[Effectiveness of empirical Helicobacter pylori eradication therapy with furazolidone in Russia: results from the European Registry on Helicobacter pylori Management (Hp-EuReg)].

BACKGROUND: First-line therapy does not always provide a high level of Helicobacter pylori eradication due to the increase of H. pylori resistance to antibiotics; therefore, it remains necessary to identify the most effective rescue treatments. The purpose of this study was to evaluate the efficacy and safety of empirical H. pylori furazolidone-containing regimens. MATERIALS AND METHODS: Adult H. pylori infected patients empirically treated with furazolidone-containing eradication regimens were registered in an international, prospective, multicenter non-intervention European registry on H. pylori management (Hp-EuReg). Data were collected at AEG-REDCap e-CRF from 2013 to 2021 and the quality was reviewed. Modified intention-to-treat (mITT) effectiveness analyses were performed. RESULTS: Overall 106 patients received empirical furazolidone-containing therapy in Russia. Furazolidone was prescribed in a sequential scheme along with amoxicillin, clarithromycin and a proton pump inhibitor in 68 (64%) cases, triple regimens were prescribed in 28 (26%) patients and quadruple regimens in 10 (9.4%). Treatment duration of 7 days was assigned to 2 (1.9%) patients, 10-day eradication therapy in case of 80 (75%) and 14 days - in 24 (23%) patients. Furazolidone was mainly used in first- (79%) and second-line (21%) regimens. The methods used to diagnose H. pylori infection were: histology (81%), stool antigen test (64%), 13C-urea breath test (6.6%), and rapid urease test (1.9%). The mITT effectiveness of sequential therapy was 100%; 93% with the triple therapy and 75.5% with quadruple therapy. Compliance was reported in 98% of cases. Adverse events were revealed in 5.7% of patients, mostly nausea (3.8%). No serious adverse events were reported. CONCLUSION: Furazolidone containing eradication regimens appear to be an effective and safe empirical therapy in Russia.

[European Registry on the management of Helicobacter pylori infection: features of diagnosis and treatment in Kazan].

BACKGROUND: As part of an observational multicenter prospective study European Registry on the management of Helicobacter pylori infection, conducted on the initiative of the European H. pylori and Microbiota Study Group, the compliance of clinical practice in the management of patients with Helicobacter pylori infection in Kazan with clinical guidelines was assessed. MATERIALS AND METHODS: The data of 437 patients included into the register by clinical sites in Kazan in 20132019 were analyzed. The methods used for the initial diagnosis of H. pylori infection and eradication control were evaluated. The frequency of various eradication therapy regimens prescription was analyzed in 379 cases. Data regarding the effectiveness of eradication therapy was analyzed in 173 patients. RESULTS: The rapid urease test (44.2% of cases) and cytology/histology (60% of cases) were most often used for the initial diagnosis of H. pylori infection; however non-invasive methods such as 13C-urea breath (9.2%), serology (6.2%), H. pylori stool antigen test (2.3%) were less common. In 21.7% of patients two methods of H. pylori detection were used for primary diagnosis. The control test to evaluate the effectiveness of eradication therapy at the recommended timepoint was performed in 46.2% of patients. 13C-urea breath test (31.7%), stool PCR/stool antigen test (28.7%), rapid urease test (22.3%), cytology/histology (26.2% of cases) prevailed in the assessment of eradication rate. Standard triple therapy, including proton pump inhibitor, clarithromycin and amoxicillin was most commonly prescribed as first-line therapy (64.6% of cases). The duration of eradication therapy was 14 days in the majority of cases with pantoprazole as the most common proton pump inhibitor in standard triple therapy regimens (84.8%). The efficacy of 14-day standard triple therapy (mITT) was 87.0%. CONCLUSION: The results indicate a high frequency of non-invasive methods use for assessing the effectiveness of eradication therapy; however, the overall rate of eradication efficacy assessment is low, limiting the possibility of analyzing the eradication results. The effectiveness of the most common 14-day standard triple first-line therapy in Kazan doesnt reach the recommended 90% eradication level. This could be explained by high rate of pantoprazole use, which is not an optimal proton pump inhibitor in eradication therapy regimens.

[European registry on Helicobacter pylori management (Hp-EuReg) as a tool to evaluate and improve clinical practice in Moscow].

Continuous evaluation of the actual clinical practice of diagnosis and treatment of Helicobacter pylori is crucial in order to provide the best standard of care and to compare health outcomes with expert recommendations. AIM: to evaluate the effectiveness of the standard triple therapy (amoxicillin, clarithromycin, a proton pump inhibitor) and the standard triple therapy plus bismuth tripotassium dicitrate. MATERIALS AND METHODS: Observational, prospective, multicenter study, carried out in one single Russian centre A.S. Loginov Moscow Clinical Scientific Center as part of the Hp-EuReg. Patients were included from 2013 to November 2019 by Russian gastroenterologists. RESULTS: A total of 647 patients were collected and 330 were administered either standard triple therapy ((amoxicillin, clarithromycin, a proton pump inhibitor) or standard triple therapy plus bismuth tripotassium dicitrate. Invasive methods is dominates in the initial diagnosis of H. pylori: the frequency of use of the quick urease test decreased from 50% in 2013 to 31% in 2019. Serology was used in 27.9%. There has been an increase in the use of the13C-urea breath test from 13% in 2013 to 31% in 2019. The histological method (7.5%) and the stool antigen test (3.2%) were used less frequently. For eradication control non-invasive methods are mostly used:13C-UDT (82.7%) and the stool antigen test (14.4%). The effectiveness of standard triple therapy (mITT) was 68% with a 7-day course, 79% with a 10-day course, and 70% with a 14-day course. Combination of bismuth and standard triple therapy eradicates H. pylori (mITT) in 63%, 75% and 89%, respectively. CONCLUSION: An improvement in the clinical practice of managing patients with H. pylori infections has been noted. The standard triple therapy in combination with bismuth tripotassium dicitrate, prescribed for 14 days, is more effective.

[European registry Helicobacter pylori (Hp-EuReg): how has clinical practice changed in Russia from 2013 to 2018 years].

The multicenter prospective observational study initiated by the European Helicobacter and Microbiota Study Group (EHMSG) is conducted in 27 countries in Europe. The data from the Russian part of the European registry for the management of Helicobacter pylori infection (European Registry on the management of Helicobacter pylori infection, protocol: "Hp-EuReg") allows us to analyze the real clinical practice of diagnosis and treatment of H. pylori and compare it with international recommendations. MATERIALS AND METHODS: A comparative analysis of the data entered in the register by the Russian research centers "Hp-EuReg", in the period from 2013 to 2018, was conducted. RESULTS AND DISCUSSION: Invasive diagnostic methods prevail for the primary diagnosis of H. pylori [histology - 20.3% (in 2013 year) - 43.9% (in 2018 year), rapid urease test - 31.7% and 47.8% respectively]. The most popular mode of eradication therapy is a 10-day triple therapy (62.8-76.2%), the effectiveness of which does not exceed 79% (per protocol). Invasive tests (histology) are the leading method for control the effectiveness of therapy, however, there is a tendency towards a wider use of non-invasive methods (H. pylori stool antigen - from 17% in 2013 to 29.3% in 2018 and urea breath test from 6.9 to 18.3%, respectively). Serological test to control the effectiveness of eradication is still used from 8.2% (2013) to 6.1% (2018). Eradication therapy was not performed in 28% of patients throughout the entire observation period. CONCLUSION: In Russia, despite approved domestic and international recommendations, deviations in clinical practice persist, both during eradication therapy and in monitoring the effectiveness of eradication therapy.

European Registry on the management of Helicobacter pylori infection (Hp-EuReg): analysis of 2360 patients receiving first-line therapy in Russia.

AIM: European Registry on the management of Helicobacter pylori infection («Hp-EuReg¼) - a multicenter prospective observational study initiated by the European Helicobacter and Microbiota Study Group, conducted in 27 European countries in order to evaluate the real clinical practice of diagnosis and treatment of H. pylori and its comparison with international recommendations. MATERIALS AND METHODS: The analysis of 2360 patients entered in the register by the Russian centres of «Hp-EuReg¼ in 2013-2017, who were underwent 1st line eradication therapy. RESULTS: The most common methods of primary diagnosis of H. pylori are histological (37.7%), rapid urease test (29.2%) and serology (29.7%). The duration of eradication therapy in 9.4% of cases was 7 days, in 65.3% - 10 days, and in 25.3% - 14 days. To control the effec- tiveness of treatment, H. pylori antigen in feces (31.3%), urea breath test (23.4%) and histological method (23.3%) were used. In 3.6% cases was used serology by mistake. In 17.3% of patients control was not carried out. The effectiveness of triple therapy with a PPI, amoxicillin, clar- ithromycin (per protocol) was 67.6%, with 7-day course, 81.1% at 10-day and 86.7% at 14-day course. Eradication rate of triple therapy with addition of bismuth (per protocol) reached 90,6% in the group receiving 10-day scheme and 93.6% in the group receiving the 14-day treatment. CONCLUSION: Significant deviations of clinical practice from expert recommendations, most pronounced at the stage of monitoring the effectiveness of therapy, were noted. The suboptimal efficacy of triple therapy is shown.

Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report.

Important progress has been made in the management of Helicobacter pylori infection and in this fifth edition of the Maastricht Consensus Report, key aspects related to the clinical role of H. pylori were re-evaluated in 2015. In the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries examined new data related to H. pylori in five subdivided workshops: (1) Indications/Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public Health, (5) H. pylori and the Gastric Microbiota. The results of the individual workshops were presented to a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in the various clinical scenarios.

Validation of the Capsule Endoscopy Crohn's Disease Activity Index (CECDAI or Niv score): a multicenter prospective study.

BACKGROUND AND STUDY AIMS: The Capsule Endoscopy Crohn's Disease Activity Index (CECDAI or Niv score) was devised to measure mucosal disease activity using video capsule endoscopy (VCE). The aim of the current study was to prospectively validate the use of the scoring system in daily practice. METHODS: This was a multicenter, double-blind, prospective, controlled study of VCE videos from 62 consecutive patients with isolated small-bowel Crohn's disease. The CECDAI was designed to evaluate three main parameters of Crohn's disease: inflammation (A), extent of disease (B), and stricture (C), in both the proximal and distal segments of the small bowel. The final score was calculated by adding the two segmental scores: CECDAI = ([A1 × B1] + C1) + ([A2 × B2] + C2). Each examiner in every site interpreted 6 - 10 videos and calculated the CECDAI. The de-identified CD-ROMs were then coded and sent to the principal investigator for CECDAI calculation. RESULTS: The cecum was reached in 72 % and 86 % of examinations, and proximal small-bowel involvement was found in 56 % and 62 % of the patients, according to the site investigators and principal investigator, respectively. Significant correlation was demonstrated between the calculation of the CECDAI by the individual site investigators and that performed by the principal investigator. Overall correlation between endoscopists from the different study centers was good, with r = 0.767 (range 0.717 - 0.985; Kappa 0.66; P < 0.001). There was no correlation between the CECDAI and the Crohn's Disease Activity Index or the Inflammatory Bowel Disease Quality of Life Questionnaire or any of their components. CONCLUSION: A new scoring system of mucosal injury in Crohn's disease of the small intestine, the CECDAI, was validated. Its use in controlled trials and/or regular follow-up of these patients is advocated.

Management of precancerous conditions and lesions in the stomach (MAPS): guideline from the European Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study Group (EHSG), European Society of Pathology (ESP), and the Sociedade Portuguesa de Endoscopia Digestiva (SPED).

Atrophic gastritis, intestinal metaplasia, and epithelial dysplasia of the stomach are common and are associated with an increased risk for gastric cancer. In the absence of guidelines, there is wide disparity in the management of patients with these premalignant conditions. The European Society of Gastrointestinal Endoscopy (ESGE), the European Helicobacter Study Group (EHSG), the European Society of Pathology (ESP) and the Sociedade Portuguesa de Endoscopia Digestiva (SPED) have therefore combined efforts to develop evidence-based guidelines on the management of patients with precancerous conditions and lesions of the stomach (termed MAPS). A multidisciplinary group of 63 experts from 24 countries developed these recommendations by means of repeat online voting and a meeting in June 2011 in Porto, Portugal. The recommendations emphasize the increased cancer risk in patients with gastric atrophy and metaplasia, and the need for adequate staging in the case of high grade dysplasia, and they focus on treatment and surveillance indications and methods.

Ornithine decarboxylase G316A genotype and colorectal cancer risk.

AIM: Ornithine decarboxylase (ODC) is a modifier of adenomatous polyposis coli-dependent tumourigenesis. The G316 > A polymorphism in intron 1 of the ODC gene lies between two myc-binding domains and alters the expression of the gene to affect polyamine metabolism. This variant may be associated with recurrence of colorectal adenoma. We examined whether this variant also modified the susceptibility to sporadic colorectal cancer (CRC). METHOD: The G316 > A variant was analysed in a large (n = 754) CRC case-controlled series of hospital patient volunteers (n = 627) in the Czech Republic, and the relationship with cancer risk was estimated by conditional logistic regression. RESULTS: After adjusting for age and sex, G316 > A was associated with no decrease in CRC risk for either heterozygotes [odds ratio 0.98, 95% confidence interval (CI) 0.77-1.23] or rare allele homozygotes (odds ratio 0.92, 95% CI 0.61-1.37). CONCLUSION: The G316 > A functional variant in the ODC gene is unlikely to make much impact on reducing CRC risk regardless of the reduction in risk found for the recurrence of colorectal adenoma.

Inappropriate colonoscopic surveillance of hyperplastic polyps.

Colonoscopic surveillance of hyperplastic polyps alone is controversial and may be inappropriate. The colonoscopy surveillance register at a university teaching hospital was audited to determine the extent of such hyperplastic polyp surveillance. The surveillance endoscopy records were reviewed, those patients with hyperplastic polyps were identified, their clinical records were examined and contact was made with each patient. Of the 483 patients undergoing surveillance for colonic polyps 113 (23%) had hyperplastic polyps alone on last colonoscopy. 104 patients remained after exclusion of those under appropriate surveillance. 87 of the 104 patients (84%) were successfully contacted. 37 patients (8%) were under appropriate colonoscopic surveillance for a significant family history of colorectal carcinoma. 50 (10%) patients with hyperplastic polyps alone and no other clinical indication for colonoscopic surveillance were booked for follow up colonoscopy. This represents not only a budgetary but more importantly a clinical opportunity cost the removal of which could liberate valuable colonoscopy time for more appropriate indications.

Computer-assisted propofol administration.

The use of propofol for sedation in endoscopy may allow for better quality of sedation, quicker recovery and facilitate greater throughput in endoscopy units. The cost-effectiveness and utility of propofol sedation for endoscopic procedures is contingent on the personnel and resources required to carry out the procedure. Computer-based platforms are based on the patients response to stimulation and physiologic parameters. They offer an appealing means of delivering safe and effective doses of propofol. One such means is the bispectral index where continuous EEG recordings are used to assess the degree of sedation. Another is the closed-loop target-controlled system where a set of physical parameters, such as muscle relaxation and auditory-evoked potential, determine a level of medication appropriate to achieve sedation. Patient-controlled platforms may also be used. These electronic adjuncts may help endoscopists who wish to adopt propofol sedation to change current practices with greater confidence.

Nature meets nurture: molecular genetics of gastric cancer.

The immensity of genes and molecules implicated in gastric carcinogenesis is overwhelming and the relevant importance of some of these molecules is too often unclear. This review serves to bring us up-to-date with the latest findings as well as to look at the larger picture in terms of how to tackle the problem of solving this multi-piece puzzle. In this review, the environmental nurturing of intestinal cancer is discussed, beginning with epidemiology (known causative factors for inducing molecular change), an update of H. pylori research, including the role of inflammation and stem cells in premalignant lesions. The role of E-cadherin in the nature (genotype) of diffuse gastric cancer is highlighted, and finally the ever growing discipline of SNP analysis (including IL1B) is discussed.

Review article: Reproduction in the patient with inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) affects mainly the young population. The effect of IBD and its treatment on fertility and pregnancy is therefore an important clinical consideration. AIM: To review the best management of IBD in the reproductive and pregnant population. METHODS: A MEDLINE and an EMBASE search were performed using mainly the search phrases 'pregnancy AND IBD,''sulphasalazine AND male fertility,''abdominal surgery AND female fertility,''AZA AND placenta' and 'infliximab AND pregnancy.' No language or date restrictions were placed. References of review articles were examined. RESULTS: Overall male and female fertility are not affected by IBD. Sulphasalzine reduces male fertility. No other drugs used in IBD affect significantly fertility in humans. The risk of pregnancy-related complications and the disease behaviour during pregnancy depends mainly on disease activity at time of conception. Proactive treatment for maintenance of disease remission during gestation is recommended. Except for methotrexate, drugs used in IBD appear safe in pregnancy. Breast feeding should be encouraged. CONCLUSION: The management of IBD in the young and pregnant population remains controversial because the literature comes mostly from retrospective studies. Further studies particularly large prospective trials are needed to guide clinicians in decision making.

Genetic Mechanisms and Aberrant Gene Expression during the Development of Gastric Intestinal Metaplasia and Adenocarcinoma.

Gastric adenocarcinoma occurs via a sequence of molecular events known as the Correa's Cascade which often progresses over many years. Gastritis, typically caused by infection with the bacterium H. pylori, is the first step of the cascade that results in gastric cancer; however, not all cases of gastritis progress along this carcinogenic route. Despite recent antibiotic intervention of H. pylori infections, gastric adenocarcinoma remains the second most common cause of cancer deaths worldwide. Intestinal metaplasia is the next step along the carcinogenic sequence after gastritis and is considered to be a precursor lesion for gastric cancer; however, not all patients with intestinal metaplasia develop adenocarcinoma and little is known about the molecular and genetic events that trigger the progression of intestinal metaplasia into adenocarcinoma. This review aims to highlight the progress to date in the genetic events involved in intestinal-type gastric adenocarcinoma and its precursor lesion, intestinal metaplasia. The use of technologies such as whole genome microarray analysis, immunohistochemical analysis and DNA methylation analysis has allowed an insight into some of the events which occur in intestinal metaplasia and may be involved in carcinogenesis. There is still much that is yet to be discovered surrounding the development of this lesion and how, in many cases, it develops into a state of malignancy.

Colonoscopy completion rates--are we prepared for a national screening programme?

Colonoscopy is a difficult technique to learn. There are international standards regarding its completion rates. An audit of colonoscopy completion rates was carried out using computerized data in which the compliance with international standards was assessed. Of 909 patients overall crude and adjusted (excluding incompletion due to poor preparation and disease) caecal intubation rates were 88% and 94.1% respectively. Of those who were considered eligible for terminal ileal intubation, the crude and terminal ileal intubation rates were 47.3% and 50.3% respectively. The results indicated completion rated as per recommendations and were adequate for any colon screening programme to be successful.

Impact of Helicobacter pylori on the management of dyspepsia in primary care.

BACKGROUND: It is unclear what impact Helicobacter pylori infection has had on the management of dyspepsia in primary care and to what extent published guidelines on H. pylori are implemented in routine clinical practice. AIM: To assess the impact of H. pylori infection on the management of dyspepsia in primary care. METHODS: Patients referred by primary care doctors to an open-access 13-carbon urea breath test service over a 2-year period for their first urea breath test were included in the study. Individual breath results were linked with data on prescribing obtained from the General Medical Services prescription database. RESULTS: Of 805 patients, 374 (47%) had a positive urea breath test and 431 (54%) a negative urea breath test. Of positive urea breath test patients, only 245 (64%) were prescribed eradication therapy in the 3 months after the breath test and only 43% were referred back for re-testing. In the year after the urea breath test, there was a significant fall in prescribing of antisecretory therapy which was greatest in the patients who received H. pylori therapy (P < 0.001). CONCLUSIONS: There appears to be under and inappropriate treatment of H. pylori infection in primary care, and a low rate of re-testing after eradication, indicating that current guidelines are not well implemented in practice.

"Best practice' for Helicobacter pylori eradication in the primary care setting.

This study determined the relative cost effectiveness of proton pump inhibitor (PPI) based triple therapy regimens for Helicobacter pylori eradication in the primary care setting. Using decision tree analysis the expected cost for each H. pylori eradication strategy was determined from the cost of each treatment option multiplied by the probability of that option occurring. Probabilities were obtained using the GMS prescribing database where all patients who received amoxycillin, clarithromycin and a PPI in the ERHA region in 2002 were followed for one year. Depending on the regimen adopted, 40.8% to 46.1% of patients did not require any further medication in the year following H. pylori eradication treatment. The strategy of rabeprazole, amoxycillin and clarithromycin was the most cost effective option with a cost of Euro466 per asymptomatic patient. Two-way sensitivity analysis indicated that the cost of rabeprazole triple therapy and the duration of rabeprazole maintenance therapy would each have to increase by 30% before this strategy ceased to be the most cost effective and hence best practice option for eradicating Helicobacter pylori in the primary care setting in Ireland.

Review article: the long-term use of proton-pump inhibitors.

More than 15 years after the launch of omeprazole in 1988, proton-pump inhibitors remain central to the management of acid-suppression disorders and are unchallenged with regard to their efficacy and popularity among doctors and patients. They are considered safe despite early concerns about the possibility of an association with cancer and gastric atrophy; current concerns about long-term proton-pump inhibitor therapy are centred mainly on a possible association with fundic gland polyps and between Helicobacter pylori and gastric atrophic changes. Long-term proton-pump inhibitor usage accounts for the majority of the total proton-pump inhibitor usage. Long-term usage is difficult to define and most patients take proton-pump inhibitors non-continuously. Data indicate that a substantial proportion of long-term users do not have a clear indication for their therapy and there is thus room for reduction or rationalization of treatment. Overall, on-demand therapy is more cost-effective than continuous therapy and should be considered wherever possible.

The association between Helicobacter pylori infection and inflammatory bowel disease based on meta-analysis.

BACKGROUND: In humans there are epidemiological data suggesting a protective effect of Helicobacter pylori (H. pylori) infection against the development of autoimmune diseases and in addition, there are laboratory data illustrating H. pylori's ability to induce immune tolerance and limit inflammatory responses. Thus, numerous observational studies have examined the association between H. pylori infection and inflammatory bowel disease (IBD) with various results. OBJECTIVE: We performed a meta-analysis of available studies to better define the association of H. pylori infection and IBD. METHODS: Medical literature searches for human studies were performed through September 2014, using suitable keywords. In each study the risk ratio (RR) of H. pylori infection in IBD patients vs controls was calculated and pooled estimates were obtained using fixed- or random-effects models as appropriate. Heterogeneity between studies was evaluated using Cochran Q test and I(2) statistics, whereas the likelihood of publication bias was assessed by constructing funnel plots. RESULTS: Thirty-three studies were eligible for meta-analysis, including 4400 IBD patients and 4763 controls. Overall 26.5% of IBD patients were positive for H. pylori infection, compared to 44.7% of individuals in the control group. There was significant heterogeneity in the included studies (Q = 137.2, df (Q) =32, I(2) ( )= 77%, p < 0.001) and therefore the random-effects model of meta-analysis was used. The obtained pool RR estimation was 0.62 (95% confidence interval (CI) 0.55-0.71, test for overall effect Z = -7.04, p < 0.001). There was no evidence of publication bias. CONCLUSION: The results of this meta-analysis showed a significant negative association between H. pylori infection and IBD that supports a possible protective benefit of H. pylori infection against the development of IBD.

Optimised empiric triple and concomitant therapy for Helicobacter pylori eradication in clinical practice: the OPTRICON study.

BACKGROUND: Empiric triple therapy for Helicobacter pylori should be abandoned when clarithromycin resistance rate is >15-20%. Optimisation of triple therapy (high-dose acid suppression and 14-day duration) can increase eradication rates by 10%. AIM: To compare the efficacy and safety of optimised triple (OPT-TRI) and nonbismuth quadruple concomitant (OPT-CON) therapies. METHODS: Prospective multicentre study in 16 Spanish centres using triple therapy in clinical practice. In a 3-month two-phase fashion, the first 402 patients received an OPT-TRI therapy [esomeprazole (40 mg b.d.), amoxicillin (1 g b.d) and clarithromycin (500 mg b.d) for 14 days] and the last 375 patients an OPT-CON treatment [OPT-TRI therapy plus metronidazole (500 mg b.d)]. RESULTS: Seven-hundred seventy-seven consecutive patients were included (402 OPT-TRI, 375 OPT-CON). The OPT-CON therapy achieved significantly higher eradication rates in the per-protocol [82.3% (95% CI = 78-86%) vs. 93.8% (91-96%), P < 0.001] and intention-to-treat analysis [81.3% (78-86%) vs. 90.4% (87-93%), P < 0.001]. Adverse events (97% mild/moderate) were significantly more common with OPT-CON therapy (39% vs. 47%, P = 0.016), but full compliance with therapy was similar between groups (94% vs. 92%, P = 0.4). OPT-CON therapy was the only significant predictor of successful eradication (odds ratio, 2.24; 95% CI: 1.48-3.51, P < 0.001). The rate of participating centres achieving cure rates ≥ 90% favoured OPT-CON therapy (OPT-TRI 25% vs. OPT-CON 62%). CONCLUSIONS: Empiric OPT-CON therapy achieved significantly higher cure rates (>90%) compared to OPT-TRI therapy. Addition of metronidazole to OPT-TRI therapy increased eradication rates by 10%, resulting in more mild adverse effects, but without impairing compliance with therapy.