predicted youth at increased risk for repeated disease relapse and greater gastrointestinal health care use over the subsequent 12 months. METHODS: Eighty-six pediatric patients aged 11 to 18 years (M = 14.7, SD = 2.0), and their caregivers completed a validated anxiety questionnaire during a gastrointestinal specialty appointment (baseline). Medical records were reviewed for the subsequent year to record the number of disease relapses and gastrointestinal health care services and generate disease activity scores at baseline and 12 months. Analysis of variance was used to examine anxiety levels between those who experienced ≤1 versus ≥2 disease relapses. Poisson regressions were used to model the relationship between child- and caregiver-reported anxiety and health care use, controlling for disease activity. RESULTS: The sample was predominantly white (81%) and male (56%). Patients with higher anxiety at baseline (M = 19.6; SD = 13.7) had more frequent (≥2) disease relapses compared with those with lower anxiety at baseline (M = 12.6; SD = 10.3). Higher anxiety, irrespective of reporter, also predicted greater total gastrointestinal health care use (P < 0.01). This included hospital-based interventions (P < 0.01), but not office encounters or outpatient endoscopic procedures. Findings remained significant after controlling for disease severity (P < 0.05). CONCLUSIONS: Assessment of anxiety may be one mechanism by which to identify those youth who are most vulnerable for disease exacerbation and costly interventions in the near future.

Anxiety symptoms and disease severity in children and adolescents with Crohn disease.

OBJECTIVES: Children and adolescents diagnosed as having Crohn disease (CD), a type of inflammatory bowel disease (IBD), have increased vulnerability for anxiety symptoms that may be related to disease-related processes. The aims of this article are 3-fold: to report the proportion of pediatric patients with CD whose self-reported anxiety symptoms are indicative of distress, to describe the constellation of anxiety symptoms, and to examine the relation between anxiety and disease symptoms. METHODS: Retrospective medical chart review was performed for 93 youths with CD (ages 9-18 years) who had completed the Screen for Child Anxiety Related Disorders during their gastroenterology visit. Medical records were reviewed for demographic and disease characteristics. the Harvey-Bradshaw Index (HBI) was used as a measure of CD activity. RESULTS: Thirty percent of the youths reported experiencing elevated anxiety symptoms (Screen for Child Anxiety Related Disorder score >20), and 50% had scored above the cutoff in 1 or more anxiety domains, with school anxiety, general anxiety, and separation anxiety symptoms reported most frequently. Youth rated with moderate/severe disease activity on the HBI (n = 4) self-reported more anxiety symptoms compared with youth with inactive disease (n = 78, P = 0.03). Greater school anxiety was significantly associated with decreased well-being (P = 0.003), more abdominal pain (P < 0.001), and the number of loose stools (P = 0.01). Having extraintestinal symptoms was significantly associated with higher somatic/panic anxiety (P = 0.01). CONCLUSIONS: Implementing a brief anxiety screen in tertiary pediatric settings may be one approach to identify young patients with CD in distress. Health care providers should consider periodic assessment of school anxiety among youth with CD.

Integrating illness concerns into cognitive behavioral therapy for children and adolescents with inflammatory bowel disease and co-occurring anxiety.

PURPOSE: To examine the feasibility and preliminary benefits of an integrative cognitive behavioral therapy (CBT) with adolescents with inflammatory bowel disease and anxiety. DESIGN AND METHODS: Nine adolescents participated in a CBT program at their gastroenterologist's office. Structured diagnostic interviews, self-report measures of anxiety and pain, and physician-rated disease severity were collected pretreatment and post-treatment. RESULTS: Postintervention, 88% of adolescents were treatment responders, and 50% no longer met criteria for their principal anxiety disorder. Decreases were demonstrated in anxiety, pain, and disease severity. PRACTICE IMPLICATIONS: Anxiety screening and a mental health referral to professionals familiar with medical management issues is important.

Analysis of current treatments used in clinical practice in a pediatric summer camp population for children with inflammatory bowel disease.

BACKGROUND: Many treatment options exist for children with inflammatory bowel disease (IBD), yet the lack of clinical guidelines for management has lead to great variation in care. The purpose of this project was to evaluate current treatment modalities in children from the Northeast US who applied to the 2010 session of Camp Oasis, a Crohn's and Colitis Foundation of America (CCFA)-sponsored camp for children ages 8-17 with medically stable IBD. METHODS: Patient demographics, medical history, and current medications were entered into the camp database. The subjects were divided into two groups; Crohn's disease (CD) or ulcerative colitis/indeterminate colitis (UC/IC). In all, 164 applicants were included, 121 (74%) with CD and 43 (26%) with UC/IC. RESULTS: There were no significant differences between the two groups with respect to median age at the time of camp, median age at diagnosis, or median length of illness. Of the 121 applicants with CD, 13 (10.7%) were on an antibiotic, 56 (46.3%) were on a 5-aminosalicylate (5-ASA), 10 (8.3%) were on corticosteroids, 57 (47.1%) were on immunomodulators, and 44 (36.4%) were on a biologic agent. Six (5%) were on both an immunomodulator and a biologic agent. Of the 43 subjects with UC/IC, 27 (62.7%) were on a 5-ASA, two (4.7%) were on corticosteroids, 13 (30.2%) were on an immunomodulator, and four (9.3%) were on a biologic agent. The groups were similar with regard to surgery (20.7% for CD and 18.6% for UC/IC). CONCLUSIONS: Identifying current treatment patterns may serve to highlight variations in care among this pediatric IBD population.

Illness-specific anxiety: implications for functioning and utilization of medical services in adolescents with inflammatory bowel disease.

PURPOSE. Adolescents with inflammatory bowel disease (IBD) may be at heightened risk for developing anxiety and depression. This cross-sectional pilot study examined the relationship between anxiety and depression and health-related behaviors. METHODS. Thirty-six adolescents with diagnosed IBD, ages 12-17, and their parents were recruited from two pediatric gastroenterology medical centers. RESULTS. Clinical levels of anxiety (22%) and depressive symptoms (30%) were reported by patients. Regression analyses revealed that IBD-specific anxiety was significantly associated with greater utilization of medical services and worsened psychosocial functioning. PRACTICE IMPLICATIONS. Results provide preliminary support that IBD-specific anxiety may play an important role in disease management, yet concerns are rarely systematically assessed by health professionals.

Duodenal and rectal hematomas complicating endoscopic biopsy: use of sonography in pediatrics.

OBJECTIVE: Intramural duodenal hematomas (IDHs) after nontherapeutic endoscopic biopsy are rare. Rectal hematomas (RHs) have not been reported previously. A review of the literature revealed 18 cases of IDHs. METHODS: We reviewed 3 cases that occurred within a 4-month period at our institution. RESULTS: We report a series of 3 cases occurring within a 4-month period. In addition, we report a concurrent RH in 1 of these cases. After becoming symptomatic, 2 of these patients had a diagnosis by computed tomography, the third by sonography. All patients had conservative management and were followed with sonography. CONCLUSIONS: Sonography was found to be an accurate, safe, and nonionizing way to diagnose and follow hematomas in pediatric patients.

CBT for anxiety and associated somatic complaints in pediatric medical settings: an open pilot study.

OBJECTIVE: To examine the initial feasibility and potential efficacy of a cognitive-behavioral intervention for youth with anxiety disorders and non-medical somatic symptoms. BACKGROUND: Based on a strong relationship between somatic complaints and anxiety disorders, screening youngsters seeking medical care due to physical symptoms with no organic basis may enhance the recognition of anxiety disorders and facilitate access to appropriate services. METHOD: Seven boys and girls, ages 8 through 15, with medically unexplained gastrointestinal complaints and anxiety disorders received a 12-session cognitive-behavioral intervention targeting anxiety and physical symptoms. Assessments were conducted at baseline and following treatment. RESULTS: All participants were classified as treatment responders. Three of the seven participants no longer met diagnostic criteria for their principal anxiety disorder. Children's physical discomfort decreased from a moderate to minimal level based on self- and parent-reports. CONCLUSIONS: Our modified cognitive-behavioral approach has promise for reducing anxiety and somatic symptoms in children seeking medical care.

NOD2/CARD15 variants are associated with lower weight at diagnosis in children with Crohn's disease.

OBJECTIVES: NOD2/CARD15 variants have recently been shown to be associated with Crohn's disease (CD). No analysis of NOD2/CARD15 gene variants has so far been reported in pediatric patients. Therefore, our aim was to analyze NOD2/CARD15 gene variants in children with CD and to perform genotype-phenotype analyses. METHODS: We studied 101 children with CD and 136 healthy controls. Detailed phenotypic information was obtained from each patient. Patients were genotyped for the three NOD2/CARD15 variants R702W (single nucleotide polymorphism 8 [SNP8]), G908R (SNP12), and L1007fs (SNP13), and genotype-phenotype correlations were performed. RESULTS: We found 33 NOD2/CARD15 mutations in 29 of 101 patients (29%). The frequency of NOD2 variation was 31% in white (n=87) compared with 11% in controls (chi2=14; p=0.0001; OR=3.7; 95% CI=1.7-7.8). Four white patients but not control subjects were compound heterozygotes. NOD2/CARD15 variants were significantly associated with ileal disease (chi2=4.5; p=0.03; OR=5; 95% CI=0.9-35.9). Of the children with NOD2/CARD15 variants, 44% were < or =5th percentile for weight at diagnosis, whereas only 15% of children without mutations were < or =5th percentile (chi2=8.7; p=0.003; OR=4.5; 95% CI=1.4-14.4). Similar trends were observed for height but they did not reach statistical significance. CONCLUSIONS: Our results demonstrate that: 1) the three NOD2/CARD15 variants confer risk to CD in children; 2) NOD2/CARD15 variants are associated with ileal disease in children as in adults; and 3) NOD2/CARD15 variants are associated with lower weight percentiles at diagnosis in children and a tendency toward lower height percentile, suggesting an association between growth in children with CD.