Patient Education in a 14-month Randomised Trial Fails to Improve Adherence in Ulcerative Colitis: Influence of Demographic and Clinical Parameters on Non-adherence.

BACKGROUND AND AIM: Recent observational studies document that non-adherence to mesalamine therapy during remission is frequent. We aimed to investigate patient impact of patient education using objective assessments of adherence. METHODS: A 14-month randomised, prospective clinical trial of adherence to mesalamine was conducted in 248 patients with ulcerative colitis [UC], Colitis Activity Index [CAI] ≤ 9, receiving standard care [n = 122] versus a standardised patient education programme [n = 126]. Primary endpoint was adherence at all visits (5-aminosalicylic acid [5-ASA] urine levels). Secondary endpoints included quality of life (inflammatory bowel disease questionnaise [IBDQ]), disease activity, partial adherence, and self-assessment of adherence. RESULTS: Patient allocation was well balanced. Baseline non-adherence was high in quiescent/mildly active UC [52.4%] without difference between the groups (52.4% of patients in the education group versus 52.5% in the standard care group [p = 0.99]). No difference between the intervention group and standard care was seen in IBDQ, partial adherence, self-assessment of adherence, or therapy satisfaction at all visits. We suggest a model in which individual risks for non-adherence are driven by patients with young age, short disease duration, and low education levels. CONCLUSIONS: Non-adherence is frequent in a population with quiescent/mildly active UC. Although more than 25% of the population was not in remission at the various time points, no relationship between disease activity and adherence was seen over the 14-month observation period. Physicians should maximise their efforts to motivate high-risk patients for adherence. Future trials should use objective exposure assessments to examine the impact of continuous education and consultations on the background of individual risks to develop non-adherence.

Randomized trial of rifabutin-based triple therapy and high-dose dual therapy for rescue treatment of Helicobacter pylori resistant to both metronidazole and clarithromycin.

BACKGROUND: The clinical management of Helicobacter pylori infected patients who failed standard eradication therapies remains a challenge. AIM: To investigate the efficacy of rifabutin-based triple therapy and high-dose dual therapy for rescue treatment of H. pylori, and the correlation between cytochrome P450 2C19 (CYP2C19) polymorphisms and treatment outcome. METHODS: Patients infected with H. pylori resistant to both metronidazole and clarithromycin (n = 145) were randomized to either esomeprazole 20 mg, rifabutin 150 mg and amoxicillin 1 g, each given b.d. for 7 days (ERA), or to omeprazole 40 mg and amoxicillin 1000 mg, each given t.d.s. for 14 days (OA). Crossover therapy was offered in cases of persistent infection. CYP2C19 polymorphisms were determined by polymerase chain reaction restriction fragment length polymorphism. RESULTS: Intention-to-treat and per-protocol eradication rates were: ERA 74% (62.4-83.6) and 78% (66.7-87.3); high-dose OA 70% (57.5-79.7) and 75% (62.5-84.5). Crossover therapy was successful in seven of 10 patients with ERA and in eight of 10 patients with OA. Premature discontinuation of treatment occurred in 2% and 5% of patients, respectively. There was only a non-significant trend to lower eradication rates in homozygous extensive metabolizers. CONCLUSIONS: Triple therapy with esomeprazole, rifabutin and amoxicillin and high-dose omeprazole/amoxicillin are comparable and effective and safe for rescue therapy of H. pylori regardless of the patient's CYP2C19 genotype.

Esomeprazole-based one-week triple therapy with clarithromycin and metronidazole is effective in eradicating Helicobacter pylori in the absence of antimicrobial resistance.

AIM: This study aimed to investigate the effectiveness of a one-week triple therapy with esomeprazole, clarithromycin and metronidazole for eradication of Helicobacter pylori infection in the absence of antimicrobial resistance. METHODS: Patients testing positive for H. pylori susceptible to metronidazole and clarithromycin (E-test) were randomized to receive a one-week regimen with either esomeprazole 2 x 20 mg or omeprazole 2 x 20 mg in combination with clarithromycin 2 x 250 mg and metronidazole 2 x 400 mg. Follow-up endoscopy with histology and culture and/or rapid urease test was performed 4-8 weeks after the end of treatment. RESULTS: Eighty patients were randomized. Helicobacter pylori infection was cured in 38/39 patients of the esomeprazole group and 31/33 patients of the omeprazole group (per protocol 97.4% (95% confidence interval [CI], 86.2-99.9), 93.7% (95% CI, 79.2-99.2), P=0.59); intention-to-treat 90.4% (95% CI: 77.4-97.3), 81.6% (95% CI: 65.7-92.3), respectively. No major side effects occurred. Minor side effects occurred in eight (20%) and six (23%) patients during esomeprazole and omeprazole therapy, respectively. Post-treatment susceptibility testing revealed resistance to both metronidazole and clarithromycin in two of the three patients who failed. CONCLUSION: We conclude that esomeprazole, clarithromycin and metronidazole as one-week triple therapy is effective for eradication of H. pylori in the absence of antimicrobial resistance.

Focal inflammatory infiltrations in gastric biopsy specimens are suggestive of Crohn's disease. Crohn's Disease Study Group, Germany.

BACKGROUND: Crohn's disease is a systemic inflammatory disease that may involve all regions of the gut. METHODS: Thirty-six patients with Crohn's disease and 36 age- and sex-matched control patients were prospectively evaluated by upper endoscopy. Biopsy specimens were taken from the oesophagus, duodenum, and 10 locations in the antrum and corpus. RESULTS: Granulomas were found in four patients (11.13%) with Crohn's disease but in none of the control patients (P > 0.5). In 23 of 36 patients (63.9%) with Crohn's disease focal inflammatory infiltrations were found, as compared with 7 of 36 (19.4%) of the controls (P < 0.001). For focal inflammatory infiltrations, an odds ratio of 7.33 (2.55-21.38) was calculated, which increased to 20.04 (4.07-98.45) when only specimens from the angulus were considered. Helicobacter pylori infection was present in 13 of 36 controls (36.1%) and in 3 of 36 patients (8.3%) with Crohn's disease (P = 0.009). CONCLUSION: These data suggest that Crohn's disease is typically associated with focal inflammatory infiltrations of the gastric mucosa.

Helicobacter pylori reinfection is rare in peptic ulcer patients cured by antimicrobial therapy.

BACKGROUND: Cure of H. pylori infection in peptic ulcer patients significantly reduces the risk of ulcer recurrence. Since data on the rate of H. pylori reinfection in patients undergoing successful anti-H. pylori therapy are sparse, this study was conducted with the aim of determining the H. pylori reinfection rate in peptic ulcer patients receiving antibacterial treatment to heal their ulcer and cure H. pylori infection. METHODS: A total of 217 patients with H. pylori-associated duodenal or gastric ulcer were followed up after treatment with various antibacterial regimens resulting in histologically documented cure of H. pylori infection. Endoscopic and histological examinations were performed 4 weeks after completion of treatment and after 1, 2 and 5 years, or whenever dyspeptic symptoms occurred. To assess the H. pylori status two antral and two corpus biopsies were obtained for histological examination. RESULTS: Out of 217 patients with initially cured H. pylori infection 175 were available for endoscopic follow-up. At the time of analysis, 44 patients were re-examined after 1 year, 113 patients after 2 years and 18 patients after 5 years, giving a total of 360 patient years of follow-up. The mean duration of follow-up was 24.7 months. H. pylori reinfection was confirmed histologically in eight patients, three of whom becoming H. pylori-positive again within the first year of follow-up. Six of the eight patients with H. pylori reinfection also suffered an ulcer relapse. Eight cases of reinfection in 360 patient years represents an overall reinfection rate of 2.2%. Within the first 2 years of follow-up the reinfection rate was 0.8% per year. CONCLUSION: Our data suggest that H. pylori reinfection is rare in peptic ulcer patients receiving successful anti-H. pylori therapy. H. pylori reinfection frequently coincides with ulcer recurrence. Cure of H. pylori infection results in cure of peptic ulcer disease, provided H. pylori reinfection does not occur.

Severity of Helicobacter pylori gastritis predicts duodenal ulcer recurrence.

BACKGROUND: Helicobacter pylori gastritis is suggested to be the underlying condition leading to duodenal ulcer disease. The aim of the study was to investigate the relationship between chronic active H. pylori gastritis and the risk of duodenal ulcer (DU) recurrence. METHODS: One hundred and eighty-eight patients were followed up with regard to the evolution of their H. pylori gastritis after they had received antibacterial or acid-suppressing treatment for their DU. Four weeks, 1 year, and 2 years after treatment and in the case of DU recurrence several morphologic indicators of gastritis were studied histologically in the antrum and corpus. RESULTS: In patients who were cured of H. pylori infection a significant and long-lasting regression of all gastritis variables were observed. patients with persistent H. pylori infection after antibacterial treatment showed only a temporary regression of all gastritis variables. In the overall group of patients who received acid-suppressive therapy there was no change in gastritis. However, in the subgroup of patients who received omeprazole monotherapy, no change in the antrum but a statistically significant increase of gastritis in the corpus was observed. The grade of antral gastritis at the end of treatment was significantly and positively correlated with the risk of DU recurrence and was independent of the kind of pretreatment (18.5% recurrences in grade-2 versus 86% in grade-4 gastritis). CONCLUSIONS: The data show that the grade of gastritis is an important risk factor for duodenal ulcer recurrence. Cure of H. pylori infection is associated with healing of chronic H. pylori-associated gastritis. These data lend considerable support to the hypothesis that H. pylori gastritis is the most important factor among those leading to duodenal ulcer disease.

Cure of gastric ulcer disease after cure of Helicobacter pylori infection--German Gastric Ulcer Study.

BACKGROUND: Helicobacter pylori infection is associated with gastric ulcer disease in about 75% of cases. OBJECTIVE: The aim of this study was to determine whether H. pylori eradication reduces gastric ulcer relapse rates. DESIGN: The study was randomized, controlled, multicentric and investigator blinded, and was conducted at three university hospitals, two teaching hospitals, and by six practising gastroenterologists. METHODS: During a period of 1 year 152 patients with gastric ulcers were randomly assigned to one of two treatment regimens: omeprazole 20 mg daily in the morning for 8 weeks (74 patients), or bismuth subsalicylate 600 mg three times daily for 8 weeks combined with 500 mg amoxicillin twice daily and 1000 mg tinidazole twice daily for the first 10 days (triple therapy) (78 patients). Follow-up examinations were performed 6, 12 and 18 months after treatment and whenever ulcer symptoms occurred. RESULTS: Of the 152 randomized patients five were excluded because of gastric cancer, 10 missed follow-up examinations and seven receiving triple therapy terminated treatment because of side effects. Of the remaining 130 patients, five of 69 (7.2%) in the omeprazole and six of 61 (9.8%) in the triple group were H. pylori negative. After 8 weeks' therapy, the gastric ulcer was healed in 85.9% (omeprazole) and in 81.8% triple) in H. pylori-positive patients, and in 80% (omeprazole) and 16.7% (triple) in H. pylori-negatives. H. pylori was eradicated in 8.1% of the patients who received omeprazole monotherapy and in 78.2% receiving triple therapy, and in 8.1% and 69.4% in an intention-to-treat analysis. The subsequent relapse rates during a follow-up period of 12 months were 50% in the omeprazole group and 4% in the triple group. Gastric ulcer relapse was observed in 49% of patients who were H. pylori positive and in 2% who were H. pylori negative after treatment. CONCLUSION: The data show that the presence of H. pylori is an important predictor of gastric ulcer relapse and that eradication of H. pylori may heal gastric ulcer disease.

Recurrence of duodenal ulcers during five years of follow-up after cure of Helicobacter pylori infection.

BACKGROUND: Chronic Helicobacter pylori-associated gastritis is now widely accepted as one of the most important pathogenic factors in duodenal ulcer disease. However, little is known about for how long patients remain free of duodenal ulcer relapses after H. pylori infection has been cured. In the present study, we investigated remission time during a 5-year follow-up period after anti-H. pylori treatment. METHODS: The patients were randomly allocated to treatment with either a combination of 3 x 600 mg bismuth subsalicylate and 2 x 1000 mg amoxycillin or 3 x 600 mg bismuth subsalicylate monotherapy. Endoscopy, including histological and microbiological examination of biopsies, was performed 4 weeks after termination of treatment and after 1 and 2 years. During the third, fourth and fifth years of the follow-up period, patients were monitored twice a year for symptoms compatible with ulcer relapse and for their use of anti-ulcer medication. Endoscopic and histological examinations were carried out whenever symptoms occurred. RESULTS: Of 56 evaluated patients, 47 showed healing of ulcers after bismuth subsalicylate plus amoxycillin compared with 44 of 57 after bismuth subsalicylate monotherapy. H. pylori infection was cured in 52% (29 of 56) of the patients after combined therapy and in 4% (2 of 57) after the monotherapy. The cumulative duodenal ulcer relapse rates after 5 years were 38% (18 of 47) after the combined therapy and 75% (33 of 44) after the monotherapy. In patients who were cured of H. pylori infection, the cumulative duodenal ulcer relapse rate after 5 years was 9.7% (3 of 31), compared with 81.7% (49 of 60) in those patients who remained H. pylori-positive after treatment (P < 0.001). In two of the three patients who suffered duodenal ulcer relapse after being cured of H. pylori infection, H. pylori was present again at the time of relapse. CONCLUSION: The data suggest that curing H. pylori infection results in long-term cure of duodenal ulcer disease and that duodenal ulcer relapses in successfully treated patients are most often associated with H. pylori reinfection.