Adam Mezoff

Evaluation of the pediatric crohn disease activity index: a prospective multicenter experience.

Background and Objectives: Longitudinal assessment of disease activity is necessary for studies of therapeutic intervention in children with Crohn disease. The Pediatric Crohn Disease Activity Index (PCDAI) was developed a decade ago for such a purpose, but it function has only been examined in a small number of studies with a limited number of patients. The primary objectives of the present study were to develop cut scores reflecting disease activity as determined by physician global assessment (PGA) and to evaluate the responsiveness of the PCDAI to changes in patient condition after therapeutic interventions. Methods: Data were derived from a prospective database of newly diagnosed children with inflammatory bowel disease established in 2002 at 18 pediatric gastroenterology centers in the United States and Canada. At diagnosis, at 30 days and 3 months after diagnosis, and quarterly thereafter, children (<16 years of age) with Crohn disease had disease assessment performed by PGA and PCDAI. Disease management was provided according to the dictates of the attending gastroenterologist and not by predetermined protocol. Results: 181 patients had concomitant PGA and PCDAI performed at diagnosis, and 95 of these had similar assessment at short-term follow up. Mean ± SD PCDAI scores for mild, moderate, and severe disease by PGA at diagnosis were 19.5 ± 10.4, 32.2 ± 12.7, and 47.8 ± 14.9, respectively (P < 0.001 for all comparisons). Mean ± SD PCDAI for inactive disease after treatment was 5.2 ± 5.4. Receiver operating characteristic (ROC) curve analysis suggested that: 1) activity of moderate/severe disease was best reflected by a PCDAI of ≥30 points, 2) clinical response (moderate/severe disease improving to mild/inactive) was best reflected by a decrease in PCDAI of ≥12.5 points, and 3) a PCDAI < 10 best reflected inactive disease. Conclusions: PCDAI scores accurately reflect disease activity as assessed by physician global assessment. A PCDAI score of ≥30 has acceptable sensitivity and specificity to indicate disease of moderate/severe activity. A PCDAI decrease of 12.5 points or greater following therapeutic intervention accurately reflects a clinically significant response. The PCDAI is an appropriate tool for intervention trials in Crohn disease in children.

Effect of early immunomodulator use in moderate to severe pediatric Crohn disease

Background: The immunomodulators (IMs) 6‐mercaptopurine and azathioprine decrease corticosteroid dependence and maintain remission in Crohns disease (CD). We describe IM use in newly diagnosed pediatric CD, comparing outcomes of “early” versus “late” initiation of therapy. Methods: Data were obtained from pediatric CD patients enrolled in a prospective, multicenter observational study. Moderate/severe disease patients treated with IM were compared for outcomes of remission, corticosteroid use, infliximab therapy, hospitalizations, and CD‐related surgery based on timing of initiation of IM therapy. Results: In all, 247 children met the criteria (60% male, mean age 11.9 years); 199 were treated with IM within 1 year of diagnosis; 150 between 0–3 months (early), 49 between 3–12 months (late). Both groups showed a decrease in corticosteroid use by 12 months, at which time proportionately fewer early group patients had received corticosteroids in the preceding quarter (22%) than late groups patients (41%)(P = 0.013). The number of hospitalizations per patient was also noted to be significantly lower in the early group over the 2‐year follow‐up (P = 0.03). No difference was noted in the rates of remission, infliximab use over time, or surgery. Conclusions: 80% of children with newly diagnosed moderate to severe CD are treated with IM within 1 year. Early IM use is associated with reduced corticosteroid exposure and possibly fewer hospitalizations per patient.

Laboratory Values for Children With Newly Diagnosed Inflammatory Bowel Disease

OBJECTIVE. The goal was to determine how often common laboratory tests yield normal results at the time of diagnosis for children with inflammatory bowel disease. METHODS. Data were obtained from a registry of children with newly diagnosed inflammatory bowel disease who were enrolled prospectively in 18 US/Canadian centers. Laboratory values investigated included hemoglobin level, platelet count, albumin level, and erythrocyte sedimentation rate. Disease severity was categorized by physician global assessment. RESULTS. A total of 526 children (mean age: 11.6 years; 58% male; 392 with Crohn disease and 134 with ulcerative colitis) were studied. All 4 values were normal for 21% of patients with mild Crohn disease and 54% with mild ulcerative colitis. In contrast, only 3.8% of children with moderate/severe Crohn disease and 4.3% with moderate/severe ulcerative colitis had normal results for all 4 tests. The erythrocyte sedimentation rate was least likely to be normal; overall, 26% of patients with inflammatory bowel disease had a normal erythrocyte sedimentation rate, including 18% with moderate/severe disease. Hemoglobin levels were normal for 32%, platelet counts for 50%, and albumin levels for 60%. There was no clear association between Crohn disease location and either severity or number of normal laboratory values. In contrast, there were direct correlations between ulcerative colitis disease severity and both the extent of bowel inflammation and the number of abnormal laboratory tests. CONCLUSION. The presence of normal screening laboratory studies should not dissuade clinicians from considering a diagnosis of inflammatory bowel disease.

Health‐related quality of life in the first year after a diagnosis of pediatric inflammatory bowel disease

Background and Aims: Assessment of health‐related quality of life (HRQOL) is of increasing importance in the evaluation of new therapies for inflammatory bowel disease (IBD). Available data concerning HRQOL in pediatric patients are sparse and uniformly cross‐sectional. The aim of this study was to describe HRQOL and influential factors in newly diagnosed pediatric patients with Crohns disease and ulcerative colitis during the first 12 months after diagnosis. Materials and Methods: Participants were drawn from a large, prospectively derived observational IBD registry of pediatric patients studied through 18 U.S. and Canadian centers. Patients who had completed a baseline IMPACT questionnaire and for whom there were 12 months of follow‐up data available were included. In addition to description of cohort, factors that were believed to influence HLQOL were assessed during the course of the year from diagnosis. Results: Two hundred eighteen children met inclusion criteria (77% Crohns disease, 23 % ulcerative colitis, mean age 12.7 ± 1.9 years). Mean total IMPACT score at baseline was 154, 181 at 6 months, and 191 at 1 year (possible range 0‐238, with increasing scores representing better quality of life). Repeated measures analysis showed that age and disease severity significantly negatively affected the IMPACT scores during the course of the year. Conclusions: In this large prospective pediatric IBD cohort, significant improvement in HRQOL is noted during the year from diagnosis. Mean IMPACT scores varied significantly depending on the disease severity and also decreased with increasing age.

Polyethylene glycol for constipation in children younger than eighteen months old.

Background: Polyethylene glycol (PEG) is a safe and effective treatment for constipation in children older than 18 months. Data on its safety and efficacy in infants are lacking. The goal of this study was to determine safety, efficacy, and optimal dose of polyethylene glycol powder for treatment of constipation in patients younger than 18 months. Methods: The authors reviewed the charts of patients younger than 18 months treated with PEG 3350 for constipation. The initial dose, effective maintenance dose, response to therapy, duration of therapy, and side effects were recorded. Results: Twenty-eight patients younger than 18 months of age treated with PEG were identified (3, age 0–5 months; 9, age 6–11 months; 16, age 12–17 months). Mean duration of therapy was 6.2 ± 5 months (range, 3 weeks–21 months). Mean initial dose was 0.88 g/kg/day (range, 0.26–2.14 g/kg/day). Mean effective maintenance dose was 0.78 g/kg/day (range, 0.26–1.26 g/kg/day). PEG relieved constipation in 97.6% of patients. One infant experienced increased gas per rectum and four others experienced transient diarrhea that resolved after adjusting the dose. Conclusion: Oral powdered polyethylene glycol at a maintenance dose of 0.78 g/kg/day is safe and effective for patients younger than 18 months. Dose and safety profiles are similar for those reported in older children.

Hepatitis B Virus Screening for Internationally Adopted Children

OBJECTIVES. The objectives of this study were to estimate the prevalence of hepatitis B virus protection, infection, and recovery among internationally adopted children and to examine the need for repeat testing 6 months after arrival in the United States. METHODS. From November 1999 through October 2006, 1282 international adoptees were screened for hepatitis B virus, and results were examined with regard to age, gender, and birth country. The prevalence of hepatitis B virus protection, infection, and recovery was determined. RESULTS. The prevalence of hepatitis B virus in internationally adopted children at our large international adoption center was 4%, including 1.1% with acute or chronic infection and 2.9% with resolved infection. Overall, 64% of internationally adopted children had evidence of hepatitis B virus immunization, with protective antibodies. We also report a case that highlights the need for repeat serological testing to detect hepatitis B virus infection or immunization in internationally adopted children who might have been infected or vaccinated just before adoption and thus not have serological evidence in initial testing. CONCLUSIONS. These data reinforce the American Academy of Pediatrics recommendations regarding hepatitis B virus screening and infection control measures for international adoptees.

Mechanisms of increased susceptibility of immature and weaned pigs to Escherichia coli heat-stable enterotoxin

ABSTRACT: Pigs demonstrate an increased sensitivity and susceptibility to Escherichia coli heat-stable enterotoxin (STa) in the 1st wk of life and immediately after weaning. To determine the possible mechanisms for this increased susceptibility, we compared STa binding, guanylate cyclase activation, and photoaffinity cross-linking to porcine jejunal brush border membranes prepared from immature (≤ wk of age) versus adult pigs as well as 3-wk-old weaned versus unweaned pigs. The STa binding capacity of immature pigs was nearly twice that of adult pigs (11.73 ± 1.52 versus 6.00 ± 0.96 x 10-11 mol/L, p < 0.001), and the STa binding capacity of weaned pigs was nearly three times greater than that of unweaned pigs (17.48 ± 2.10 versus 4.86 ± 1.02 x 10-11 mol/L, p < 0.001). Scatchard analysis suggested a single class of STa receptor, with an association of binding constant of ∼109 L/mol at all ages. Maximum guanylate cyclase response (expressed as pmol cyclic GMP generated/mg brush border membrane protein/min) was greater in immature versus adult pigs (1312 ± 831 versus 320 ± 92, p < 0.02). Weaned pigs had a greater maximum guanylate cyclase activation than unweaned pigs (1126 ± 692 versus 624 ± 298); however, this difference was not statistically significant. Autoradiograms demonstrated specific cross-linking of 125I-STa to a number of distinct radiolabeled bands (62, 66, 84, 92, 160, and 165 kD). There was a difference in the size and trypsin sensitivity of these radiolabeled bands as a function of age and weaning. Treatment with trypsin decreased the intensity of the 160 to 165-kD bands while increasing the intensity of the 62− to 66− and 84− to 92-kD bands. These differences in STa binding, guanylate cyclase activation, and STa receptor size may increase the susceptibility of pigs during the 1st wk of life and at weaning to STa-mediated diarrheal disease.

Vitamin D deficiency and low bone mineral density in pediatric and young adult intestinal failure.

Objectives: The aim of the present study was to determine the prevalence and predisposing factors for vitamin D deficiency and low bone mineral density (BMD) in patients with intestinal failure (IF). Methods: A retrospective review of patients with IF managed at the Cincinnati Childrens Hospital Medical Center. IF was defined as history of parenteral nutrition (PN) >30 days. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D (25 (OH) D) <20 ng/dL. Reduced BMD was defined using dual x-ray absorptiometry z score ⩽–2. A binary logistic regression model was used to test for association of significant risk factors and the outcome variables after univariate analyses. Results: One hundred and twenty-three patients with median age of 4 years (range 3–22 years) were evaluated. Forty-nine (39.8%) patients had at least a documented serum 25 (OH) D deficiency during the study interval, whereas 10 of 80 patients (12.5%) with dual x-ray absorptiometry scans completed had a low BMD z score. Age at study entry was associated with both 25 (OH) D deficiency (P = 0.01) and low BMD z score (P = 0.03). Exclusive PN at study entry was associated with reduced bone mass (P = 0.03). There was no significant association between vitamin D deficiency and low BMD z score (P = 0.31). Conclusions: The risk of 25 (OH) D deficiency and low BMD z score increases with age among patients with IF. Strategies for monitoring and preventing abnormal bone health in older children receiving exclusive PN need to be developed and evaluated.

Importance of addressing anxiety in youth with functional abdominal pain: suggested guidelines for physicians.

Functional abdominal pain (FAP) is a common pediatric disorder associated with impairment in functioning that may persist for the long term. Anxiety is common in youth with FAP, and may be an important factor in predicting youth who are at greatest risk for increased impairment because of pain symptoms. In this article, we examine the relation between anxiety and impairment in youth with FAP. Furthermore, we explore various biopsychosocial factors (eg, neurobiological substrates, coping strategies, social factors) that may be implicated in the relation among FAP, anxiety, and increased impairment. Finally, we propose physician guidelines for screening and treatment of youth with FAP and co-occurring anxiety. Youth with FAP and co-occurring anxiety may benefit from cognitive-behavioral therapy in the context of multidisciplinary care.

Use of Wireless Capsule Endoscopy in the Management of Severe Henoch-Schonlein Purpura

Henoch-Schonlein purpura is a multisystem vasculitis that primarily affects children. Characteristic symptoms include purpura of the lower extremities and buttocks, abdominal pain, arthralgias, and hematuria. Gastrointestinal bleeding occurs in ∼50% of children and, although often self-limiting, can be significant. Wireless capsule endoscopy has been found to be safe and effective for children over 10 years of age. It is now the preferred imaging modality for evaluating gastrointestinal bleeding from the small intestine. Here we report an unusual case of chronic Henoch-Schonlein purpura vasculitis, primarily affecting the gastrointestinal tract, in which wireless capsule endoscopy was helpful in evaluating and directing treatment options.