Bess T. Schoen

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;)

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;)

Improved Outcomes in a Quality Improvement Collaborative for Pediatric Inflammatory Bowel Disease

OBJECTIVES: Unintended variation in the care of patients with Crohn disease (CD) and ulcerative colitis (UC) may prevent achievement of optimal outcomes. We sought to improve chronic care delivery and outcomes for children with inflammatory bowel disease by using network-based quality improvement methods. METHODS: By using a modified Breakthrough Series collaborative structure, 6 ImproveCareNow Network care centers tested changes in chronic illness care and collected data monthly. We used an interrupted time series design to evaluate the impact of these changes. RESULTS: Data were available for 843 children with CD and 345 with UC. Changes in care delivery were associated with an increase in the proportion of visits with complete disease classification, measurement of thiopurine methyltransferase (TPMT) before initiation of thiopurines, and patients receiving an initial thiopurine dose appropriate to their TPMT status. These were significant in both populations for all process variables (P < .01) except for measurement of TPMT in CD patients (P = .12). There were significant increases in the proportion of CD (55%–68%) and UC (61%–72%) patients with inactive disease. There was also a significant increase in the proportion of CD patients not taking prednisone (86%–90%). Participating centers varied in the success of achieving these changes. CONCLUSIONS: Improvements in the outcomes of patients with CD and UC were associated with improvements in the process of chronic illness care. Variation in the success of implementing changes suggests the importance of overcoming organizational factors related to quality improvement success.

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;)

Inflammatory bowel disease in African-American children living in Georgia.

We describe the clinical characteristics of inflammatory bowel disease (IBD) African-American compared with non-African-American children. We identified 172 children with IBD; forty-nine (29%) were African-American. Median symptom duration before IBD diagnosis in African-American children (6 months) was shorter than that of non-African-American children (10 months). The most frequent presenting symptom was hematochezia (ulcerative colitis) and abdominal pain (Crohns disease) in both racial groups. The estimated incidence of Crohns disease in African-Americans ranged from 7 per 100,000 to 12 per 100,000, whereas the observed incidence in those with ulcerative colitis was between 5 and 7 per 100,000 during the 10 years of the study. Our pilot study suggests that IBD may be more common in African-American children than previously reported. Prospective population-based studies would be useful to determine whether inheritable factors linked with ethnicity are associated with IBD.

Vitamin D status and bone mineral density in African American children with Crohn disease.

Background: Vitamin D deficiency and low bone mineral density (BMD) are complications of inflammatory bowel disease. Vitamin D deficiency is more prevalent among African Americans compared with whites. There are little data comparing differences in serum 25-hydroxyvitamin D (25OHD) concentrations and BMD between African American and white children with Crohn disease (CD). Methods: We compared serum 25OHD concentrations of African American children with CD (n = 52) to white children with CD (n = 64) and healthy African American controls (n = 40). We also analyzed BMD using dual-energy x-ray absorptiometry results from our pediatric CD population. Results: African American children with CD had lower serum 25OHD concentrations (16.1 [95% confidence interval, CI 14.5–17.9] ng/mL) than whites with CD (22.3 [95% CI 20.2–24.6] ng/mL; P < 0.001). African Americans with CD and controls exhibited similar serum 25OHD concentration (16.1 [95% CI 14.5–17.9] vs 16.3 [95% CI 14.4–18.4] ng/mL; NS). African Americans with CD exhibited no difference in serum 25OHD concentration when controlling for seasonality, disease severity, and surgical history, although serum 25OHD concentration was significantly decreased in overweight children (body mass index ≥85%, P = 0.003). Multiple regression analysis demonstrated that obese African American girls with CD had the lowest serum 25OHD concentrations (9.6 [95% CI 6.8–13.5] ng/mL). BMD was comparable between African American and white children with CD (z score −0.4 ± 0.9 vs −0.7 ± 1.2; NS). Conclusions: African American children with CD are more likely to have vitamin D deficiency compared with white children with CD, but have similar BMD. CD disease severity and history of surgery do not affect serum 25OHD concentrations among African American children with CD. African American children have low serum 25OHD concentrations, independent of CD, compared with white children. Future research should focus on how race affects vitamin D status and BMD in children with CD.

Infliximab Optimization Based on Therapeutic Drug Monitoring in Pediatric Inflammatory Bowel Disease

Background: Infliximab (IFX) is an effective treatment for the management of moderate to severe inflammatory bowel disease (IBD). Low-serum IFX levels are associated with the development of antibodies to IFX (ATI), which subsequently associated with clinical relapse and increased morbidity. The primary purpose of this study is to examine the relation between dose and interval to IFX level. Secondary goal is to evaluate the relation between IFX level and ATI in a pediatric IBD population. Methods: We performed a retrospective chart review of all children diagnosed with IBD and treated with IFX at a tertiary care pediatric IBD center. We performed our analysis based on prescribed dosing intervals and rounded dose up to 5 or 10 mg/kg as indicated in clinical practice. Results: Our study included 278 samples from 129 children on IFX. ATI were detected in 37 samples (13.3%). Low IFX levels (<3 &mgr;g/mL) were detected in 37.2% of children receiving IFX. Samples with ATI present had significantly lower levels of IFX than samples in which ATI were not present. For the dose 5 mg/kg, Q6 dosing had significantly higher IFX levels than Q8 dosing (P = 0.009). Higher IFX levels were seen with interval shortening rather than dose escalation. Conclusions: We demonstrate that low IFX levels are associated with development of immunogenicity to IFX as measured by ATI. We demonstrate that interval shortening rather than dose escalation results in higher IFX levels. We suggest that given the high number of IFX levels below 3 &mgr;g/mL in patients, early IFX level evaluation or primary initiation of Q6 week dosing be considered.

Pilot Study Evaluating Efficacy of 2 Regimens for Hypovitaminosis D Repletion in Pediatric Inflammatory Bowel Disease

Objectives: Vitamin D is critical for skeletal health; hypovitaminosis D is common in pediatric inflammatory bowel disease (IBD), yet optimal repletion therapy is not well studied. We aimed to conduct a pilot trial comparing the efficacy of 2 vitamin D regimens of weekly dosing for the repletion of hypovitaminosis D in pediatric IBD. Methods: Subjects identified from our IBD clinic with 25-hydroxyvitamin D (25[OH]D) concentrations <30 ng/mL were randomized to 10,000 (n = 18) or 5000 (n = 14) IU of oral vitamin D3/10 kg body weight per week for 6 weeks. Serum 25(OH)D, Ca, and parathyroid hormone concentrations were measured at baseline, week 8, and week 12. Results: In the higher dosing group, serum 25(OH)D increased from 23.7 ± 8.5 ng/mL at baseline to 49.2 ± 13.6 ng/mL at 8 weeks; P < 0.001. In the lower dosing group, serum 25(OH)D increased from 24.0 ± 7.0 ng/mL at baseline to 41.5 ± 9.6 ng/mL at 8 weeks; P < 0.001. At 12 weeks, serum 25(OH)D concentrations were 35.1 ± 8.4 and 30.8 ± 4.2 ng/mL for the higher and lower dose regimens, respectively. Mean serum Ca and parathyroid hormone concentrations did not significantly change during the study. No patient exhibited hypercalcemia, and no serious adverse events occurred. Conclusions: Both treatment arms were safe and effective at normalizing vitamin D nutriture in pediatric IBD. Although significant repletion of 25(OH)D concentration was achieved in both dosing groups at 8 weeks, this effect was lost by the 12-week follow-up. Maintenance vitamin D therapy following initial repletion is likely required to maintain long-term normalized vitamin D status.

Use of Reticulocyte Hemoglobin Content in the Assessment of Iron Deficiency in Children with Inflammatory Bowel Disease

Background: Iron deficiency and anemia affect up to 50% to 75% of patients with inflammatory bowel disease (IBD). Iron deficiency in IBD may be difficult to diagnose because of the effect of inflammation on iron status biomarkers. Thus, there is a need for better methods to accurately determine iron status in IBD. Objective: The aim of the study was to investigate the association of inflammation with hemoglobin content of reticulocytes (CHr) and the utility of CHr in comparison to standard iron biomarkers. Methods: We conducted a cross-sectional study of children with IBD. Iron biomarkers (CHr, ferritin, soluble transferrin receptor [sTfR], hepcidin, hemoglobin) were measured along with systemic biomarkers of inflammation (C-reactive protein, &agr;1-acid glycoprotein]. Spearman correlations were used to evaluate the relation of inflammation and iron biomarkers. The criterion standard for iron deficiency was defined as inflammation-corrected ferritin <15 &mgr;g/L or sTfR >8.3 mg/L. Receiver operating characteristic curves were used to estimate the prognostic values of all iron biomarkers to identify patients with iron deficiency. Results: We analyzed data in 62 children ages 5 to 18 years. Sixty-nine percent of our subjects had Crohn disease and 31% had ulcerative colitis, of which 42% were girls and 53% African American. The prevalence of anemia was 32%, of iron deficiency was 52% using ferritin <15 &mgr;g/L or sTfR >8.3 mg/L, 39% using red blood cell distribution width of >14.5%, 26% using body iron stores of <0 mg/kg body weight, 25% using CHr of <28 pg, and 11% using mean corpuscular volume of <75 fL/cell. The prevalence of elevated CRP or AGP was 48%. After correcting ferritin and sTfR levels for inflammation, the prevalence of iron deficiency was 68%. CHr was correlated with C-reactive protein (rs −0.44, P < 0.001) and &agr;1-acid glycoprotein (rs −0.37, P < 0.05). The optimal prognostic value for inflammation-adjusted CHr to predict iron deficiency was 34 pg (area under the receiver operating characteristic of 0.70), with 88% sensitivity and 30% specificity. Conclusions: Iron deficiency and anemia are common in this pediatric IBD cohort. All explored iron biomarkers, including CHr, were affected by inflammation and should be adjusted. A single iron biomarker is unlikely to best predict iron deficiency in pediatric IBD. Iron intervention studies are needed to examine the response of iron biomarkers to iron supplementation in the setting of inflammation.

Mucosal Healing in Clinical Practice: A Single-Center Pediatric IBD Experience

Background: Mucosal healing (MH) is associated with improved clinical outcomes in patients with Crohns disease (CD) and ulcerative colitis (UC). MH as a target for treatment has been suggested, although there is little pediatric data. The goal of this study was to evaluate MH in clinical practice in pediatric patients with inflammatory bowel disease in clinical remission. Methods: A retrospective review of electronic health record data was performed on all patients with CD or UC who underwent at least 2 colonoscopies from 2010 through 2016. Only patients in clinical remission undergoing a scope for MH were included in our study. The incidence of MH and histologic healing (HH) was analyzed, along with cumulative rates of MH in each group. MH was defined by both physician assessment of MH and an endoscopic score of zero for CD and UC. Results: A total of 76 patients with CD and 28 patients with UC underwent at least one MH scope while in clinical remission. Of the 76 patients with CD, 51 patients (67%) demonstrated MH by physician assessment, 34 patients (45%) demonstrated MH by a simple endoscopic score for CD of zero, and 35 patients (46%) demonstrated HH. Of the 28 patients with UC, 20 patients (71%) demonstrated MH by physician assessment, 10 patients (36%) demonstrated MH by a Mayo score of zero, and 10 patients (36%) demonstrated HH. Nineteen patients underwent a second MH scope and 11 (58%) demonstrated MH by physician assessment, 7 patients (37%) demonstrated MH by simple endoscopic score for CD or Mayo scores of zero, and 5 patients (26%) demonstrated HH. Of those patients with active disease, 21 of 25 patients with CD underwent escalation of therapy, whereas 8 of 8 patients with UC underwent escalation of therapy. Cumulative rates of MH when defined by physician assessment were 79% (60 of 76 patients) in CD and 79% (22 of 28 patients) in UC. Conclusions: MH is feasible in pediatric CD and UC, and rates of cumulative MH in pediatric patients are similar to previously published adult data. In children with inflammatory bowel disease in clinical remission, approximately one-third demonstrate active disease at endoscopy.