The Montreal Definition and Classification of Gastroesophageal Reflux Disease: A Global Evidence-Based Consensus

Background Studies in animals and an open-label trial have suggested a role for antibodies to tumor necrosis factor alpha, specifically chimeric monoclonal antibody cA2, in the treatment of Crohn's disease. Methods We conducted a 12-week multicenter, double-blind, placebo-controlled trial of cA2 in 108 patients with moderate-to-severe Crohn's disease that was resistant to treatment. All had scores on the Crohn's Disease Activity Index between 220 and 400 (scores can range from 0 to about 600, with higher scores indicating more severe illness). Patients were randomly assigned to receive a single two-hour intravenous infusion of either placebo or cA2 in a dose of 5 mg per kilogram of body weight, 10 mg per kilogram, or 20 mg per kilogram. Clinical response, the primary end point, was defined as a reduction of 70 or more points in the score on the Crohn's Disease Activity Index at four weeks that was not accompanied by a change in any concomitant medications. Results At four weeks, 81 percent of the patients given 5 mg of cA2 per kilogram (22 of 27 patients), 50 percent of those given 10 mg of cA2 per kilogram (14 of 28), and 64 percent of those given 20 mg of cA2 per kilogram (18 of 28) had had a clinical response, as compared with 17 percent of patients in the placebo group (4 of 24) (p Conclusions A single infusion of cA2 was an effective short-term treatment in many patients with moderate-to-severe, treatment-resistant Crohn's disease.

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A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group.

Publication bias in clinical research

https://www.gastrojournal.org/article/S0016-5085(06)00508-7/pdf

Functional gastroduodenal disorders

Background: Guidelines on the management of Helicobacter pylori , which cover indications for management and treatment strategies, were produced in 2000. Aims: To update the guidelines at the European Helicobacter Study Group (EHSG) Third Maastricht Consensus Conference, with emphasis on the potential of H pylori eradication for the prevention of gastric cancer. Results: Eradication of H pylori infection is recommended in ( a ) patients with gastroduodenal diseases such as peptic ulcer disease and low grade gastric, mucosa associated lymphoid tissue (MALT) lymphoma; ( b ) patients with atrophic gastritis; ( c ) first degree relatives of patients with gastric cancer; ( d ) patients with unexplained iron deficiency anaemia; and ( e ) patients with chronic idiopathic thrombocytopenic purpura. Recurrent abdominal pain in children is not an indication for a “test and treat” strategy if other causes are excluded. Eradication of H pylori infection ( a ) does not cause gastro-oesophageal reflux disease (GORD) or exacerbate GORD, and ( b ) may prevent peptic ulcer in patients who are naive users of non-steroidal anti-inflammatory drugs (NSAIDs). H pylori eradication is less effective than proton pump inhibitor (PPI) treatment in preventing ulcer recurrence in long term NSAID users. In primary care a test and treat strategy using a non-invasive test is recommended in adult patients with persistent dyspepsia under the age of 45. The urea breath test, stool antigen tests, and serological kits with a high accuracy are non-invasive tests which should be used for the diagnosis of H pylori infection. Triple therapy using a PPI with clarithromycin and amoxicillin or metronidazole given twice daily remains the recommended first choice treatment. Bismuth-containing quadruple therapy, if available, is also a first choice treatment option. Rescue treatment should be based on antimicrobial susceptibility. Conclusion: The global burden of gastric cancer is considerable but varies geographically. Eradication of H pylori infection has the potential to reduce the risk of gastric cancer development.

https://gut.bmj.com/content/gutjnl/56/6/772.full.pdf

Current concepts in the management of Helicobacter pylori infection - The Maastricht III Consensus Report

Background: The diagnosis of gastroesophageal reflux disease (GERD) rests primarily on recognition of symptom patterns that are classical for reflux disease, but little attention has been paid to t...

The Usefulness of a Structured Questionnaire in the Assessment of Symptomatic Gastroesophageal Reflux Disease

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. Conclusions: Omeprazole, 20 and 10 mg once daily, provides rapid relief of heartburn in patients without endoscopic oesophagitis.

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

We randomly assigned 71 patients with active chronic Crohn's disease who were resistant to or intolerant of corticosteroids to treatment with oral cyclosporine (5 to 7.5 mg per kilogram of body weight per day) or placebo for three months. Disease activity was assessed on a clinical grading scale without knowledge of the treatment given. At the end of the treatment period, 22 of the 37 cyclosporine-treated patients (59 percent) had improvement, as compared with 11 of the 34 placebo-treated patients (32 percent) (P = 0.032). During cyclosporine treatment, there was significant improvement in plasma orosomucoid levels (P = 0.0025) and the Crohn's Disease Activity Index (P = 0.00012). The effect of treatment became evident after two weeks. In the subsequent three months, during which the patients were gradually withdrawn from treatment, the improvement continued in 14 of the 37 patients (38 percent) in the cyclosporine group and in 5 of the 34 (15 percent) in the placebo group (P = 0.034). No serious adverse events were observed. We conclude that cyclosporine has a beneficial therapeutic effect in patients with active chronic Crohn's disease and resistance to or intolerance of corticosteroids.

https://www.nejm.org/doi/pdf/10.1056/NEJM198909283211301?listPDF=true

A placebo-controlled, double-blind, randomized trial of cyclosporine therapy in active chronic Crohn's disease.

Objectives: To determine whether eradication of Helicobacter pylori relieves the symptoms of functional dyspepsia. Design: Multicentre randomised double blind placebo controlled trial. Subjects: 278 patients infected with H pylori who had functional dyspepsia. Setting: Predominantly secondary care centres in Australia, New Zealand, and Europe. Intervention: Patients randomised to receive omeprazole 20 mg twice daily, amoxicillin 1000 mg twice daily, and clarithromycin 500 mg twice daily or placebo for 7 days. Patients were followed up for 12 months. Main outcome measures: Symptom status (assessed by diary cards) and presence of H pylori (assessed by gastric biopsies and 13C-urea breath testing using urea labelled with carbon-13). Results:H pylori was eradicated in 113 patients (85%) in the treatment group and 6 patients (4%) in the placebo group. At 12 months follow up there was no significant difference between the proportion of patients treated successfully by intention to treat in the eradication arm (24%, 95% confidence interval 17% to 32%) and the proportion of patients treated successfully by intention to treat in the placebo group (22%, 15% to 30%). Changes in symptom scores and quality of life did not significantly differ between the treatment and placebo groups. When the groups were combined, there was a significant association between treatment success and chronic gastritis score at 12 months; 41/127 (32%) patients with no or mild gastritis were successfully treated compared with 21/123 (17%) patients with persistent gastritis (P=0.008). Conclusion: No convincing evidence was found that eradication of H pylori relieves the symptoms of functional dyspepsia 12 months after treatment. Key messages Dyspepsia (pain or discomfort centred in the upper abdomen) is frequently unexplained; such patients are classed as having functional (or non-ulcer) dyspepsia H pylori gastritis is common in patients with functional dyspepsia but the benefits of treatment are controversial No significant benefit in relief of symptoms was found between patients successfully treated for H pylori infection and those with persistent infection Eradication of H pylori does not relieve the symptoms of functional dyspepsia

Eradication of Helicobacter pylori in functional dyspepsia: randomised double blind placebo controlled trial with 12 months' follow up

Aim

: To observe the natural course of gastro-oesophageal reflux disease (GERD) in patients without oesophagitis following effective symptom relief, and to determine the place of acid pump inhibitor therapy in the long-term management of these patients



Methods

: We investigated the efficacy of on-demand therapy with omeprazole 20 mg or 10 mg, or placebo in a double-blind, randomized multicentre trial It involved 424 patients with troublesome heartburn without endoscopic evidence of oesophagitis in whom heartburn had been resolved with short-term treatment Patients were told to take study medication on demand once daily on recurrence of symptoms until symptoms resolved over a 6-month period They also had access to antacids The primary efficacy variable was time to discontinuation of treatment, due to unwillingness to continue



Results

: According to life-table analysis, after 6 months the remission rates were 83% (95% CI: 77–89%) with omeprazole 20 mg, 69% (61–77%) with omeprazole 10 mg, and 56% (46–64%) with placebo (P < 001 for all intergroup differences) The mean (sd) number of study medications used per day in these groups was 043 (027), 041 (027) and 047 (027), respectively The use of antacids was highest in the placebo group and lowest in the omeprazole 20 mg group Treatment failure was associated with more than a doubling of antacid use, and a deterioration in patient quality of life



Conclusions

: Approximately 50% of patients with heartburn who do not have oesophagitis need acid inhibitory therapy in addition to antacid medication to maintain a normal quality of life On-demand therapy with omeprazole 20 mg, is an effective treatment strategy in these patients

Karsten Lauritsen

Papers

The Usefulness of a Structured Questionnaire in the Assessment of Symptomatic Gastroesophageal Reflux Disease

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

A placebo-controlled, double-blind, randomized trial of cyclosporine therapy in active chronic Crohn's disease.

Eradication of Helicobacter pylori in functional dyspepsia: randomised double blind placebo controlled trial with 12 months' follow up

On demand therapy with omeprazole for the long-term management of patients with heartburn without oesophagitis--a placebo-controlled randomized trial.