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.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.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.This study demonstrates that the ANMA CC tool can be a useful for Asian patients with CC.
Abstract We previously reported the safety and immunogenicity data from a randomized trial comparing the monovalent (MV) recombinant protein Beta-variant (MVB.1.351) and MV ancestral protein (MVD614) booster vaccines with AS03 adjuvant (Sanofi/GSK) to mRNA BNT162b2 vaccine (Pfizer-BioNTech). First booster of the vaccines was administered in adult participants previously primed with 2 doses of BNT162b2. A subset of these participants with available blood samples collected at Day 0 (D0), at 28 days (D28), and 3 months (M3) post-booster were contacted for additional testing (195/208 participants). The persistence of cross-neutralizing antibodies, including against Omicron BA.1 and BA.4/5, up to 3 months after boosting was evaluated using a validated pseudovirus neutralization assay. The data showed that the MVB.1.351 vaccine induced higher and durable cross-neutralizing antibodies against Omicron subvariants up to 3 months after boosting compared to a MV ancestral and the mRNA BNT162b2 booster vaccine.
Purpose: The effect of rabeprazole (RAB) 20 mg on the antiplatelet activity of clopidogrel (CLO) in relation to CYP2C19 genotype status was evaluated. Methods: 36 male healthy volunteers with different CYP2C19 genotypes measured in the study were enrolled in this open label, randomized, 3-way crossover study to receive once daily either RAB 20 mg, omeprazole (OME) 20 mg or placebo (PLB) for 7 days plus CLO 75 mg with 2-3 weeks wash out between treatment phases. The primary endpoint was the relative decrease on Day 7 in platelet reactivity index (ΔPRI) (ITT population) as derived from VASP phosphorylation level assay. The primary hypothesis was that the effect of RAB on ΔPRI is not inferior (NI) to placebo (NI was met if upper limit of the 90% CI was <10). Secondary endpoints were the ΔPRI in Good Antiplatelet Responders to CLO (defined as subjects with at least a 30% decrease in ΔPRI (n = 18)). The responses of different CYP2C19 genotype subgroups were also evaluated within each population. Results: The effect of RAB 20 mg on ΔPRI is NI to PLB in either ITT or Good Responder populations regardless of different genotype status (EM or IM) although the extensive metabolizers (EM) showed greater reductions in ΔPRI than intermediate metabolizers (IM). The effect of OME tended to be greater than RAB in both populations; however, there were no statistical differences across treatments within CYP2C19 genotypes. The responses in Poor Metabolizer (PM) in both population and IM in Good Antiplatelet Responders were not statistically evaluated due to very small sample size. In the Good Antiplatelet Responders population all but 3 subjects were classified as EM. In this subset of subjects the effect of OME was ΔPRI = 7.1% (90% CI ranging 1.2-13.0%) relative to PLB. This exceeds the 10% NI criteria and demonstrates an adequate level of sensitivity to detect drug induced changes in this population. In the same subset of subjects, the administration of RAB increased ΔPRI of 2.4% (90% CI ranging -3.5 to 8.3%) relative to PLB. This value does not exceed the 10% NI criteria. Therefore, in this subset of subjects, RAB but not OME was shown to be not inferior to PLB. Conclusion: RAB 20 mg is non-inferior to placebo as related to CLO antiplatelet activity, in EM subjects both in the ITT population and in the good antiplatelet responders regardless of CYP2C19 genotypes (EM, IM). OME did not meet NI in EM subjects in the good antiplatelet responders. Disclosure: BOGDANA COUDSY - Employee: Janssen, CHRISTIAN FUNCKBRENTANO - consultant: Janssen; Research Support: Janssen, ANNE BLANCHARD - Research Support: Janssen, JEAN SZYMEZAK - Research Support: Janssen, MICHAEL FRANK - Research Support: Janssen, VERONIQUE REMONES - Research Support: Janssen, BHAVNA SOLANKI - Employee: Janssen, MATHIEU MOLIMARD - Research Support: Janssen, DOMINIQUE DUCINT - Research Support: Janssen, MICHEL AZIZI - Research Support: Janssen, PASCALE GAUSSEM - Research Support: Janssen.Table: Relative change in VASP platelet reactivity index (ΔPRI [%])- ITT populationTable: Relatice change in VASP platelet reactivity index (ΔPRI [%])- good antiplatelet responders
Increased body mass index (BMI) is associated with a higher risk of gastroesophageal reflux disease (GORD). To investigate whether overweight/obesity affects proton pump inhibitor pharmacodynamics when used in a single dose in patients with GORD. 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). 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. 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.
