Systematic review: faecal transplantation for the treatment of Clostridium difficile-associated disease.

BACKGROUND: Management of recurrent Clostridium difficile-associated disease (CDAD), particularly in elderly patients, remains clinically challenging. Faecal transplantation (FT) may restore normal microbiota and break the cycle of recurrent CDAD. AIM: To critically appraise the clinical research evidence on the safety and effectiveness of FT compared with standard care in the treatment of patients with CDAD. METHODS: A comprehensive literature search was conducted by a research librarian to identify relevant studies published between 2000 and 2011. The Cochrane Library, PubMed, EMBASE, CINAHL, Biological Abstracts, BIOSIS Previews and Web of Science were searched using the following Medical Subject Headings (MeSH) terms and keywords, alone or in combination: Clostridium infections/Clostridium difficile/pseudomembranous/colitis/faeces/rectal/colon flora/gastrointestinal/nasogastric tube/enema/donor/transplant/infusion/bacteriotherapy/human probiotic infusion. Methodological quality of the included case series studies was assessed in terms of patient selection criteria, consecutive recruitment, prospective data collection, reporting of lost to follow-up, and follow-up rates. RESULTS: No controlled studies were found. Based on the weak evidence from seven full-text case series studies of 124 patients with recurrent/refractory CDAD, FT appears to be a safe and effective procedure. In most cases (83%) symptoms improved immediately after the first FT procedure, and some patients stayed diarrhoea free for several months or years. CONCLUSIONS: Although these results appear to be promising, the treatment effects of faecal transplantation cannot be determined definitively in the absence of a control group. Results from randomised controlled trials that compare faecal transplantation to oral vancomycin without or with a taper regimen will help to better define the role of faecal transplantation in the management of recurrent CDAD.

Systematic literature review and pooled analyses of risk factors for finding adenomas at surveillance colonoscopy.

BACKGROUND AND STUDY AIM: Colorectal cancer (CRC) screening guidelines recommend surveillance after polypectomy. There is variation in the surveillance intervals that are being advised. This variation also affects adherence. Surveillance intervals need to be based on risk factors at index. We therefore aimed to systematically review risk factors of adenoma findings at surveillance colonoscopy. METHODS: A systematic literature search was performed up to September 2009. Studies that reported on follow-up colonoscopy findings with stratification for index characteristics were included. Pooled relative risks (RR) were calculated using random effects models, and heterogeneity was determined by means of the I2-statistic. RESULTS: A total of 27 studies met the inclusion criteria. The most important risk factors for adenoma findings were the presence on index colonoscopy of the following: advanced adenomas (RR: 1.81), ≥ 3 adenomas (RR: 1.64), size ≥ 10 mm (RR: 1.66), and age ≥ 60 years (RR: 1.65). The presence of villous adenomas, high grade dysplasia, proximal adenomas, and male gender were associated with less profound increases in RR. Marked variation in study design and substantial heterogeneity between studies was observed. CONCLUSIONS: Convincing evidence exists that patients with advanced adenomas, ≥ 3 adenomas, adenomas ≥ 10 mm, or age ≥ 60 years have an increased risk of adenoma recurrence. The evidence for other baseline findings for an increased risk of adenoma recurrence is inconclusive. Marked variation and consistently lower RRs in studies of medium or low quality emphasize the necessity for well performed and well reported studies. Given the high impact of surveillance on patients and service providers, there is need for further assessment of the risk(s) of adenoma recurrence.

Risk of colorectal carcinoma in post-liver transplant patients: a systematic review and meta-analysis.

Liver transplant patients (LTx) have an increased risk for developing de novo malignancies, but for colorectal cancer (CRC) this risk is less clear. We aimed to determine whether the CRC risk post-LTx was increased. A systematic search was performed in MEDLINE and Cochrane databases to identify studies published between 1986 and 2008 reporting on the risk of CRC post-LTx. The outcomes were (1) CRC incidence rate (IR per 100,000 person-years (PY)) compared to a weighted age-matched control population using SEER and (2) relative risk (RR) for CRC compared to the general population. If no RR data were available, the RR was estimated using SEER. Twenty-nine studies were included. The overall post-LTx IR was 119 (95% CI 88-161) per 100,000 PY. The overall RR was 2.6 (95% CI 1.7-4.1). The non-primary sclerosing cholangitis (PSC) IR was 129 per 100,000 PY (95% CI 81-207). Compared to SEER (71 per 100,000 PY), the non-PSC RR was 1.8 (95% CI 1.1-2.9). In conclusion, the overall transplants and the subgroup non-PSC transplants have an increased CRC risk compared to the general population. However, in contrast to PSC, non-PSC transplants do not need an intensified screening strategy compared to the general population until a prospective study further defines recommendations.

Pyrosequencing assay to rapidly detect clarithromycin resistance mutations in Canadian Helicobacter pylori isolates.

BACKGROUND: Mutations at positions 2142 or 2143 in the twocopy 23S ribosomal RNA gene of Helicobacter pylori are highly predictive of in vitro clarithromycin resistance and failure of clarithromycin-containing treatment regimens. OBJECTIVE: To design an assay to rapidly detect these mutations using rapid polymerase chain reaction and pyrosequencing, a novel method of 'sequencing by synthesis', and to test this assay with a collection of Canadian H pylori isolates. METHODS: Forty-two H pylori isolates (24 clarithromycin-resistant, 18 clarithromycin-susceptible) were studied. A target region in the 23S gene was rapidly amplified and sequenced by pyrosequencing. RESULTS: Mutations at one of the two positions studied were present in 20 of the 24 (83%) clarithromycin-resistant isolates; 13 had double- copy A2143G mutations, four had double-copy A2142G mutations and three had single-copy A2143G mutations. There were no mutations in 17 of the 18 (94%) susceptible isolates. A single-copy A2142G mutation was detected in one susceptible isolate. CONCLUSIONS: The pyrosequencing assay developed was able to detect and differentiate mutations at positions 2142 and 2143 in either one or both copies of the H pylori 23S ribosdomal RNA gene. Further study is needed to determine whether this pyrosequencing assay can be used to determine H pylori susceptibility to clarithromycin from clinical specimens such as stools or gastric biopsies.

Diagnostic utility of alarm features for colorectal cancer: systematic review and meta-analysis.

OBJECTIVE: Colorectal cancer is the second most common cause of cancer death in Europe and North America. Alarm features are used to prioritize access to urgent investigation, but there is little information concerning their utility in the diagnosis of colorectal cancer. METHODS: A systematic review and meta-analysis of the published literature was carried out to assess the diagnostic accuracy of alarm features in predicting colorectal cancer. Primary or secondary care-based studies in unselected cohorts of adult patients with lower gastrointestinal symptoms were identified by searching MEDLINE, EMBASE and CINAHL (up to October 2007). The main outcome measures were accuracy of alarm features or statistical models in predicting the presence of colorectal cancer after investigation. Data were pooled to estimate sensitivity, specificity, and positive and negative likelihood ratios. The quality of the included studies was assessed according to predefined criteria. RESULTS: Of 11 169 studies identified, 205 were retrieved for evaluation. Fifteen studies were eligible for inclusion, evaluating 19 443 patients, with a pooled prevalence of colorectal carcinoma of 6% (95% CI 5% to 8%). Pooled sensitivity of alarm features was poor (5% to 64%) but specificity was >95% for dark red rectal bleeding and abdominal mass, suggesting that the presence of either rules the diagnosis of colorectal cancer in. Statistical models had a sensitivity of 90%, but poor specificity. CONCLUSIONS: Most alarm features had poor sensitivity and specificity for the diagnosis of colorectal carcinoma, whilst statistical models performed better in terms of sensitivity. Future studies should examine the utility of dark red rectal bleeding and abdominal mass, and concentrate on maximising specificity when validating statistical models.

Helicobacter pylori infection in Canadian and related Arctic Aboriginal populations.

In 2006, the Canadian Helicobacter Study Group identified Aboriginal communities among Canadian population groups most at risk of Helicobacter pylori-associated disease. The objective of this systematic review was to summarize what is known about the H pylori-associated disease burden in Canadian and related Arctic Aboriginal populations to identify gaps in knowledge. Six health literature databases were systematically searched to identify reports on H pylori prevalence in Canadian population groups, or any topic related to H pylori in Canadian Aboriginals, Alaska Natives or Aboriginals of other Arctic regions. Identified reports were organized by subtopic and summarized in narrative form. Key data from studies of H pylori prevalence in defined populations were summarized in tabular form. A few Arctic Aboriginal communities were represented in the literature: two Canadian Inuit; one Canadian First Nation; two Greenland Inuit; one Russian Chutkotka Native; and several Alaska Native studies. These studies uniformly showed elevated H pylori prevalence; a few studies also showed elevated occurrence of H pylori-related diseases and high rates of treatment failure. Based on the evidence, it would be warranted for clinicians to relax the criteria for investigating H pylori and related diseases in patients from Arctic Aboriginal communities, and to pursue post-therapy confirmation of eradication. Additional community-based research is needed to develop public health policies for reducing H pylori-associated health risks in such communities.

Generation of dyspeptic symptoms by direct acid infusion into the stomach of healthy Japanese subjects.

OBJECTIVE: The relationship between acid and dyspeptic symptoms has not been fully understood. AIM: To investigate the type and severity of dyspeptic symptoms induced by direct acid infusion into the stomach of Japanese healthy subjects. METHODS: This was a multi-centre, cross-over, randomized, double-blind study in 27 healthy subjects (mean age 27). Each fasted subject received two tests with 150 mL of 0.1 mol/L hydrochloric acid infusion (15 mL/min for 10 min) and the same volume of pure water infusion. The type and severity of symptoms were assessed by a 10 cm visual analogue scale administered every 2 min up to 30 min. RESULTS: Various symptoms were reported after both acid and water infusions. Most of the symptoms were more severe after acid infusion compared with water infusion (acid vs. water: discomfort 1.8 +/- 0.4 vs. 0.5 +/- 0.1, pain 0.6 +/- 0.3 vs. 0.1 +/- 0.1, reflux 1.0 +/- 0.3 vs. 0.3 +/- 0.1 and satiety 1.1 +/- 0.4 vs. 0.2 +/- 0.1). The area under curve for dysmotility like symptoms (heavy feeling in the stomach, bloating, nausea or feeling sick, and belching) was significantly higher in acid infusion, and symptoms continued after infusion of the acid. CONCLUSION: Acid induced into stomach induced dysmotility-like predominant dyspeptic symptoms in Japanese healthy control subjects, demonstrating the possible importance of acid in symptom generation.

Systematic review of the use of patients' own medications in acute care institutions.

BACKGROUND: Patients' own medications (POM) are medications that patients have obtained in the community setting and bring to the hospital when admitted. The practice of using POMs has not been well studied. OBJECTIVE: To identify benefits, risks and other impacts on the use of POM in hospitals. METHODS: A systematic search of the literature and internet was conducted for articles in the English language dated from 1984 to 2004. PubMed, CINAHL, IPA, and Embase databases were searched with combinations of the following text words: patient, own, drug, medication, medicine. References of relevant articles and specific journals were hand-searched. RESULTS: Nineteen primary studies that provided information on the benefits and risks of POMs were identified. Benefits included decreased wastage of POMs, improving the accuracy of admission orders, opportunities for patient counselling and continuity of care between acute and primary care. Hospitals must address liability and workload concerns but may benefit from savings to their drug budget. DISCUSSION: Only a limited number of studies were found that addressed the benefits, risks and costs of using POMs in hospitals. These studies had small sample sizes with limitations in the quality of the study design. Nevertheless, the literature contained examples of benefits to the patient and hospital, as well as assistance with practical issues. Further research is needed to evaluate the benefits and risks of using POMs. Hospital policies should describe identification, storage and documentation procedures to address liability and risk concerns. Implementation of policies to use POMs should include an evaluation component, which could include a comprehensive economic analysis of drug costs and staff workload.

The prevalence of Barrett's oesophagus in a cohort of 1040 Canadian primary care patients with uninvestigated dyspepsia undergoing prompt endoscopy.

BACKGROUND: The prevalence of Barrett's oesophagus in patients undergoing gastroscopy may be influenced by possible referral bias. AIM: To present the prevalence of Barrett's oesophagus from the the Canadian Adult Dyspepsia Empirical Therapy Prompt Endoscopy study and to explore potential risk factors for its presence. METHODS: Patients had not been on treatment for dyspepsia for 2-4 weeks prior to endoscopy, which was performed within 10 working days of presentation. RESULTS: Barrett's oesophagus was endoscopically suspected in 53 of 1040 cases (5%) and histologically confirmed by the presence of intestinal metaplasia in 25 (2.4%). The prevalence of biopsy-proven Barrett's oesophagus was 4% in patients with dominant reflux-like symptoms. Sixty-four percent with confirmed Barrett's oesophagus had dominant reflux-like symptoms compared with 37% without Barrett's oesophagus. Barrett's oesophagus was more common in patients >50 years of age; 68% of cases were males. The mean duration of symptoms was 10 years, yet 16% had symptoms of <1-year duration. Endoscopic reflux oesophagitis was present in 68% of confirmed Barrett's oesophagus patients. CONCLUSIONS: Barrett's oesophagus is confirmed on biopsy in about half of endoscopically suspected Barrett's oesophagus patients. Barrett's oesophagus is more common in males, in those with dominant reflux-like symptoms, and in patients with a longer symptom history.

Validation of a 7-point Global Overall Symptom scale to measure the severity of dyspepsia symptoms in clinical trials.

BACKGROUND: Currently there is no consensus on the optimal method to measure the severity of dyspepsia symptoms in clinical trials. AIM: To validate the 7-point Global Overall Symptom scale. METHODS: The Global Overall Symptom scale uses a 7-point Likert scale ranging from 1 = no problem to 7 = a very severe problem. Validation was performed in two randomized-controlled trials (n = 1121 and 512). Construct validity: Global Overall Symptom was compared with the Quality of Life in Reflux And Dyspepsia, Gastrointestinal Symptom Rating Scale, Reflux Disease Questionnaire and 10 specific symptoms using Spearman correlation coefficients. Test-retest reliability: The Intraclass Correlation Coefficient was calculated for patients with stable dyspepsia defined by no change in Overall Treatment Effect score over two visits. Responsiveness: effect size and standardized response mean were also calculated. RESULTS: Construct validity: Change in Global Overall Symptom score correlated significantly with Quality of Life for Reflux And Dyspepsia, Gastrointestinal Symptom Rating Scale, Reflux Disease Questionnaire and specific symptoms (all P < 0.0002). Reliability: The Intraclass Correlation Coefficient was 0.62 (n = 205) and 0.42 (n = 270). Responsiveness: There was a positive correlation between change in Global Overall Symptom and change in symptom severity. The effect size and standardized response mean were 1.1 and 2.1, respectively. CONCLUSION: The Global Overall Symptom scale is a simple, valid outcome measure for dyspepsia treatment trials.

Validation of a symptom diary for patients with gastro-oesophageal reflux disease.

BACKGROUND: Symptom diaries are potentially attractive but, because of concerns about patient compliance, they have had limited use in clinical trials. We assessed the validity and responsiveness of a symptom diary for patients with gastro-oesophageal reflux disease. METHODS: We included 215 patients with gastro-oesophageal reflux disease after starting treatment for 4 weeks with 40 mg esomeprazole once daily. Patients recorded whether they experienced night-time heartburn (yes/no), the severity of daytime heartburn on a scale from 1 (no heartburn) to 4 (severe heartburn) and their antacid use. Patients also completed a number of disease-specific and preference-based Health-related Quality of Life questionnaires at baseline and follow-up. RESULTS: Consistent with a priori predictions, daytime heartburn showed moderate to strong correlations with the Quality of Life in Reflux and Dyspepsia questionnaire (0.36-0.67) and four scales of symptom severity (0.36-0.70) for baseline, follow-up and change scores, but low correlations with the Standard Gamble. Responsiveness of the daytime heartburn item was excellent with a mean change from baseline to follow-up of -1.3 (95% CI -1.4 to -1.1) and a standardized response mean of 1.33 while responsiveness of the daily antacid use item was moderate (mean change scores -1.8 tablets taken, 95% CI -2.3 to -1.3 and standardized response mean of 0.64). CONCLUSIONS: The excellent psychometric properties of this simple gastro-oesophageal reflux disease diary make it an attractive measure for future trials.

Systematic review: the efficacy of intermittent and on-demand therapy with histamine H2-receptor antagonists or proton pump inhibitors for gastro-oesophageal reflux disease patients.

AIM: To perform a systematic review on the efficacy of intermittent and on-demand therapy with either histamine H2-receptor antagonists or proton pump inhibitors for patients with erosive oesophagitis or symptomatic heartburn. METHOD: We conducted randomized-controlled trials of non-continuous therapy in gastro-oesophageal reflux disease patients. RESULTS: Fourteen studies met inclusion criteria. Because of variation in outcome measures statistical pooling of results was not possible. Results were analysed qualitatively. Four studies evaluated intermittent therapy of treatment 3 days a week with omeprazole 20 mg or daily with ranitidine which were not efficacious compared to a daily proton pump inhibitor. Famotidine 10 and 20 mg, ranitidine 75 mg and cimetidine 200 mg were efficacious in five on-demand studies for relief of symptomatic heartburn episodes. In three of four studies, evaluating only non-erosive (endoscopy-negative) gastro-oesophageal reflux disease patients, esomeprazole 20 and 40 mg and omeprazole 10 and 20 mg a day were efficacious using willingness to continue as an endpoint. Lansoprazole 30 mg and omeprazole 20 mg maintained symptom control in 60-70% of healed oesophagitis patients. CONCLUSIONS: Intermittent proton pump inhibitor or H2-receptor antagonist therapy is not effective in maintaining control in oesophagitis patients. H2-receptor antagonists are effective for relief of heartburn episodes. On-demand proton pump inhibitor therapy may work in a proportion of non-erosive gastro-oesophageal reflux disease patients.

Heartburn-dominant, uninvestigated dyspepsia: a comparison of 'PPI-start' and 'H2-RA-start' management strategies in primary care--the CADET-HR Study.

BACKGROUND: There are few data on empiric, stepped therapy for heartburn relief or subsequent relapse in primary care. AIMS: To compare heartburn relief produced by a proton pump inhibitor-start or an H(2)-receptor antagonist-start with step-up therapy, as needed, followed by a treatment-free period to assess relapse. METHODS: Heartburn-dominant uninvestigated dyspepsia patients from 46 primary care centres were randomized to one of two active treatment strategies: omeprazole 20 mg daily (proton pump inhibitor-start) or ranitidine 150 mg bid (H2-receptor antagonist-start) for the first 4-8 weeks, stepping up to omeprazole 40 or 20 mg daily, respectively, for 4-8 weeks for persistent symptoms. Daily diaries documented heartburn relief (score < or = 3/7 on < or = of 7 prior days) and relapse (score > or = 4 on > or = 2 of 7 prior days). RESULTS: For 'proton pump inhibitor-start' (n = 196) vs. 'H2-receptor antagonist-start' (n = 194), respectively, heartburn relief occurred in 55.1% vs. 27.3% (P < 0.001) at 4 weeks and in 88.3% vs. 87.1% at 16 weeks. After therapy, 308 patients were heartburn-free (159 vs. 149); median times to relapse were 8 vs. 9 days and cumulative relapse rates were 78.6% vs. 75.8%, respectively. CONCLUSIONS: An empiric 'proton pump inhibitor-start' strategy relieves heartburn more effectively than an 'H2-receptor antagonist-start' strategy up to 12 weeks but has no effect on subsequent relapse, which is rapid in most patients.

Interaction of bismuth subsalicylate with fruit juices, ascorbic acid, and thiol-containing substrates to produce soluble bismuth products active against Clostridium difficile.

Bismuth subsalicylate (BSS), the active ingredient of Pepto-Bismol, has been used for many years to treat various disorders of the gastrointestinal tract. Using mass spectrometry and the agar dilution method, we determined that insoluble BSS interacts with certain dietary components and organic substrates to produce water-soluble products with activity against Clostridium difficile.

Systematic review: the methodological quality of trials affects estimates of treatment efficacy in functional (non-ulcer) dyspepsia.

AIM: To evaluate treatment efficacy using objective quality criteria. METHODS: A systematic review was performed of randomized controlled trials of endoscopically investigated dyspepsia (1979-2003) using the Jadad score and Rome II guidelines. The Jadad score differentiated studies as 'high quality' (score 4-5/5) vs. 'poor quality' (score 1-3/5). Three key Rome II guidelines on study design (cut-off of 0/3 or > 0/3) were also compared with the Jadad score. RESULTS: Poor quality trials suggested a benefit of prokinetic therapy [relative risk (RR) of remaining dyspeptic, 0.47; 95% confidence interval (CI), 0.39-0.56), which was not confirmed in high quality trials (RR, 1.0; 95% CI, 0.84-1.19). There was a marked benefit of H2-receptor antagonist therapy in poor quality trials (RR, 0.68; 95% CI, 0.61-0.76), but a marginal benefit in good quality trials (RR, 0.87; 95% CI, 0.79-0.97). Trial quality did not affect the small statistically significant benefit seen with Helicobacter pylori eradication. Two high quality trials suggested a limited benefit with the use of proton pump inhibitors, with no poor quality trials to provide a comparison. Separation of the studies by the Rome II criteria had a similar impact on the calculated treatment estimates. CONCLUSIONS: The magnitude of benefit of prokinetic and H2-receptor antagonist therapies reported in previous meta-analyses has been over-estimated. The quality of trials has an impact on the efficacy estimates of treatment. The Rome II criteria for study methodology may be appropriate for judging study quality.

Economic evaluation of Helicobacter pylori eradication in the CADET-Hp randomized controlled trial of H. pylori-positive primary care patients with uninvestigated dyspepsia.

BACKGROUND: Adult Helicobacter pylori-positive patients by 13C-urea breath test with uninvestigated dyspepsia symptoms were randomized to 1-week eradication treatment with omeprazole, metronidazole and clarithromycin (OMC) vs. omeprazole and placebo antimicrobials (OPP) in the Canadian Adult Dyspepsia Empiric Treatment-H. pylori-positive (CADET-Hp) study. AIM: To perform an economic evaluation of this 1-year study. METHODS: Following blind eradication treatment, family practitioners managed patients according to their usual practices. Health resource utilization information was collected prospectively. From the mean costs of the health resources consumed and the treatment outcomes, the incremental cost-effectiveness ratios and incremental net benefits of eradication treatment vs. OPP were determined. RESULTS: Eradication therapy significantly improved dyspepsia symptoms (treatment success: OMC, 50%; OPP, 36%; P = 0.02). The incremental cost-effectiveness ratio of OMC vs. OPP was - 387 Canadian dollars (CAD$) per treatment success (90% CI, - CAD$1707, CAD$607), indicating a lower cost with treatment success. The incremental net benefit analysis showed that H. pylori eradication was cost-effective if the willingness-to-pay value exceeded a nominal figure of CAD$100 from a health service perspective or CAD$607 from the societal perspective. CONCLUSION: In uninvestigated patients presenting with dyspepsia at the primary care level, eradication of H. pylori in those who are H. pylori positive leads to a cost-effective improvement in dyspepsia symptoms compared with a strategy of not eradicating H. pylori in these patients.

Multilaboratory comparison of proficiencies in susceptibility testing of Helicobacter pylori and correlation between agar dilution and E test methods.

Susceptibility testing was performed at seven Canadian microbiology laboratories and the Helicobacter Reference Laboratory, Halifax, Nova Scotia, Canada, to assess susceptibility testing proficiency and the reproducibility of the results for clarithromycin and metronidazole and to compare the Epsilometer test (E test) method to the agar dilution reference method. Control strain Helicobacter pylori ATCC 43504 (American Type Culture Collection) and 13 clinical isolates (plus duplicates of four of these strains including ATCC 43504) were tested blindly. The National Committee for Clinical Laboratory Standards (NCCLS) guidelines for agar dilution testing were followed, and the same suspension of organisms was used for agar dilution and E test. Antimicrobials and E test strips were provided to the investigators. Methods were provided on a website (www.Helicobactercanada.org). Each center reported MICs within the stated range for strain ATCC 43504. Compared to the average MICs, interlaboratory agreements within 2 log(2) dilutions were 90% (range, 69 to 100%) for clarithromycin by agar dilution, with seven very major errors [VMEs], and 85% (range, 65 to 100%) by E test, with three VMEs. Interlaboratory agreements within 2 log(2) dilutions were 83% (range, 50 to 100%) for metronidazole by agar dilution, with six VMEs and eight major errors (MEs), and 75% (range, 50 to 94%) by E test, with four VMEs and four MEs. At lower and higher concentrations of antibiotic, E test MICs were slightly different from agar dilution MICs, but these differences did not result in errors. When a standardized protocol based on NCCLS guidelines was used, most participants in this study correctly identified clarithromycin- and metronidazole-susceptible and -resistant strains of H. pylori 93% of the time by either the agar dilution or E test method, and the numbers of errors were relatively equivalent by both methods.

One-week triple therapy with esomeprazole, clarithromycin and metronidazole provides effective eradication of Helicobacter pylori infection.

AIM: To compare the eradication rates of treatment with esomeprazole, metronidazole and clarithromycin (EMC) vs. omeprazole, metronidazole and clarithromycin (OMC), given for 7 days. OMC treatment was followed by 3 weeks of treatment with 20 mg omeprazole alone; the EMC group received placebo. METHODS: A randomized, double-blind, controlled study was conducted in 36 Canadian centres. Patients had a minimum 3-month history of dyspepsia, with or without a previous history of peptic ulcer disease, and were Helicobacter pylori positive by urea breath test. The eradication of H. pylori was determined by two negative breath tests performed at least 4 and 8 weeks following the completion of treatment. RESULTS: The intention-to-treat and per protocol populations consisted of 379 and 339 patients, respectively. The success rates of EMC/placebo were 76% (144/190) by intention-to-treat and 80% (138/172) by per protocol analysis; for OMC/omeprazole, the rates were 72% (137/189) and 75% (125/167), respectively. The difference between the two treatment groups was not significant. Treatment was well tolerated. CONCLUSIONS: A 7-day regimen of esomeprazole, metronidazole and clarithromycin is effective and well tolerated for the eradication of H. pylori infection.

Impact of Helicobacter pylori eradication on heartburn in patients with gastric or duodenal ulcer disease -- results from a randomized trial programme.

BACKGROUND: Helicobacter pylori infection has been proposed as a protective factor against the development of gastro-oesophageal reflux disease. AIM: To study heartburn and endoscopic findings before and after H. pylori eradication therapy in patients with peptic ulcer disease. METHODS: In a multicentre trial programme, patients (n = 1497) were randomized to the omeprazole triple therapy group or to the control group, and were followed for 1-6 months after treatment. Patients in whom the infection was eradicated were compared with those in whom infection persisted. The severity of heartburn was measured at baseline and at each return visit. Endoscopy was performed 6 months after therapy in two of the five studies. RESULTS: In patients with duodenal ulcer, there was a significantly lower prevalence of heartburn after successful eradication of H. pylori relative to that after failed eradication (estimated odds ratio, 0.48). The reduction in the prevalence of heartburn in patients with gastric ulcer was independent of the post-treatment H. pylori status. In studies in which ulcer relapse was included in the model, this factor emerged as a significant factor for heartburn. The observed incidence of oesophagitis at the last visit was not influenced by H. pylori status. CONCLUSIONS: Eradication of H. pylori in patients with peptic ulcer disease was associated with a reduced prevalence of heartburn. Prevention of ulcer relapse could be the true cause of this reduction.