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Notes: Background : Triple therapy with proton pump inhibitor, clarithromycin and amoxicillin and, in the event of eradication failure, quadruple therapy with proton pump inhibitor, bismuth, tetracycline and metronidazole have been proposed in Maastricht as the optimal sequential treatment of Helicobacter pylori infection.Aim : To compare two second-line regimens with quadruple therapy.Methods : One hundred and eighty patients with a previous failed course of standard therapy were randomly given one of the following 7-day treatments: ranitidine bismuth citrate 400 mg b.d. plus amoxicillin 1 g b.d. and tinidazole 500 mg b.d. (RBCAT), pantoprazole 40 mg b.d. plus amoxicillin 1 g b.d. and levofloxacin 500 mg/day (PAL) and pantoprazole 40 mg b.d., bismuth citrate 240 mg b.d., tetracycline 500 mg q.d.s. and metronidazole 500 mg b.d. (PBTM). The eradication rate was assessed by 13C-urea breath test. Side-effects and compliance were evaluated by a standardized questionnaire and by counting returned medication.Results : The RBCAT, PAL and PBTM groups achieved mean intention-to-treat eradication rates of 85%, 63% and 83%, respectively (P 〈 0.05 for PAL vs. either RBCAT or PBTM). Compliance was optimal in all patients, although side-effects were more commonly observed in the PBTM group than in the other two patient groups (P 〈 0.0001).Conclusions : Both RBCAT and PBTM can be used as second-line therapies. Conversely, PAL did not achieve satisfactory eradication rates.

Notes: Background: No placebo-controlled clinical trials have yet been published on the efficacy of therapy in older subjects with oesophagitis.Aim: To evaluate the efficacy of pantoprazole in preventing the recurrence of oesophagitis in elderly subjects.Methods: One hundred and sixty-four patients aged 65 years and over with acute oesophagitis were treated openly with pantoprazole, 40 mg daily, for 8 weeks. Patients with documented healing of erosive oesophagitis were then treated with pantoprazole, 20 mg daily, for 6 months. Thereafter, cured patients were randomized to receive pantoprazole, 20 mg daily, or placebo for the following 6 months. Clinical evaluations were performed every 2 months, and endoscopy was repeated after 8 weeks and after 6 and 12 months and/or whenever symptoms suggested a relapse of oesophagitis.Results: After 8 weeks, the healing rates of oesophagitis were 81.1% (75.1–87.1%) and 93.7% (89.7–97.7%) by intention-to-treat and per protocol analyses, respectively. After 6 months, the corresponding values were 82% (75.4–88.5%) and 92.4% (87.6–97.2%), respectively. After 12 months, the per protocol and intention-to-treat healing rates of oesophagitis were 95.1% (88.5–100%) and 79.6% (68.3–90.9%), respectively, in the treatment group vs. 32.7% (19.9–45.4%) and 30.4% (18.3–42.4%), respectively, in the placebo group (P = 0.0001). Heartburn, acid regurgitation and chest pain were significantly associated with the relapse of oesophagitis (P = 0.0001), whereas hiatus hernia, Helicobacter pylori infection, concomitant diseases and treatments were not.Conclusion: In the elderly, pantoprazole was highly effective in healing and reducing the relapse of oesophagitis; discontinuing active treatment after 6 months was associated with a significant increase in the relapse rate.

Notes: Advancing age may influence clarithromycin’s pharmacokinetics. No studies have yet compared the effects of different dosages of clarithromycin in combination with a proton pump inhibitor and amoxicillin in elderly patients.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:To compare the efficacy and tolerability of clarithromycin 250 mg vs. clarithromycin 500 mg twice daily (b.d.) in combination with pantoprazole and amoxicillin in elderly patients.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:One hundred and fifty-four elderly patients with H. pylori-associated ulcer disease or chronic gastritis were consecutively randomized to receive pantoprazole 40 mg daily plus amoxicillin 1 g, and either clarithromycin 250 mg b.d. (PAC 250) or clarithromycin 500 mg b.d. (PAC 500). Two months after therapy, endoscopy and gastric biopsies were repeated.〈section xml:id="abs1-4"〉〈title type="main"〉Results:The cure rates of H. pylori infection in the PAC 250 and PAC 500 groups were, respectively, 83% and 79% (ITT analysis) and 94% and 88% (PP analysis) (P=N.S.). Significant decreases in chronic gastritis activity both in the body (P 〈 0.00001) and the antrum (P 〈 0.0001) of the stomach were found in H. pylori-cured patients, independently of clarithromycin dosage. Four patients in PAC 250 (5%) and seven in PAC 500 (9%) reported adverse events (P=N.S.). One patient in PAC 250 (25%) and three in PAC 500 (43%) discontinued the study because of these drug-related side-effects (P=N.S.).〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:In elderly patients, 1-week triple therapy with a proton pump inhibitor, amoxicillin and clarithromycin is a highly effective and well tolerated anti-H. pylori treatment. With this combination, clarithromycin at the lower dose of 250 mg b.d. achieved excel- lent cure rates and minimized adverse events and costs.

Notes: This was a randomized, double-blind, multicentre, short-term study comparing ranitidine and nizatidine at the standard dosages of 300 mg at bedtime. In 49 centres in Italy, all peptic ulcer patients aged over 65 years and with endoscopically documented acute disease were considered eligible for the study. Clinical check-ups were repeated every 3 weeks, while the endoscopic and biochemical assessments were scheduled at 6 and (in unhealed patients) 12 weeks. Statistics: chi-squared test, Fisher's exact test, Student t-test for unpaired data. The study included 170 duodenal ulcer and 75 gastric ulcer patients. Of these, 83/17 duodenal ulcer and 38/75 gastric ulcer patients were treated with nizatidine 300 mg and the remainder with ranitidine 300 mg. The groups were well-matched for common clinical data. Eight patients dropped out. Healing rates at 6 and 12 weeks were 81.9% and 91.5% for nizatidine-treated duodenal ulcer patients versus 78.1% and 94.2% for ranitidinetreated duodenal ulcer cases (P: N.S.); 6 and 12-week healing rates were 76.3% and 89.5% for nizatidinetreated gastric ulcer patients versus 67.6% and 83.8% for ranitidine-treated gastric ulcer patients (P: N.S.). No slow healing risk factors were found. Only minor adverse events were registered. In conclusion: ranitidine 300 mg and nizatidine 300 mg both proved effective and safe in the treatment of acute peptic ulceration in the elderly.

Notes: Background: Specific data on anti-H. pylori treatments in elderly people are very scarce. The aim of the study was to evaluate in the elderly the efficacy of different anti-H. pylori therapies and the behaviour of serum anti-H. pylori antibodies, pepsinogen A and C, and PGA/PGC ratio induced by the anti-H. pylori treatment. Methods: One hundred and twenty-one dyspeptic patients aged 〉60 years (mean age, 73 years; range, 61–89 years) with H. pylori-positive gastric ulcers (17 patients), duodenal ulcers (33 patients) or chronic gastritis (71 patients) were treated with one of the following anti-H. pylori treatments: (A) omeprazole 20 mg/day plus azithromycin 500 mg/day for 3 days; (B) omeprazole 20 mg/day plus azithromycin 500 mg/day for 3 days plus metronidazole 250 mg q.d.s. for 7 days; (C) omeprazole 40 mg/day plus azithromycin 500 mg/day for 3 days plus metronidazole 250 q.d.s. for 7 days; (D) omeprazole 20 mg/day plus clarithromycin 250 b.d. for 7 days; (E) omeprazole 20 mg/day plus clarithromycin 250 b.d. for 7 days plus metronidazole 250 q.d.s. for 7 days; and (F) omeprazole 40 mg/day plus clarithromycin 250 mg b.d. for 7 days plus metronidazole 250 mg q.d.s. for 7 days. At the baseline and 2 months after therapy, endoscopy and serum anti-H. pylori antibodies, pepsinogen A and C, and PGA/PGC ratio were measured. Results: Ten patients (8.2%) dropped out of the study. Six patients (4.9%) reported side-effects. The eradication rates of the six regimens, expressed using intention-to-treat and per protocol analysis, were, respectively: (A) 39% and 44%; (B) 50% and 56%; (C) 65% and 77%; (D) 47% and 50%; (E) 85% and 90%; and (F) 83% and 87%. The triple therapy for regimens E and F was significantly more effective than dual therapies (regimens A and D; intention-to-treat=P〈0.007, per protocol=P〈0.001) or the triple therapy for regimens B and C (intention-to-treat=P〈0.009, per protocol=P〈0.03). Patients cured of H. pylori infection showed a significant decrease in the activity of gastritis (P〈0.0001), a significant drop in IgG anti-H. pylori (P=0.0004) and pepsinogen C (P〈0.0001), and an increase in PGA/PGC ratio (P〈0.001), while patients remaining H. pylori-positive showed no changes in the serum parameters. Conclusions: In the elderly, triple therapy with omeprazole +metronidazole+clarithromycin for 1 week is well tolerated and highly effective; anti-H. pylori antibody and PGC serum levels decrease soon after anti-H. pylori therapy only in patients cured of H. pylori infection.

Notes: The prevalence of Helicobacter pylori infection increases with age world-wide, reaching levels of 40–60% in asymptomatic elderly subjects and over 70% in elderly patients with gastroduodenal diseases. However, the percentage of H. pylori-positive elderly patients who are treated for their infection remains very low.Data are now available that demonstrate the benefit of curing H. pylori infection in elderly patients with H. pylori-associated peptic ulcer disease and severe chronic gastritis. Furthermore, the cure of H. pylori may prevent the progression of intestinal metaplasia and gastric atrophy. New studies are needed to clarify the role of eradication in elderly patients with non-ulcer dyspepsia and gastro-oesophageal reflux disease and in those who use non-steroidal anti-inflammatory drugs. H. pylori infection may be easily diagnosed by histological evaluation, rapid urease test or culture performed on gastric biopsies taken during endoscopy. However, the biopsy site must be carefully selected in elderly patients. For non-invasive monitoring of H. pylori infection after treatment, the 13C-urea breath test has significantly higher accuracy than serology in the elderly; further studies are needed to clarify the role of the H. pylori stool antigen test in old age.One-week proton pump inhibitor-based triple therapy regimens, including clarithromycin, amoxicillin and/or nitroimidazoles, are highly effective and well tolerated in elderly patients. Low doses of both proton pump inhibitors and clarithromycin (in combination with standard doses of amoxicillin or nitroimidazoles) are sufficient. Low compliance and antibiotic resistance are the main factors related to treatment failure in old age.

Notes: To compare the efficacy of pantoprazole vs. a one-week Helicobacter pylori eradication therapy for the prevention of NSAID-related gastroduodenal damage.〈section xml:id="abs1-2"〉〈title type="main"〉Methods:Patients over 60 years old with symptoms and/or a history of ulcer who needed NSAID treatment were evaluated by endoscopy. H. pylori positive subjects who had no severe gastroduodenal lesions were randomized to take, concomitantly with NSAID therapy, either: (i) pantoprazole 40 mg daily plus amoxycillin 1 g b.d. and clarithromycin 250 mg b.d. for 1 week (35 subjects, Group PAC) or (ii) pantoprazole 40 mg daily for 1 month (34 subjects, Group P). Endoscopy was repeated after 1 month.〈section xml:id="abs1-3"〉〈title type="main"〉Results:A significantly higher incidence of severe gastroduodenal damage was found in Group PAC than in Group P (29% vs. 9%, P 〈 0.05). The percentages of patients worsened, unchanged and improved after 1 month were, respectively: Group PAC: 46%, 46%, and 9% and Group P: 7%, 65%, and 29% (P 〈 0.0008). The percentage of H. pylori-negative subjects was 89% in Group PAC and 52% in Group P (P=0.0009). The incidence of gastroduodenal damage was higher in Group PAC treatment failures than in cured patients (50% vs. 25.8%, P=ns).〈section xml:id="abs1-4"〉〈title type="main"〉Conclusion:One month of pantoprazole was more effective than a proton pump inhibitor-based triple therapy in the prevention of gastroduodenal damage in elderly H. pylori-positive NSAID users.

Notes: The relationship between serum parameters of gastric function and Helicobacter pylori infection in human immunodeficiency virus (HIV)-positive patients is almost unknown.〈section xml:id="abs1-2"〉〈title type="main"〉Aims:To investigate in HIV-infected patients: (i) the relationship between serum gastrin and serum pepsinogens over the progressive phases of HIV-related disease; (ii) the impact of H. pylori infection on gastrin and pepsinogen serum levels and its relation to antral histology; (iii) the prevalence of parietal cell autoantibodies.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:Fifty-nine HIV-positive patients were studied by upper endoscopy plus gastric antral biopsy. Serum samples were tested for gastrin, pepsinogen A, pepsinogen C and parietal cell autoantibodies.〈section xml:id="abs1-4"〉〈title type="main"〉Results:In patients without overt acquired immunodeficiency syndrome (AIDS), or with a CD4+ count of 〉 100 × 106 cells/L, mean serum levels of gastrin and pepsinogen C were higher than in subjects with AIDS or with a CD4+ count of 〈 100 × 106 cells/L (P 〈 0.01). Only one patient was found to be positive for parietal cell autoantibodies. H. pylori infection was associated with increased values of gastrin and pepsinogen C only in HIV-positive patients without AIDS or with a CD4+ count of 〉 100 × 106 cells/L. Atrophy was more frequent in patients with overt AIDS than in those without overt AIDS (57% vs. 33%, P=N.S.), and/or in patients with a CD4+ count of 〈 100 × 106 cells/L than in those with a CD4+ count of 〉 100 × 106 cells/L (62% vs. 26%, P 〈 0.05).〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:HIV-positive patients without overt AIDS have increased serum levels of gastrin and pepsinogen C compared with HIV-positive patients with overt AIDS.

Notes: Background:  The association between coxib or non-steroidal anti-inflammatory drug use with gastrointestinal symptoms and drug prescriptions in ambulatory elderly patients is not well defined.Aim:  To evaluate the association between non-steroidal anti-inflammatory drug NSAID and coxib use with gastrointestinal symptoms and therapies in elderly subjects managed by their general practitioner.Materials:  The study was carried out by 133 general practitioners in Italy. By using a structured interview, sex, age, physical function, current medications, new drug prescriptions and upper gastrointestinal symptoms were registered from all elderly subjects who were referred to their general practitioners during a 2-week period. The numbers of hospitalizations, gastrointestinal bleeding events and gastrointestinal diagnostic procedures occurring during the last 6-month period were recorded.Results:  Included in this study were 5515 elderly subjects. The overall prevalence of drug use was 92%. Musculo-skeletal drugs were taken by 15% of patients; NSAIDs were taken by 6%, and coxibs by 3% of patients. A significantly higher prevalence of upper gastrointestinal symptoms was observed in elderly NSAID users compared with coxib users and non-users of musculo-skeletal drugs (44% vs. 33% vs. 32% respectively, P = 0.001). The prescriptions of drugs for acid-related disorders were significantly higher in patients who were concomitantly taking NSAID rather than coxibs (13% vs. 6%, P 〈 0.01). The prescriptions of drugs for acid-related disorders were significantly associated with the presence of upper gastrointestinal symptoms (OR = 1.7, 95% CI = 1.6–1.9), previous gastrointestinal disorders (OR = 1.1, 95% CI = 1.0–1.3) and NSAID use (OR = 1.5, 95% CI = 1.0–2.2), but no coxib use.Conclusion:  In this elderly population, upper gastrointestinal symptoms and prescriptions for gastroenterological drugs were higher in non-steroidal anti-inflammatory drug users than coxib users and non-users of musculo-skeletal drugs.

Notes: Background : Although administration of gastroprotective drugs may reduce the risk of peptic ulcers associated with the chronic use of non-steroidal anti-inflammatory drugs or aspirin, no consensus exists as to whether this co-therapy is effective for short-term prevention, particularly in old age.Aim : To evaluate the risk of peptic ulcer associated with acute and chronic non-steroidal anti-inflammatory drugs or aspirin therapy in elderly subjects, and the influence of antisecretory treatment on this risk.Methods : The study included 676 elderly non-steroidal anti-inflammatory drugs or aspirin users and 2435 non-users who consecutively underwent upper gastrointestinal endoscopy. The use of non-steroidal anti-inflammatory drugs and/or aspirin as well as antisecretory drugs (H2-blockers and proton-pump inhibitors) was evaluated by a structured interview. Diagnosis of gastric and duodenal ulcer as well as Helicobacter pylori infection were carried out by endoscopy and histological examination of the gastric mucosa.Results : About 47.3% of patients were acute and 52.7% chronic users of non-steroidal anti-inflammatory drugs or aspirin. The risk of peptic ulcer, adjusted for age, gender, H. pylori infection and antisecretory drug use was higher in acute (gastric ulcer: odds ratio, OR =4.47, 95% CI: 3.19–6.26 and duodenal ulcer: OR =2.39, 95% CI: 1.73–3.31) than chronic users (gastric ulcer: OR = 2.80, 95% CI: 1.97–3.99 and duodenal ulcer: OR = 1.68, 95% CI: 1.22–2.33). Proton-pump inhibitor treatment was associated with a reduced risk of peptic ulcer in both acute (OR = 0.70, 95% CI: 0.24–2.04) and chronic (OR = 0.32, 95% CI: 0.15–0.67) non-steroidal anti-inflammatory drugs/aspirin users. Conversely, concomitant treatment with H2-blockers was associated with a significantly higher risk of peptic ulcer both in acute (OR = 10.9, 95% CI: 3.87–30.9) and chronic (OR = 6.26, 95% CI: 2.56–15.3) non-steroidal anti-inflammatory drugs/aspirin users than non-users. Proton-pump inhibitor treatment resulted in an absolute risk reduction of peptic ulcer by 36.6% in acute and 34.6% in chronic non-steroidal anti-inflammatory drugs/aspirin users; indeed, the number needed to treat to avoid one peptic ulcer in elderly non-steroidal anti-inflammatory drugs/aspirin users was three both in acute and chronic users.Conclusions : These findings suggest that proton-pump inhibitor co-treatment is advisable in symptomatic elderly patients who need to be treated with non-steroidal anti-inflammatory drugs and/or aspirin for a short period of time.