Global Prevalence of Helicobacter pylori Infection and Incidence of Gastric Cancer Between 1980 and 2022.

BACKGROUND & AIMS: We aimed to assess the secular trend of the global prevalence of Helicobacter pylori (H pylori) infection in adults and children/adolescents and to show its relation to that of gastric cancer incidence. METHODS: We performed a systematic review and meta-analysis to calculate overall prevalence, adjusted by multivariate meta-regression analysis. The incidence rates of gastric cancer were derived from the Global Burden of Disease Study and Cancer Incidence in Five Continents. RESULTS: Of the 16,976 articles screened, 1748 articles from 111 countries were eligible for analysis. The crude global prevalence of H pylori has reduced from 52.6% (95% confidence interval [CI], 49.6%-55.6%) before 1990 to 43.9% (95% CI, 42.3%-45.5%) in adults during 2015 through 2022, but was as still as high as 35.1% (95% CI, 30.5%-40.1%) in children and adolescents during 2015 through 2022. Secular trend and multivariate regression analyses showed that the global prevalence of H pylori has declined by 15.9% (95% CI, -20.5% to -11.3%) over the last 3 decades in adults, but not in children and adolescents. Significant reduction of H pylori prevalence was observed in adults in the Western Pacific, Southeast Asian, and African regions. However, H pylori prevalence was not significantly reduced in children and adolescents in any World Health Organization regions. The incidence of gastric cancer has decreased globally and in various countries where the prevalence of H pylori infection has declined. CONCLUSIONS: The global prevalence of H pylori infection has declined during the last 3 decades in adults, but not in children and adolescents. The results raised the hypothesis that the public health drive to reduce the prevalence of H pylori as a strategy to reduce the incidence of gastric cancer in the population should be confirmed in large-scale clinical trials.

Indications of Helicobacter pylori Eradication Treatment and Its Influence on Prescriptions and Effectiveness (Hp-EuReg).

BACKGROUND: The influence of indications for Helicobacter pylori investigation on prescriptions and effectiveness is unknown. The aim of the study was to assess the impact of indications for H. pylori investigation on prescriptions, effectiveness, compliance, and tolerance. METHODS: International, prospective, non-interventional registry of the management of H. pylori infection by European gastroenterologists (Hp-EuReg). Treatment-näive patients registered from 2013 to 2023 at e-CRF AEG-REDCap were analyzed. The effectiveness was assessed by modified intention-to-treat analysis. RESULTS: Overall, 53,636 treatment-naïve cases from 34 countries were included. Most frequent indications were: dyspepsia with normal endoscopy (49%), non-investigated dyspepsia (20%), duodenal ulcer (11%), gastric ulcer (7.7%), and gastroesophageal reflux disease (GERD) (2.6%). Therapy effectiveness varied by indication: duodenal ulcer (91%), gastric ulcer (90%), preneoplastic lesions (90%), dyspepsia with normal endoscopy (89%), GERD (88%), and non-investigated dyspepsia (87%). Bismuth-metronidazole-tetracycline and clarithromycin-amoxicillin-bismuth quadruple therapies achieved 90% effectiveness in all indications except GERD. Concomitant clarithromycin-amoxicillin-tinidazole/metronidazole reached 90% cure rates except in patients with non-investigated dyspepsia; whereas sequential clarithromycin-amoxicillin-tinidazole/metronidazole proved optimal (≥90%) in patients with gastric ulcer only. Adverse events were higher in patients treated for dyspepsia with normal endoscopy and duodenal ulcer compared with the remaining indications (23% and 28%, p < 0.001). Therapeutic compliance was higher in patients with duodenal ulcer and preneoplastic lesions (98% and 99%, p < 0.001). CONCLUSION: In Europe, patients with gastric or duodenal ulcers and preneoplastic lesions showed higher H. pylori treatment effectiveness. Bismuth and non-bismuth quadruple therapies achieved optimal results in almost all indications. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02328131.

An efficient strategy for evaluating new non-invasive screening tests for colorectal cancer: the guiding principles.

OBJECTIVE: New screening tests for colorectal cancer (CRC) are rapidly emerging. Conducting trials with mortality reduction as the end point supporting their adoption is challenging. We re-examined the principles underlying evaluation of new non-invasive tests in view of technological developments and identification of new biomarkers. DESIGN: A formal consensus approach involving a multidisciplinary expert panel revised eight previously established principles. RESULTS: Twelve newly stated principles emerged. Effectiveness of a new test can be evaluated by comparison with a proven comparator non-invasive test. The faecal immunochemical test is now considered the appropriate comparator, while colonoscopy remains the diagnostic standard. For a new test to be able to meet differing screening goals and regulatory requirements, flexibility to adjust its positivity threshold is desirable. A rigorous and efficient four-phased approach is proposed, commencing with small studies assessing the test's ability to discriminate between CRC and non-cancer states (phase I), followed by prospective estimation of accuracy across the continuum of neoplastic lesions in neoplasia-enriched populations (phase II). If these show promise, a provisional test positivity threshold is set before evaluation in typical screening populations. Phase III prospective studies determine single round intention-to-screen programme outcomes and confirm the test positivity threshold. Phase IV studies involve evaluation over repeated screening rounds with monitoring for missed lesions. Phases III and IV findings will provide the real-world data required to model test impact on CRC mortality and incidence. CONCLUSION: New non-invasive tests can be efficiently evaluated by a rigorous phased comparative approach, generating data from unbiased populations that inform predictions of their health impact.

The role of defensive information processing in population-based colorectal cancer screening uptake.

BACKGROUND: Internationally, colorectal cancer screening participation remains low despite the availability of home-based testing and numerous interventions to increase uptake. To be effective, interventions should be based on an understanding of what influences individuals' decisions about screening participation. This study investigates the association of defensive information processing (DIP) with fecal immunochemical test (FIT)-based colorectal cancer screening uptake. METHODS: Regression modeling of data from a cross-sectional survey within a population-based FIT screening program was conducted. The survey included the seven subdomains of the McQueen DIP measure. The primary outcome variable was the uptake status (screening user or nonuser). Multivariable logistic regression was used to estimate the odds ratio (OR) for screening nonuse by DIP (sub)domain score, with adjustments made for sociodemographic and behavioral factors associated with uptake. RESULTS: Higher scores (equating to greater defensiveness) on all DIP domains were significantly associated with lower uptake in the model adjusted for sociodemographic factors. In the model with additional adjustments for behavioral factors, the suppression subdomains of "deny immediacy to be tested" (OR, 0.53; 95% confidence interval [CI], 0.43-0.65; p < .001) and "self-exemption" (OR, 0.80; 95% CI, 0.68-0.96; p < .001) independently predicted nonuse of FIT-based screening. CONCLUSIONS: This is the first study outside the United States that has identified DIP as a barrier to colorectal cancer screening uptake, and it is the first focused specifically on FIT-based screening. The findings suggest that two suppression barriers, namely denying the immediacy to be tested and self-exempting oneself from screening, may be promising targets for future interventions to improve uptake.

Current Trends in the Management of Helicobacter pylori Infection in Serbia: Preliminary Results from the European Registry on H. pylori Management.

BACKGROUND: Helicobacter pylori (H. pylori) is the most common chronic bacterial infection. Treatment effectiveness remains a subject of debate considering bacterial antimicrobial resistance. Our aim was to analyze the diagnostic methods and eradication treatments for H. pylori infection in Serbia. METHODS: An observational multicenter prospective study was conducted in Serbia, as part of the European Registry on H. pylori Management (Hp-EuReg). Demographics, treatment indication, diagnostic methods, previous eradication attempts, and treatment were collected at AEG-REDCap e-CRF. Modified intention-to-treat (mITT) and per-protocol (PP) effectiveness analyses were performed. Safety, compliance, and bacterial antimicrobial resistance rates were reported. Data were quality checked. RESULTS: Overall, 283 patients were included, with a mean age of 55 ± 15 years. Dyspepsia (n = 214, 77%) was the most frequent treatment indication, and histology (n = 144, 51%) was the most used diagnostic method. Overall eradication rate was 95% (PP) and 94% (mITT). Most prevalent first-line therapy was quadruple PPI + clarithromycin + amoxicillin + metronidazole, with a 96% effectiveness (p < 0.001). Second-line main treatment choice was triple amoxicillin + levofloxacin, with a 95% effectiveness (p < 0.05). Single-capsule Pylera® was the most prescribed third-line therapy, with 100% effectiveness (p < 0.05). Longer treatment duration was associated with a higher eradication rate in first-line therapy (p < 0.05). Clarithromycin and quinolone resistance rates in first-line were 24% and 8.3%, respectively. The overall adverse events' incidence rate was 13.4%, and therapy compliance was 97%. CONCLUSIONS: Considering the high eradication rate, 14-day non-bismuth quadruple concomitant therapy is a reasonable first-line choice, while quinolone-based therapy and single-capsule Pylera® should be considered as rescue therapy options.

Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report.

Helicobacter pyloriInfection is formally recognised as an infectious disease, an entity that is now included in the International Classification of Diseases 11th Revision. This in principle leads to the recommendation that all infected patients should receive treatment. In the context of the wide clinical spectrum associated with Helicobacter pylori gastritis, specific issues persist and require regular updates for optimised management.The identification of distinct clinical scenarios, proper testing and adoption of effective strategies for prevention of gastric cancer and other complications are addressed. H. pylori treatment is challenged by the continuously rising antibiotic resistance and demands for susceptibility testing with consideration of novel molecular technologies and careful selection of first line and rescue therapies. The role of H. pylori and antibiotic therapies and their impact on the gut microbiota are also considered.Progress made in the management of H. pylori infection is covered in the present sixth edition of the Maastricht/Florence 2021 Consensus Report, key aspects related to the clinical role of H. pylori infection were re-evaluated and updated. Forty-one experts from 29 countries representing a global community, examined the new data related to H. pylori infection in five working groups: (1) indications/associations, (2) diagnosis, (3) treatment, (4) prevention/gastric cancer and (5) H. pylori and the gut microbiota. The results of the individual working groups were presented for 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 various clinical fields.

Empirical rescue treatment of Helicobacter pylori infection in third and subsequent lines: 8-year experience in 2144 patients from the European Registry on H. pylori management (Hp-EuReg).

OBJECTIVE: To evaluate the use, effectiveness and safety of Helicobacter pylori empirical rescue therapy in third and subsequent treatment lines in Europe. DESIGN: International, prospective, non-interventional registry of the clinical practice of European gastroenterologists. Data were collected and quality reviewed until October 2021 at Asociación Española de Gastroenterología-Research Electronic Data Capture. All cases with three or more empirical eradication attempts were assessed for effectiveness by modified intention-to-treat and per-protocol analysis. RESULTS: Overall, 2144 treatments were included: 1519, 439, 145 and 41 cases from third, fourth, fifth and sixth treatment lines, respectively. Sixty different therapies were used; the 15 most frequently prescribed encompassed >90% of cases. Overall effectiveness remained <90% in all therapies. Optimised treatments achieved a higher eradication rate than non-optimised (78% vs 67%, p<0.0001). From 2017 to 2021, only 44% of treatments other than 10-day single-capsule therapy used high proton-pump inhibitor doses and lasted ≥14 days. Quadruple therapy containing metronidazole, tetracycline and bismuth achieved optimal eradication rates only when prescribed as third-line treatment, either as 10-day single-capsule therapy (87%) or as 14-day traditional therapy with tetracycline hydrochloride (95%). Triple amoxicillin-levofloxacin therapy achieved 90% effectiveness in Eastern Europe only or when optimised. The overall incidence of adverse events was 31%. CONCLUSION: Empirical rescue treatment in third and subsequent lines achieved suboptimal effectiveness in most European regions. Only quadruple bismuth-metronidazole-tetracycline (10-day single-capsule or 14-day traditional scheme) and triple amoxicillin-levofloxacin therapies reached acceptable outcomes in some settings. Compliance with empirical therapy optimisation principles is still poor 5 years after clinical practice guidelines update. TRIAL REGISTRATION NUMBER: NCT02328131.

Comparative Effectiveness of Multiple Different First-Line Treatment Regimens for Helicobacter pylori Infection: A Network Meta-analysis.

BACKGROUND & AIMS: A number of double, triple, and quadruple therapies have been proposed as first-line empiric treatments for Helicobacter pylori infection. However, knowledge of their worldwide and regional comparative efficacy is lacking. We examined the comparative effectiveness of all empirically used first-line regimens tested against standard triple treatment using a network meta-analysis of published randomized controlled trials. METHODS: Data extracted from eligible randomized controlled trials were entered into a Bayesian network meta-analysis to investigate the comparative efficacy of H pylori infection empiric first-line regimens and to explore their effectiveness rank order. The ranking probability for each regimen was evaluated by means of surfaces under cumulative ranking values. RESULTS: Sixty-eight eligible randomized controlled trials were included, giving a total of 92 paired comparisons with 22,975 patients randomized to 8 first-line regimens. The overall results showed that only vonoprazan triple therapy and reverse hybrid therapy achieved cure rates of >90%. Levofloxacin triple therapy performed best in Western countries (eradication rate 88.5%). The comparative effectiveness ranking showed that vonoprazan triple therapy had the best results, whereas standard triple therapy was the least efficacious regimen (surfaces under cumulative ranking 92.4% vs 4.7% respectively; odds ratio, 3.80; 95% credible interval, 1.62-8.94). CONCLUSIONS: For first-line empiric treatment of H pylori infection, vonoprazan triple therapy and reverse hybrid therapy achieved high eradication rates of >90%. Levofloxacin triple therapy achieved the highest eradication rates in Western countries. Standard triple therapy was the least efficacious regimen in this network meta-analysis.

IOIBD Recommendations for Clinical Trials in Ulcerative Proctitis: The PROCTRIAL Consensus.

BACKGROUND & AIMS: Clinical trials evaluating biologics and small molecules in patients with ulcerative colitis are predominantly excluding ulcerative proctitis. The objective of the Definition and endpoints for ulcerative PROCtitis in clinical TRIALs initiative was to develop consensus statements for definitions, inclusion criteria, and endpoints for the evaluation of ulcerative proctitis in adults. METHODS: Thirty-five international experts held a consensus meeting to define ulcerative proctitis, and the endpoints to use in clinical trials. Based on a systematic review of the literature, statements were generated, discussed, and approved by the working group participants using a modified Delphi method. Consensus was defined as at least 75% agreement among voters. RESULTS: The group agreed that the diagnosis of ulcerative proctitis should be made by ileocolonoscopy and confirmed by histopathology, with the exclusion of infections, drug-induced causes, radiation, trauma, and Crohn's disease. Ulcerative proctitis was defined as macroscopic extent of lesions limited to 15 cm distance from the anal verge in adults. Primary and secondary endpoints were identified to capture response of ulcerative proctitis to therapy. A combined clinical and endoscopic primary endpoint for the evaluation of ulcerative proctitis disease activity was proposed. Secondary endpoints that should be evaluated include endoscopic remission, histologic remission, mucosal healing, histologic endoscopic mucosal improvement, disability, fecal incontinence, urgency, constipation, and health-related quality of life. CONCLUSIONS: In response to the need for guidance on the design of clinical trials in patients with ulcerative proctitis, the Definition and end points for ulcerative PROCtitis in clinical TRIALs consensus provides recommendations on the definition and endpoints for ulcerative proctitis clinical trials.

Room for Improvement in the Treatment of Helicobacter pylori Infection: Lessons from the European Registry on H. pylori Management (Hp-EuReg).

BACKGROUND: Managing Helicobacter pylori infection requires constant decision making, and each decision is open to possible errors. AIM: The aim was to evaluate common mistakes in the eradication of H. pylori, based on the "European Registry on Helicobacter pylori management". METHODS: European Registry on Helicobacter pylori management is an international multicentre prospective noninterventional registry evaluating the decisions and outcomes of H. pylori management by European gastroenterologists in routine clinical practice. RESULTS: Countries recruiting more than 1000 patients were included (26,340 patients). The most common mistakes (percentages) were: (1) To use the standard triple therapy where it is ineffective (46%). (2) To prescribe eradication therapy for only 7 to 10 days (69%). (3) To use a low dose of proton pump inhibitors (48%). (4) In patients allergic to penicillin, to prescribe always a triple therapy with clarithromycin and metronidazole (38%). (5) To repeat certain antibiotics after eradication failure (>15%). (6) Failing to consider the importance of compliance with treatment (2%). (7) Not to check the eradication success (6%). Time-trend analyses showed progressive greater compliance with current clinical guidelines. CONCLUSION: The management of H. pylori infection by some European gastroenterologists is heterogeneous, frequently suboptimal and discrepant with current recommendations. Clinical practice is constantly adapting to updated recommendations, although this shift is delayed and slow.

European Registry on Helicobacter pylori management (Hp-EuReg): patterns and trends in first-line empirical eradication prescription and outcomes of 5 years and 21 533 patients.

OBJECTIVE: The best approach for Helicobacter pylori management remains unclear. An audit process is essential to ensure clinical practice is aligned with best standards of care. DESIGN: International multicentre prospective non-interventional registry starting in 2013 aimed to evaluate the decisions and outcomes in H. pylori management by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap. Variables included demographics, previous eradication attempts, prescribed treatment, adverse events and outcomes. Data monitoring was performed to ensure data quality. Time-trend and geographical analyses were performed. RESULTS: 30 394 patients from 27 European countries were evaluated and 21 533 (78%) first-line empirical H. pylori treatments were included for analysis. Pretreatment resistance rates were 23% to clarithromycin, 32% to metronidazole and 13% to both. Triple therapy with amoxicillin and clarithromycin was most commonly prescribed (39%), achieving 81.5% modified intention-to-treat eradication rate. Over 90% eradication was obtained only with 10-day bismuth quadruple or 14-day concomitant treatments. Longer treatment duration, higher acid inhibition and compliance were associated with higher eradication rates. Time-trend analysis showed a region-dependent shift in prescriptions including abandoning triple therapies, using higher acid-inhibition and longer treatments, which was associated with an overall effectiveness increase (84%-90%). CONCLUSION: Management of H. pylori infection by European gastroenterologists is heterogeneous, suboptimal and discrepant with current recommendations. Only quadruple therapies lasting at least 10 days are able to achieve over 90% eradication rates. European recommendations are being slowly and heterogeneously incorporated into routine clinical practice, which was associated with a corresponding increase in effectiveness.

Negative emotions and cancer fatalism are independently associated with uptake of Faecal Immunochemical Test-based colorectal cancer screening: Results from a population-based study.

Although systematic colorectal cancer screening is efficacious, many programmes suffer from low uptake. Few behavioural or attitudinal factors have been identified as being associated with participation in colorectal cancer screening. We explored knowledge, beliefs about cancer, subjective health literacy, emotional attitudes to screening, and social influences among individuals invited to a population-based screening programme. Regression modelling of a cross-sectional survey of 2299 individuals (users and non-users) of a population-based Faecal Immunochemical Test (FIT) screening programme in Dublin was conducted. Questions were derived from previous theoretically-informed qualitative work and assessed using previously used and validated measures. The primary outcome variable was uptake status (User/Participation or Non-User/Non-participation); multivariable logistic regression was used to estimate the odds ratios (OR) for screening participation. Stronger fatalistic beliefs independently predicted lower uptake (OR = 0.94; 95% CI 0.90-0.98; P = 0.003). Those aged <65 who disagreed that "cancer can often be cured" also had lower uptake (OR = 0.43; 95% CI 0.22-0.82: P = 0.017). Agreement that the test was disgusting and tempting fate predicted lower uptake (OR = 0.16: 95% CI 0.10-0.27: p < 0.001), while the influence of a partner on decision to be screened was associated with higher uptake (OR = 1.32; 95% CI 1.15-1.50: P < 0.001). Negative cancer-related and screening-related beliefs and emotions are associated with non-participation in FIT (-based screening). Research is warranted to explore if these negative beliefs and emotions are modifiable and, if so, whether this would improve screening uptake. The association between the influence of a partner and screening participation present a challenge around improving uptake among those not in co-habiting relationships.

Helicobacter pylori Eradication Rates in Slovenia in the Period from 2017 to 2019: Data from the European Registry on H. pylori Management.

BACKGROUND: Helicobacter pylori (H. pylori) is the most common chronic bacterial infection in the world, affecting over 50% of the world's population. H. pylori is a grade I carcinogen, responsible for the development of 89% of noncardia gastric cancers. In the present study, we analyzed the data for H. pylori eradication treatments in Slovenia after the 3rd national recommendations were implemented. PATIENTS AND METHODS: Slovenia is part of the European Registry on H. pylori Management since the Registry was launched in 2013. Data were collected at Asociación Española de Gastroenterología-Research Electronic Data Capture electronic case report form from September 2017 to December 2019. H. pylori eradication treatment was assessed by modified intention-to-treat (mITT) and per-protocol analyses. RESULTS: Overall, 853 patients from 3 medical institutions were included. Effectiveness with first-line 14-day triple therapy with a proton-pomp-inhibitor (PPI), clarithromycin 500 mg, amoxicillin 1,000 mg, all BID, was 93% by mITT (714 patients). In patients allergic to penicillin, first-line 14-day triple therapy with PPI-clarithromycin-metronidazole achieved 83% effectiveness by mITT (35 patients). Second-line 14-day triple therapy with a PPI-amoxicillin-levofloxacin achieved 89% mITT eradication rate (51 patients). Second-line therapy with the 10-day three-in-one single capsule containing bismuth-tetracycline-metronidazole achieved optimal effectiveness (100% mITT) in 10 patients (p = 0.02). CONCLUSIONS: Slovenia is a country with <15% H. pylori resistance to clarithromycin. Triple therapy with a PPI plus 2 antibiotics during 14 days reported optimal effectiveness (over 90%). Ten-day quadruple-bismuth second-line therapy had better results than 14-day triple therapy with levofloxacin.

Risk of Progression of Gastric Intestinal Metaplasia Is Significantly Greater When Detected in Both Antrum and Body.

BACKGROUND: Gastric cancer (GC) is the fifth leading cause of cancer-related death worldwide. GC is usually preceded by a cascade of well-defined precursor lesions, set in place by an environmental trigger (H. pylori) including intestinal metaplasia (GIM) and dysplasia. AIMS: To investigate the rates of progression of GIM to dysplasia and GC in a region of low gastric cancer incidence. METHODS: We identified all patients diagnosed with GIM between January 1, 2008, and June 30, 2012. Any repeat upper endoscopy more than 1 year after index diagnosis and before December 31, 2018, was considered follow-up. Carcinomas the bulk of which were macroscopically located below the OGJ were considered primary gastric cancer. RESULTS: Progression to more advanced lesions was observed in six patients (0.6%). Four patients (three male) developed GC at median age 74 years (SD 6). Two patients progressed to dysplasia (one male) at median age 71 years (SD 4). Patients with GIM in both gastric antrum and body were significantly more likely to progress than those with GIM in only one location (3.1% vs. 0.4%) (p value 0.017). Fifty-eight patients who had H. pylori eradicated were followed up. No progression to dysplasia or GC was noted in this group, with 28 patients having persistent GIM at follow-up. CONCLUSION: Patients with GIM in both antrum and body had a significantly increased risk of progression and warrant close attention. This is comparable to routinely followed premalignant conditions such as Barrett's esophagus and Colonic Polyps, and appropriate surveillance protocols should be followed in this group.

European Registry on Helicobacter pylori management (Hp-EuReg): First-line Therapy in Israel.

BACKGROUND: The antibiotic resistance profile of Helicobacter pylori (H. pylori) is constantly changing. Up-to-date and reliable data for the effectiveness of first-line H. pylori treatment protocols are necessary to provide evidence-based best-practice guidelines. OBJECTIVES: To determine the effectiveness, compliance and safety of first-line treatment for H. pylori in Israel. METHODS: An observational, prospective, multicenter study was conducted in tertiary referral centers in Israel, as part of the European registry on H. pylori management (Hp-EuReg). H. pylori-infected patients were included from 2013 to March 2020. Data collected included demographics, clinical data, diagnostic tests, previous eradication attempts, current treatment, compliance, adverse events, and treatment outcome result. RESULTS: In total, 242 patients were registered, including 121 (50%) who received first-line therapy, 41% of these individuals received clarithromycin based triple therapy and 58.9% received a four-drug regimen. The overall effectiveness of first-line therapy was 85% and 86% by modified intention-to-treat and per protocol analyses, respectively. The effectiveness of both sequential and concomitant therapies was 100% while clarithromycin-based triple therapy achieved an eradication rate of 79%. Treatment eradication was higher among patients who received high dose proton pump inhibitor (PPI) compared to those treated with low dose PPI (100% vs. 81.5% respectively, P < 0.01). No difference in treatment effectiveness was found between 7-, 10-, and 14-day treatment. CONCLUSIONS: The effectiveness of clarithromycin-based triple therapy is suboptimal. First-line treatment of H. pylori infection should consist of four drugs, including high dose PPI, according to international guidelines.

Combination of Bismuth and Standard Triple Therapy Eradicates Helicobacter pylori Infection in More than 90% of Patients.

BACKGROUND & AIMS: Due to the poor eradication rates of standard triple therapy, the addition of bismuth salts has been proposed for first-line eradication of Helicobacter pylori. We assessed the effectiveness and safety of the combination of bismuth and the standard, clarithromycin-containing triple therapy in eradication of H pylori infection, using data from a large multi-center registry. METHODS: We performed an interim analysis of data from the European Registry on H pylori Management, a prospective trial registering clinical data and outcomes from infected patients from 27 countries in Europe since 2013. We extracted data on 1141 treatment-naïve patients who received first-line treatment with bismuth salts (240 mg) and a proton pump inhibitor (57% received esomeprazole, 18% received omeprazole, 11% received pantoprazole, and 14% received rabeprazole), amoxicillin (1 g), and clarithromycin (500 mg), all taken twice daily. RESULTS: Intention to treat and per-protocol rates of eradication were 88% and 94%, respectively. Intention to treat eradication increased to 93% in patients who received 14-day treatments. Adverse events occurred in 36% of patients; 76% of these events were mild, with a mean duration of 6 days. In multivariate analysis, eradication was associated with treatment compliance (odds ratio [OR], 13.0), a double dose (equivalent to 40 mg omeprazole) of proton pump inhibitor (OR, 4.7), and 14-day duration of treatment (OR, 2.0). CONCLUSIONS: In an analysis of data from a large multi-center registry, we found the addition of bismuth to 14-day standard triple therapy with clarithromycin and amoxicillin to eradicate H pylori infection in more than 90% of patients, based on intention to treat analysis, with an acceptable safety profile and level of adherence. ClinicalTrials.gov no: NCT02328131.

Review - Treatment of Helicobacter pylori infection 2020.

This review summarizes important studies regarding Helicobacter pylori therapy published from April 2019 to April 2020. The main themes that emerge involve studies assessing antibiotic resistance, and there is also growing momentum behind the utility of vonoprazan as an alternative to proton pump inhibitor (PPI) therapy and also bismuth-based regimens as a first-line regimen. Antibiotic resistance is rising wherever it is being assessed, and clarithromycin resistance in particular has reached a point where it may no longer be a viable therapy without previous testing in many regions of the world. The evidence for the efficacy of a bismuth-based quadruple therapy as a first-line therapy is now very clearly established, and there is substantial evidence that it is the best performing first-line therapy. The utility of vonoprazan as an alternative to PPI therapy, especially in resistant and difficult-to-treat groups, has also been considered in great detail this year, and it may offer an opportunity in the near future to reduce the problem of antibiotic resistance.

Bismuth quadruple regimen with tetracycline or doxycycline versus three-in-one single capsule as third-line rescue therapy for Helicobacter pylori infection: Spanish data of the European Helicobacter pylori Registry (Hp-EuReg).

BACKGROUND: Different bismuth quadruple therapies containing proton-pump inhibitors, bismuth salts, metronidazole, and a tetracycline have been recommended as third-line Helicobacter pylori eradication treatment after failure with clarithromycin and levofloxacin. AIM: To evaluate the efficacy and safety of third-line treatments with bismuth, metronidazole, and either tetracycline or doxycycline. METHODS: Sub-study with Spanish data of the "European Registry on H pylori Management" (Hp-EuReg), international multicenter prospective non-interventional Registry of the routine clinical practice of gastroenterologists. After previous failure with clarithromycin- and levofloxacin-containing therapies, patients receiving a third-line regimen with 10/14-day bismuth salts, metronidazole, and either tetracycline (BQT-Tet) or doxycycline (BQT-Dox), or single capsule (BQT-three-in-one) were included. Data were registered at AEG-REDCap database. Univariate and multivariate analyses were performed. RESULTS: Four-hundred and fifty-four patients have been treated so far: 85 with BQT-Tet, 94 with BQT-Dox, and 275 with BQT-three-in-one. Average age was 53 years, 68% were women. Overall modified intention-to-treat and per-protocol eradication rates were 81% (BQT-Dox: 65%, BQT-Tet: 76%, BQT-three-in-one: 88%) and 82% (BQT-Dox: 66%, BQT-Tet: 77%, BQT-three-in-one: 88%), respectively. By logistic regression, higher eradication rates were associated with compliance (OR = 2.96; 95% CI = 1.01-8.84) and no prior metronidazole use (OR = 1.96; 95% CI = 1.15-3.33); BQT-three-in-one was superior to BQT-Dox (OR = 4.46; 95% CI = 2.51-8.27), and BQT-Tet was marginally superior to BQT-Dox (OR = 1.67; 95% CI = 0.85-3.29). CONCLUSION: Third-line H pylori eradication with bismuth quadruple treatment (after failure with clarithromycin and levofloxacin) offers acceptable efficacy and safety. Highest efficacy was found in compliant patients and those taking 10-day BQT-three-in-one or 14-day BQT-Tet. Doxycycline seems to be less effective and therefore should not be recommended.

Helicobacter pylori first-line and rescue treatments in patients allergic to penicillin: Experience from the European Registry on H pylori management (Hp-EuReg).

BACKGROUND: Experience in Helicobacter pylori eradication treatment of patients allergic to penicillin is very scarce. A triple combination with a PPI, clarithromycin (C), and metronidazole (M) is often prescribed as the first option, although more recently the use of a quadruple therapy with PPI, bismuth (B), tetracycline (T), and M has been recommended. AIM: To evaluate the efficacy and safety of first-line and rescue treatments in patients allergic to penicillin in the "European Registry of H pylori management" (Hp-EuReg). METHODS: A systematic prospective registry of the clinical practice of European gastroenterologists (27 countries, 300 investigators) on the management of H pylori infection. An e-CRF was created on AEG-REDCap. Patients with penicillin allergy were analyzed until June 2019. RESULTS: One-thousand eighty-four patients allergic to penicillin were analyzed. The most frequently prescribed first-line treatments were as follows: PPI + C + M (n = 285) and PPI + B + T + M (classic or Pylera® ; n = 250). In first line, the efficacy of PPI + C + M was 69%, while PPI + B + T + M reached 91% (P < .001). In second line, after the failure of PPI + C + M, two rescue options showed similar efficacy: PPI + B + T + M (78%) and PPI + C + levofloxacin (L) (71%) (P > .05). In third line, after the failure of PPI + C + M and PPI + C + L, PPI + B + T + M was successful in 75% of cases. CONCLUSION: In patients allergic to penicillin, a triple combination with PPI + C + M should not be generally recommended as a first-line treatment, while a quadruple regimen with PPI + B + T + M seems to be a better option. As a rescue treatment, this quadruple regimen (if not previously prescribed) or a triple regimen with PPI + C + L could be used but achieved suboptimal (<80%) results.

Irish data on the safety and efficacy of vedolizumab in the treatment of inflammatory bowel disease.

SUMMARY: This study reviews the safety and efficacy of treatment with vedolizumab for patients with inflammatory bowel disease across 9 Irish hospitals. It generates valuable and timely real-world data on treatment outcomes to add to the existing evidence base. Our population represents a refractory cohort with most patients previously exposed to at least one anti-TNFa agent and expressing an inflammatory phenotype. Results are reassuringly similar to larger international studies with additional insights into potential predictors of treatment response. This study further supports the safety and efficacy of vedolizumab in the treatment of inflammatory bowel disease. Key SummaryVedolizumab has growing real world data on its safety and efficacy in the treatment of IBD. Data on predictors of response are lacking. Studies such as VARSITY require new real-world data to help identify the place VDZ will occupy in the treatment algorithm for IBDThis study provides national Irish data on the safety and efficacy of VDZ in the treatment of IBD. It gives insight into various predictors of response for both UC and CD. It strengthens the available body of evidence on the use of VDZ and helps us determine its position on the treatment algorithm.