Demographic and Clinical Correlates of Mucosal Disaccharidase Deficiencies in Children With Functional Dyspepsia.

BACKGROUND: A subset of children with functional gastrointestinal disorders (FGIDs), which includes functional dyspepsia, may have duodenal disaccharidase deficiencies. OBJECTIVES: To determine the frequency, demographics, and clinical characteristics associated with duodenal disaccharidase deficiencies in children with functional dyspepsia. METHODS: Children ages 4 to 18 years undergoing esophagogastroduodenoscopy (EGD) evaluation for dyspepsia were enrolled in either a retrospective (study 1) or prospective (study 2) evaluation. Those with histologic abnormalities were excluded. Duodenal biopsies were obtained for disaccharidase enzyme analysis. In the retrospective study, both demographic and clinical characteristics were obtained via chart review. In the prospective study, parents completed the Rome II Questionnaire on Gastrointestinal Symptoms before the EGD. RESULTS: One hundred and twenty-nine children (n = 101, study 1; n = 28, study 2) were included. Mean age was 11.2 ±â€Š3.8 (SD) years in study 1 and 10.6 ±â€Š3.2 years in study 2. Forty-eight (47.5%) of subjects in study 1 and 13 (46.4%) of subjects in study 2 had at least 1 disaccharidase deficiency identified. All of those with a disaccharidase deficiency in both studies had lactase deficiency with 8 (7.9%) and 5 (17.9%) of those in studies 1 and 2, respectively, having an additional disaccharidase deficiency. The second most common disaccharidase deficiency pattern was that of pan-disaccharidase deficiency (PDD) in both studies. In study 1 (where both race and ethnicity were captured), self-identified Hispanic (vs non-Hispanic, P < 0.05) and non-white (vs white, P < 0.01) children were more likely to have lactase deficiency. Age, sex, and type of gastrointestinal symptom were not associated with presence or absence of a disaccharidase deficiency. CONCLUSIONS: Approximately half of children with functional dyspepsia undergoing EGD were identified as having a disaccharidase deficiency (predominantly lactase deficiency). Race/ethnicity may be associated with the likelihood of identifying a disaccharidase deficiency. Other clinical characteristics were not able to distinguish those with versus without a disaccharidase deficiency.

Endoscopic retrograde cholangiography for pediatric choledocholithiasis: Assessing the need for endoscopic intervention.

AIM: To assess pediatric patients for choledocholithiasis. We applied current adult guidelines to identify predictive factors in children. METHODS: A single-center retrospective analysis was performed at a tertiary children's hospital. We evaluated 44 consecutive pediatric patients who underwent endoscopic retrograde cholangiography (ERCP) for suspected choledocholithiasis. Patients were stratified into those with common bile duct stones (CBDS) at ERCP vs those that did not using the American Society of Gastrointestinal Endoscopy (ASGE) guidelines (Very Strong and Strong criteria) for suspected CBDS. RESULTS: CBDS were identified in 84% at the time of ERCP. Abdominal ultrasound identified CBDS in 36% of patients. Conjugated bilirubin ≥ 0.5 mg/dL was an independent risk factor for CBDS (P = 0.003). The Very Strong (59.5%) and Strong (48.6%) ASGE criteria identified the majority of patients (P = 0.0001). A modified score using conjugated bilirubin had a higher sensitivity (81.2% vs 59.5%) and more likely to identify a stone than the standard criteria, odds ratio of 25.7 compared to 8.8. Alanine aminotransferase and gamma-glutamyl transferase values identified significant differences in a subset of patients with odds ratio of 4.1 and 3.25, respectively. CONCLUSION: Current adult guidelines identified the majority of pediatric patients with CBDS, but specific pediatric guidelines may improve detection, thus decreasing risks and unnecessary procedures.

Quality indicators for pediatric colonoscopy: results from a multicenter consortium.

BACKGROUND AND AIMS: Currently, there are no quality measures specific to children undergoing GI endoscopy. We aimed to determine the baseline quality of pediatric colonoscopy by using the Pediatric Endoscopy Database System-Clinical Outcomes Research Initiative (PEDS-CORI), a central registry. METHODS: We conducted prospective data collection by using a standard computerized report generator and central registry (PEDS-CORI) to examine key quality indicators from 14 pediatric centers between January 2000 and December 2011. Specific quality indicators, including bowel preparation, ileal intubation rate, documentation of American Society of Anesthesiologists Physical Status Classification System (ASA) class, and procedure time, were compared during the study period. RESULTS: We analyzed 21,807 colonoscopy procedures performed in patients with a mean age of 11.5 ± 4.8 years. Of the 21,807 reports received during the study period, 56% did not include bowel preparation quality, and 12.7% did not include ASA classification. When bowel preparation was reported, the quality was described as excellent, good, or fair in 90.3%. The overall ileal intubation rate was 69.4%, and 15.6% reported cecal intubation only, calculated to be 85% cecum or ileum intubation. Thus, 15% of colonoscopy procedures did not report reaching the cecum or ileum. When excluding the proportion of procedures not intended to reach the ileum (31.5%), the overall ileal intubation rate increased to 84.0%. The rate of ileum examination varied from 85% to 95%, depending on procedure indication. CONCLUSIONS: Colonoscopy reports from our central registry revealed significant variations and inconsistent documentation in pediatric colonoscopy. Our study identifies areas for quality improvement and highlights the need for developing accepted quality measures specific to pediatric endoscopy.

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.

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.

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.

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.

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.

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.

Mucosal and Cellular Immune Responses to Norwalk Virus.

BACKGROUND: Noroviruses are a leading cause of acute gastroenteritis worldwide. Mucosal and cellular immune responses remain poorly understood, with most studies of noroviruses having focused on serological responses to infection. METHODS: We used saliva, feces, and peripheral blood mononuclear cells collected from persons who were administered Norwalk virus (NV) to characterize mucosal (salivary and fecal immunoglobulin A [IgA]) and cellular (NV-specific IgA and immunoglobulin G [IgG] antibody-secreting cells and total and NV-specific IgA and IgG memory B cells) immune responses following infection. RESULTS: Prechallenge levels of NV-specific salivary IgA and NV-specific memory IgG cells correlated with protection from gastroenteritis, whereas prechallenge levels of NV-specific fecal IgA correlated with a reduced viral load. Antibody-secreting cell responses were biased toward IgA, while memory B-cell responses were biased toward IgG. NV-specific memory B cells but not antibody-secreting cells persisted 180 days after infection. CONCLUSIONS: NV-specific salivary IgA and NV-specific memory IgG cells were identified as new correlates of protection against NV gastroenteritis. Understanding the relative importance of mucosal, cellular, and humoral immunity is important in developing vaccine strategies for norovirus disease prevention.

Experimental human infection with Norwalk virus elicits a surrogate neutralizing antibody response with cross-genogroup activity.

The human noroviruses (NoVs) are genetically diverse, rapidly evolving RNA viruses and are the major cause of epidemic gastroenteritis of humans. Serum antibodies that block the interaction of NoVs and NoV viruslike particles (VLPs) with host attachment factors are considered surrogate neutralizing antibodies in the absence of cell culture and small-animal replication models for the human NoVs. A serological assay for NoV-blocking antibodies was used to assess the breadth of the heterotypic antibody response in the context of an experimental challenge study with a human NoV. Heterotypic histo-blood group antigen (HBGA)-blocking activity against GI.4, GI.7, and GII.4 NoVs increased significantly in the serum of individuals (n = 18) infected with Norwalk virus (GI.1). Although the fold increases and peak titers of heterotypic antibody were more modest than titers of antibody reactive with the challenge antigen, Norwalk virus infection elicited a serological rise even against the novel Sydney variant of GII.4 NoVs. These observations indicate that the development of a broadly cross-protective NoV vaccine containing a limited number of genotypes may be possible.

New Diagnostic Strategies for Detection of Helicobacter pylori Infection in Pediatric Patients.

Helicobacter pylori (H pylori) is a common chronic bacterial infection that is an important cause of peptic ulcer disease and gastroduodenal disease in children. H pylori is also associated with extragastric manifestations, including growth reduction, iron-deficiency anemia, and idiopathic thrombocytopenic purpura. Current guidelines recommend endoscopy with biopsy for the definitive demonstration of H pylori infection. In contrast to serology, the fecal antigen test and the urea breath test provide reliable, sensitive, and specific results for detecting active H pylori infection in children before and after treatment. The first-line treatment option for pediatric patients is triple therapy with a proton pump inhibitor and 2 antibiotics, which include amoxicillin and clarithromycin or metronidazole. Decreasing eradication rates and the emergence of antibiotic-resistant strains of H pylori have led to the use of other treatments, such as sequential therapy or triple therapy with newer antibiotics, particularly in geographic areas with high rates of antibiotic resistance. Patients should be tested after treatment to confirm eradication, as the absence of symptoms does not necessarily mean that H pylori is no longer present. This clinical roundtable monograph provides an overview of H pylori infection, as well as expert insight into the diagnosis and management of H pylori infection in children.

Outcomes of children after esophagogastroduodenoscopy for chronic abdominal pain.

BACKGROUND & AIMS: Chronic abdominal pain is the most common indication for esophagogastroduodenoscopy (EGD) in children. However, little is known about the accuracy of EGD-based diagnosis or the outcomes of the patients who undergo this procedure. We examined the diagnostic yield of EGD and short-term outcomes of children who underwent this procedure for chronic abdominal pain. METHODS: We conducted a prospective study of 290 children (4-18 years old; mean age, 11.9 ± 3.5 years; 93 girls) who underwent EGD for the primary indication of chronic abdominal pain (216 with at least 1 alarm feature) at a US pediatric gastroenterology referral center. We collected data on demographic features (age, sex), clinical characteristics (alarm features, Rome III criteria), and EGD results for each patient. All subjects with diagnostic lesions were followed for at least 1 year after EGD to determine short-term outcomes. RESULTS: Overall, EGD provided an accurate diagnosis for 109 children (38%). Diagnoses included esophagitis (21.0%), eosinophilic gastroenteritis (4.1%), eosinophilic esophagitis (3.8%), Helicobacter pylori infection (2.0%), celiac disease (0.6%), and Crohn's disease (0.4%). Short-term outcomes were available for 81% of patients with diagnostic findings, and medical therapy was effective in approximately 67% of these children. CONCLUSIONS: EGD is valuable for the diagnosis of children with abdominal pain, with a 38% diagnostic yield. EGD identified disorders for which medical therapy was effective in 67% of children during the year after diagnosis.

Determination of the 50% human infectious dose for Norwalk virus.

BACKGROUND: Noroviruses are the most common cause of gastroenteritis in the United States. An understanding of the infectious dose of these viruses is important for risk assessment studies. METHODS: Healthy adults were enrolled in a randomized, double-blind, placebo-controlled evaluation of different dosages of Norwalk virus. Eligible subjects were monitored for clinical gastroenteritis, and infection status was determined. The presence of virus in vomitus was also assessed. RESULTS: Fifty-seven persons were enrolled; 8 received placebo and an additional 8 persons were considered to be nonsusceptible on the basis of being secretor negative. Twenty-one persons were infected (all blood group O or A), and 67% of those infected developed viral gastroenteritis. The 50% human infectious dose was calculated to be 3.3 reverse transcription polymerase chain reaction units (approximately 1320 genomic equivalents [gEq]) for secretor-positive blood group O or A persons and 7.0 (approximately 2800 gEq) for all secretor-positive persons. The time of illness onset was inversely correlated with inoculum dose. The maximal concentration of virus shedding was higher for persons with gastroenteritis. Norwalk virus was identified in 15 of 27 (56%) vomitus samples at a median concentration of 41 000 gEq/mL. CONCLUSIONS: The 50% human infectious dose measured is higher than previous estimates and similar to that of other RNA viruses. Clinical Trials Registration NCT00138476.

Duration of disease may predict response to infliximab in pediatric ulcerative colitis.

BACKGROUND: Infliximab (IFX) is an established treatment modality for moderate to severe pediatric ulcerative colitis (UC). The purpose of this study was to identify clinical and laboratory parameters, which predict response to IFX in pediatric UC defined by colectomy as the primary outcome measure. Postsurgical complications were examined as well. METHODS: A retrospective chart review was performed on children younger than 19 years who received IFX therapy at Texas Children's Hospital, Houston, Texas for the treatment of UC from January 2005 to April 2012. Demographics, laboratory data, clinical subtype, duration of disease, transfusion requirement, number of IFX infusions, concurrent medications, and postoperative complication with regard to IFX exposure were examined. RESULTS: Forty-seven patients (22 male and 25 female; average age at diagnosis: 11.4 y) received IFX. Twenty-six (55.3%) required colectomy, 20 (42.6%) of which occurred within a year of therapy initiation. Disease duration <20 months before IFX initiation, increased the likelihood of a colectomy within a year [OR: 3.8 (95% CI, 1.6-13.3), P=0.044]. Blood transfusion requirement before IFX was associated with higher rates of colectomy within a year [OR: 9.78 (95% CI, 2.2-43.3), P=0.0028]. Preoperative exposure to IFX within 8 weeks did not significantly increase postoperative complications (P=0.26). Serum albumin levels at diagnosis did not predict colectomy. CONCLUSIONS: Shorter disease duration and need for blood transfusion may be useful indicators of limited response to IFX in pediatric UC.

Magnet ingestions in children presenting to US emergency departments, 2002-2011.

BACKGROUND AND OBJECTIVE: In the last 10 years, there have been an increasing number of case reports concerning gastrointestinal injury related to magnet ingestions; however, the magnitude of the problem remains to be clearly defined. The aim of the study was to examine the epidemiology of magnet ingestion-related emergency department (ED) visits among children in the United States. METHODS: We performed a trend analysis using a nationally representative sample from the US Consumer Product Safety Commission, National Electronic Injury Surveillance System (NEISS) database for ED visits involving magnet ingestion in children younger than 18 years from 2002 to 2011. RESULTS: A national estimate of 16,386 (95% CI 12,175-20,598) children younger than 18 years presented to EDs in the United States during the 10-year study period with possible magnet ingestion. The incidence of visits increased 8.5-fold (from 0.45/100,000 to 3.75/100,000) from 2002 to 2011 with a 75% average annual increase per year. The majority of patients reported to have ingested magnets were younger than 5 years (54.7%). From 2009 to 2011 there was an increase in older children ingesting multiple small and/or round magnets, with a mean average age of 7.1 ± 0.56 years during the study period. CONCLUSIONS: There has been an alarming increase in ED visits for magnet ingestion in children. Increased public education and prevention efforts are needed.

Oral prucalopride in children with functional constipation.

BACKGROUND AND OBJECTIVES: Prucalopride is a selective, high-affinity 5-HT4 receptor agonist with gastrointestinal prokinetic activities. The aim of this study was to evaluate the pharmacokinetics, efficacy, safety, and tolerability of prucalopride oral solution in children, ages 4 years or older to 12 years or younger, with functional constipation. METHODS: A single oral dose of 0.03 mg/kg prucalopride was administered to 38 children to characterize prucalopride pharmacokinetics (NCT01674166). Thereafter, 37 children entered an open-label extension period in which 0.01 to 0.03 mg/kg of prucalopride was administered once per day for 8 weeks to investigate efficacy, safety, and tolerability (NCT01670669). RESULTS: Mean (standard deviation [SD]) Cmax, tmax, and AUC∞ (area under the plasma concentration-time curve from time 0 to infinity) were 3.8 (0.6) ng/mL, 1.8 (0.9) hour, and 65.3 (10.6) ng · h · mL, respectively, with limited (16%) variability in Cmax and AUC∞. Mean (SD) t1/2 was 19.0 (3.1) hours. On average, mean (SD) renal clearance (0.25 [0.08] L · h · kg) accounted for 54% of the apparent total plasma clearance (0.46 [0.07] L · h · kg). The apparent volume of distribution was 12.6 (2.6) L/kg. Prucalopride treatment resulted in a mean bowel movement frequency of 6.8/week, normal stool consistency, and reduced frequency of fecal incontinence. During the 8-week extension, 70% of study participants had at least 1 adverse event (all but 1 of mild/moderate intensity, 19% considered related to prucalopride). No children discontinued prucalopride because of adverse events. CONCLUSIONS: The pharmacokinetic profile of a single dose of prucalopride oral solution (0.03 mg · kg · day) generally resembled the profile in adults (2-mg tablet) but reflected lower systemic exposure in children. Prucalopride treatment for 8 weeks demonstrated an apparent favorable efficacy and tolerability profile in children with functional constipation.

Antibody responses to norovirus genogroup GI.1 and GII.4 proteases in volunteers administered Norwalk virus.

An assay was developed to detect antibodies against two norovirus proteases among participants in a Norwalk virus (GI.1) challenge study. Prechallenge seroprevalence was lower against the protease from the homologous GI.1 virus than against protease from a heterologous GII.4 strain. Seroresponses were detected for 14 of 19 (74%) infected persons.