Troels Havelund

Heartburn without Oesophagitis: Efficacy of Omeprazole Therapy and Features Determining Therapeutic Response

BACKGROUND Data are limited on the value of effective antisecretory therapy in the relief of heartburn in patients without oesophagitis. METHODS Patients with heartburn, without endoscopic signs of oesophagitis, were randomized to double-blind treatment with omeprazole, 20 or 10 mg once daily, or placebo, for 4 weeks (n = 509). Pre-treatment oesophageal acid exposure was assessed using 24-h intra-oesophageal pH monitoring. Heartburn was assessed at 2 and 4 weeks. RESULTS At 4 weeks the proportion of patients with complete absence of heartburn was 46% (95% confidence interval, 39-53%) with 20 mg omeprazole, 31% (25-38%) with 10 mg omeprazole, and 13% (7-20%) with placebo. Satisfaction with therapy was reported by 66%, 57%, and 31% of the patients, respectively. CONCLUSION Omeprazole, 20 and 10 mg once daily, provides rapid relief of heartburn in patients without endoscopic oesophagitis.

Small-bowel neoplasms in patients undergoing video capsule endoscopy : a multicenter European study

BACKGROUND AND STUDY AIM Small-bowel tumors account for 1% - 3% of all gastrointestinal neoplasms. Recent studies with video capsule endoscopy (VCE) suggest that the frequency of these tumors may be substantially higher than previously reported. The aim of the study was to evaluate the frequency, clinical presentation, diagnostic/therapeutic work-up, and endoscopic appearance of small-bowel tumors in a large population of patients undergoing VCE. PATIENTS AND METHODS Identification by a questionnaire of patients with VCE findings suggesting small-bowel tumors and histological confirmation of the neoplasm seen in 29 centers of 10 European Countries. RESULTS Of 5129 patients undergoing VCE, 124 (2.4%) had small-bowel tumors (112 primary, 12 metastatic). Among these patients, indications for VCE were: obscure gastrointestinal bleeding (108 patients), abdominal pain (9), search for primary neoplasm (6), diarrhea with malabsorption (1). The main primary small-bowel tumor type was gastrointestinal stromal tumor (GIST) (32%) followed by adenocarcinoma (20%) and carcinoid (15%); 66% of secondary small-bowel tumors were melanomas. Of the tumors, 80.6% were identified solely on the basis of VCE findings. 55 patients underwent VCE as the third procedure after negative bidirectional endoscopy. The lesions were single in 89.5% of cases, and multiple in 10.5%. Retention of the capsule occurred in 9.8% of patients with small-bowel tumors. After VCE, 54/124 patients underwent 57 other examinations before treatment; in these patients enteroscopy, when performed, showed a high diagnostic yield. Treatment was surgery in 95% of cases. CONCLUSIONS Our data suggest that VCE detects small-bowel tumors in a small proportion of patients undergoing this examination, but the early use of this tool can shorten the diagnostic work-up and influence the subsequent management of these patients.

Quality of life in patients with heartburn but without esophagitis: effects of treatment with omeprazole

OBJECTIVES:Because improvement in quality of life (QoL) is an important therapeutic goal in patients with heartburn but without esophagitis, the aim of the present study was to compare the impact of omeprazole 20 mg or 10 mg daily with that of placebo on QoL in patients with heartburn as the predominant symptom.METHODS:QoL was measured at baseline and after 4 wk using two validated questionnaires, the Psychological General Well-Being (PGWB) index and the Gastrointestinal Symptom Rating Scale.RESULTS:The two questionnaires were completed by 163 patients in the omeprazole 20 mg group, 163 in the omeprazole 10 mg group, and 82 in the placebo group. The reflux dimension of the Gastrointestinal Symptom Rating Scale showed a significant improvement in terms of reflux symptoms on omeprazole 20 mg versus omeprazole 10 mg and placebo, and on omeprazole 10 mg compared with placebo. The total score of the PGWB index improved significantly more on both doses of omeprazole than on placebo. The mean scores rose from 96.8 to 103.9 on omeprazole 20 mg, from 98.4 to 106.0 on omeprazole 10 mg, and from 98.0 to 100.6 on placebo. All dimensions of the PGWB index improved on treatment with omeprazole, but the improvements were most pronounced in the dimensions depicting anxiety, depressed mood, and self-control.CONCLUSIONS:It is concluded that treatment with omeprazole 20 mg and omeprazole 10 mg restores QoL to a level comparable with that observed in a healthy population.

Effect of Omeprazole on the Outcome of Endoscopically Treated Bleeding Peptic Ulcers Randomized Double-Blind Placebo-Controlled Multicentre Study

Background: Haemostasis is highly pH-dependent and severely impaired at low pH. However, there is no clear evidence that acid-suppressing drugs have beneficial effects in peptic ulcer haemorrhage. Endoscopic haemostatic treatment provides important reduction in morbidity and may be more efficient when a neutral intragastric pH is maintained. Methods: We conducted a double-blind, placebo-controlled multicentre study of intravenous infusion of omeprazole (80 mg as bolus, followed by 8 mg/h) or placebo for 72 h. All patients received 20 mg omeprazole orally from day 3 until follow-up on day 21. Only patients with ulcer haemorrhage, endoscoped within 12 h after admission, and with a history or signs of circulatory failure and spurting bleeding, oozing bleeding, visible vessel, or clot, were included. Endoscopic intervention was aimed at when spurting bleeding, oozing bleeding, or a visible vessel was observed. The primary efficacy measure was the worst ranking on an overall outcome scale (5 = death, 4 = surge...

Proton Pump Inhibitor or Testing for Helicobacter pylori as the First Step for Patients Presenting with Dyspepsia? A Cluster-Randomized Trial

OBJECTIVES:The optimal approach for management of patients with dyspepsia has not been determined. The aim of this study was to compare the efficacy of three strategies for management of dyspepsia: empirical antisecretory therapy, testing for Helicobacter pylori (H. pylori), or a combination of the two.METHODS:Cluster-randomized trial in general practices. Initial treatment with proton pump inhibitor (PPI) was performed in 222 patients, H. pylori test-and-eradicate in 250 patients, and PPI followed by H. pylori-testing if symptoms improved in 250 patients. Symptoms, quality of life, patient satisfaction, and use of resources were recorded during a 1-yr follow-up.RESULTS:The prevalence of H. pylori infection was 24%. We found no difference among the three strategies (p = 0.16) in terms of the proportion of days without dyspeptic symptoms. After 1 yr gastrointestinal symptom scores and quality-of-life scores had improved significantly and equally in the three groups (p < 0.001), but no statistically significant differences were found among the groups. The mean use of endoscopies per patient after 1 yr was higher in the PPI group (0.36 [95% CI 0.30–0.43]) than in the test-and-eradicate group (0.28 [95% CI 0.23–0.34]) and the combination group (0.22 [95% CI 0.17–0.27]), p = 0.02. H. pylori-positive patients given eradication therapy had more days without dyspeptic symptoms (p < 0.001), used less antisecretory therapy (p < 0.01), and were more satisfied (p < 0.001) than H. pylori-negative patients.CONCLUSION:The strategies based on H. pylori test enjoyed similar symptom resolution, but reduced endoscopic workload and lower 1-yr total costs compared with empirical antisecretory therapy.

Omeprazole in the Long-Term Treatment of Gastro-oesophageal Reflux Disease: A Double-Blind Randomized Dose-Finding Study

BACKGROUND Omeprazole is effective in the treatment of reflux oesophagitis, and it is important to determine the lower dose limit with still appropriate clinical efficacy. METHODS Patients with endoscopic oesophagitis grade 1-4 (N = 220) were randomized to double-blind treatment with 20 mg or 40 mg omeprazole daily for 4-8 weeks. Those healed after this initial treatment phase were re-randomized to double-blind treatment with 20 mg omeprazole daily (n = 67), 10 mg omeprazole daily (n = 68), or placebo (n = 33) for 6 months. Remission was defined as the absence of any endoscopic sign of oesophagitis. RESULTS Healing rates were increased with 40 mg omeprazole, the therapeutic gain compared with the 20-mg dose being 15% after 4 and 8 weeks. The proportion of patients in remission after 6 months was 59% with 20 mg omeprazole, 35% with 10 mg omeprazole, and 0% with placebo. CONCLUSION Maintenance treatment with 10 mg omeprazole can prevent recurrence of oesophagitis in about one-third of patients with all grades of oesophagitis, and 20 mg omeprazole in about twice as many.

Efficacy of omeprazole in lower grades of gastro-oesophageal reflux disease.

Grade I oesophagitis is usually considered to be a less severe form of gastro-oesophageal reflux disease (GORD). However, with regard to symptom severity, patients without macroscopic mucosal lesions have been shown not to differ from those with more severe oesophagitis. A number of controlled trials on the efficacy of omeprazole in GORD have included patients with lower grades of the disease. The results show that the differences in efficacy between omeprazole and H2-receptor antagonists, which have been established for the treatment of erosive and ulcerative oesophagitis, also extend to patients with grade I oesophagitis (erythema and friability). In these studies, omeprazole provided more rapid symptom resolution and histological improvement than ranitidine. In one double-blind comparative trial, complete endoscopic normalization of the oesophageal mucosa was observed in 90% of patients with grade I oesophagitis within 4 weeks of treatment with omeprazole, 40 mg once daily, compared with 55% of those treated with ranitidine, 150 mg twice daily; at 8 weeks the mucosa in all patients in the omeprazole group had completely healed at endoscopy, while oesophagitis was still present in 21% of the patients receiving ranitidine. A separate 6-month, placebo-controlled maintenance study was performed in patients who had completed a short-term study and who had total relief from the major symptoms of GORD and complete healing of endoscopic oesophagitis. All patients given placebo had an endoscopic recurrence (i.e. endoscopic grade I or more) and this was associated with the return of symptoms in 75% of cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Targeting the Gut–Liver Axis in Cirrhosis: Antibiotics and Non-Selective β-Blockers

The gut–liver axis in cirrhosis and portal hypertension is gaining increasing attention as a key pathophysiological mechanism responsible for progression of liver failure and development of complications such as spontaneous infections and hepatocellular carcinoma. Antibiotics and non-selective β-blockers (NSBB) intercept this axis and each drug has proven efficacy in clinical trials. A synergistic effect is a hitherto unproven possibility. There is an increasing body of evidence supporting improved outcome with expanded use of NSBB and antibiotic therapy beyond current indications. This review addresses the issue of pharmacological treatment of cirrhosis and portal hypertension with antibiotics and NSBB. We discuss their mechanism of action and suggest that combining the two treatment modalities could potentially reduce the risk of complications.

Efficacy of a pectin-based anti-reflux agent on acid reflux and recurrence of symptoms and oesophagitis in gastro-oesophageal reflux disease.

Objective: Gastro‐oesophageal reflux disease may be treated with a drug forming a floating neutral raft in the stomach. The pectin‐based raft‐forming anti‐reflux agent Aflurax® (Idoflux®) was examined, first regarding reduction of oesophageal acid exposure, and next as to its efficacy as maintenance treatment in patients with healed oesophagitis. Design: Double‐blind, placebo‐controlled randomized clinical trials. Setting: Open access endoscopy unit. Participants: Fourteen patients with erosive oesophagitis had measurement of acid exposure. Eighty‐eight patients with healed erosive/ulcerative oesophagitis and relief of heartburn after pre‐treatment with omeprazole received maintenance treatment. Interventions: Crossover 12‐h oesophageal pH monitoring during Aflurax/placebo treatment. Maintenance treatment for up to 6 months with two tablets of Aflurax 1200mg or placebo four times daily. Main outcome measures: Percentage time pH less than 4 in 6 plus 6h (upright + supine). Time to recurrence of moderate or severe heartburn (life table analysis). Results: The median (interquartile range) acid exposure times in the upright position were: 3.1% (1.6‐13.0%) on Aflurax versus 6.7% (2.5‐14.9%) on placebo (P=0.10). In the supine position no difference was found (Aflurax 13.7%, placebo 13.2%). The time to recurrence of heartburn with Aflurax treatment was prolonged significantly; after 6 months the life table estimates were 48% of patients in remission on Aflurax versus 8% on placebo (P=0.01). Following treatment, erosive oesophagitis was found in 17/34 on Aflurax versus 28/38 on placebo (P<0.05). Conclusion: Aflurax significantly delays recurrence of moderate or severe heartburn and erosive oesophagitis, when used as maintenance treatment. The acid exposure was not significantly reduced with pH monitoring.

Omeprazole 20 mg three days a week and 10 mg daily in prevention of duodenal ulcer relapse

In a double-blind, parallel-group clinical trial of 195 patients with duodenal ulcers who after a short-term study had relief of pain and healed ulcers proved endoscopically, 65 were randomized to receive 20 mg omeprazole 3 days a week (once in the morning from Friday to Sunday), 64 to receive 10 mg omeprazole once daily in the morning, and 66 to receive placebo for up to 6 months. The patients underwent repeat endoscopy with biopsy of the gastric fundic mucosa (qualitative assessment of argyrophilic cell population), assessment of symptoms, and laboratory screening with measurement of basal serum gastrin concentrations at 3 and 6 months or more often if indicated by recurrence of symptoms. At 3 months, endoscopically proved ulcer relapse occurred in 16% receiving 20 mg omeprazole 3 days a week; 21% receiving 10 mg omeprazole daily; and 50% receiving placebo. At 6 months, corresponding rates were 23%, 27%, and 67% with 95% confidence intervals of difference between the placebo group and omeprazole groups of 28%-60% and 24%-56% (P less than 0.00001), respectively, and between omeprazole groups of -19%-11% (NS). No major clinical or laboratory side effects were noted. Thus both omeprazole regimens are effective and safe in preventing duodenal ulcer relapse.