On-demand proton pump inhibitory treatment in overweight/obese patients with gastroesophageal reflux disease: are there pharmacodynamic arguments for using higher doses?

BACKGROUND: Increased body mass index (BMI) is associated with a higher risk of gastroesophageal reflux disease (GORD). AIM: To investigate whether overweight/obesity affects proton pump inhibitor pharmacodynamics when used in a single dose in patients with GORD. METHODS: Post hoc analyses by patient BMI were performed on data from two single-center, double-blind, single-dose, crossover studies comparing the pharmacodynamics of rabeprazole 20 mg and pantoprazole 40 mg in GORD patients with a history of nocturnal heartburn. The primary endpoint was the mean percentage of time with intragastric pH >4 between lean and overweight/obese patients (BMI <25 and ≥25). RESULTS: 24 h baseline intragastric pH values were not different between BMI groups. The pharmacodynamic effects of both proton pump inhibitors were not significantly different between BMI groups, and no evidence was found for an interaction between BMI and treatment. As compared with pantoprazole, rabeprazole showed a significantly greater effect on the antisecretory response for both BMI groups. CONCLUSIONS: Overweight/obesity in GORD patients does not appear to affect the antisecretory efficacy of a single dose of rabeprazole and pantoprazole. These data do not support adapting the dosage of rabeprazole and pantoprazole according to BMI in GORD patients when administered as an on-demand therapy schedule.

Assessment of the Asian Neurogastroenterology and Motility Association Chronic Constipation Criteria: An Asian Multicenter Cross-sectional Study.

BACKGROUND/AIMS: There is a need for a simple and practical tool adapted for the diagnosis of chronic constipation (CC) in the Asian population. This study compared the Asian Neurogastroenterology and Motility Association (ANMA) CC tool and Rome III criteria for the diagnosis of CC in Asian subjects. METHODS: This multicenter, cross-sectional study included subjects presenting at outpatient gastrointestinal clinics across Asia. Subjects with CC alert symptoms completed a combination Diagnosis Questionnaire to obtain a diagnosis based on 4 different diagnostic methods: self-defined, investigator's judgment, ANMA CC tool, and Rome III criteria. The primary endpoint was the level of agreement/disagreement between the ANMA CC diagnostic tool and Rome III criteria for the diagnosis of CC. RESULTS: The primary analysis comprised of 449 subjects, 414 of whom had a positive diagnosis according to the ANMA CC tool. Rome III positive/ANMA positive and Rome III negative/ANMA negative diagnoses were reported in 76.8% and 7.8% of subjects, respectively, resulting in an overall percentage agreement of 84.6% between the 2 diagnostic methods. The overall percentage disagreement between these 2 diagnostic methods was 15.4%. A higher level of agreement was seen between the ANMA CC tool and self-defined (374 subjects [90.3%]) or investigator's judgment criteria (388 subjects [93.7%]) compared with the Rome III criteria. CONCLUSION: This study demonstrates that the ANMA CC tool can be a useful for Asian patients with CC.

[Application of the recommendations of the conference of consensus in front of symptoms ENT, respiratory or thoracic pains considered as due to a gastroesophageal reflux disease]. / Application des recommandations de la conférence de consensus devant des symptômes ORL, respiratoires ou des douleurs thoraciques considérés comme dus à un reflux gastro-œsophagien.

AIMS: The primary objectives of this observatory were: (1) to assess the prevalence of extradigestive symptoms (EDS) (asthma, pharyngeal pain, chronic hoarseness, nocturnal breathlessness, chronic or nocturnal cough, non-cardiac chest pain) which are suspected of being associated with gastro-oesophageal reflux (GERD) in a population consulting in general practice; (2) to compare the diagnostic and therapeutic approach adopted initially and at follow-up to the recommendations of the French-Belgian Consensus Conference on adult GERD (1999). METHODS: The survey was conducted among 578 general practitioners (GPs). All EDS were investigated in patients (≥ 18 y.o.) consulting over 3 days. Only patients considered a priori as having GERD related EDS were included in study. At each visit (initial and at 1 and 4 months), the diagnostic and therapeutic approach was analyzed, scored, and the GP's certainty regarding the accountability of GER in the EDS rated using the visual analogue scale (VAS). The criteria used by GPs to evaluate GER accountability as certain or doubtful were examined. RESULTS: Out of 33,487 consulting patients, 14% presented EDS (cough: 6.7%; ENT symptoms: 7.7%; chest pain: 2.3%). Among patients presenting EDS, 22% (1063) were included in the study based on suspicion of GERD, whereas 45% (481) had neither history nor digestive symptoms typically associated with GERD. The diagnostic approach did not vary whether the patient presented typical EDS associated symptoms (A+) or not (A-): 83.7% of patients (A+) versus 86.5% (A-) immediately received acid reflux treatment; 4.6% (A+) versus 7.9% (A-) underwent additional testing and 5.2% (A+) versus 4.4% (A-) were referred to a specialist. In 87% of cases, acid reflux treatment included a proton pump inhibitor (PPI) (half-dose: 47.2%, standard dose 50.3%, double dose 2.5%); in 8.1% of patients initial acid reflux treatment included an H2 antagonist while in 3.2% of patients treatment included prokinetic drugs. At 4 months of follow-up, GERD accountability was considered certain in 74.7% of the patients included in the assessment (794/1063). The GPs opinion was based on response to acid reflux treatment in 92% of cases, on endoscopy in 6.7% of cases, on pH monitoring in 0.3% of cases and on a specialist's opinion in 6% of cases. CONCLUSION: There is a considerable difference between the recommendations of the French-Belgian Consensus Conference on adult GERD and the practices observed in general medicine. The diagnostic and therapeutic approaches were empirical with recourse to additional exams in less than 10% of cases. The degree of certainty as to GERD accountability was based primarily on response to PPI treatment.

Does BMI affect the clinical efficacy of proton pump inhibitor therapy in GERD? The case for rabeprazole.

BACKGROUND: Increased BMI is associated with a higher risk of gastroesophageal reflux disease. AIMS: To investigate whether overweight/obesity (BMI≥25 kg/m(2)) affects rabeprazole clinical efficacy versus omeprazole in patients with erosive esophagitis (EE). PATIENTS AND METHODS: Post-hoc analysis of EE healing rate and symptom response stratified by patient BMI was performed on data from a multicenter, double-blind, randomized, 4-to-8-week trial comparing EE healing with rabeprazole (20 mg daily) and omeprazole (20 mg daily). Analysis of variance, two-sample t-test, Blackwelder's test for equivalence, log-rank, and Cochran-Mantel-Haenszel tests were used to analyze comparisons. RESULTS: In the two BMI groups (<25 kg/m(2) and ≥25 kg/m(2) respectively), rabeprazole and omeprazole were equally effective for mucosal healing regardless of patient's BMI (N=542, P>0.05). However, in overweight/obese patients, rabeprazole was significantly faster than omeprazole in inducing heartburn relief during the first treatment week (P<0.0001). CONCLUSIONS: Results of this study show that the clinical efficacy of rabeprazole is maintained in overweight/obese patients with gastroesophageal reflux disease and suggest that this subgroup of patients may derive, from rabeprazole, even greater benefit than lean patients.