Dennis L. Christie

Serum Immune Responses Predict Rapid Disease Progression among Children with Crohn's Disease: Immune Responses Predict Disease Progression

BACKGROUND AND AIM:Crohns disease (CD) is a heterogeneous disorder characterized by diverse clinical phenotypes. Childhood-onset CD has been described as a more aggressive phenotype. Genetic and immune factors may influence disease phenotype and clinical course. We examined the association of immune responses to microbial antigens with disease behavior and prospectively determined the influence of immune reactivity on disease progression in pediatric CD patients.METHODS:Sera were collected from 196 pediatric CD cases and tested for immune responses: anti-I2, anti-outer membrane protein C (anti-OmpC), anti-CBir1 flagellin (anti-CBir1), and anti-Saccharomyces-cerevisiae (ASCA) using ELISA. Associations between immune responses and clinical phenotype were evaluated.RESULTS:Fifty-eight patients (28%) developed internal penetrating and/or stricturing (IP/S) disease after a median follow-up of 18 months. Both anti-OmpC (p < 0.0006) and anti-I2 (p < 0.003) were associated with IP/S disease. The frequency of IP/S disease increased with increasing number of immune responses (p trend = 0.002). The odds of developing IP/S disease were highest in patients positive for all four immune responses (OR (95% CI): 11 (1.5–80.4); p= 0.03). Pediatric CD patients positive for ≥1 immune response progressed to IP/S disease sooner after diagnosis as compared to those negative for all immune responses (p < 0.03).CONCLUSIONS:The presence and magnitude of immune responses to microbial antigens are significantly associated with more aggressive disease phenotypes among children with CD. This is the first study to prospectively demonstrate that the time to develop a disease complication in children is significantly faster in the presence of immune reactivity, thereby predicting disease progression to more aggressive disease phenotypes among pediatric CD patients.

Cognitive-Behavioral Therapy for Children With Functional Abdominal Pain and Their Parents Decreases Pain and Other Symptoms

OBJECTIVES:Unexplained abdominal pain in children has been shown to be related to parental responses to symptoms. This randomized controlled trial tested the efficacy of an intervention designed to improve outcomes in idiopathic childhood abdominal pain by altering parental responses to pain and childrens ways of coping and thinking about their symptoms.METHODS:Two hundred children with persistent functional abdominal pain and their parents were randomly assigned to one of two conditions—a three-session intervention of cognitive-behavioral treatment targeting parents responses to their childrens pain complaints and childrens coping responses, or a three-session educational intervention that controlled for time and attention. Parents and children were assessed at pretreatment, and 1 week, 3 months, and 6 months post-treatment. Outcome measures were child and parent reports of child pain levels, function, and adjustment. Process measures included parental protective responses to childrens symptom reports and child coping methods.RESULTS:Children in the cognitive-behavioral condition showed greater baseline to follow-up decreases in pain and gastrointestinal symptom severity (as reported by parents) than children in the comparison condition (time × treatment interaction, P<0.01). Also, parents in the cognitive-behavioral condition reported greater decreases in solicitous responses to their childs symptoms compared with parents in the comparison condition (time × treatment interaction, P<0.0001).CONCLUSIONS:An intervention aimed at reducing protective parental responses and increasing child coping skills is effective in reducing childrens pain and symptom levels compared with an educational control condition.

Upper Gastrointestinal Fiberoptic Endoscopy in Pediatric Patients

One hundred and forty-two pediatric patients between age 1 month and 20 years had 163 endoscopic procedures. Of 66 with chronic abdominal pain, 21 had a source identified endoscopically that was seen in only 15 by esophagogram and upper gastrointestinal series. Of 31 with nausea, vomiting, dysphagia, and/or odynophagia and retrosternal pain, endoscopy demonstrated the source in 19 patients and radiographic studies in 14. Of 34 with hematemesis and/or melena, 26 had a bleeding site identified endoscopically but only 4 of 28 had an identified source by radiographic studies. Duodenal and gastric ulcers and hemorrhagic gastritis were the commonest cases of upper gastrointestinal bleeding and organically of chronic adbominal pain. Functional abdominal pain was the commonest cause of chronic abdominal pain in those endoscoped. Foreign bodies were removed from the esophagus and stomach of 6 patients and dislodged in 2 others. Caustic ingestion was recognized in the esophagus and stomach of 2 patients who did not have mouth burns. The GIF-P2-prototype with four-way tip control and ability to retroflex 180 degree up, 60 degree down, and 100 degree right and left was superior to GIF-P1 and CF-P-prototype for visualization of the entire esophagus, stomach, duodenal bulb, and postbulbar area in patients less than 10 years old. Visualization of the duodenal bulb was possible in 28 of 29 pediatric patients, and of the postbulbar area in 25 of 26 in whom it was attempted. Infants who weighed as little as 3 to 5 kg were successfully examined. Retroflexion was possible in 29 of 30 to see the fundus and cardioesophageal junction. Patients older than 10 years were better examined with the GIF-D because of its increased ability to transmit light. Sedation for the school-age child with 0.5 to 1.0 mg per kg of diazepam and 1 to 2 mg per kg of meperidine given intravenously provides excellent sedation in most instances. General anesthesia is preferable for the preschooler and infant. Minor complications occurred in 2 patients who received less than adequate sedation and in 1 patient with general anesthesia.

Dietary protein intolerance in infants with transient methemoglobinemia and diarrhea

Of 17 infants requiring hospitalization for primary soy or cow milk protein intolerance, six infants (35%) had transient methemoglobinemia. Reexposure to the offending protein caused diarrhea, metabolic acidosis, and transient methemoglobinemia in all patients. These six patients represented 65% of the total hospitalizations resulting from methemoglobinemia of any cause.

Twelve-Month Follow-up of Cognitive Behavioral Therapy for Children With Functional Abdominal Pain

OBJECTIVEnTo determine whether a brief intervention for children with functional abdominal pain and their parents responses to their childs pain resulted in improved coping 12 months later.nnnDESIGNnProspective, randomized, longitudinal study.nnnSETTINGnFamilies were recruited during a 4-year period in Seattle, Washington, and Morristown, New Jersey.nnnPARTICIPANTSnTwo hundred children with persistent functional abdominal pain and their parents.nnnINTERVENTIONSnA 3-session social learning and cognitive behavioral therapy intervention or an education and support intervention.nnnMAIN OUTCOME MEASURESnChild symptoms and pain-coping responses were monitored using standard instruments, as was parental response to child pain behavior. Data were collected at baseline and after treatment (1 week and 3, 6, and 12 months after treatment). This article reports the 12-month data.nnnRESULTSnRelative to children in the education and support group, children in the social learning and cognitive behavioral therapy group reported greater baseline to 12-month follow-up decreases in gastrointestinal symptom severity (estimated mean difference, -0.36; 95% CI, -0.63 to -0.01) and greater improvements in pain-coping responses (estimated mean difference, 0.61; 95% CI, 0.26 to 1.02). Relative to parents in the education and support group, parents in the social learning and cognitive behavioral therapy group reported greater baseline to 12-month decreases in solicitous responses to their childs symptoms (estimated mean difference, -0.22; 95% CI, -0.42 to -0.03) and greater decreases in maladaptive beliefs regarding their childs pain (estimated mean difference, -0.36; 95% CI, -0.59 to -0.13).nnnCONCLUSIONSnResults suggest long-term efficacy of a brief intervention to reduce parental solicitousness and increase coping skills. This strategy may be a viable alternative for children with functional abdominal pain.nnnTRIAL REGISTRATIONnclinicaltrials.gov Identifier: NCT00494260.

Cognitive Mediators of Treatment Outcomes in Pediatric Functional Abdominal Pain

Objectives:Cognitive-behavioral (CB) interventions improve outcomes for many pediatric health conditions, but little is known about which mechanisms mediate these outcomes. The goal of this study was to identify whether changes in targeted process variables from baseline to 1 week posttreatment mediate improvement in outcomes in a randomized controlled trial of a brief CB intervention for idiopathic childhood abdominal pain. Materials and Methods:Two hundred children with persistent functional abdominal pain and their parents were randomly assigned to 1 of 2 conditions: a 3-session social learning and CB treatment (N=100), or a 3-session educational intervention controlling for time and attention (N=100). Outcomes were assessed at 3-, 6-, and 12-month follow-ups. The intervention focused on altering parental responses to pain and on increasing adaptive cognitions and coping strategies related to pain in both parents and children. Results:Multiple mediation analyses were applied to examine the extent to which the effects of the social learning and CB treatment condition on child gastrointestinal (GI) symptom severity and pain as reported by children and their parents were mediated by changes in targeted cognitive process variables and parents’ solicitous responses to their child’s pain symptoms. Reductions in parents’ perceived threat regarding their child’s pain mediated reductions in both parent-reported and child-reported GI symptom severity and pain. Reductions in children’s catastrophic cognitions mediated reductions in child-reported GI symptom severity but no other outcomes. Reductions in parental solicitousness did not mediate outcomes. Discussion:Results suggest that reductions in reports of children’s pain and GI symptoms after a social learning and CB intervention were mediated at least in part by decreasing maladaptive parent and child cognitions.

Gastric Acid Hyperscretion in Children With Duodenal Ulcer

Rates of gastric hydrochloric acid secretion were compared in 10 children with active duodenal ulcer (DU) and 14 non-duodenal ulcer children. Duodenal ulcer was diagnosed by gastroduodenoscopy or by evidence of an ulcer crater on upper gastrointestinal radiographs. Duodenal ulcer disease was excluded in the comparison group by similar criteria. Basal acid output in DU children tended to be higher, but the difference was not statistically significant (P greater than 0.05). Maximal acid output was significantly higher in DU children than in the comparison group whether expressed as milliequivalents per hour (P less than 0.025) or as milliequivalents per kilogram per hour (P less than 0.005). Peak acid output also showed a statistically significant difference (milliequivalents per hour, milliequivalents per kilogram per hour, (P less than 0.05). These findings demonstrate that, on the average, hypersecretion of gastric acid does occur in children with duodenal ulcer disease.

Anti-gliadin antibody panel and xylose absorption test in screening for celiac disease.

We prospectively evaluated the use of a widely used commercially available anti-gliadin antibody (AGA) panel, and compared it with the xylose absorption test in screening pediatric patients with possible celiac disease for small intestinal biopsy. Sixty children were investigated with a I-h xylose absorption test, IgG and IgA AGA panels, and small bowel biopsy; 15 patients were diagnosed with celiac disease. The xylose was sensitive (93%) but not specific (47%) for celiac disease. The IgG AGA test had high sensitivity (100%) but low specificity (58%), while the IgA AGA test had low sensitivity (53%) but high specificity (93%) in screening for celiac disease. We conclude that the AGA panel currently available in the United States is comparable to, but not significantly different than, the xylose absorption test when used as the only laboratory test in screening for celiac disease. A two-step screening process would have best improved our ability to predict celiac disease. We recommend screening with the AGA panel, and obtaining a xylose test if only the IgG is abnormal. Biopsies should be performed in cases with high IgA AGA, or with abnormal IgG AGA and xylose values. This approach is clinically preferable, does not add cost, and spares children from unnecessary small bowel biopsies.

Effects of a Cognitive Behavioral Therapy Intervention Trial to Improve Disease Outcomes in Children with Inflammatory Bowel Disease.

Background:Studies testing the efficacy of behavioral interventions to modify psychosocial sequelae of inflammatory bowel disease in children are limited. This report presents outcomes through a 6-month follow-up from a large randomized controlled trial testing the efficacy of a cognitive behavioral intervention for children with inflammatory bowel disease and their parents. Methods:One hundred eighty-five children aged 8 to 17 years with a diagnosis of Crohns disease or ulcerative colitis and their parents were randomized to one of two 3-session conditions: (1) a social learning and cognitive behavioral therapy condition or (2) an education support condition designed to control for time and attention. Results:There was a significant overall treatment effect for school absences due to Crohns disease or ulcerative colitis (P < 0.05) at 6 months after treatment. There was also a significant overall effect after treatment for child-reported quality of life (P < 0.05), parent-reported increases in adaptive child coping (P < 0.001), and reductions in parents maladaptive responses to childrens symptoms (P < 0.05). Finally, exploratory analyses indicated that for children with a higher level of flares (2 or more) prebaseline, those in social learning and cognitive behavioral therapy condition experienced a greater reduction in flares after treatment. Conclusions:This trial suggests that a brief cognitive behavioral intervention for children with inflammatory bowel disease and their parents can result in improved child functioning and quality of life, and for some children may decrease disease activity.

A double blind crossover study of metoclopramide versus placebo for facilitating passage of multipurpose biopsy tube.

Intravenous metoclopramide (M) was compared to placebo (P) by a double blind crossover design to determine whether M was superior to P in difficult cases of intubation of the small intestine, using a multipurpose biopsy tube and capsule. Metoclopramide decreased intubation time in 20 volunteers successfully intubated with M and P (P less than 0.05). Of 9 subjects, 8 were intubated to ligament of Treitz with M but not with P (P less than 0.01). Of 29 volunteers, 22 were successfully intubated by 15 min when M was given, but only 9 of the 29 could be intubated in 15 min with P (P less then 0.001). Of 29 volunteers receiving M, 9 experienced side effects but none were serious. This study demonstrated that M is superior to P in decreasing intubation time of a small intestinal biopsy capsule and is particularly useful in patients who may not otherwise be sucessfully intubated.