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The comparative effectiveness of proton pump inhibitor versus prokinetic therapy in relieving the symptoms of patients with functional dyspepsia remains unknown. Whether the Rome III subgroups predict therapeutic response has not been investigated. This was an open-label, parallel randomized controlled trial. A total of 329 adult outpatients fulfilling the Rome III criteria for functional dyspepsia were randomly allocated to receive either lansoprazole 30 mg once daily (n = 166) or mosapride 5 mg thrice daily (n = 163) for 2 weeks. Enrolled patients were evaluated with the validated Hong Kong Index questionnaire for symptom severity at baseline and at the end of the trial. The primary outcome was symptom relief as defined by the Hong Kong Index, and the secondary outcome was decrease of symptom scores. Post-hoc multivariate logistic regression analysis was conducted to identify independent predictors for therapeutic response. After 2-week therapy, 50.6% (84/166) and 47.85% (78/163) of the patients treated with lansoprazole and mosapride, respectively, achieved significant symptom relief (odds ratio 1.12, 95% confidence interval 0.72–1.72, p = 0.62). Differences in decreases of symptom scores between lansoprazole and mosapride receivers were also insignificant (−0.08, 95% confidence interval −1.25 to 1.09, p = 0.89). Therapeutic responses to either pharmacotherapy did not differ in the subgroup of patients fulfilling the criteria for epigastric pain syndrome (n = 256) or in those fulfilling the criteria for postprandial distress syndrome (n = 161). Multivariate logistic regression confirmed that the treatment allocation and Rome III subgroup were unrelated to treatment outcome. The effectiveness of proton pump inhibitor therapy and that of prokinetic therapy in functional dyspepsia are not different, and cannot be predicted by Rome III subgroups (ClinicalTrials.gov number, NCT00663897).

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Reflux oesophagitis is a common clinical disorder associated with significant morbidity. Proton pump inhibitors are the current pharmacotherapy of choice, but not all treated patients achieve symptom relief. Little is known about the efficacy of mosapride, a prokinetic agent which decreases episodes of gastro-oesophageal reflux, as an adjunct to proton pump inhibitors in improving the symptoms of reflux oesophagitis. WHAT THIS STUDY ADDS Mosapride was generally not more effective than placebo as an adjunct therapy to a standard dose of lansoprazole in decreasing the symptom burden of patients with reflux oesophagitis. However, in a subgroup with more severe symptoms, combination therapy with lansoprazole and mosapride was possibly superior to monotherapy with lansoprazole. AIMS To investigate if mosapride, a prokinetic agent, was an effective adjunct to acid suppression in improving the symptoms of reflux oesophagitis. METHODS Patients (n= 96) with reflux oesophagitis were randomly assigned to either mosapride (5 mg three times daily) or placebo for 4 weeks. Symptom severity was assessed by a validated questionnaire at enrolment, 4 and 8 weeks after medication. The primary outcome for the first 4 weeks was decrease in symptom scores. After a 3 day washout period, patients initially allocated to mosapride crossed over to placebo and vice versa for the next 4 weeks. The outcome of the second phase was maintenance of symptom control. All patients received lansoprazole (30 mg once daily) throughout study. RESULTS The decreased symptom score after 4 weeks of treatment with lansoprazole and mosapride (n= 50) was 13.42 +/- 1.16 (mean +/- SEM), similar to that of lansoprazole plus placebo (10.85 +/- 1.03, n= 46), with an insignificant difference of 2.57 (95% CI -0.53, 5.67, P= 0.103). However, a sub-group analysis for patients with pre-treatment scores of >18 points (n= 48) revealed that lansoprazole plus mosapride achieved a greater reduction of symptom score than lansoprazole plus placebo (18.22 +/- 1.91 vs. 12.88 +/- 1.65; mean difference of 5.34, 95% CI 0.28, 10.40, P= 0.039). In the second phase, there was no difference between lansoprazole with mosapride or placebo in maintaining symptom control (39/44 or 86.64% vs. 41/50 or 82%, P= 0.401). Subgroup analysis for those with substantial residual symptoms revealed similar results. CONCLUSION Compared with placebo, mosapride generally does not provide additional benefit to a standard dose of lansoprazole in patients with reflux oesophagitis, except possibly in the subgroup of severely symptomatic patients.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • An adjunct to endoscopy, proton pump inhibitor (PPI) is effective pharmacotherapy in high-risk patients with peptic ulcer bleeding (PUB). • An intravenous 80-mg bolus and 192 mg day−1 successive infusion for 3 days is the currently recommended dosing modality in administering PPI. WHAT THIS STUDY ADDS • Clinical outcomes are not different in PUB patients receiving infusional pantoprazole at either 192 mg or 160 mg day−1 for 3 days. • The effective dosage of PPI may not be as high as currently recommended. • In view of cost-effectiveness, a lower dosage (160 mg day−1) of infusional PPI may be adopted in the management of PUB. AIM The optimal dosage of proton pump inhibitor in bleeding peptic ulcers remains controversial. The aim was to compare the clinical effectiveness of two doses of infusional pantoprazole in peptic ulcer bleeding. METHODS Peptic ulcer patients (n= 120) with bleeding stigmata were enrolled after successful endoscopic therapy. After an initial bolus injection of 80 mg pantoprazole, patients were randomized to receive continuously infused pantoprazole at either 192 mg day−1 or 40 mg every 6 h (i.e. 160 mg day−1) for 3 days. Clinical outcomes between the two groups within 14 days were compared, with 14-day recurrent bleeding regarded as the primary end-point. RESULTS Both groups (n= 60 each) were well matched in demographic and clinical factors upon entry. Bleeding totally recurred in 11 (9.2%) patients, with six (10%) in the 192 mg day−1 group and five (8.3%) in the 160 mg day−1 group (relative risk of bleeding recurrence between two treatments 1.2; 95% CI 0.39, 3.72). All secondary outcomes between the two groups were similar, including the amount of blood transfusion (mean 1179 ml vs. 1203 ml, P > 0.1), hospital stay (mean 9.5 days vs. 9.9 days, P > 0.1), need for surgery (n= 1 vs. n= 0, P > 0.1), and mortality (n= 1 vs. n= 0, P > 0.1). CONCLUSIONS Following endoscopic haemostasis, infusional pantoprazole at either 192 mg day−1 or 40 mg every 6 h appear similar.

Functional dyspepsia is a heterogeneous symptom complex that may be subdivided into postprandial distress syndrome and epigastric pain syndrome. We aimed to investigate differences among these subgroups in psychopathological factors and personality traits.We enrolled 187 consecutive outpatients (72.2% female patients, mean age 42.6 years) with functional dyspepsia based on the Rome III criteria. Patients were interviewed and evaluated by the Brief Symptom Rating Scale and the short-form Maudsley personality inventory for severity of psychopathology and personality traits. Multiple linear regression models were built for each psychopathological dimension and personality trait to assess the independent association with each subclass diagnosis of functional dyspepsia.There was an overlap (n=64, 34.2%) between the patients diagnosed with epigastric pain syndrome (n=157, 84.0%) and those with postprandial distress syndrome (n=94, 50.3%). Patients with symptoms compatible with both syndromes were psychopathologically more severe than either subgroup without overlapping. Multiple linear regression analysis demonstrated that the diagnosis of postprandial distress syndrome was independently associated with higher scores in overall psychopathological stress, and specifically in somatization (P=0.034), depression (P=0.028), phobia (P=0.044), and additional symptoms (P0.001). However, epigastric pain syndrome was not associated with psychopathology. Postprandial distress was univariately associated with neuroticism, but the association was insignificant in the multivariate analysis (P=0.136).The Rome III subgroups of functional dyspepsia significantly overlap. Patients fulfilling criteria for both subgroups had symptoms that were psychopathologically more severe than those of patients without overlapping. Diagnosis of postprandial distress syndrome, but not epigastric pain syndrome, is independently associated with psychopathological factors.

a b s t r a c t Background: Whether clinical features can stratify priority of endoscopy remains controversial for dys- peptic patients with high background prevalence of upper gastrointestinal cancer. Aim: To examine the predictive performance of clinical features for cancerous lesions in dyspeptic patients in Taiwan. Methods: Between April 2008 and July 2009, 2530 consecutive dyspeptic outpatients underwent prospec- tive evaluation with standardized questionnaire and then upper gastrointestinal endoscopy. Performance of using age thresholds and alarm symptoms to predict malignancy was determined. Independent risk factors associated with malignancy and those with negative endoscopic findings were identified. Results: Malignant lesions were found in 31 patients (1.2%) and were independently associated with age, male gender, gastrointestinal bleeding, weight loss, and alcohol consumption. Any symptom of weight loss, bleeding and dysphagia, or simply age >45 years predicted 97% of cancer cases, with the sensitivity, specificity, positive and negative predictive values being 96.8%, 29.3%, 1.7%, and 99.9%, respectively. This strategy achieved a low negative likelihood ratio (0.11) and a high diagnostic odds ratio (12.45). Negative endoscopic finding (n = 1377, 54.4%) was independently associated with younger age, female gender, no use of non-steroidal anti-inflammatory drug, and no tobacco or alcohol consumption. Conclusions: Absence of weight loss, dysphagia, and gastrointestinal bleeding predicts low likelihood of malignancy in dyspeptic Taiwanese patients aged

Background: Clopidogrel is a prodrug requiring a cytochrome (CYP)2C19-dependent conversion to become active. Usage of proton pump inhibitors (PPIs) might attenuate clopidogrel's platelet inhibitory effect. Methods: We performed a meta-analysis of studies in Pubmed, Ovid, ISI Science, and Embase. Primary analysis was based on definite outcomes including all cause mortality, cardiac death, myocardial infarction, and/or stroke. Secondary analysis also incorporated probable cardiac events which included re-hospitalization for cardiac symptoms or revascularization procedures. Odds ratios were obtained for studies with definite and probable endpoints and were combined using a random-effects model. Risk difference (RD) was defined as the difference in disease/event rate between the control and treatment. Results: We reviewed 898 publications and found 8 relevant studies: 2 were excluded due to data quality and 1 was excluded because controls used PPIs. 5 studies were analyzed, including 2 published articles and 3 abstracts. 2 meta-analysis were conducted: the first considered only the published articles and the second considered all 5 studies. (Figure) Usage of clopidogrel + PPI was associated with a small non-significant increase in definite events (Risk Difference (RD) 0.0083, 95% CI -0.00022 to 1.2). When probable events were included, the risk difference was significant (RD 0.066, 95% CI 0.055 to 0.077). There was evidence of heterogeneity (p=0.028) between studies. Conclusions: This metaanalysis does not support an adverse relationship between clopidogrel and PPIs when the primary focus was death or definite cardiovascular events.