One-week acid suppression trial in uninvestigated dyspepsia patients with epigastric pain or burning to predict response to 8 weeks' treatment with esomeprazole: a randomized, placebo-controlled study.

BACKGROUND: While empiric acid-suppressive therapy for uninvestigated dyspepsia patients with symptoms of epigastric pain or burning is standard practice, it is unknown whether an early response to therapy predicts outcome. AIM: To evaluate whether a 1-w acid suppression trial is effective for predicting 8-w response in such patients. METHODS: Helicobacter pylori-negative patients (aged 18-50 years) in primary care with uninvestigated epigastric pain or burning were randomized to esomeprazole 40 mg q.d.s. or b.d. for 1w, followed by esomeprazole 40 mg q.d.s. or placebo for 7w. Each day, patients rated the severity of their symptoms. RESULTS: Based on the last 3d, 1-w response rates were 39% (231 of 588) and 43% (258 of 596) with esomeprazole 40 mg q.d.s. and b.d., respectively. Based on the last 7d, response rates at 4w were 38% (283 of 738) and 25% (93 of 380) for esomeprazole and placebo, respectively, and 47% (339 of 716) and 34% (124 of 368), respectively, at 8w (both P < 0.001 vs. placebo). The sensitivity and specificity of esomeprazole treatment were 58% and 70%, respectively, at 8w. CONCLUSION: A 1-w acid suppression trial is of limited clinical value for predicting 8-w response in patients with symptoms of epigastric pain or burning. Esomeprazole provides greater symptom control than placebo at 4w and 8w.

Is ranitidine therapy sufficient for healing peptic ulcers associated with non-steroidal anti-inflammatory drug use?

Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) increases the risk of serious gastroduodenal events. To minimise these risks, patients often require concomitant acid-suppressive therapy. We conducted a literature review of clinical trials examining use of ranitidine 150 mg twice daily to heal gastroduodenal ulcers (GU) in NSAID recipients. Seven studies were identified. After 8 weeks' treatment with ranitidine, GU healing rates ranged from 50% to 74% and rates of duodenal ulcer (DU) healing ranged from 81% to 84%. Ranitidine was more effective when NSAIDs were discontinued (healing rates reaching 95% and 100%, respectively). The ulcer healing rate with sucralfate was similar to that of ranitidine. However, proton pump inhibitor (PPI) therapy was associated with significantly greater rates of both GU and DU healing than ranitidine; 8-week GU rates were 92% and 88% with esomeprazole 40 mg and 20 mg, respectively (vs. 74% with ranitidine, p < 0.01). For omeprazole, 8-week healing rates were 87% with omeprazole 40 mg and 84% with omeprazole 20 mg (vs. 64% for ranitidine, p < 0.001), and for lansoprazole the corresponding values were 73-74% and 66-69% for the 30 mg and 15 mg doses, respectively (vs. 50-53% for ranitidine, p < 0.05). In the PPI study reporting DU healing the values were 92% for omeprazole 20 mg (vs. 81% for ranitidine, p < 0.05) and 88% for omeprazole 40 mg (p = 0.17 vs. ranitidine). NSAID-associated GU are more likely to heal when patients receive concomitant treatment with a PPI rather than ranitidine.

Esomeprazole 40 mg i.v. provides faster and more effective intragastric acid control than pantoprazole 40 mg i.v.: results of a randomized study.

BACKGROUND: Oral esomeprazole 40 mg provides greater acid control than oral pantoprazole 40 mg. AIM: To compare the effects on intragastric acid control of esomeprazole 40 mg administered intravenously with pantoprazole 40 mg intravenously. METHODS: Healthy Helicobacter pylori-negative male and female subjects were enrolled into this single-centre, open, randomized, two-way crossover study. Esomeprazole 40 mg intravenously and pantoprazole 40 mg intravenously were administered as 15-min infusions once daily at 09:00 hours for 5 days. Continuous 24-h intragastric pH monitoring was carried out at baseline and on days 1 and 5. RESULTS: pH-data were available for all 25 subjects who completed the study. Esomeprazole 40 mg intravenously resulted in 8.3 and 13.9 h with an intragastric pH > 4 on days 1 and 5 compared with 5.3 and 9.0 h, respectively for pantoprazole 40 mg intravenously (day 1: P < 0.001, day 5: P < 0.0001). During the first 4 h of dosing on day 1 corresponding values were 1.7 and 0.6 h respectively (P < 0.0001). A mean median pH above 4 on day 5 was only attained with esomeprazole 40 mg intravenously. CONCLUSIONS: Once-daily dosing with esomeprazole 40 mg intravenously provides faster and more pronounced intragastric acid control than pantoprazole 40 mg intravenously.

Effects of acupuncture on skin temperature in children with neurological disorders and cold feet: an exploratory study.

In a single subject design, acupuncture effects on peripheral skin temperature were studied in six children with cold feet associated with cerebral palsy, progressive encephalopathy or Smith-Lemli-Opitz syndrome. Skin temperature was measured at fixed points on the forehead, suprasternal fossa, hand dorsum and palm, foot dorsum and sole from a distance of 3 cm with a Raytek Raynger ST2L. Acupuncture needles were inserted in arms or legs with or without electrical stimulation. Three children displayed a brief rise in temperature in the hands and one in the feet. A tendency towards a cumulative effect in improved skin temperature occurred in two of three children receiving additional sessions. One child did not respond to acupuncture. It is possible that acupuncture may increase skin temperature in some children with cold extremities of neurological origin. Studies in larger groups are needed.

Lansoprazole versus omeprazole in short-term treatment of reflux oesophagitis. Results of a Scandinavian multicentre trial.

To evaluate the therapeutic potential of the newly developed proton pump inhibitor lansoprazole in patients with reflux oesophagitis, we performed a double-blind randomized clinical trial comparing 20 mg omeprazole and 30 mg lansoprazole, involving 229 patients at 9 Scandinavian hospitals. The treatment period was 4 or 8 weeks, and main efficacy variables were healing of endoscopic changes, relief of reflux symptoms, and occurrence of adverse events. No significant difference in terms of healing was found, either after 4 or after 8 weeks' treatment. Patients receiving lansoprazole experienced a greater improvement in heartburn after 4 weeks (p = 0.03), and there was a similar trend for acid regurgitation. Lansoprazole was found to be an effective and safe alternative to omeprazole in short-term treatment of moderate reflux oesophagitis.

A study of the interaction of omeprazole and warfarin in anticoagulated patients.

1. Thirty-five patients on continuous therapy with warfarin were given omeprazole 20 mg once daily and placebo each for 3 weeks according to a two-centre randomised double-blind cross-over design. 2. Blood samples were obtained once weekly during the run-in and follow-up periods as well as during the first 2 weeks of each treatment period, and twice during the last week of each treatment period. Plasma concentrations of R- and S-warfarin were measured by h.p.l.c. and the anticoagulant effect was assessed using the Trombotest. 3. Twenty-eight patients were evaluated. The mean plasma concentration of R-warfarin was increased by 9.5% during omeprazole treatment compared with placebo, while that of S-warfarin, the more active isomer, was unaffected. The coagulation time was not significantly changed (106 s during omeprazole and 98 s during placebo). Corresponding TT-values (Trombotest) were 8.8 and 9.9 (NS).

Sucralfate versus placebo in reflux esophagitis. A double-blind multicenter study.

The healing capacity and symptom relief were studied in 138 patients with symptomatic endoscopically verified reflux esophagitis treated with sucralfate (n = 69) or placebo (n = 69), 1 g four times daily (granules suspended in half a glass of water), for at most up to 12 weeks. The reflux esophagitis (modified Savary-Miller scale) was distributed with 71 patients having grade 1, 39 patients having grade 2 or 3, and 28 patients having grade 4. All patients were told to follow the antireflux regimen. Antacid tablets were supplied, to be used only for the relief of severe pain, and were counted. The esophageal lesions were completely healed in 42% (sucralfate) and 35% (placebo) after 6 weeks of treatment (NS). Corresponding cumulative healing rates at 12 weeks of treatment were 54% and 41% (NS), respectively. The symptom improvement, however, was significantly better in the sucralfate group after 3 weeks of treatment. The results indicate a symptomatic benefit of sucralfate in reflux esophagitis.

Recurrent ulcer after treatment with cimetidine or sucralfate.

The recurrence of peptic ulcer disease after successful treatment with 400 mg cimetidine twice daily or 1 g sucralfate four times daily was investigated in a double-blind, 1-year follow-up study. Endoscopy was performed if ulcer symptoms recurred and 2-4 and 9-11 months after endoscopically confirmed healing of the initial ulcer. No anti-ulcer medication was permitted during the follow-up period. The recurrence rates were 71% in the cimetidine group (n = 143) and 68% in the sucralfate group (n = 115) (p greater than 0.3). The rate of asymptomatic ulcer relapse was 26% in the cimetidine and 23% in the sucralfate group (p greater than 0.4). The time to relapse did not differ between the treatment groups (p greater than 0.3). In the cimetidine group smokers had a higher 12-month recurrence rate than non-smokers, 83% compared with 58% (p less than 0.01). The corresponding figures in the sucralfate group were 76% and 57% (p = 0.057). The median time to recurrence in the cimetidine-treated group was 17 weeks among smokers, compared to 43 weeks among non-smokers (p less than 0.001). In the sucralfate-treated group the median time to recurrence was 23 weeks among smokers and 32 weeks among non-smokers (p greater than 0.3). Pre-study use of non-steroidal anti-inflammatory drugs and the time to healing of the initial ulcer did not influence the relapse rates in either of the treatment groups.

Relapse rate of healed duodenal, prepyloric, and gastric ulcers treated either with sucralfate or cimetidine.

A multicenter double-blind study was designed to compare the relapse rates of peptic ulcers after initial healing with a cytoprotective agent and a histamine (H2)-receptor antagonist. Patients with endoscopically verified prepyloric or duodenal ulcers were treated with cimetidine 400 mg twice daily or sucralfate 1 g four times daily for a maximum of eight weeks; gastric ulcers were treated for up to 12 weeks. Patients with healed ulcers were followed up to 12 months, during which time anti-ulcer medication was not permitted. Control endoscopy was performed two to four and nine to 11 months after healing and at the time of symptomatic relapse. A total of 258 patients were followed for 12 months; of these, 143 had been previously treated with cimetidine and 115 had been treated with sucralfate. The relapse rates and the median time to relapse did not differ between the two groups. After 12 months, 71 percent of the previously cimetidine-treated patients and 68 percent of the sucralfate-treated patients had experienced a relapse. Smoking significantly increased the relapse rate and shortened the time to relapse in the total study population and among cimetidine-treated patients; it had no such effect in the sucralfate-treated group.

Geographic differences in the prevalence and distribution of large-bowel polyps--colonoscopic findings.

The large-bowel polyp pattern in two widely separated geographic regions of Sweden, Bollnäs in the central part and Trelleborg in the south, was studied prospectively by colonoscopic polypectomy. In Bollnäs 11.8% of 1,153 patients had neoplastic, and 3.8% hyperplastic, polyps. In Trelleborg 29% of 1,040 patients had neoplastic, and 17.3% hyperplastic, polyps. Furthermore, the Trelleborg patients had, on average, more polyps per patients than their Bollnäs counterparts: 2.0 versus 1.5 neoplastic, and 2.1 versus 1.7 hyperplastic, polyps. There was a marked difference in the anatomic location of the polyps between the two regions: in Trelleborg 55.4% of the neoplastic, and 40.5% of the hyperplastic polyps were distributed above the rectosigmoid, compared with 20.9% and 26.4%, respectively, in Bollnäs. The findings offer an explanation of the fact that the incidence of colorectal carcinoma in the Malmö region, close to the Trelleborg area, is the highest in Sweden.

Short-term treatment of prepyloric ulcer. Comparison of sucralfate and cimetidine.

A double-blind, randomized, multicenter study was performed to compare the effect of sucralfate (1 g qid) and cimetidine (400 mg bid) in the treatment of prepyloric ulcer. Altogether 142 patients (68 in the sucralfate and 74 in the cimetidine group) with endoscopically confirmed ulcer within 2 cm of the pylorus completed the study. Endoscopic follow up was performed after four weeks and, if the ulcer was not healed, after eight weeks of treatment. After four weeks, 65% of the ulcers in the sucralfate group were healed, compared to 70% in the cimetidine group. There was no significant difference between sucralfate and cimetidine at either time point. The 95% confidence interval for the difference in ulcer healing with sucralfate or cimetidine ranged from +4 to -19% at eight weeks. Said another way, with an observed difference of 7% (83% vs 90%), the 95% confidence limit ranged from 4% in favor of sucralfate to 19% in favor of cimetidine. Symptomatic relief, antacid intake, and side effects did not differ significantly between the two groups. The healing rate of prepyloric ulcer in this study is similar to that reported for duodenal ulcer after four and eight weeks when treated with sucralfate or cimetidine. Sucralfate is safe and as effective as cimetidine in the short-term treatment of prepyloric ulcer.

Ulcer recurrences following initial ulcer healing with sucralfate or cimetidine.

Ulcer relapses after short-term treatment of duodenal, prepyloric and gastric ulcers with Cimetidine 400 mg b.d. or Sucralfate 1 g q.i.d. were studied in 270 patients over one year. Endoscopic examinations were carried out 2-4 and 9-11 months after ulcer healing or when symptoms occurred. Ulcer relapses were found in 59% of the Cimetidine-treated patients and 51% of those treated with Sucralfate, and a further 21% and 16% respectively had endoscopically verified erosive gastroduodenitis. The cumulative recurrence rate in smokers was 82% and that in non-smokers 51% (p less than 0.001). Relapses among the Cimetidine patients occurred more often in those who smoked or had irregular working hours. The onset of the relapse was not related ulcer healing time. The ulcer relapses appeared in the same region as the initial ulcer in 88% of cases and exactly at the original site in 33%. These results suggest that cytoprotection by Sucralfate did not result in fewer or later relapses than acid reduction by Cimetidine. Cigarette smoking obviously increases the risk of relapse in patients with healed peptic ulcers.

Treatment of peptic ulcers--acid reduction or cytoprotection?

In a Swedish multicenter double blind trial cimetidine was compared to sucralfate in the treatment of peptic ulcer. Patients with endoscopically verified gastric, prepyloric and duodenal ulcers were treated with cimetidine 400 mg x 2 or sucralfate 1 g x 4 for four to eight weeks. Gastric ulcers were treated up to 12 weeks. Patients with healed ulcers were followed for up to 12 months. During follow-up without any anti ulcer treatment control endoscopy was performed 2-4 and 9-11 months after endoscopic healing and at symptomatic recurrence. 647 patients were studied (334 cimetidine and 313 sucralfate). 258 patients were included in the 12 months' follow up: of these 143 were previously treated with cimetidine and 115 with sucralfate. Healing rates were 92% in patients treated with cimetidine and 87% in those given sucralfate (ns). Symptomatic relief and ulcer recurrence did not differ between the treatments. Smoking significantly increased recurrence rate and shortened the time to recurrence in the cimetidine treated patients, but not in the sucralfate group. Cimetidine and sucralfate compared well in all aspects of acute peptic ulcer treatment and recurrence during one year of follow up.

Treatment of acute duodenal ulcer--a Swedish multicenter study.

Medical ulcer therapy focuses on enhancing mucosal defence mechanisms or reducing intraluminal acidity. In this Swedish multicenter, randomized double-blind study these two principles were compared in the treatment of acute duodenal ulcerations. Sucralfate (Andapsin 1g X 4) or cimetidine (Tagamet 400mg X 2), together with antacid tablets (Novalucol), were supplied to patients with acute ulcerations in the pyloric ring or duodenal bulb. Endoscopy was performed at inclusion, after four weeks and in some patients also after eight weeks. Besides healing rate, symptoms and antacid intake, smoking and side effects were recorded on a special protocol. 371 patients from 15 centers completed the trial. At inclusion the patient groups did not differ in any essential aspect. At four weeks 71% of 177 patients on sucralfate and 77% of 194 on cimetidine were healed. The corresponding figures for eight weeks were 86% (suc) and 92% (cim). The difference is not significant, the 95% confidence interval for the difference in ulcer healing efficacy of sucralfate compared with cimetidine at eight weeks was -12% to +5%. Antacid intake and symptoms decreased rapidly and equally in both groups. Side effects related to the treatments were uncommon. It is concluded that sucralfate and cimetidine, representing two different principles in medical ulcer treatment, are both very effective and compare well in the short term treatment of acute duodenal ulcer.

Swedish multicenter study on prepyloric and gastric ulcer.

A double-blind, randomized, multicenter study was performed to compare the effects of sucralfate and cimetidine for the short-term treatment of gastric and prepyloric ulcers. Ulcer healing was evaluated endoscopically at 4-week intervals up to 8 weeks in the PPU study and up to 12 weeks in the GU study. A total of 142 PPU and 134 GU patients completed the study. The overall healing rates after 8 weeks in the PPU study were 83% for the sucralfate group and 90% for the cimetidine group (NS), while the cumulative healing rates after 12 weeks in the GU study were 98% for the sucralfate group and 94% for the cimetidine group (NS). The confidence interval means that the 95% confidence limit ranges from 11% in favour of sucralfate to 2% in favour of cimetidine in the GU study and corresponding figures of 4% 19% in the PPU study. There were significantly more patients in the cimetidine group taking antacid tablets after 3 weeks in the GU study. Symptomatic relief did not differ significantly. Reported side effects and symptoms, pooled together with our duodenal ulcer study, were mostly non-specific and in some part related to the ulcer disease. In conclusion, sucralfate and cimetidine are both excellent healing agents for the short-term treatment of PPU and GU. Both give rapid and good symptomatic relief with no side effects of any importance.

Short term treatment of gastric ulcer: a comparison of sucralfate and cimetidine.

A double blind randomised study was undertaken to compare sucralfate and cimetidine in short term treatment of gastric ulcer. The study included 149 patients with endoscopically confirmed gastric ulcerations. Patients with prepyloric ulcers 2 cm or less from the pyloric ring were not accepted for participation in the trial. Ulcer healing was assessed endoscopically at four week intervals. A total of 134 patients completed the study. The cumulative healing rates after 12 weeks were 98% for sucralfate and 94% for cimetidine treated patients. After four and eight weeks, the healing rates were 61% and 94% for sucralfate and 69% and 94% for the cimetidine-treated group respectively. No statistically significant differences in healing rates were seen. The 95% confidence interval was calculated for the difference between the ulcer healing rates of sucralfate and cimetidine. This interval was found to range between +11% and -2% after 12 weeks of treatment - that is, the healing efficacy of sucralfate was calculated to be at most 11% better or 2% worse than that of cimetidine. No significant differences in symptom relief, side effects or antacid intake were found.

Short-term treatment of duodenal ulcer. A comparison of sucralfate and cimetidine.

A multicenter randomized double-blind study was performed to compare a cytoprotective agent (sucralfate) and an acid-reducing agent (cimetidine) in the treatment of duodenal ulcer. Patients with acute ulcerations in the pyloric ring and duodenal bulb confirmed by endoscopy were included in the trial. All patients were examined after 4 and, if not cured, after 8 weeks. A total of 371 patients from 15 centers completed the trial. The patient groups were comparable. At 8 weeks 86% of 177 patients receiving sucralfate treatment were cured, compared with 92% of 194 receiving cimetidine (NS). The corresponding figures at 4 weeks were 71% (sucralfate) and 77% (cimetidine) (NS). The 95% confidence interval for the difference in ulcer healing efficacy of sucralfate compared with cimetidine at 8 weeks was -12% to +5%. Antacid intake and symptoms decreased rapidly in both groups. Three patients were withdrawn owing to side effects. It is concluded that sucralfate and cimetidine. representing two different approaches to ulcer therapy, are both very effective and compare well with regard to ulcer healing, symptom relief, and side effects in the short-term treatment of acute duodenal ulcer.