Esomeprazole for the Treatment of Erosive Esophagitis in Children: An International, Multicenter, Randomized, Parallel-Group, Double-Blind (for Dose) Study.

BACKGROUND: Acid suppression with a proton pump inhibitor is standard treatment for gastroesophageal reflux disease and erosive esophagitis in adults and increasingly is becoming first-line therapy for children aged 1-17 years. We evaluated endoscopic healing of erosive esophagitis with esomeprazole in young children with gastroesophageal reflux disease and described esophageal histology. METHODS: Children aged 1-11 years with endoscopically or histologically confirmed gastroesophageal reflux disease were randomized to esomeprazole 5 or 10 mg daily (<20 kg) or 10 or 20 mg daily (≥ 20 kg) for 8 weeks. Patients with erosive esophagitis underwent an endoscopy after 8 weeks to assess healing of erosions. RESULTS: Of 109 patients, 49% had erosive esophagitis and 51% had histologic evidence of reflux esophagitis without erosive esophagitis. Of the 45 patients who had erosive esophagitis and underwent follow-up endoscopy, 89% experienced erosion resolution. Dilation of intercellular space was reported in 24% of patients with histologic examination. CONCLUSIONS: Esomeprazole (0.2-1.0 mg/kg) effectively heals macroscopic and microscopic erosive esophagitis in this pediatric population with gastroesophageal reflux disease. Dilation of intercellular space may be an important histologic marker of erosive esophagitis in children.

Esomeprazole for the Treatment of GERD in Infants Ages 1-11 Months.

OBJECTIVES: Gastroesophageal reflux disease (GERD) is present in pediatric patients when reflux of gastric contents causes troublesome symptoms and/ or complications. The present study evaluates the efficacy and safety of esomeprazole in infants ages 1 to 11 months with GERD. METHODS: In this multicenter randomized, double-blind, placebo-controlled, parallel-group, treatment-withdrawal study, infants received open-label, weight-adjusted doses of esomeprazole (2.5-10 mg) once daily for 2 weeks. Infants with symptom improvement were randomized to esomeprazole (weight-adjusted doses [2.5-10 mg]) or placebo for 4 weeks. The primary endpoint was time to discontinuation owing to symptom worsening based on global assessments by the parent/guardian and physician. Adverse events were recorded. RESULTS: Of the 98 patients enrolled, 81 (82.7%) experienced symptom improvement determined by physician global assessment (PGA) during open-label esomeprazole treatment; 80 entered the double-blind phase. During this phase, discontinuation rates owing to symptom worsening were 48.8% (20/41) for placebo-treated versus 38.5% (15/39) for esomeprazole-treated patients (hazard ratio 0.69; P = 0.28). Posthoc analysis of infants with symptomatic GERD (ie, no diagnostic procedure performed) revealed that time to discontinuation was significantly longer with esomeprazole than placebo (hazard ratio 0.24; P = 0.01); the complementary subgroup difference was not significant (hazard ratio 1.39; P = 0.48). Esomeprazole was well tolerated. CONCLUSIONS: The discontinuation rate owing to symptom worsening did not differ significantly between infants receiving esomeprazole versus those receiving placebo. Improved diagnostic criteria in this age group are needed to identify infants with GERD who may benefit from acid suppression therapy.

Esomeprazole for the Treatment of Erosive Esophagitis in Children: An International, Multicenter, Randomized, Parallel-Group, Double-Blind (for Dose) Study.

BACKGROUND: Acid suppression with a proton pump inhibitor is standard treatment for gastroesophageal reflux disease and erosive esophagitis in adults and increasingly is becoming first-line therapy for children aged 1-17 years. We evaluated endoscopic healing of erosive esophagitis with esomeprazole in young children with gastroesophageal reflux disease and described esophageal histology. METHODS: Children aged 1-11 years with endoscopically or histologically confirmed gastroesophageal reflux disease were randomized to esomeprazole 5 or 10 mg daily (< 20 kg) or 10 or 20 mg daily (≥ 20 kg) for 8 weeks. Patients with erosive esophagitis underwent an endoscopy after 8 weeks to assess healing of erosions. RESULTS: Of 109 patients, 49% had erosive esophagitis and 51% had histologic evidence of reflux esophagitis without erosive esophagitis. Of the 45 patients who had erosive esophagitis and underwent follow-up endoscopy, 89% experienced erosion resolution. Dilation of intercellular space was reported in 24% of patients with histologic examination. CONCLUSIONS: Esomeprazole (0.2-1.0 mg/kg) effectively heals macroscopic and microscopic erosive esophagitis in this pediatric population with gastroesophageal reflux disease. Dilation of intercellular space may be an important histologic marker of erosive esophagitis in children.

Esomeprazole for the Treatment of GERD in Infants Ages 1-11 Months.

OBJECTIVES: Gastroesophageal reflux disease (GERD) is present in pediatric patients when reflux of gastric contents causes troublesome symptoms and/ or complications. The present study evaluates the efficacy and safety of esomeprazole in infants ages 1 to 11 months with GERD. METHODS: In this multicenter randomized, double-blind, placebo-controlled, parallel-group, treatment-withdrawal study, infants received open-label, weight-adjusted doses of esomeprazole (2.5-10 mg) once daily for 2 weeks. Infants with symptom improvement were randomized to esomeprazole (weight-adjusted doses [2.5-10 mg]) or placebo for 4 weeks. The primary endpoint was time to discontinuation owing to symptom worsening based on global assessments by the parent/guardian and physician. Adverse events were recorded. RESULTS: Of the 98 patients enrolled, 81 (82.7%) experienced symptom improvement determined by physician global assessment (PGA) during open-label esomeprazole treatment; 80 entered the double-blind phase. During this phase, discontinuation rates owing to symptom worsening were 48.8% (20/41) for placebo-treated versus 38.5% (15/39) for esomeprazole-treated patients (hazard ratio 0.69; P = 0.28). Posthoc analysis of infants with symptomatic GERD (ie, no diagnostic procedure performed) revealed that time to discontinuation was significantly longer with esomeprazole than placebo (hazard ratio 0.24; P = 0.01); the complementary subgroup difference was not significant (hazard ratio 1.39; P = 0.48). Esomeprazole was well tolerated. CONCLUSIONS: The discontinuation rate owing to symptom worsening did not differ significantly between infants receiving esomeprazole versus those receiving placebo. Improved diagnostic criteria in this age group are needed to identify infants with GERD who may benefit from acid suppression therapy.

Safety and Tolerability of Esomeprazole in Children With Gastroesophageal Reflux Disease.

OBJECTIVES: To evaluate safety, tolerability, and symptom improvement with once-daily esomeprazole in children with endoscopically proven gastroesophageal reflux disease (GERD). PATIENTS AND METHODS: In this 8-week, multicenter, randomized, uncontrolled, double-blind study, children ages 1 to 11 years were stratified by weight to receive esomeprazole 5 or 10 mg (children < 20 kg) or 10 or 20 mg (children ≥ 20 kg) once daily. Safety and tolerability was assessed by evaluating adverse events (AEs; both treatment- and non-treatment-related AEs) and changes from baseline in medical history, physical examinations, and clinical laboratory tests. Investigators scored symptom severity every 2 weeks using the Physician's Global Assessment (PGA). Patients' parents rated GERD symptoms of heartburn, acid regurgitation, and epigastric pain (none to severe, 0-3) at baseline (based on past 72 hours) and daily (from past 24 hours). RESULTS: Of 109 patients randomized, 108 had safety data. AEs were experienced by 68.0% and 65.2% of children <20 kg receiving esomeprazole 5 and 10 mg, respectively, and 83.9% and 82.8% of children ≥ 20 kg receiving esomeprazole 10 and 20 mg, respectively, regardless of causality. Overall, only 9.3% of patients reported 13 treatment-related AEs; the most common were diarrhea (2.8% [3/108]), headache (1.9% [2/108]), and somnolence (1.9% [2/108]). Vomiting, a serious AE in 2 patients, was not judged by the investigator to be related to treatment. At the final visit, PGA scores improved significantly from baseline (P < 0.001). Of 58 patients with moderate to severe baseline PGA symptom scores, 91.4% had lower scores by the final visit. GERD symptom scores were significantly improved from baseline to the final week of the study in all of the treatment groups (P < 0.01) CONCLUSIONS:: In children ages 1 to 11 years with endoscopically proven GERD, esomeprazole (at daily doses of 5, 10, or 20 mg) was generally well tolerated. The frequency and severity of GERD-related symptoms were significantly reduced during the active treatment period.

Safety and Tolerability of Esomeprazole in Children With Gastroesophageal Reflux Disease.

OBJECTIVES: To evaluate safety, tolerability, and symptom improvement with once-daily esomeprazole in children with endoscopically proven gastroesophageal reflux disease (GERD). PATIENTS AND METHODS: In this 8-week, multicenter, randomized, uncontrolled, double-blind study, children ages 1 to 11 years were stratified by weight to receive esomeprazole 5 or 10 mg (children < 20 kg) or 10 or 20 mg (children ≥ 20 kg) once daily. Safety and tolerability was assessed by evaluating adverse events (AEs; both treatment- and non-treatment-related AEs) and changes from baseline in medical history, physical examinations, and clinical laboratory tests. Investigators scored symptom severity every 2 weeks using the Physician's Global Assessment (PGA). Patients' parents rated GERD symptoms of heartburn, acid regurgitation, and epigastric pain (none to severe, 0-3) at baseline (based on past 72 hours) and daily (from past 24 hours). RESULTS: Of 109 patients randomized, 108 had safety data. AEs were experienced by 68.0% and 65.2% of children < 20 kg receiving esomeprazole 5 and 10 mg, respectively, and 83.9% and 82.8% of children ≥ 20 kg receiving esomeprazole 10 and 20 mg, respectively, regardless of causality. Overall, only 9.3% of patients reported 13 treatment-related AEs; the most common were diarrhea (2.8% [3/108]), headache (1.9% [2/108]), and somnolence (1.9% [2/108]). Vomiting, a serious AE in 2 patients, was not judged by the investigator to be related to treatment. At the final visit, PGA scores improved significantly from baseline (P < 0.001). Of 58 patients with moderate to severe baseline PGA symptom scores, 91.4% had lower scores by the final visit. GERD symptom scores were significantly improved from baseline to the final week of the study in all of the treatment groups (P < 0.01) CONCLUSIONS: In children ages 1 to 11 years with endoscopically proven GERD, esomeprazole (at daily doses of 5, 10, or 20 mg) was generally well tolerated. The frequency and severity of GERD-related symptoms were significantly reduced during the active treatment period.

Single-dose pharmacokinetic properties of esomeprazole in children aged 1 - 11 years with endoscopically proven GERD: a randomized, open-label study.

OBJECTIVE: To assess the overall exposure after a single dose of esomeprazole in children with gastroesophageal reflux disease (GERD). MATERIALS: Oral esomeprazole administered as an intact capsule with 30 - 180 mL of water, or as an opened capsule mixed with as much as 1 tablespoon of applesauce followed by 30 - 180 mL of water. METHODS: In this randomized, open-label study of children aged 1 - 11 years with endoscopically proven GERD, patients weighing 8 - < 20 kg were randomized to a single 5- or 10-mg oral dose of esomeprazole, and patients weighing >= 20 kg were randomized to a single 10- or 20-mg oral dose of esomeprazole. Esomeprazole exposure (AUC(0-∞)), AUC from zero to last measurable concentration (AUC(0-t)), maximum plasma concentration (C(max)), time to C(max) (t(max)), terminal-phase half-life, apparent oral clearance, and apparent volume of distribution were determined. RESULTS: 28 patients were randomized to receive esomeprazole: 14 patients weighing 8 to < 20 kg received esomeprazole 5 mg (n = 7) or 10 mg (n = 7), and 14 patients weighing ≥20 kg received esomeprazole 10 mg (n = 6) or 20 mg (n = 8). Children weighing 8 - < 20 kg had a 1.8-fold higher exposure with the 10-mg vs. 5-mg dose (AUC(0-∞), 1.32 vs. 0.73 µmol·h/L, respectively); children weighing ≥ 20 kg had a 4.4-fold higher exposure with the 20-mg vs. 10-mg dose (AUC(0-∞), 3.06 vs. 0.69 µmol·h/L). C(max) was 2.2-fold higher for the 10-mg vs. 5-mg dose (8 to < 20 kg) and 2.4-fold higher for the 20-mg vs.10-mg dose (>= 20 kg). CONCLUSIONS: The pharmacokinetics of single-dose esomeprazole were dose-dependent in children weighing >= 20 kg but not in children weighing 8 to < 20 kg.

Two single group, prospective, baseline-controlled feeding studies in infants and children with chronic diarrhea fed a hypoallergenic free amino acid-based formula.

BACKGROUND: Infants and children with chronic diarrhea (CD) often require specialized foods or parenteral nutrition (PN) to achieve adequate nutrient intakes to support growth and development. We assessed the efficacy of an amino acid-based formula (AAF) in supporting growth and improving symptoms in infants and children with CD from multiple etiologies. METHODS: Two studies were conducted: CD study in children (CD-C) and CD study in infants (CD-I). Each was a single group, baseline-controlled study in which each subject served as his/her own control. At enrollment, all subjects had CD lasting > 2 weeks and had ≥ 4 stools/day. Subjects were fed an AAF for 80 days starting at SD5, and were assessed at SD 28 and 84. RESULTS CD-C: 18 of 19 subjects completed the study. At enrollment, the mean age was 5.6 ± 0.7 years, the most common diagnosis was short bowel syndrome (SBS) (n = 13), and 5 subjects with SBS were on PN. Subjects achieved significant increases in weight-for-age z-scores (p = 0.026). Over 50% of subjects achieved improvements in clinical outcomes targeted most frequently by their physicians. Of the five subjects on PN at enrollment, four had substantial weight gain and four had their PN requirements decreased. CD-I: 22 of 27 subjects completed the study. At enrollment, the mean age was 3.3 ± 0.3 months, the most common diagnosis was food allergy (n = 20), and no subjects were on PN. Subjects achieved significant increases in weight-for-age z-scores (p = 0.0023), significant decreases in the number of stools/day (p = 0.0012), and improvements in stool consistency (p = 0.0024). Over 80% of subjects achieved improvements in the clinical outcomes targeted most frequently by their physicians. CONCLUSIONS: Infants and children with CD fed an AAF for three months displayed significant improvements in weight-for-age z-scores and clinical symptoms. Children dependent on PN also grew well and four of five decreased their dependence on PN. TRIAL REGISTRATION: Both trials were registered on ClinTrials.gov (CD-C, NCT01812629; CD-I, NCT01820494).

Helicobacter pylori Status May Differentiate Two Distinct Pathways of Gastric Adenocarcinoma Carcinogenesis.

BACKGROUND: We evaluated the phenotype of sporadic gastric cancer based on HP status and binding of a tumor risk marker monoclonal, Adnab-9. METHODS: We compared a familial GC kindred with an extremely aggressive phenotype to HP-positive (HP+) and -negative (HP-) sporadic gastric adenocarcinoma (GC) patients in the same community to determine if similar phenotypes exist. This might facilitate gene discovery to understand the pathogenesis of aggressive GC phenotypes, particularly with publications implicating immune-related gene-based signatures, and the development of techniques to gauge the stance of the innate immune system (InImS), such as the FERAD ratio (blood ferritin:fecal Adnab-9 binding OD-background binding). Resection specimens for the sporadic and familial group were stained for HP and examined for intestinal metaplasia (IM) and immunostaining for Adnab-9. Familial kindred specimens were also tested for the E-cadherin mutation and APC (adenomatous polyposis coli). Survival was evaluated. RESULTS: Of 40 GC patients, 25% were HP+ with a greater proportion of intestinal metaplasia (IM) and gastric atrophy than the HP- group. The proband of the familial GC kindred, a 32-year-old mother with fatal GC, was survived by 13-year-old identical twins. Twin #1 was HP- with IM and Twin #2 was HP+. Both twins subsequently died of GC within two years. The twins did not have APC or E-cadherin mutations. The mean overall survival in the HP+ sporadic GC group was 2.47 ± 2.58 years and was 0.57 ± 0.60 years in the HP- group (p = 0.01). Survival in the kindred was 0.22 ± 0.24 years. Adnab-9 labeling was positive in fixed tissues of 50% of non-familial GC patients and in gastric tissue extract from Twin #2. The FERAD ratio was determined separately in six prospectively followed patient groups (n = 458) and was significantly lower in the gastric cancer patients (n = 10) and patients with stomach conditions predisposing them to GC (n = 214), compared to controls (n = 234 patients at increased risk for colorectal cancer but without cancer), suggesting a failure of the InImS. CONCLUSION: The HP+ sporadic GC group appears to proceed through a sequence of HP infection, IM and atrophy before cancer supervenes, and the HP- phenotype appear to omit this sequence. The familial cases may represent a subset with both features, but the natural history strongly resembles that of the HP- group. Two different paths of carcinogenesis may exist locally for sporadic GC. The InImS may also be implicated in prognosis. Identifying these patients will allow for treatment stratification and early diagnosis to improve GC survival.

Esomeprazole for the treatment of GERD in infants ages 1-11 months.

OBJECTIVES: Gastroesophageal reflux disease (GERD) is present in pediatric patients when reflux of gastric contents causes troublesome symptoms and/or complications. The present study evaluates the efficacy and safety of esomeprazole in infants ages 1 to 11 months with GERD. METHODS: In this multicenter randomized, double-blind, placebo-controlled, parallel-group, treatment-withdrawal study, infants received open-label, weight-adjusted doses of esomeprazole (2.5-10 mg) once daily for 2 weeks. Infants with symptom improvement were randomized to esomeprazole (weight-adjusted doses [2.5-10 mg]) or placebo for 4 weeks. The primary endpoint was time to discontinuation owing to symptom worsening based on global assessments by the parent/guardian and physician. Adverse events were recorded. RESULTS: Of the 98 patients enrolled, 81 (82.7%) experienced symptom improvement determined by physician global assessment (PGA) during open-label esomeprazole treatment; 80 entered the double-blind phase. During this phase, discontinuation rates owing to symptom worsening were 48.8% (20/41) for placebo-treated versus 38.5% (15/39) for esomeprazole-treated patients (hazard ratio 0.69; P = 0.28). Posthoc analysis of infants with symptomatic GERD (ie, no diagnostic procedure performed) revealed that time to discontinuation was significantly longer with esomeprazole than placebo (hazard ratio 0.24; P = 0.01); the complementary subgroup difference was not significant (hazard ratio 1.39; P = 0.48). Esomeprazole was well tolerated. CONCLUSIONS: The discontinuation rate owing to symptom worsening did not differ significantly between infants receiving esomeprazole versus those receiving placebo. Improved diagnostic criteria in this age group are needed to identify infants with GERD who may benefit from acid suppression therapy.

Healing of erosive esophagitis and improvement of symptoms of gastroesophageal reflux disease after esomeprazole treatment in children 12 to 36 months old.

OBJECTIVES: The aim of the study was to evaluate erosive esophagitis healing and symptom improvement with once-daily esomeprazole in children ages 12 to 36 months with endoscopically or histologically proven gastroesophageal reflux disease (GERD). PATIENTS AND METHODS: Data from children ages 12 to 36 months were included in a post-hoc analysis of an 8-week, multicenter, randomized, and double-blind by dose strata study of patients ages 1 to 11 years with endoscopically or histologically confirmed GERD. Children were randomized to receive esomeprazole 5 or 10 mg once daily. Patients underwent endoscopy and, if required, mucosal biopsy at baseline. Patients who had erosive esophagitis (graded using the Los Angeles classification system) at baseline underwent a follow-up endoscopy at final study visit to assess healing of erosive esophagitis. Investigators scored severity of GERD symptoms at baseline and every 2 weeks using the Physician Global Assessment. RESULTS: Thirty-one of 109 primary study patients ages 12 to 36 months were included in the post hoc analysis. At baseline, 15 patients (48.4%) had erosive esophagitis, underwent follow-up endoscopy, and were healed after 8 weeks of esomeprazole treatment. Of the 19 patients with moderate-to-severe baseline Physician Global Assessment symptom scores, 84.2% had lower scores by the final visit. Following esomeprazole treatment, GERD symptoms were significantly improved from baseline to final visit (P ≤ 0.0018). CONCLUSIONS: Esomeprazole 5 or 10 mg may be used to successfully treat erosive esophagitis and symptoms of GERD in children as young as 1 year. Moreover, although not yet validated in pediatric patients, the Los Angeles classification system was useful in grading erosive esophagitis in children ages 12 to 36 months.

Esomeprazole for the treatment of erosive esophagitis in children: an international, multicenter, randomized, parallel-group, double-blind (for dose) study.

BACKGROUND: Acid suppression with a proton pump inhibitor is standard treatment for gastroesophageal reflux disease and erosive esophagitis in adults and increasingly is becoming first-line therapy for children aged 1-17 years. We evaluated endoscopic healing of erosive esophagitis with esomeprazole in young children with gastroesophageal reflux disease and described esophageal histology. METHODS: Children aged 1-11 years with endoscopically or histologically confirmed gastroesophageal reflux disease were randomized to esomeprazole 5 or 10 mg daily (< 20 kg) or 10 or 20 mg daily (> or = 20 kg) for 8 weeks. Patients with erosive esophagitis underwent an endoscopy after 8 weeks to assess healing of erosions. RESULTS: Of 109 patients, 49% had erosive esophagitis and 51% had histologic evidence of reflux esophagitis without erosive esophagitis. Of the 45 patients who had erosive esophagitis and underwent follow-up endoscopy, 89% experienced erosion resolution. Dilation of intercellular space was reported in 24% of patients with histologic examination. CONCLUSIONS: Esomeprazole (0.2-1.0 mg/kg) effectively heals macroscopic and microscopic erosive esophagitis in this pediatric population with gastroesophageal reflux disease. Dilation of intercellular space may be an important histologic marker of erosive esophagitis in children. TRIAL REGISTRATION: D9614C00097; ClinicalTrials.gov identifier NCT00228527.

Urea breath test in children: the United States prospective, multicenter study.

BACKGROUND: The urea breath test (UBT) is generally considered the gold standard for the diagnosis of Helicobacter pylori infections in adults. GOALS: To investigate the utility and accuracy of urea breath testing in children from the United States. METHODS: Children scheduled to undergo upper gastrointestinal endoscopy for various clinical symptoms underwent a 13C-UBT using the US standard protocol for adults. Results were compared with rapid urease testing (RUT), culture, and histology. H. pylori positivity was defined according to the FDA, Division of Anti-Infective Drug Products criteria, i.e. positive culture and/or positive RUT and histology. H. pylori negativity was defined as all tests negative. Results were evaluated by delta over baseline (DOB) and urea hydrolysis rate (UHR). RESULTS: A total of 176 children from five centers were evaluated; 48 were infected. Compared to the defined standard, the results with the UBT based on delta over baseline (DOB) cut-off value (positive: > or = 2.4 per thousand) showed that the sensitivity and specificity of the UBT were 97.9% and 96.1%, respectively. Based on the UHR cut-off value (positive: > or = 10.0 microg/min), the sensitivity and specificity were 95.8% and 99.2%. In young children (2- to 5-year olds), sensitivity and specificity of UHR method were higher than the DOB method (100% and 100% vs 100% and 82.4%, respectively). CONCLUSION: The US standard (13)C-UBT proved to be both simple and accurate for the diagnosis of H. pylori infections in children. The UHR method to calculate of (13)C-UBT result provided excellent results for children of all ages.

Effects of esomeprazole treatment for gastroesophageal reflux disease on quality of life in 12- to 17-year-old adolescents: an international health outcomes study.

BACKGROUND: Although gastroesophageal reflux disease (GERD) is common in adolescents, the burden of GERD on health-related quality of life (HRQOL) in adolescents has not been previously evaluated. Therefore, the objective of the study was to examine the effect of GERD on HRQOL in adolescents. METHODS: This international, 31-site, 8-week safety study randomized adolescents, aged 12 to 17 years inclusive, with GERD to receive esomeprazole 20 or 40 mg once daily. The Quality of Life in Reflux and Dyspepsia questionnaire (QOLRAD), previously validated in adults, consists of 25 questions grouped into 5 domains: emotional distress, sleep disturbance, food/drink problems, physical/social functioning, and vitality. The QOLRAD was administered at the baseline and week-8 (final) visits. RESULTS: Of the 149 patients randomized, 134 completed the QOLRAD at baseline and final visits and were eligible for analysis of their HRQOL data. Baseline QOLRAD scores indicated GERD had a negative effect on the HRQOL of these adolescents, especially in the domains of vitality and emotional distress, and problems with food/drink. At the final visit, mean scores for all 5 QOLRAD domains improved significantly (P < .0001); change of scores (ie, delta) for all domains met or exceeded the adult QOLRAD minimal clinically significant difference standard of 0.5 units. CONCLUSION: GERD had a negative effect on QOL in adolescents. After esomeprazole treatment, statistically and clinically significant improvements occurred in all domains of the QOLRAD for these adolescents. TRIAL REGISTRATION: D9614C00098; ClinicalTrials.gov Identifier NCT00241501.

Safety and tolerability of esomeprazole in children with gastroesophageal reflux disease.

OBJECTIVES: To evaluate safety, tolerability, and symptom improvement with once-daily esomeprazole in children with endoscopically proven gastroesophageal reflux disease (GERD). PATIENTS AND METHODS: In this 8-week, multicenter, randomized, uncontrolled, double-blind study, children ages 1 to 11 years were stratified by weight to receive esomeprazole 5 or 10 mg (children <20 kg) or 10 or 20 mg (children >or=20 kg) once daily. Safety and tolerability was assessed by evaluating adverse events (AEs; both treatment- and non-treatment-related AEs) and changes from baseline in medical history, physical examinations, and clinical laboratory tests. Investigators scored symptom severity every 2 weeks using the Physician's Global Assessment (PGA). Patients' parents rated GERD symptoms of heartburn, acid regurgitation, and epigastric pain (none to severe, 0-3) at baseline (based on past 72 hours) and daily (from past 24 hours). RESULTS: Of 109 patients randomized, 108 had safety data. AEs were experienced by 68.0% and 65.2% of children <20 kg receiving esomeprazole 5 and 10 mg, respectively, and 83.9% and 82.8% of children >or=20 kg receiving esomeprazole 10 and 20 mg, respectively, regardless of causality. Overall, only 9.3% of patients reported 13 treatment-related AEs; the most common were diarrhea (2.8% [3/108]), headache (1.9% [2/108]), and somnolence (1.9% [2/108]). Vomiting, a serious AE in 2 patients, was not judged by the investigator to be related to treatment. At the final visit, PGA scores improved significantly from baseline (P < 0.001). Of 58 patients with moderate to severe baseline PGA symptom scores, 91.4% had lower scores by the final visit. GERD symptom scores were significantly improved from baseline to the final week of the study in all of the treatment groups (P < 0.01) CONCLUSIONS: In children ages 1 to 11 years with endoscopically proven GERD, esomeprazole (at daily doses of 5, 10, or 20 mg) was generally well tolerated. The frequency and severity of GERD-related symptoms were significantly reduced during the active treatment period.

Safety and symptom improvement with esomeprazole in adolescents with gastroesophageal reflux disease.

OBJECTIVES: The primary objective was to assess the safety of esomeprazole 20 or 40 mg once daily in adolescents with clinically diagnosed gastroesophageal reflux disease (GERD). A secondary aim was to assess changes in GERD symptoms after esomeprazole therapy. PATIENTS AND METHODS: In this multicenter, randomized, double-blind study, adolescents ages 12 to 17 years inclusive received esomeprazole 20 or 40 mg once daily for 8 weeks. Adverse events and changes in clinical parameters (eg, physical examination, laboratory measurements) were evaluated to assess safety. Patients or their parents or guardians scored symptom severity daily, and investigators scored overall GERD symptom severity every 2 weeks using a 4-point scale. RESULTS: In the 148 adolescents with safety data, treatment-related and non-treatment-related adverse events were reported by 75% and 78% of patients in the esomeprazole 20- and 40-mg groups, respectively. Twenty-two patients (14.9%) experienced adverse events that were considered related to treatment; the most common were headache (8%, 12/148), abdominal pain (3%, 4/148), nausea (2%, 3/148), and diarrhea (2%, 3/148). No serious adverse events or clinically important findings in other safety assessments were observed. At baseline, 68% (100/147) had heartburn, 63% (93/147) had epigastric pain, 57% (84/147) had acid regurgitation, and 15% (22/147) had vomiting symptoms. Symptom scores decreased significantly in both the esomeprazole 20-mg and 40-mg groups by the final study week (P < 0.0001). Investigators rated 63.1% (94/149) of the patients as having moderate or severe symptoms at baseline; at the final visit, this percentage decreased significantly to 9.3% (13/140; P < .0001). CONCLUSIONS: In adolescent patients with GERD, esomeprazole 20 or 40 mg daily for 8 weeks was well tolerated, and GERD-related symptoms were significantly reduced from baseline values in both groups.

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 Crohn's 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% Crohn's 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.

Expression of intestinal ornithine decarboxylase during postnatal development in neonatal rats.

Ornithine decarboxylase (ODC) has been shown to play an essential role in intestinal growth and maturation in rats. However, the regulatory mechanisms have not been fully elucidated. We studied the mechanisms of expression of intestinal ODC during postnatal development. Rat small intestinal mucosa was obtained from postnatal days 10, 15, 17, 19, 21, 24 and 30. Intestinal mucosa was assayed for ODC and sucrase activities. In addition, intestinal ODC mRNA, and ODC protein levels were also measured. The results showed that the intestinal sucrase activity was low before postnatal day 19. The sucrase activity then increased steadily from day 19 up to day 30. Intestinal ODC activities remained low from postnatal day 10 to day 17. A sharp increase in ODC activity was noted on day 19, which peaked on day 24 (a 20-fold increase from its low basal level) and declined on day 30. Intestinal ODC proteins followed the same pattern of postnatal expression as that of ODC activity. In contrast, ODC mRNA did not show significant change throughout the study period. The possible mechanisms by which intestinal ODC mRNA levels remain practically unchanged during postnatal development are discussed. We conclude that the ontogenic increase in sucrase activity, a marker for intestinal maturation, occurs at the same time to that of the induction of ODC activity. We also suggest that the induction of intestinal ODC activity during postnatal development is the result of post-transcriptional events or other cellular mechanisms. A better understanding of the regulation of polyamine biosynthesis during postnatal development of the small intestine will provide insights contributing to the maturation of the small intestine.

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 Crohn's 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.

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

Probiotics are widely used by patients with Crohn's 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.