Ashish S. Patel

Prevalence and epidemiology of overweight and obesity in children with inflammatory bowel disease

Background: Obesity is a significant public health threat to children in the United States. The aims were to: 1) Determine the prevalence of obesity in a multicenter cohort of children with inflammatory bowel disease (IBD); 2) Evaluate whether overweight and obese status is associated with patient demographics or disease characteristics. Methods: We used data from the ImproveCareNow Collaborative for pediatric IBD, a multicenter registry of children with IBD, collected between April 2007 and December 2009. Children ages 2–18 years were classified into body mass index (BMI) percentiles. Bivariate analyses and multivariate logistic regression were used to compare demographic and disease characteristics by overweight (BMI >85%) and obese (BMI >95%) status. Results: The population consisted of 1598 children with IBD. The prevalence of overweight/obese status in pediatric IBD is 23.6%, (20.0% for Crohns disease [CD] and 30.1% for ulcerative colitis [UC] and indeterminate colitis [IC]). African American race (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.10–2.48) and Medicaid insurance (OR 1.67, 95% CI 1.19–2.34) were positively associated with overweight/obese status. Prior IBD‐related surgery (OR 1.73, 95% CI 1.07–2.82) was also associated with overweight and obese status in children with CD. Other disease characteristics were not associated with overweight and obesity in children with IBD. Conclusions: Approximately one in five children with CD and one in three with UC are overweight or obese. Rates of obesity in UC are comparable to the general population. Obese IBD patients may have a more severe disease course, as indicated by increased need for surgery. Sociodemographic risk factors for obesity in the IBD population are similar to those in the general population. (Inflamm Bowel Dis 2010;)

Increased Effectiveness of Early Therapy With Anti-Tumor Necrosis Factor-α vs an Immunomodulator in Children With Crohn's Disease

BACKGROUND & AIMS Standard therapy for children newly diagnosed with Crohns disease (CD) includes early administration of immunomodulators after initial treatment with corticosteroids. We compared the effectiveness of early (≤3 mo after diagnosis) treatment with an anti-tumor necrosis factor (TNF)α with that of an immunomodulator in attaining clinical remission and facilitating growth of pediatric patients. METHODS We analyzed data from the RISK study, an observational research program that enrolled patients younger than age 17 diagnosed with inflammatory (nonpenetrating, nonstricturing) CD from 2008 through 2012 at 28 pediatric gastroenterology centers in North America. Patients were managed by physician dictate. From 552 children (median age, 11.8 y; 61% male; 63% with pediatric CD activity index scores >30; and median C-reactive protein level 5.6-fold the upper limit of normal), we used propensity score methodology to identify 68 triads of patients matched for baseline characteristics who were treated with early anti-TNFα therapy, early immunomodulator, or no early immunotherapy. We evaluated relationships among therapies, corticosteroid and surgery-free remission (pediatric CD activity index scores, ≤10), and growth at 1 year for 204 children. Treatment after 3 months was a covariate. RESULTS Early treatment with anti-TNFα was superior to early treatment with an immunomodulator (85.3% vs 60.3% in remission; relative risk, 1.41; 95% confidence interval [CI], 1.14-1.75; P = .0017), whereas early immunomodulator therapy was no different than no early immunotherapy (60.3% vs 54.4% in remission; relative risk, 1.11; 95% CI, 0.83-1.48; P = .49) in achieving remission at 1 year. Accounting for therapy after 3 months, early treatment with anti-TNFα remained superior to early treatment with an immunomodulator (relative risk, 1.51; 95% CI, 1.20-1.89; P = .0004), whereas early immunomodulator therapy was no different than no early immunotherapy (relative risk, 1.00; 95% CI, 0.75-1.34; P = .99). The mean height z-score increased compared with baseline only in the early anti-TNFα group. CONCLUSIONS In children newly diagnosed with comparably severe CD, early monotherapy with anti-TNFα produced better overall clinical and growth outcomes at 1 year than early monotherapy with an immunomodulator. Further data will be required to best identify children most likely to benefit from early treatment with anti-TNFα therapy.

ImproveCareNow: The development of a pediatric inflammatory bowel disease improvement network

&NA; There is significant variation in diagnostic testing and treatment for inflammatory bowel disease. Quality improvement science methods can help address unwarranted variations in care and outcomes. Methods: The ImproveCareNow Network was established under the sponsorship of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the American Board of Pediatrics as a prototype for a model of improving subspecialty care that included three components: 1) creating enduring multicenter collaborative networks of pediatric subspecialists, 2) sharing of performance data collected in patient registries, and 3) training in quality improvement. The network began with a focus on improving initial diagnostic testing and evaluation, the classification of the severity and extent of disease, the detection and treatment of inadequate nutrition and growth, and the appropriate dosing of immunomodulator medications. Changes are based on an evidence‐based model of chronic illness care involving the use of patient registries for population management, previsit planning, decision support, promoting self‐management, and auditing of care processes. Results: Currently, patients are being enrolled at 23 sites. Through 2009, data have been analyzed on over 2500 patients from over 7500 visits. Initial results suggest improvements in both care processes (e.g., appropriate medication dosing and completion of a classification bundle that includes the patients diagnosis, disease activity, distribution and phenotype, growth status, and nutrition status) and outcomes (e.g., the percentage of patients in remission). Conclusions: These improvements suggest that practice sites are learning how to apply quality improvement methods to improve the care of patients. (Inflamm Bowel Dis 2011;)

Short pediatric Crohn's disease activity index for quality improvement and observational research†

Background: Practical and objective instruments to assess pediatric Crohns disease (CD) activity are required for observational research and quality improvement. The objectives were: 1) to determine the feasibility of completing the Pediatric Crohns Disease Activity Index (PCDAI) and the Abbreviated PCDAI (APCDAI); and 2) to create a Short PCDAI by retaining and reweighting the most practical and informative components. Methods: Physicians in the ImproveCareNow Collaborative for pediatric inflammatory bowel disease (IBD) were asked to record components of the PCDAI and assign a Physician Global Assessment (PGA) of disease severity at each patient encounter. We assessed the feasibility of the PCDAI, the APCDAI, and the individual index components by determining the proportion of visits in which data were recorded. We created a short index by retaining and reweighting components of the PCDAI completed in ≥80% of visits. The feasibility of the Short PCDAI and its ability to discriminate between PGA categories were evaluated using descriptive statistics. Results: This study population included 1355 subjects with CD (6373 visits). The PCDAI and APCDAI were complete in 16.7% and 44.1% of visits, respectively. A Short PCDAI, including general well‐being, abdominal pain, stools, weight, abdominal exam, and extraintestinal manifestations were completed in 66.5% of visits. The correlation between the Short PCDAI and PGA was similar to that of the PCDAI (r = 0.60, P < 0.001 versus 0.61, P < 0.001). Conclusions: The Short PCDAI is a practical and valid tool to measure pediatric CD activity. Its use should facilitate quality improvement and observational research. (Inflamm Bowel Dis 2011;)

Prediction of complicated disease course for children newly diagnosed with Crohn's disease: a multicentre inception cohort study

BACKGROUND Stricturing and penetrating complications account for substantial morbidity and health-care costs in paediatric and adult onset Crohns disease. Validated models to predict risk for complications are not available, and the effect of treatment on risk is unknown. METHODS We did a prospective inception cohort study of paediatric patients with newly diagnosed Crohns disease at 28 sites in the USA and Canada. Genotypes, antimicrobial serologies, ileal gene expression, and ileal, rectal, and faecal microbiota were assessed. A competing-risk model for disease complications was derived and validated in independent groups. Propensity-score matching tested the effect of anti-tumour necrosis factor α (TNFα) therapy exposure within 90 days of diagnosis on complication risk. FINDINGS Between Nov 1, 2008, and June 30, 2012, we enrolled 913 patients, 78 (9%) of whom experienced Crohns disease complications. The validated competing-risk model included age, race, disease location, and antimicrobial serologies and provided a sensitivity of 66% (95% CI 51-82) and specificity of 63% (55-71), with a negative predictive value of 95% (94-97). Patients who received early anti-TNFα therapy were less likely to have penetrating complications (hazard ratio [HR] 0·30, 95% CI 0·10-0·89; p=0·0296) but not stricturing complication (1·13, 0·51-2·51; 0·76) than were those who did not receive early anti-TNFα therapy. Ruminococcus was implicated in stricturing complications and Veillonella in penetrating complications. Ileal genes controlling extracellular matrix production were upregulated at diagnosis, and this gene signature was associated with stricturing in the risk model (HR 1·70, 95% CI 1·12-2·57; p=0·0120). When this gene signature was included, the models specificity improved to 71%. INTERPRETATION Our findings support the usefulness of risk stratification of paediatric patients with Crohns disease at diagnosis, and selection of anti-TNFα therapy. FUNDING Crohns and Colitis Foundation of America, Cincinnati Childrens Hospital Research Foundation Digestive Health Center.

PedsQL gastrointestinal symptoms module: feasibility, reliability, and validity.

Objective: The objective of this study was to report on the measurement properties of the Pediatric Quality of Life Inventory (PedsQL) Gastrointestinal Symptoms Module for patients with functional gastrointestinal (GI) disorders (FGIDs) and organic GI diseases, hereafter referred to as “GI disorders,” for patient self-report ages between 5 and 18 and parent proxy-report for ages between 2 and 18 years. Methods: The 74-item PedsQL GI Module and 23-item PedsQL Generic Core Scales were completed in a 9-site study by 584 patients and 682 parents. Patients had physician-diagnosed GI disorders (such as chronic constipation, functional abdominal pain, irritable bowel syndrome, functional dyspepsia, Crohn disease, ulcerative colitis, gastroesophageal reflux disease). Results: Fourteen unidimensional scales were derived measuring stomach pain, stomach discomfort when eating, food and drink limits, trouble swallowing, heartburn and reflux, nausea and vomiting, gas and bloating, constipation, blood, diarrhea, worry, medicines, and communication. The PedsQL GI Module Scales evidenced excellent feasibility, excellent reliability for the Total Scale Scores (patient self-report &agr; = 0.97, parent proxy-report &agr; = 0.97), and good-to-excellent reliability for the 14 individual scales (patient self-report &agr; = 0.67–0.94, parent proxy-report &agr; = 0.77–0.95). Intercorrelations with the Generic Core Scales supported construct validity. Individual Symptoms Scales known-groups validity across 7 GI disorders was generally supported. Factor analysis supported the unidimensionality of the individual scales. Conclusions: The PedsQL GI Module Scales demonstrated acceptable-to-excellent measurement properties and may be used as common metrics to compare GI-specific symptoms in clinical research and practice both within and across patient groups for FGIDs and organic GI diseases.

Update in Pediatrics: Focus on Fat-Soluble Vitamins

This article provides an update on fat-soluble vitamins (A, D, E, and K) in the healthy pediatric population and in children with chronic disease states that commonly cause deficiencies, specifically cystic fibrosis and cholestatic liver disease. For each fat-soluble vitamin, the biological function, nutrition availability, absorption, deficiency, toxic states, and monitoring parameters are defined.

Fecal Calprotectin in Children with the Enthesitis-related Arthritis Subtype of Juvenile Idiopathic Arthritis

To the Editor: Subclinical gut inflammation is present in two-thirds of adult and pediatric patients with spondyloarthritis (SpA)1,2 and predicts a chronic course of arthritis2,3. Thus, there may be value in evaluating the gut in patients with SpA. However, commonly used tests, such as colonoscopy, barium studies, and computed tomography, are limited by expense, invasiveness, or radiation exposure4, prompting a need for noninvasive surrogate markers. Serologic markers revealed a large number of false-positive tests5. Fecal calprotectin is a sensitive and specific marker for the presence of inflammatory bowel disease or other intestinal illnesses6. This test has not heretofore been used to assess for subclinical gut inflammation in patients with arthritis. In this study, we measured fecal calprotectin levels in children with enthesitis-related arthritis (ERA), comparing them to children with non-SpA subtypes of juvenile idiopathic arthritis (JIA), as well as children with unrelated connective tissue diseases (CTD) and noninflammatory control subjects. We enrolled 4 groups of children: (1) 9 with the ERA subtype of JIA; (2) 17 with other subtypes of JIA [persistent oligoarticular, n = 6; extended oligoarticular, n = 1; rheumatoid factor-negative (RF–) polyarticular, n = 8; RF+ polyarticular, n = 2]; (3) 9 with unrelated CTD (dermatomyositis, n = 3; localized scleroderma, n = … Address correspondence to Dr. Punaro; E-mail: Marilynn.Punaro{at}TSRH.org.

A subset of cranial fasciitis is associated with dysregulation of the Wnt/β-catenin pathway

Cranial fasciitis, an unusual fibroproliferative lesion that occurs in the scalp of infants, is considered a posttraumatic reactive process similar to nodular fasciitis. Its pathobiology has not been investigated. Over the last 15 years, we diagnosed cranial fasciitis in six children; in one case, the lesion recurred after 4 years. This lesion and two others showed aberrant, diffuse nuclear reactivity for β-catenin. One of the lesions with aberrant nuclear β-catenin occurred in a child with a history of familial adenomatous polyposis (FAP) and a germline frameshift adenomatous polyposis coli (APC) mutation, c.878delG. The other APC allele in this tumor showed an acquired nonsense mutation, c.4132C → T. Both these mutations lead to translation of a truncated APC protein. The other two cases of cranial fasciitis with aberrant nuclear β-catenin occurred sporadically. One of these showed a point mutation, c.122C → T, in exon 3 of CTNNB1. This mutation causes replacement of threonine with isoleucine at codon 41, leading to loss of a phosphorylation site in the β-catenin protein. The third case with nuclear β-catenin staining was the single one that showed recurrence. This tumor did not show mutations in exon 3 of CTNNB1 or in exons 8/9/16 of APC. The results of this small study indicate a dysregulation of the Wnt/β-catenin pathway in a subset of cranial fasciitis, suggesting that this subset is pathobiologically related to desmoid fibromatoses rather than to nodular fasciitis. Occasional cases of cranial fasciitis may be associated with FAP and serve as an early indicator of this disease, information that would be important in the early diagnosis of FAP in patients without a family history of polyposis.

Lymphocytic esophagitis in children

Background:Lymphocytic esophagitis (LE) is a term recently suggested for the finding of >20 intraepithelial lymphocytes/high-power field in an esophageal biopsy with no more than a rare granulocyte. Two prior studies of LE suggested an association of LE with Crohns disease (CD) in young patients, but there has been no systematic review of a large pediatric cohort to determine the prevalence and clinical associations of LE in children. Methods:All esophageal biopsies performed at a tertiary care pediatric medical center in 2005 were identified (580 biopsies from 545 unique patients). A blinded histologic review was performed to identify LE cases (>50 intraepithelial lymphocytes/high-power field; <1 granulocyte/50 intraepithelial lymphocytes). Clinical characteristics, endoscopic findings, and follow-up data for each case were reviewed independently by a pediatric gastroenterologist. Results:Thirty-one patients with LE (5.7%) and 49 patients with CD (8.9%) were found among the 545 patients. Six of the 31 LE patients (19%) and 43 of the 514 non-LE patients (8.4%) had CD (P < 0.05). The remaining LE patients had various other clinical diagnoses with no significant clinical correlates. LE was identified in 6 of 49 patients with CD (12.2%) and 25 of 496 patients without CD (5.0%) (P < 0.05). Patients with both LE and CD had a more prominent lymphocytic infiltrate than LE patients without CD. Conclusions:LE seems to be more prevalent in children than in adults and has a significant association with CD in this age group.