Clinical Diagnosis Of Gastroesophageal Reflux Disease Research Articles

Question Prompt List as a Communication Tool for Adults With Gastroesophageal Reflux Disease: Incorporation of Patients' Perspectives.

Question prompt lists (QPLs) are structured sets of disease-specific questions intended for patient use, enhancing the patient-physician communication by encouraging patients to ask relevant questions during a consultation. Recently, a preliminary 78 question gastroesophageal reflux disease (GERD) specific QPL was created by 12 esophageal experts through a modified Delphi (RAND/University of California, Los Angeles) technique. Patients' perspectives and opinions on each question, however, had not been accounted for in the preliminary expert' version. The aim was to modify a preliminary experts' QPL, specific to adults with GERD, following patient perspectives and opinions. A preliminary GERD QPL was modified through patient input and opinions. Thirty-eight patients with a clinical diagnosis of GERD followed at Stanford University Esophageal Clinic between January and November 2019 were consented to modify the preliminary 78 question expert QPL version. After receiving the QPL in Qualtrics (Provo, UT) by a direct e-mail invitation, patients independently rated questions on a 5-point Likert scale, where 1="should not be included," 2="unimportant," 3="don't know/depends," 4="important," and 5="essential." Questions were accepted for inclusion in the QPL with an a priori interagreement of 80% ranking in the range of 4 to 5. At the end, patients were encouraged to propose additional questions to incorporate into the QPL by open-endedly asking "Are there questions we didn't ask, that you think we should?" Twenty-three patients with GERD (19 female, median age 64) fully participated and modified the existing QPL (60.5%). Of the 78 questions from the preliminary GERD QPL, 66 questions (84.6%) were accepted for inclusion. The question with the highest agreement among patients rating a question as essential consisted of "what habits, food, and drinks do I have to avoid?" (82.6%). Questions eliminated because of disagreement included "What is the natural history of GERD," "Do I have a high chance to die from my Barrett's?," and "Why are you prescribing an antidepressant to treat my GERD?" Nine patients suggested additional questions totaling to 16 separate questions, including "What type of surgeries are there to help GERD?," "What stage is my GERD?," "What are the odds/percentage of getting cancer from GERD?" Incorporating the suggested questions, the final GERD QPL-created by esophageal experts and modified by patients-consisted of 82 questions. Esophageal experts and GERD patients have a high level of agreement on important questions, though there is some variation in perspective. Future studies can simplify this list and measure the impact of a shared GERD QPL on patients' decisional conflict and perceived involvement in care.

Adenoma in Ectopic Pancreas: A Case Report

Introduction: The presence of pancreatic tissue that lacks anatomical or vascular communication with the pancreatic organ has a frequency in autopsy studies that ranges between 0.5% and 13.7%. It is most commonly found in the stomach, specifically in the antrum. Treatment is not clearly established. Surgical resection is recommended in symptomatic patients whose only cause of symptoms is ectopic pancreatic tissue or cancerous formations. Objective: Report a case of ectopic pancreatic adenoma given its low incidence. Case Report: This study reports the case of a 45-year-old male with a history of clinical diagnosis of gastroesophageal reflux disease and a Nissen fundoplication. He presented poor evolution 6 months after the surgery. An endoscopy which revealed postpyloric “polyp” at the level of the duodenal bulb and an inconclusive histopathological study of the same were performed. Reassessment with CT showed a tumor in the first portion of the duodenum measured at 2.2cm, without adenopathies, and a normal-appearing pancreas. It has been made a subtotal gastrectomy and Roux “Y” reconstruction, without complications, with good postoperative evolution, discharged at home on the sixth day. With hematoxylin and eosin technique, the histopathology report reported bile duct adenoma originating in ectopic pancreatic tissue, positive immunohistochemistry for cytokeratin 7 (IHC-7), predominantly expressed by ductal epithelial cells of the pancreatobiliary tract. The patient after surgery had a good clinical evolution and disappearance of symptoms. Conclusion: The clinical cases of rare pathologies are presented to increase the world bibliography and to be able to compare the diagnosis and treatment. In this case, a heterotopic pancreatic adenoma was presented, which is a diagnostic challenge.

The Effect of Maternal Eating Habits and Diet Modulation on Infantile Gastroesophageal Reflux Disease Signs and Symptoms: A Randomized Clinical Trial

Background: According to the instructions of Iranian traditional medicine (ITM), modification of breast milk through nursing mothers, is the first step in the treatment of infant disorders. In fact, maternal lifestyle, especially diet and eating habits, can change the quality and quantity of breast milk. The modern medical literature emphasizes that exclusive breastfeeding is the optimal nutrition for infants with gastroesophageal reflux disease (GERD). Objectives: The present study was conducted to evaluate the effect of maternal eating principles and diet based on ITM on infantile GERD symptoms. Methods: Exclusive-breastfeeding, under 5 - month infants with clinical diagnosis of GERD and their nursing mothers, were selected for this 6-weeks parallel randomized, controlled trial. All participants were randomly assigned to the intervention and the control group. The mothers of infants in the intervention group received ITM-based dietary principles, and feeding-positioning modifications were trained to the mothers of all infants of both groups, because of observation of ethical issues (not deprived of standard treatment). Age-Specific Questionnaire for Infants (GSQ-I) was used to assess the frequency and intensity of the GERD symptoms. Measuring the difference between the mean Composite Symptom Score (CSS) in week 0, 4, and 6, between the intervention group and the control group, was the main outcome of this study. Results: Both the intervention and control groups had statistically significant differences in the mean CSS of week 4 and 6 compared with baseline (P < 0.05). Also, there was a significant reduction of the mean CSS values in the intervention group compared to the control group (P < 0.05). Conclusions: Maternal eating principles and diet based on Iranian Traditional Medicine appears to affect the reduction of infantile GERD signs and symptoms.

461 Obstructive Sleep Apnea Is Associated With an Increased Risk of Barrett's Esophagus

INTRODUCTION: Current guidelines suggest screening at-risk groups of patients for Barrett's esophagus (BE), a precursor to esophageal cancer. Although BE and obstructive sleep apnea (OSA) have common risk factors, including elevated body mass index (BMI) and gastroesophageal reflux disease (GERD), the relationship between these two conditions has not been well established. METHODS: Retrospectively, all patients who had undergone a polysomnography and esophagogastroduodenoscopy (EGD) at West Virginia University Hospital from 2013 to 2018 were identified and divided into groups based on the presence or absence of OSA. Clinical course and procedure reports were reviewed to identify relevant variables. RESULTS: 1091 patients met inclusion criteria. 60.9% were female, and mean age of participants was 53.5 years. Univariate analysis revealed that male gender, age, diagnosis of OSA, severity of OSA, and a clinical diagnosis of GERD were associated with Barrett's esophagus (P values < 0.05). Multiple logistic regression incorporating age, sex, clinical diagnosis of GERD, smoking history, BMI, Helicobacter pylori status, and presence of hiatal hernia was utilized. Patients with OSA had an increased risk of Barrett's esophagus when compared with those without OSA [P < 0.001, Odds Ratio 3.26 (1.72-6.85)]. The risk increased with increasing severity of OSA, categorized in apnea-hyponea index increments of 10. In a separate multivariable regression model where OSA was graded in AHI increments of 10, an increased risk for Barrett's esophagus with every 10 point increase in AHI was found (OR 1.10, 95% CI: 1.02 – 1.19). BMI, evaluated in increments of 5, was not associated with BE. The association of OSA with BE remained unchanged in a separate model incorporating a binary variable with BMI of greater than 30 used as a surrogate for central adiposity. CONCLUSION: OSA is associated with Barrett's esophagus, a relationship that is independent of other known risk factors. Additionally, this risk increases with increasing severity of OSA. Future efforts should determine if patients with severe OSA need to be screened for Barrett's esophagus due to its potential for causing esophageal cancer.

Independent association of obstructive sleep apnea with Barrett's esophagus.

Current guidelines suggest screening at-risk groups of patients for Barrett's esophagus (BE), a precursor to esophageal cancer. Although BE and obstructive sleep apnea (OSA) have common risk factors, including elevated body mass index and gastroesophageal reflux disease (GERD), the relationship between these two conditions has not been well established. Retrospectively, all patients who had undergone a polysomnography and esophagogastroduodenoscopy at West Virginia University Hospital from 2013 to 2018 were identified and divided into groups on the basis of the presence or absence of OSA. Clinical course and procedure reports were reviewed to identify relevant variables. One thousand ninety-one patients met inclusion criteria; 60.9% were female, and mean age of participants was 53.5years. Univariate analysis revealed that male gender, age, diagnosis of OSA, severity of OSA, and a clinical diagnosis of GERD were associated with BE (P values<0.05). Multiple logistic regression incorporating age, sex, clinical diagnosis of GERD, smoking history, body mass index, Helicobacter pylori status, and presence of hiatal hernia was utilized. Patients with OSA had an increased risk of BE than had those without OSA (P<0.001, odds ratio 3.26 [1.72-6.85]). The risk increased with increasing severity of OSA, categorized in apnea-hypopnea index increments of 10. Obstructive sleep apnea is associated with BE, a relationship that is independent of other known risk factors. Additionally, this risk increases with increasing severity of OSA. Future efforts should determine if patients with severe OSA need to be screened for BE due to its potential for causing esophageal cancer.

A cross-sectional study on prevalence of gastro esophageal reflux disease in regurgitant infant and children with evaluation of IGERQ score

Background: Gastro Esophageal Reflux Disease (GERD) is the most common esophageal disorder in children of all ages. GER becomes pathological when reflux increase in frequency and intensity, associated with esophageal and respiratory symptoms. Thus, the study was determined to assess the prevalence of GERD in regurgitant children of age 6 to 24 months with evaluation of IGERQ score (Infant Gastro Esophageal Reflux Questionnaire).Methods: A descriptive study was conducted in Gastroenterology Department, Institute of child Health and Hospital for Children, Egmore, Chennai from September 2007 to September 2009. 123 regurgitant children of age 6-24 months were enrolled. Clinical examination and validated questionnaire with total score of 25 was used. Data analysis was aided by EPI info programme. Chi square with P value &lt;0.05 was considered statistically significant. IGERQ score was evaluated by calculating sensitivity, specificity, positive predictive valve and negative predictive valve.Results: The prevalence of GERD in regurgitant infant and children is 30.8%. Refusal of feeds and poor weight in regurgitant children significantly correlated with GERD. sensitivity was 84%, specificity was 96%, positive predictive value was 91%, negative predictive value was 93%Conclusions: Clinical diagnosis of GERD is sufficient in most instances and a questionnaire may aid in diagnosis the disease. IGERQ score is easily adaptable. IGERQ score &gt;5 has high specificity positive and negative predictive value but reproducibility in our population need further evaluation.

Increased Risk for Colon Polyps in Patients with Reflux Disease.

Previous studies have found an increased risk for colonic neoplasm in patients with Barrett's esophagus. It is unknown whether such risk applies similarly to other types of gastroesophageal reflux disease (GERD). To test whether GERD represents a risk factor for the occurrence of colon polyps. The Miraca Life Sciences Database is a large national electronic repository of histopathologic records of patients distributed throughout the entire USA. A case-control study evaluated whether presence of (1) Barrett's metaplasia, (2) erosive esophagitis on endoscopy or histologic signs of reflux esophagitis, (3) clinical diagnosis of GERD, (4) any type of GERD affected the occurrence hyperplastic polyps (HP), sessile serrated adenomas/polyps (SSA/P), or tubular adenomas (TA) among 228,506 subjects undergoing bidirectional endoscopy. Multivariate logistic regression analyses were used to calculate odds ratios and their 95% confidence intervals for the risk of HP, TA or SSA/P associated with various types of GERD and adjusted for age, sex, and presence of H. pylori. The analysis revealed positive associations between GERD and all types of colon polyps. These associations applied similarly to HP (1.47, 1.44-1.50), TA (1.30, 1.27-1.32), and SSA/P (1.52, 1.46-1.58). They also applied to different forms of GERD, showing a trend toward stronger associations, that is higher odds ratios, with Barrett's metaplasia or erosive esophagitis than clinical diagnosis of GERD. All types of GERD represent a risk factor for the occurrence of different colon polyps, such as HP, TA, or SSA/P.

Higher Prevalence of Non-erosive Reflux Disease (NERD) Than Erosive Reflux Disease (ERD) in Type 2 Diabetes Mellitus (T2DM) Patients

Introduction: The annual prevalence of Gastroesophageal Reflux Disease (GERD) is estimated to be 28% and of Diabetes Mellitus Type 2 (T2DM) is 9.3% in the US adult population. This reflects a sharp increase in prevalence for both GERD and T2DM over the last decade. A subset of T2DM patients with neuropathy may have more GERD symptoms. Low grade dysplasia was seen twice as much in T2DM patients versus non-diabetic pts. The aim is to assess the endoscopic findings in GERD patients with and without T2DM.Table 1: Patient's Demographic and Endoscopic FindingsMethods: In this retrospective cross sectional study, after obtaining IRB approval, pertinent data were collected on all patients 18 years of age or older who underwent an outpatient endoscopy at our institution from July 2011 until July 2015. Results: Of 567 patients who had an outpatient EGD, 376 (66.3%) had clinical diagnosis of GERD, table 1. 320 (87.7 %) patients had non- erosive reflux disease. Sixty-five patients (17.3%) had concomitant diabetes (table 1) and neuropathy was present in 17 patients. Erosive reflux disease was seen in 6.3% vs. 13.6% of GERD patients with and without diabetes (P: 0.14). Those diabetic patients complicated with neuropathy tend to have higher rate of erosive reflux disease (10.5% vs. 5.6%, P: 0.60) and salmon colored mucosa (21.1% vs. 5.4%, P: 0.16). Conclusion: Our preliminary data are in accordance with current findings of GERD patients, higher prevalence of NERD with PPI therapy. Although patients with T2DM had less erosive reflux disease compared to those without T2DM, those with T2DM complicated with neuropathy had a higher rate of erosive reflux disease, however this did not reach statistical significance. Patients with T2DM and neuropathy showed a trend to have more salmon colored mucosa compared to those without this complication. Further validation with larger studies is required.

The most common errors in the management of gastroesophageal reflux

Gastro-Esophageal Reflux (GER) occurs in more than two-thirds of otherwise healthy children and is one of the major reason for referral to paediatricians; in fact, a quarter of all paediatric visits in the first six months of life [1] and numerous accesses to the paediatric gastroenterologist services are secondary to GER. GER is defined as the passage of gastric contents into the esophagus and is different from gastroesophageal reflux disease (GERD), which includes all the symptoms and/or complications associated with GER [2]. GER is considered a physiological normal process which occurs several times a day in healthy infants, children and adults. GER is usually associated with transient lower esophageal sphincter relaxations independent from swallowing, which allow the passage of gastric contents into the esophagus. Episodes of GER in healthy adults tend to occur after meals, lasting less than three minutes and usually do not cause symptoms. Although we know less on the normal physiology of newborns and infants, regurgitation is the most visible symptom and tends to occur daily in 50% of all infants with a peak incidence between 4 and 6 months of life [3]. For the majority of paediatric patients (especially in infants), the clinical history and the objective appraisal, in the absence of danger signals, are sufficient to reliably diagnose a not complicated GER and initiate conservative treatment strategies; in general, the diagnostic tests are not always necessary. The reliability of the symptoms to make the clinical diagnosis of GERD is higher in children younger than 8 years, reporting heartburn: only in this case, the doctor can make a diagnosis of Gastro Esophageal Reflux Syndrome and give an indication for therapy [4]. To date, no single symptom or set of symptoms can be trusted, and then used to diagnose GERD in children or to predict which patients are more likely to respond to therapy [2]. The only exception is the child (age> 8y.o.) reporting a history of long-term heartburn with or without vomiting. The new ESPGHAN/NASPGHAN guidelines [2] describe different treatment options for the treatment of infants / children with GER and GERD. In particular, they emphasized the changes in lifestyle, because it can effectively reduce the symptoms of both infants and children. They are based on a combination of changes of milk formulas and positional therapy. In infants with GER, it can be effective the changes to the mother's diet if children are breastfed, change the formula in use, reducing the volume of the single meal associated with an increased frequency of feedings. In particular, the guidelines stress that the allergy to milk proteins may have a clinical presentation similar to GERD. A strategy of nutritional intervention involves the use of thickened formulas that are able to decrease the regurgitation. A recent meta-analysis has shown that the anti regurgitation formula have the following functions: a) increase the number of infants without regurgitation; b) reduce the number of episodes of regurgitation and vomiting daily; c); increase the weight recovery of the infant, d) although they do not change the 24 hours pH study [4].

Obstructive Sleep Apnea Is a Risk Factor for Barrett's Esophagus

Common risk factors for obstructive sleep apnea (OSA) and Barrett's esophagus (BE) include obesity and gastroesophageal reflux disease (GERD). The aims of this study were to assess the association between OSA and BE and to determine whether the association is independent of GERD and body mass index (BMI). Patients who had undergone a diagnostic polysomnogram and esophagogastroduodenoscopy were identified by using Mayo Clinic (Rochester, Minnesota) databases from January 2000-November 2011. They were randomly matched for age, sex, and BMI at time of polysomnogram into the following groups: BE but no OSA (n = 36), OSA but no BE (n = 78), both (n = 74), or neither (n = 74). Clinical and demographic variables were abstracted from medical records. The association between OSA and BE was assessed by using a multiple variable logistic model that incorporated age, sex, BMI, clinical diagnosis of GERD, and smoking history. Subjects with OSA had an 80% increased risk for BE compared with subjects without OSA (odds ratio, 1.8; 95% confidence interval, 1.1-3.2; P = .03). These findings were independent of age, sex, BMI, GERD, and smoking history. Increasing severity of OSA, measured by using the apnea-hypopnea index, was associated with an increased risk of BE (odds ratio, 1.2 per 10-unit increase in apnea-hypopnea index; 95% confidence interval, 1.0-1.3; P = .03). In this case-control study, OSA was associated with an increased risk of BE, potentially through BMI and GERD independent mechanisms. Patients with OSA may benefit from evaluation for BE.

Sa1362 Differences in Esophageal Motility Including Esophageal Peristaltic Transitional Zone Between Patients With Globus Sensation With and Without GERD

Background & Aims: High-resolution manometry (HRM) capable of pressure monitoring from the pharynx to the stomach together with pressure topography plotting represents an unquestionable evolution in esophageal manometry. HRM is useful in localizing and characterizing the transitional zone (TZ) that exists between the proximal and distal esophageal contractile segments. Although far less common than distal peristaltic or lower esophageal sphincter abnormalities, some studies suggested that TZ defects might be related to dysphagia. Globus sensation is a common symptom and gastroesophageal reflux disease (GERD) has been considered to be one of the important causes, although its pathogenesis is poorly understood. The aim of this study was to investigate differences in esophageal motility including TZ between patients with globus sensation related and unrelated to GERD. Methods: From September 2007 through March 2011, 128 consecutive patients (56 men, 72 women; mean age 53.2 years) who had globus sensation and/or heartburn occurring at least several times per week were recruited. After blood tests, ultrasonography, laryngoscope and endoscopy, 4 patients were excluded from the study because of organic disease. The remaining 124 patients underwent HRM. All patients completed a self-administered 7point Likert scale questionnaire about upper gastrointestinal symptoms before undergoing diagnostic tests. The clinical diagnosis of GERD was made when the Frequency Scale for Symptoms of GERD score was 8 points or higher. Results: Patients were divided into 3 groups: globus sensation with GERD (Group A) (26 men, 40 women; mean age 54.2 years), GERD only (Group B) (18 men, 4 women; mean age 51.3 years) and globus sensation only (Group C) (14 men, 14 women; mean age 54.9 years). As to the esophageal motility, the ratio of normal peristalsis in Group A was significantly lower than the Group C (65.2±4.8 % in Group A vs. 80.8±5.1% in Group C, P< 0.05). On the other hand, temporal prolongation (0.9±0.2 s in Group A vs. 2.6±0.2 s in Group C, P< 0.05) and spatial elongation of TZ (1.5±0.2 cm in Group A vs. 4.3±0.3 cm in Group C, P< 0.05) was significantly larger in Group C compared to those in Group A. Conclusions: This study showed that globus sensation related to GERD was associated with esophageal body dysfunction, while globus sensation unrelated to GERD was associated with coordination failure in TZ.

M1909 Randomized, Double-Blind Clinical Outcomes, Safety, and Tolerability Study of Pantoprazole Delayed-Release Granules in Children Aged 1 to 5 Years with Endoscopically Proven Symptomatic Gastroesophageal Reflux Disease (GERD)

G A A b st ra ct s (vomiting, dehydration, apnea, and stridor). Conclusions: In infants aged 1 through 11 mo with a clinical diagnosis of GERD, the 1.2-mg/kg equivalent dose provided statistically significant increases in mean gastric pH and percentage of time with gastric pH >4, and decreases in normalized AUC of esophageal H+ activity compared to baseline. For both doses, esophageal reflux area and normalized AUC of esophageal H+ activity decreased, indicating that the increase in the gastric pH did, in fact, result in a reduction of the pH of the refluxate. Both doses were well tolerated. The results support the choice of the 1.2mg/kg dose for infants 1 through 11 months when short-term treatment with pantoprazole is being considered.

Gastroesophageal Reflux Disease, Acid Suppression, and Mycobacterium avium Complex Pulmonary Disease

Weekly symptoms of gastroesophageal reflux disease (GERD) occur in 20% of the population, and GERD has been implicated in the pathophysiology of many respiratory diseases. Microaspiration of contaminated water is a potential portal of entry for Mycobacterium avium complex (MAC) organisms into the respiratory tract, and acid-suppression therapy may enhance the survival of mycobacteria in the stomach. This study aimed to assess the prevalence of GERD, swallowing disorders, reflux symptoms, and acid-suppression therapy in patients with MAC lung disease (MAC positive [MAC+]), and to compare these patients to control subjects without MAC lung disease (MAC negative [MAC-]). Clinical information was collected on 58 MAC+ patients and 58 age- and sex-matched MAC- patients who were asked to complete a DeMeester questionnaire of reflux symptoms and to identify any acid-suppressive medication consumed. A clinical diagnosis of GERD was documented in 23 of 52 MAC+ patients (44.2%), compared to 16 MAC- patients (27.6%) [p = 0.019]. MAC+ patients consumed significantly more histamine type 2 receptor antagonists and prokinetic agents, and MAC- patients consumed more antacids. The mean DeMeester questionnaire score (+/- SD) for MAC+ patients was 1.39 +/- 1.8, and for MAC- patients was 0.88 +/- 1.4. (p = 0.098). Aspiration was suspected in nine MAC+ patients (15.5%), compared to three MAC- patients (5.2%) [p = 0.032]. There was no association between GERD and radiologic presentation of MAC disease. Consolidation and nodules > 5 mm were more common in those receiving acid suppression than those who were not. GERD, acid suppression, and clinically suspected aspiration are more common in patients with MAC lung disease than in similar patients without MAC disease.

Pharmacokinetic properties of esomeprazole in children aged 1 to 11 years with symptoms of gastroesophageal reflux disease: A randomized, open-label study

Objective: The aim of this study was to assess the overall exposure, other pharmacokinetic (PK) properties, and tolerability of esomeprazole magnesium after repeated oral doses of 5, 10, and 20 mg in pediatric patients who had symptoms of gastroesophageal reflux disease (GERD). Methods: This randomized, open-label study was conducted at West Coast Clinical Trials, Long Beach, California. Boys and girls aged 1 to 11 years who had a clinical diagnosis of GERD were included and stratified by age (1–5 years [younger group] and 6–11 years [older group]). For this 5-day study, children in the younger group were randomly assigned to receive 1 esomeprazole 5- or 10-mg capsule PO QD, and those in the older group were randomly assigned to receive 1 esomeprazole 10- or 20-mg capsule PO QD. On days 1 to 4, study medications were administered with the supervision of the study personnel 1 hour before breakfast. Blood samples were collected within 0.5 hour before and 0.5, 1, 1.5, 2, 3, 4, 5, and 6 hours after study drug administration on day 5. Plasma concentrations of esomeprazole were measured using reverse-phase liquid chromatography and mass-spectrometric detection. Tolerability assessments were performed by reviewing the number and severity of adverse events (collected via spontaneous reporting and direct questioning) and findings from the physical examination, which included vital-sign measurements and laboratory analysis (hematology, biochemistry, and urinalysis). Site personnel supervised the administration of the study drug to ensure compliance with treatment. Results: The study included 31 children (17 boys, 14 girls; mean age, 5 years; 18 children in the younger group, 13 in the older group). A total of 27 children were included in the PK analysis. In the younger group, the geometric mean AUC 0−∞ and C max values in the esomeprazole 10-mg group were >2-fold that in the 5-mg group (AUC 0−∞, 4.83 and 0.74 pmol · h/L [0.32 and 0.04 μmol · h · L −1/kg], respectively; C max, 2.98 and 0.62 μmol/L [0.19 and 0.03 μmol/L · kg −1], respectively). In the older group, the geometric mean AUC 0−∞ and C max values for the 20-mg dose group were ∼2-fold those for the 10-mg dose group (AUC 0−∞, 6.28 and 3.70 μmol · h/L [0.21 and 0.12 pmol · h · L −1/kg], respectively; C max, 3.73 and 1.77 μmol/L [0.13 and 0.06 μmol/L · kg 1], respectively). For the 10-mg esomeprazole dose, the geometric mean body-weight-normalized apparent oral clearance was ∼50% higher in the younger group compared with the older group (0.40 and 0.25 L/h · kg −1, respectively). Thirty patients were included in the tolerability analysis. The adverse events that occurred were skin excoriation, discolored feces, and skin laceration (1 [3.3%] patient each); none were considered related to treatment. Conclusions: The results of this small study suggest that, in children aged 1 to 11 years who had GERD, the PK properties of esomeprazole may be both dose and age dependent and that younger children might have a more rapid metabolism of esomeprazole per kilogram of body weight compared with older children. Esomeprazole was well tolerated at doses of 5, 10, and 20 mg in the pediatric patients studied.

Effect of Single Doses of Rabeprazole 20 mg and Pantoprazole 40 mg on 24-Hour Intragastric Acidity in Gastroesophageal Reflux Disease (GERD) Patients with Nocturnal Heartburn

Purpose: PPIs with rapid and prolonged control of acid secretion may be useful for treating nocturnal GERD symptoms. This study compared the antisecretory effects of single doses of rabeprazole sodium (RAB) 20 mg and pantoprazole sodium (PAN) 40 mg tablets in patients with a clinical diagnosis of GERD and a history of nocturnal heartburn (≥1 episode/wk). Methods: This open-label, randomized, 2-way crossover comparison enrolled H pylori-negative subjects to receive RAB 20 mg and PAN 40 mg (single oral doses) in the morning (≥14-day washout). Intragastric pH was measured from 24 h before (day 0) until 24 h after dosing (day 1). Patients fasted from 2200 h the evening before until ∼0900 h on day 0 and 1, and had standard meals/drinks 1, 4, and 10 h after dosing on day 1 and at corresponding times on day 0. Primary end point was 24-h area under intragastric pH–time curve (AUC0–24) on days 0 and 1. Secondary end points included AUC for 0–5, 5–11, 11–14, and 14–24 h;% time pH >3 and >4 over 24 h and for 0–14 and 14–24 h; and safety/tolerability. Results: 31 patients (male, n = 19; mean age, 44 yr) were enrolled (evaluable population, n = 29). Preliminary results show that day-1 mean intragastric pH AUC0–24 was significantly higher for RAB vs PAN: 319,692 vs 259,921 pH units. sec, respectively (evaluable population; P < 0.0001). In the ITT and evaluable (Table 1) populations, mean pH AUC was significantly higher for RAB (P ≤ 0.024) in all time intervals studied, including overnight (14–24-h). Mean day 1% time pH >3 and >4 was significantly higher for RAB (P ≤ 0.004) during the 24 h after dosing and all time intervals (ITT and evaluable populations). Both treatments were well tolerated.Table: No Caption available.Conclusions: Overall and during all time intervals, including overnight, a single oral dose of RAB 20 mg increased intragastric pH more than did PAN 40 mg in GERD patients with nocturnal heartburn. Research supported by Eisai Ltd., London, UK; Eisai Inc., Teaneck, NJ, USA; and Janssen Pharmaceutica Inc., Titusville, NJ, USA.

Role of esophageal function tests in diagnosis of gastroesophageal reflux disease.

Clinicians typically make the diagnosis of gastroesophageal reflux disease (GERD) from the clinical findings and then prescribe acid-suppressing drugs. Endoscopy is usually done for persistent or severe symptoms. Esophageal function tests (EFTs: esophageal manometry and 24-hr pH monitoring) are generally reserved for patients who have the most severe disease, including those being considered for surgery. We hypothesized that EFTs are more accurate than symptoms and endoscopy in the diagnosis of GERD. This was a retrospective study undertaken in a university tertiary care center. Between October 1989 and November 1998, 822 patients with a clinical diagnosis of GERD (based on symptoms and endoscopic findings) were referred for EFTs. The patients were divided into two groups depending on whether the 24-hr pH monitoring score showed GERD (group A, GERD-; group B, GERD+). The groups were compared with respect to the incidence and severity of symptoms, presence of a hiatal hernia on barium x-rays, presence and severity of esophagitis on endoscopy, and esophageal motility. In all, 247 patients (30%) had normal reflux scores (group A, GERD-), and 575 patients (70%) had abnormal scores (Group B, GERD+). Eighty percent of group A and 88% of group B had been treated with acid-suppressing medications. The incidence of heartburn and regurgitation was similar in the two groups. Grade I-II esophagitis was diagnosed by endoscopy in 25% of group A and 35% of group B, and grade III esophagitis in 4% of group A and 11% of group B. Esophageal manometry showed that group B more often had esophageal dysmotility, consisting of a hypotensive lower esophageal sphincter and abnormal esophageal peristalsis. These data show that: (1) symptoms were unreliable for diagnosing GERD; (2) endoscopic evidence of grade I-II esophagitis was diagnostically nonspecific, and grade III was much less certain than claimed in other reports; and (3) pH monitoring identified patients with GERD and stratified them according to the severity of the disease. We conclude that esophageal manometry and pH monitoring are important in diagnosing GERD accurately. More liberal use of these tests early in patient management would avoid much improper and costly medical therapy and would help single out for special attention the patients with GERD who have the most severe disease.

On-demand therapy in gastroesophageal reflux disease: a comparison of the early effects of single doses of fast-dissolving famotidine wafers and ranitidine tablets

In this double-masked, double-dummy, randomized, single crossover study, we compared single doses of a fast-dissolving wafer formulation of famotidine with a conventional tablet formulation of ranitidine in patients with gastroesophageal reflux disease (GERD). Patient preference, time until symptomatic relief, and predictive characteristics of early responders were assessed. Eligible patients had a clinical diagnosis of GERD and symptoms of GERD of sufficient severity to require relief. The study treatment was one dose of famotidine (20-mg wafer) and one dose of ranitidine (150-mg tablet), which were given in a randomized order and taken as needed. The patients were instructed to measure the symptomatic effects on a seven-point categorical scale (1 = worse to 7 = free of symptoms) at 15, 30, 45, 60, 120, and 180 minutes. After the clinical phase of the trial, the patients indicated their global assessment of efficacy and their preference for the wafer or the tablet. Of the 829 patients who completed the study, significantly more preferred the wafer to the tablet. While there was no significant difference in the global assessment of efficacy, the famotidine wafer provided significantly better relief than the ranitidine tablet during the first hour after dosing. However, at 120 and 180 minutes, the degree of relief was similar for the two drugs. The time until a clinically significant effect was also similar for the two drugs, and approximately one half of the patients experienced such improvement within 3 hours. Multivariate analyses disclosed no predictive characteristics of early symptomatic effect