Development and psychometric evaluation of 2 age-stratified versions of the Pediatric GERD Symptom and Quality of Life Questionnaire.

OBJECTIVES: The Pediatric Gastroesophageal Reflux Disease Symptom and Quality of Life Questionnaire (PGSQ) represents 2 related age-stratified tools developed to assess pediatric gastroesophageal reflux disease (GERD). These include the PGSQ-Cp (for children ages 2 to 8 years, parent/caregiver report) and the PGSQ-A (for adolescents ages 9-17 years). The objective of the present study was to develop and evaluate PGSQ measurement properties. MATERIALS AND METHODS: The PGSQ items were generated based on information from focus groups, expert clinician review, and cognitive debriefing interviews. The symptoms of pediatric GERD and the effect of these symptoms were addressed. The tools were evaluated in a 3-week psychometric evaluation with participants from 11 clinical sites in the United States. The study included other measures such as the Pediatric Quality of Life questionnaire (PedsQL) and clinician-rated GERD severity. After item reduction, internal consistency, reproducibility, construct validity, known-group validity, and responsiveness were assessed. RESULTS: The 231 participants included 75 parents of children ages 2 to 8 years and 75 children ages 9 to 17 years with GERD and 41 parents of children and 40 children ages 9 to 17 years without GERD. Exploratory factor analysis demonstrated 4 symptom subscales for the PGSQ-Cp and 3 symptom subscales for the PGSQ-A. Both had subscales for total impact and school impact. High to moderate internal consistency was observed, ranging from 0.76 to 0.96 for the PGSQ-Cp and from 0.67 to 0.94 for the PGSQ-A. The PGSQ significantly differentiated between patients with GERD and controls (P < 0.0001, PGSQ-Cp; P < 0.0022-0.0001, PGSQ-A) and demonstrated responsiveness. CONCLUSIONS: These results support the reliability, validity, and responsiveness of both versions of the PGSQ. The instruments should be useful for clinical studies.

A global, evidence-based consensus on the definition of gastroesophageal reflux disease in the pediatric population.

OBJECTIVES: To develop an international consensus on the definition of gastroesophageal reflux disease (GERD) in the pediatric population. METHODS: Using the Delphi process, a set of statements was developed and voted on by an international panel of eight pediatric gastroenterologists. Statements were based on systematic literature searches using Medline, EMBASE, and CINAHL. Voting was conducted using a six-point scale, with consensus defined, a priori, as agreed by 75% of the group. The strength of each statement was assessed using the GRADE system. RESULTS: There were four rounds of voting. In the final vote, consensus was reached on 98% of the 59 statements. In this vote, 95% of the statements were accepted by seven of eight voters. Consensus items of particular note were: (i) GERD is present when reflux of gastric contents causes troublesome symptoms and/or complications, but this definition is complicated by unreliable reporting of symptoms in children under the age of approximately 8 years; (ii) histology has limited use in establishing or excluding a diagnosis of GERD; its primary role is to exclude other conditions; (iii) Barrett's esophagus should be defined as esophageal metaplasia that is intestinal metaplasia positive or negative; and (iv) extraesophageal conditions may be associated with GERD, but for most of these conditions causality remains to be established. CONCLUSIONS: The consensus statements that comprise the Definition of GERD in the Pediatric Population were developed through a rigorous process. These statements are intended to be used for the development of future clinical practice guidelines and as a basis for clinical trials.

Multicenter, double-blind, randomized, placebo-controlled trial assessing the efficacy and safety of proton pump inhibitor lansoprazole in infants with symptoms of gastroesophageal reflux disease.

OBJECTIVE: To assess the efficacy and safety of lansoprazole in treating infants with symptoms attributed to gastroesophageal reflux disease (GERD) that have persisted despite a >or= 1-week course of nonpharmacologic management. STUDY DESIGN: This multicenter, double-blind, parallel-group study randomized infants with persisting symptoms attributed to GERD to treatment with lansoprazole or placebo for 4 weeks. Symptoms were tracked through daily diaries and weekly visits. Efficacy was defined primarily by a >or= 50% reduction in measures of feeding-related crying and secondarily by changes in other symptoms and global assessments. Safety was assessed based on the occurrence of adverse events (AEs) and clinical/laboratory data. RESULTS: Of the 216 infants screened, 162 met the inclusion/exclusion criteria and were randomized. Of those, 44/81 infants (54%) in each group were responders--identical for lansoprazole and placebo. No significant lansoprazole-placebo differences were detected in any secondary measures or analyses of efficacy. During double-blind treatment, 62% of lansoprazole-treated subjects experienced 1 or more treatment-emergent AEs, versus 46% of placebo recipients (P= .058). Serious AEs (SAEs), particularly lower respiratory tract infections, occurred in 12 infants, significantly more frequently in the lansoprazole group compared with the placebo group (10 vs 2; P= .032). CONCLUSIONS: This study detected no difference in efficacy between lansoprazole and placebo for symptoms attributed to GERD in infants age 1 to 12 months. SAEs, particularly lower respiratory tract infections, occurred more frequently with lansoprazole than with placebo.

Pediatric gastroesophageal reflux clinical practice guidelines: joint recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN).

OBJECTIVE: To develop a North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) international consensus on the diagnosis and management of gastroesophageal reflux and gastroesophageal reflux disease in the pediatric population. METHODS: An international panel of 9 pediatric gastroenterologists and 2 epidemiologists were selected by both societies, which developed these guidelines based on the Delphi principle. Statements were based on systematic literature searches using the best-available evidence from PubMed, Cumulative Index to Nursing and Allied Health Literature, and bibliographies. The committee convened in face-to-face meetings 3 times. Consensus was achieved for all recommendations through nominal group technique, a structured, quantitative method. Articles were evaluated using the Oxford Centre for Evidence-based Medicine Levels of Evidence. Using the Oxford Grades of Recommendation, the quality of evidence of each of the recommendations made by the committee was determined and is summarized in appendices. RESULTS: More than 600 articles were reviewed for this work. The document provides evidence-based guidelines for the diagnosis and management of gastroesophageal reflux and gastroesophageal reflux disease in the pediatric population. CONCLUSIONS: This document is intended to be used in daily practice for the development of future clinical practice guidelines and as a basis for clinical trials.

Step-up and step-down approaches to treatment of gastroesophageal reflux disease in children.

The single biggest change in the approach to treating pediatric gastroesophageal reflux disease (GERD) in recent years has been the empiric use of proton pump inhibitors (PPIs) for symptoms suspected to be those of GERD. In other words, PPIs have been used increasingly as a first-line concurrent diagnostic test and treatment before any investigation. Although this approach is useful for some patients, there are a number of caveats about its application to children. In general, these caveats are related to age per se (eg, infancy) and to age-related symptoms and severity of GERD itself. The most important caveats relate to the prescription of empiric PPI therapy in infants--which generally is to be avoided--and to how PPIs are used in older children--specifically, the advisability of empiric trials being of limited duration. Even in children with proven reflux esophagitis, GERD is not chronic and relapsing in all; thus, trials of therapy withdrawal are warranted. In light of many factors, including the burgeoning literature on potential risks of infections in acid-suppressed children and adults, caution with dose and duration of acid-suppressive drugs in children is urged. The role of antireflux surgery is also mentioned.

Characteristics of children receiving proton pump inhibitors continuously for up to 11 years duration.

OBJECTIVE: To characterize those pediatric patients who receive long-term proton pump inhibitors (PPIs) and to determine the safety of long-term use of PPIs in this population. STUDY DESIGN: Patient databases were screened for long-term PPI use, defined as more than 9 months of continuous prescription, between 1989 and 2004. RESULTS: The median duration of PPI use in the 166 patients in the study group was 3 years (range, 0.75 to 11.25 years). A total of 80 patients used PPIs for 3 to 11 years duration; 35 of these for more than 5 years, and 15 for more than 8 years. Mean age at initial prescription was 7.8 years. At least 1 gastroesophageal reflux disease (GERD)-predisposing disorder was present in 79% of the patients; the major disorders were neuromotor (in 66%) and esophageal atresia (in 14.5%). No GERD-predisposing disorder was present in 35 patients (21%). Endoscopic findings included hiatal hernia in 39% and histologically proven Barrett's esophagus in 4.8%. Omeprazole was used in 90% of the patients; lansoprazole, in 7%. Six adverse reactions seen in 4 patients were potentially related to PPI (nausea and diarrhea, skin rash, agitation, and irritability). CONCLUSIONS: Children with underlying GERD-predisposing disorders compose the majority of long-term PPI users. Few adverse reactions to these drugs occur, and discontinuation of the drug is seldom indicated. These preliminary data suggest that PPIs may be efficacious and safe for continuous use for up to 11 years' duration in children.

Canadian Helicobacter Study Group Consensus Conference: Update on the approach to Helicobacter pylori infection in children and adolescents--an evidence-based evaluation.

As an update to previously published recommendations for the management of Helicobacter pylori infection, an evidence-based appraisal of 14 topics was undertaken in a consensus conference sponsored by the Canadian Helicobacter Study Group. The goal was to update guidelines based on the best available evidence using an established and uniform methodology to address and formulate recommendations for each topic. The degree of consensus for each recommendation is also presented. The clinical issues addressed and recommendations made were: population-based screening for H. pylori in asymptomatic children to prevent gastric cancer is not warranted; testing for H. pylori in children should be considered if there is a family history of gastric cancer; the goal of diagnostic interventions should be to determine the cause of presenting gastrointestinal symptoms and not the presence of H. pylori infection; recurrent abdominal pain of childhood is not an indication to test for H. pylori infection; H. pylori testing is not required in patients with newly diagnosed gastroesophageal reflux disease; H. pylori testing may be considered before the use of long-term proton pump inhibitor therapy; testing for H. pylori infection should be considered in children with refractory iron deficiency anemia when no other cause has been found; when investigation of pediatric patients with persistent or severe upper abdominal symptoms is indicated, upper endoscopy with biopsy is the investigation of choice; the 13C-urea breath test is currently the best noninvasive diagnostic test for H. pylori infection in children; there is currently insufficient evidence to recommend stool antigen tests as acceptable diagnostic tools for H. pylori infection; serological antibody tests are not recommended as diagnostic tools for H. pylori infection in children; first-line therapy for H. pylori infection in children is a twice-daily, triple-drug regimen comprised of a proton pump inhibitor plus two antibiotics (clarithromycin plus amoxicillin or metronidazole); the optimal treatment period for H. pylori infection in children is 14 days; and H. pylori culture and antibiotic sensitivity testing should be made available to monitor population antibiotic resistance and manage treatment failures.

Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment.

During the last decade, clinical practice saw a rapid increase of patients with esophageal eosinophilia who were thought to have gastroesophageal reflux disease (GERD) but who did not respond to medical and/or surgical GERD management. Subsequent studies demonstrated that these patients had a "new" disease termed eosinophilic esophagitis (EE). As recognition of EE grew, so did confusion surrounding diagnostic criteria and treatment. To address these issues, a multidisciplinary task force of 31 physicians assembled with the goal of determining diagnostic criteria and making recommendations for evaluation and treatment of children and adults with suspected EE. Consensus recommendations were based upon a systematic review of the literature and expert opinion. EE is a clinicopathological disease characterized by (1) Symptoms including but not restricted to food impaction and dysphagia in adults, and feeding intolerance and GERD symptoms in children; (2) > or = 15 eosinophils/HPF; (3) Exclusion of other disorders associated with similar clinical, histological, or endoscopic features, especially GERD. (Use of high dose proton pump inhibitor treatment or normal pH monitoring). Appropriate treatments include dietary approaches based upon eliminating exposure to food allergens, or topical corticosteroids. Since EE is a relatively new disease, the intent of this report is to provide current recommendations for care of affected patients and defining gaps in knowledge for future research studies.