Vasundhara Tolia

A randomized, double-blind trial of lactobacillus GG versus placebo in addition to standard maintenance therapy for children with Crohn's disease

&NA; Probiotics are widely used by patients with Crohns disease (CD) in an attempt to improve their health, but few controlled studies have been done to evaluate the efficacy of these therapies. We conducted a randomized, placebo‐controlled trial of the probiotic Lactobacillus rhamnosus strain GG (LGG) to see if the addition of LGG to standard therapy prolonged remission in children with CD. Concomitant medications allowed in the study included aminosalicylates, 6‐mercaptopurine, azathioprine, and low‐dose alternate day corticosteroids. Seventy‐five children (age range, 5‐21 yr) with CD in remission were randomized to either LGG (n = 39) or placebo (n = 36) and followed for up to 2 years. The median time to relapse was 9.8 months in the LGG group and 11.0 months in the placebo group (P = 0.24); 31% (12/39) of patients in the LGG group developed a relapse compared with 6/36 (17%) of the placebo group (P = 0.18). The LGG was well tolerated, with a side effect profile comparable with placebo. This study suggests that LGG does not prolong time to relapse in children with CD when given as an adjunct to standard therapy.

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.

Complementary Medicine Use in Children and Young Adults With Inflammatory Bowel Disease

OBJECTIVES:We examined the use of complementary alternative medicine (CAM) in children and young adults with inflammatory bowel disease.METHODS:After validation of a questionnaire and completion of a pilot survey, children and young adults with inflammatory bowel disease were enrolled in three centers of pediatric gastroenterology (Boston, Detroit, and London).RESULTS:Two hundred eight questionnaires were completed in total (Boston, 120; Detroit, 37; London, 51). Ages ranged from 3.8 to 23.0 yr, 58% were male, 57% had Crohns disease, and 35% had ulcerative colitis. The frequency of CAM use was 41%. The most common CAMs were megavitamin therapy (19%), dietary supplements (17%), and herbal medicine (14%). Parental CAM use and the number of adverse effects from conventional medicines were predictors of CAM use (odds ratio = 1.9, 95% CI = 1.2–3.1, p = 0.02; odds ratio = 1.3, 95% CI = 1.2–1.5, p < 0.001, respectively). The most important reasons respondents gave for using CAM were side effects from prescribed medicines, prescribed medicines not working as well as they had hoped, and hoping for a cure. Fifty-nine percent of respondents not taking CAM were interested in learning more about it.CONCLUSIONS:In our survey over 40% of children with chronic inflammatory bowel disease used complementary medicine in addition to conventional therapies. Parental CAM use and number of adverse effects from conventional therapies were the only independent predictors of CAM use. Some complementary therapies have potential for adverse effects and for drug interactions with conventional treatments. Physicians should take a thorough history of CAM use in children with chronic inflammatory bowel disease.

Gastric emptying using three different formulas in infants with gastroesophageal reflux.

Summary The role of delayed gastric emptying (GE) in the pathogenesis of gastroesophageal reflux (GER) in infants is controversial at present. GE has been shown to be altered by the composition and osmolality of the feedings. This prospective study was undertaken to assess the changes in the GE and the percentage of time GER was detected by scintigraphy using three different formulas on consecutive days in infants with GER. Twenty-eight infants under 1 year of age diagnosed to have GER by extended intraesophageal pH monitoring (pH being <4.0 for >5% of the duration of the test), underwent scintigraphy on three consecutive days using the same volume per single feeding of a casein-predominant, soy, or a wheyhydrolysate formula in a randomized order. The formulas were isocaloric. Gastric emptying and percentage of GER into the esophagus were estimated for 60 min following these feedings. Mean GER percent during the study was 20.39, 17.68, and 16.34 on casein-predominant, soy, and whey-hydrolysate formulas, respectively, and was not significantly different. Mean values of GE were 39.7%, 44.6%, and 48.5% on casein, soy, and whey formula, respectively. No significant difference in GE was also observed between casein-predominant and soy formula. However, a significant difference was observed (p < 0.05) on GE between casein-predominant and whey-hydrolysate feedings. Our data suggest that formula selection may be important in the treatment of conditions associated with delayed gastric emptying.

Age-specific Questionnaires Distinguish Gerd Symptom Frequency and Severity in Infants and Young Children: Development and Initial Validation

Two gastroesophageal reflux disease (GERD) symptom questionnaires were developed and tested prospectively in a pilot study conducted in infants (1 through 11 months) and young children (1 through 4 years) with and without a clinical diagnosis of GERD. A pediatric gastroenterologist made the clinical diagnosis of GERD. Parents or guardians at 4 study sites completed the questionnaires, providing information on the frequency and severity of symptoms appropriate to the 2 age cohorts. In infants, symptoms assessed were back arching, choking or gagging, hiccups, irritability, refusal to feed and vomiting or regurgitation. In young children, symptoms assessed were abdominal pain, burping or belching, choking when eating, difficulty swallowing, refusal to eat and vomiting or regurgitation. Respondents were asked to describe additional symptoms. Symptom frequency was the number of occurrences of each symptom in the 7 days before completion of the questionnaire. Symptom severity was rated from 1 (not at all severe) to 7 (most severe). An individual symptom score was calculated as the product of symptom frequency and severity scores. The composite symptom score was the sum of the individual symptom scores. The mean composite symptom and individual symptom scores were higher in infants (P < 0.001 and P < 0.05, respectively) and young children (P < 0.001 and P < 0.05, respectively) with GERD than controls. Vomiting/regurgitation was particularly prevalent in infants with GERD (90%). Both groups with GERD were more likely to experience greater severity of symptoms. We found the GERD Symptom Questionnaire useful in distinguishing infants and young children with symptomatic GERD from healthy children.

Comparative phenotypic and CARD15 mutational analysis among African American, Hispanic, and white children with Crohn's disease

Background: Despite a large body of literature on the subject of Crohns disease (CD), very little information is available on racial/ethnic differences related to disease presentation, clinical course, and genetics. The first identified CD susceptibility gene, CARD15, seems to be present in up to 40% of white children with CD. However, the frequency of this gene among patients with CD of other racial/ethnic groups in the United States is not known. Methods: We conducted a multicenter study on African American and Hispanic children with CD to describe the phenotypic and genotypic (CARD15) features in comparison with white children with CD. We also analyzed the frequency of CARD15 mutations in large control samples from white, African American, and Hispanic children. Results: The disease location and behavior were similar among all 3 groups, with inflammatory behavior and the ileocolonic location being the most frequent phenotype. However, significantly lower frequencies of CARD15 mutations were seen in African American (P < 0.0001) and Hispanic (P < 0.0001) children with CD compared with white children with CD. This lower CARD15 frequency among African American patients with CD was also mirrored in the general population. Conclusions: Phenotypic features of CD are similar among African American and Hispanic children compared with white children. CARD15 mutations are not increased among African American and Hispanic children with CD. CARD15 mutational frequencies among African American and Hispanic children within the general population are lower compared with white children within the general population. Future genetics studies will be required to determine the relationships between genotype and CD phenotype in various ethnic and racial groups.

Analysis of the vacA, cagA, cagE, iceA, and babA2 genes in Helicobacter pylori from sixty-one pediatric patients from the Midwestern United States

This study was designed to characterize H. pylori from pediatric gastric biopsy specimens in terms of several genes (vacA, cagA, cagE, iceA1, iceA2, and babA2) proposed to be involved in the pathogenesis of this organism. Many of these genes have been studied in adult H. pylori isolates, however, these genes have not been well characterized in H. pylori from children. Using PCR we observed that 44% of the H. pylori in our biopsies shared two common genotypes (vacA s1b m1, cagA, cagE, iceA2 +/- babA2). While 26% of the H. pylori had unique genotypes. The cag pathogenicity island associated genes, cagA and cagE, were found together in 64% or our H. pylori, while 84% were iceA2 positive. The presence of the babA2 gene has been proposed to be associated with a higher risk of H. pylori related diseases, however, we found that only 36% of our H. pylori contained this gene.

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.

Evaluation of the use of botulinum toxin in children with achalasia

BACKGROUND Achalasia is rare in children. Recently, injection of botulinum toxin into the lower esophageal sphincter has been studied as an alternative to esophageal pneumatic dilatation or surgical myotomy as treatment for achalasia. In the current study, the effects of botulinum toxin were investigated in the largest known series of children with achalasia. METHODS Treatment for achalasia was assessed in 23 pediatric patients who received botulinum toxin from June 1995 through November 1998. Those who continued to receive botulinum toxin and did not subsequently undergo pneumatic dilatation or surgery were considered repeat responders. Results were compared with those of published studies evaluating the use of botulinum toxin in adults with achalasia. RESULTS Nineteen patients initially responded to botulinum toxin. Mean duration of effect was 4.2 months +/- 4.0 (SD). At the end of the study period, three were repeat responders, three experienced dysphagia but did not receive pneumatic dilatation or surgery, three underwent pneumatic dilatation, eight underwent surgery, three underwent pneumatic dilatation with subsequent surgery, and three awaited surgery. Meta-analysis shows that, in the current study group, the data point expressing time of follow-up evaluation versus percentage of patients needing one injection session without additional procedures (botulinum toxin injection, pneumatic dilatation, or surgery) falls within the curve for those in studies on adult patients receiving botulinum toxin for achalasia. CONCLUSIONS Botulinum toxin effectively initiates the resolution of symptoms associated with achalasia in children. However, one half of patients are expected to need an additional procedure approximately 7 months after one injection session. The authors recommend that botulinum toxin be used only for children with achalasia who are poor candidates for either pneumatic dilatation or surgery.

Pharmacokinetic and pharmacodynamic study of midazolam in children during esophagogastroduodenoscopy

We undertook a prospective study to evaluate the relationship between the onset and degree of sedation and the midazolam plasma concentration in children between 6 and 18 years of age during esophagogastroduodenoscopy. Thirteen boys and seven girls (median age 13.5 years) were studied. Midazolam was injected intravenously for 5 minutes, and the dose was titrated to sedation or a maximum dose of 0.1 mg/kg was given. Plasma midazolam concentration was determined just before and at 5, 10, 15, 30, 45, and 60 minutes after the start of midazolam injection. The patients level of sedation was evaluated by an assistant at each blood sampling time. Clearance, volume of distribution, and terminal elimination (beta) half-life were estimated from a biexponential fit of the serial plasma midazolam concentrations. Mean beta half-life of midazolam was 47 +/- 26 minutes and mean clearance was 10.0 +/- 5.0 ml/min per kilogram of body weight. Maximum level of sedation occurred at 5 minutes after initiation of the injection and corresponded to a mean peak midazolam serum concentration of 229 +/- 39 micrograms/L. Thereafter, a decline of mean sedation scores paralleled the decrease in midazolam concentration. Mean oxygen saturation remained greater than 94% during the study. We conclude that children metabolize and excrete midazolam more rapidly than adults do and that sedation adequate for endoscopy is safely achieved in the majority of children with a midazolam dose of 0.05 to 0.1 mg/kg and a mean peak midazolam concentration greater than 200 microgram/L.