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Background: The Patient Assessment of Constipation-Symptoms (PAC-SYM) questionnaire is frequently used in clinical trials of constipation. However, the threshold for reduction in total PAC-SYM score used to define a clinical response on this 0-4 point scale has not undergone formal appraisal, and its relationship with clinical benefit as perceived by patients has not been defined., Aim: To determine the minimal important difference in PAC-SYM score, and the optimum cut-off value for defining responders., Methods: The minimal important difference was estimated using data from six international phase 3/4, double-blind, randomised controlled trials of prucalopride in patients with chronic constipation (NCT01147926, NCT01424228, NCT01116206, NCT00485940, NCT00483886, NCT00488137), with anchor- and distribution-based approaches. Five appropriate patient-reported outcomes were selected as anchors. In addition, receiver operating characteristics (ROC) curve analyses were used to investigate responder discrimination for each anchor., Results: Data from 2884 patients were included. Minimal important difference estimates ranged from -0.52 to -0.63 across the five anchors. Estimates were not affected by study location but were consistently lower for rectal symptoms than for abdominal and stool symptoms. Distribution-based estimates were considerably lower than anchor-based estimates. ROC curve analyses showed optimum cut-off scores for discriminating responders to be similar to anchor-based minimal important difference estimates., Conclusions: Anchor-based methods gave consistent results for the minimal important difference, at approximately -0.6, and this value was close to the ROC-determined optimal cut-off scores for responder discrimination. This value could be considered in clinical practice. A slightly more conservative threshold (eg -0.75) could be used in clinical trials to reduce the placebo response rate., (© 2017 Shire International GMBH. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Objective: We evaluated the effects of cisapride (10 mg t.d.s. and 20 mg b.d.) on gastrointestinal symptoms and gastric myoelectrical activity in patients with functional dyspepsia. Myoelectrical activity was measured by electrogastrography., Methods: Patients with functional dyspepsia, defined as discomfort in the epigastrium, a negative endoscopy, and clinical symptoms of dyspepsia, were enrolled. A total of 38 patients participated in the study (23 female; 15 male; 24-72 years of age). Screening electrogastrography identified those with a normal electrogastrogram (14 subjects) and those with an abnormal electrogastrogram (24 patients). Patients were randomly assigned to 2 weeks of placebo or 2 weeks of cisapride (10 mg t.d.s.); both groups then received 2 weeks of cisapride (20 mg b.d.). Electrogastrograms were repeated at the end of each 2-week treatment period., Results: Cisapride 10 mg t.d.s. significantly improved symptoms in all patients. An additional 2 weeks of treatment with cisapride 20 mg b.d. led to continued improvement in symptoms in all patients, with significant improvement in the group with abnormal baseline electrogastrograms. Cisapride significantly improved postprandial bloating and discomfort in patients with abnormal baseline electrogastrograms. Cisapride also significantly improved postprandial gastric myoelectrical activity as measured by electrogastrography in patients with abnormal baseline electrogastrograms., Conclusion: Cisapride provides symptomatic relief and improves gastric myoelectrical abnormalities in patients with functional dyspepsia.