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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.
Subject(s)
Anti-Bacterial Agents , Helicobacter Infections , Helicobacter pylori , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Anti-Bacterial Agents/therapeutic use , Drug Therapy, Combination , Europe , Helicobacter Infections/drug therapy , Helicobacter pylori/drug effects , Prospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: There has been an increase in resistance to many of the antimicrobials used to treat Helicobacter pylori ( H. pylori ) nationally and internationally. Primary clarithromycin resistance and dual clarithromycin and metronidazole resistance are high in Ireland. These trends call for an evaluation of best-practice management strategies. OBJECTIVE: The objective of this study was to revise the recommendations for the management of H. pylori infection in adult patients in the Irish healthcare setting. METHODS: The Irish H. pylori working group (IHPWG) was established in 2016 and reconvened in 2023 to evaluate the most up-to-date literature on H. pylori diagnosis, eradication rates and antimicrobial resistance. The 'GRADE' approach was then used to rate the quality of available evidence and grade the resulting recommendations. RESULTS: The Irish H. pylori working group agreed on 14 consensus statements. Key recommendations include (1) routine antimicrobial susceptibility testing to guide therapy is no longer recommended other than for clarithromycin susceptibility testing for first-line treatment (statements 6 and 9), (2) clarithromycin triple therapy should only be prescribed as first-line therapy in cases where clarithromycin susceptibility has been confirmed (statement 9), (3) bismuth quadruple therapy (proton pump inhibitor, bismuth, metronidazole, tetracycline) is the recommended first-line therapy if clarithromycin resistance is unknown or confirmed (statement 10), (4) bismuth quadruple therapy with a proton pump inhibitor, levofloxacin and amoxicillin is the recommended second-line treatment (statement 11) and (5) rifabutin amoxicillin triple therapy is the recommend rescue therapy (statement 12). CONCLUSION: These recommendations are intended to provide the most relevant current best-practice guidelines for the management of H. pylori infection in adults in Ireland.
Subject(s)
Anti-Bacterial Agents , Clarithromycin , Drug Therapy, Combination , Helicobacter Infections , Helicobacter pylori , Proton Pump Inhibitors , Humans , Helicobacter Infections/drug therapy , Helicobacter Infections/diagnosis , Helicobacter pylori/drug effects , Ireland , Anti-Bacterial Agents/therapeutic use , Adult , Proton Pump Inhibitors/therapeutic use , Clarithromycin/therapeutic use , Metronidazole/therapeutic use , Consensus , Drug Resistance, Bacterial , Microbial Sensitivity Tests , Treatment Outcome , Bismuth/therapeutic useABSTRACT
The prevalence of Helicobacter pylori (H. pylori), a pathogen, has decreased globally in the last decade. To date, the management of H. pylori has focused on a reactive approach, whereby those diagnosed are treated with antimicrobials and acid suppression in combination. This review article provides an overview of the shift in the management of H. pylori from a reactive approach towards a proactive 'screen and treat' approach; the article reflects the current pharmacological landscape for H. pylori treatment by exploring similarities such as the first-line prescription of quadruple therapy in most countries and provides a summary table of the best practice guidance from Europe, Asia, and North America. It explores significant ongoing challenges in management, such as rising antimicrobial resistance rates, and explores a potential 'work smart' approach to antimicrobial susceptibility testing. We explore the role of registry databases in providing data on treatment efficacy and safety and how they can support a strategic approach to H. pylori treatment. We question if such a database's availability, update, and regular audit should serve as a key quality indicator in a population screening programme. Despite a call for vaccination against H. pylori and decades of research, not many have made it to a phase-three clinical trial. We explore the challenges that have complicated the development of such a vaccine, such as the genetic diversity of H. pylori, immunotolerance, and limitations of mouse models in research; we reflect on how these challenges are contributing to a low likelihood of having a vaccine in the short-medium term. Lastly, it explores the heterogeneity in research on probiotics and their role as an adjunct in the management of H. pylori.
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BACKGROUND: Adherence to Helicobacter pylori (H. pylori) eradication treatment is a cornerstone for achieving adequate treatment efficacy. OBJECTIVE: To determine which factors influence compliance with treatment. METHODS: A systematic prospective non-interventional registry (Hp-EuReg) of the clinical practice of European gastroenterologists. Compliance was considered adequate if ≥90% drug intake. Data were collected until September 2021 using the AEG-REDCap e-CRF and were subjected to quality control. Modified intention-to-treat analyses were performed. Multivariate analysis carried out the factors associated with the effectiveness of treatment and compliance. RESULTS: Compliance was inadequate in 646 (1.7%) of 38,698 patients. The non-compliance rate was higher in patients prescribed longer regimens (10-, 14-days) and rescue treatments, patients with uninvestigated dyspepsia/functional dyspepsia, and patients reporting adverse effects. Prevalence of non-adherence was lower for first-line treatment than for rescue treatment (1.5% vs. 2.2%; p < 0.001). Differences in non-adherence in the three most frequent first-line treatments were shown: 1.1% with proton pump inhibitor + clarithromycin + amoxicillin; 2.3% with proton pump inhibitor clarithromycin amoxicillin metronidazole; and 1.8% with bismuth quadruple therapy. These treatments were significantly more effective in compliant than in non-compliant patients: 86% versus 44%, 90% versus 71%, and 93% versus 64%, respectively (p < 0.001). In the multivariate analysis, the variable most significantly associated with higher effectiveness was adequate compliance (odds ratio, 6.3 [95%CI, 5.2-7.7]; p < 0.001). CONCLUSIONS: Compliance with Helicobacter pylori eradication treatment is very good. Factors associated with poor compliance include uninvestigated/functional dyspepsia, rescue-treatment, prolonged treatment regimens, the presence of adverse events, and the use of non-bismuth sequential and concomitant treatment. Adequate treatment compliance was the variable most closely associated with successful eradication.
Subject(s)
Amoxicillin , Anti-Bacterial Agents , Drug Therapy, Combination , Helicobacter Infections , Helicobacter pylori , Medication Adherence , Proton Pump Inhibitors , Registries , Humans , Helicobacter Infections/drug therapy , Helicobacter pylori/drug effects , Male , Medication Adherence/statistics & numerical data , Female , Proton Pump Inhibitors/therapeutic use , Proton Pump Inhibitors/administration & dosage , Middle Aged , Prospective Studies , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/adverse effects , Europe , Adult , Amoxicillin/therapeutic use , Amoxicillin/administration & dosage , Treatment Outcome , Clarithromycin/therapeutic use , Aged , Dyspepsia/drug therapy , Dyspepsia/microbiology , Metronidazole/therapeutic use , Metronidazole/administration & dosage , Bismuth/therapeutic use , Bismuth/administration & dosage , Bismuth/adverse effectsABSTRACT
BACKGROUND AND AIMS: Βiologic agents and small molecules have expanded the therapeutic armamentarium of moderate to severe ulcerative colitis (UC). However, their comparative efficacy and safety performance as maintenance treatments have not been sufficiently explored. We performed a systematic review and network meta-analysis (NWM) to assess the comparative efficacy and safety of all approved and emerging treatments for maintenance in moderate to severe UC. METHODS: We searched Pubmed/Medline, EMBASE, and Cochrane Library databases for relevant RCTs through April 2023. The primary endpoint was clinical remission at the end of the maintenance therapy. Data were analyzed by means of a Bayesian NWM. The ranking probability concerning efficacy and safety was evaluated by means of surfaces under cumulative ranking (SUCRA) values. RESULTS: There were 20 eligible RCTs with 7660 patients randomized to 20 treatments. RCTs were grouped into two study designs, that is, re-randomization of patients after an induction period and treat-through patients. Concerning efficacy, in re-randomized patients, upadacitinib 30â mg/day was ranked first (SUCRA 94.9%) whereas in treat-through patients etrasimod 2â mg/day was ranked first (SUCRA 91.1%). The integrated efficacy-safety hierarchical analysis, showed that tofacitinib 10â mg had the best efficacy-safety therapeutic profile in re-randomized patients, whereas in treat-through patients infliximab 3.5â mg/Kg Q8W showed the best efficacy-safety profile. CONCLUSION: For maintenance treatment, in moderate to severe UC, this NWM showed that upadacitinib 30â mg/day and etrasimod 2â mg/day were ranked best for efficacy in re-randomized and treat-through patients respectively. Tofacitinib 10â mg/day and infliximab 3.5â mg/Kg Q8W showed the best efficacy-safety therapeutic profile in re-randomized and treat-through patients respectively.
Subject(s)
Colitis, Ulcerative , Network Meta-Analysis , Colitis, Ulcerative/drug therapy , Humans , Biological Factors/therapeutic use , Treatment Outcome , Randomized Controlled Trials as Topic , Maintenance Chemotherapy/methods , Bayes Theorem , Gastrointestinal Agents/therapeutic use , Gastrointestinal Agents/adverse effects , Piperidines/therapeutic use , Piperidines/adverse effects , Remission Induction , Severity of Illness Index , PyrimidinesABSTRACT
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.
Subject(s)
Global Health , Helicobacter Infections , Stomach Neoplasms , Adolescent , Adult , Child , Humans , Helicobacter Infections/epidemiology , Helicobacter Infections/microbiology , Helicobacter Infections/diagnosis , Incidence , Prevalence , Risk Factors , Stomach Neoplasms/epidemiology , Stomach Neoplasms/microbiologyABSTRACT
BACKGROUND: Management of Helicobacter pylori (H. pylori) infection requires co-treatment with proton pump inhibitors (PPIs) and the use of antibiotics to achieve successful eradication. AIM: To evaluate the role of dosage of PPIs and the duration of therapy in the effectiveness of H. pylori eradication treatments based on the 'European Registry on Helicobacter pylori management' (Hp-EuReg). METHODS: Hp-EuReg is a multicentre, prospective, non-interventionist, international registry on the routine clinical practice of H. pylori management by European gastroenterologists. All infected adult patients were systematically registered from 2013 to 2022. RESULTS: Overall, 36,579 patients from five countries with more than 1000 patients were analysed. Optimal (≥90%) first-line-modified intention-to-treat effectiveness was achieved with the following treatments: (1) 14-day therapies with clarithromycin-amoxicillin-bismuth and metronidazole-tetracycline-bismuth, both independently of the PPI dose prescribed; (2) All 10-day (except 10-day standard triple therapy) and 14-day therapies with high-dose PPIs; and (3) 10-day quadruple therapies with clarithromycin-amoxicillin-bismuth, metronidazole-tetracycline-bismuth, and clarithromycin-amoxicillin-metronidazole (sequential), all with standard-dose PPIs. In first-line treatment, optimal effectiveness was obtained with high-dose PPIs in all 14-day treatments, in 10- and 14-day bismuth quadruple therapies and in 10-day sequential with standard-dose PPIs. Optimal second-line effectiveness was achieved with (1) metronidazole-tetracycline-bismuth quadruple therapy for 14- and 10 days with standard and high-dose PPIs, respectively; and (2) levofloxacin-amoxicillin triple therapy for 14 days with high-dose PPIs. None of the 7-day therapies in both treatment lines achieved optimal effectiveness. CONCLUSIONS: We recommend, in first-line treatment, the use of high-dose PPIs in 14-day triple therapy and in 10-or 14-day quadruple concomitant therapy in first-line treatment, while standard-dose PPIs would be sufficient in 10-day bismuth quadruple therapies. On the other hand, in second-line treatment, high-dose PPIs would be more beneficial in 14-day triple therapy with levofloxacin and amoxicillin or in 10-day bismuth quadruple therapy either as a three-in-one single capsule or in the traditional scheme.
Subject(s)
Helicobacter Infections , Helicobacter pylori , Adult , Humans , Proton Pump Inhibitors/therapeutic use , Metronidazole , Clarithromycin/therapeutic use , Levofloxacin/therapeutic use , Bismuth , Prospective Studies , Drug Therapy, Combination , Anti-Bacterial Agents/therapeutic use , Helicobacter Infections/drug therapy , Amoxicillin/therapeutic use , Tetracycline , RegistriesABSTRACT
BACKGROUND: Outcomes after ileocolonic resection in Crohn's disease [CD] are heterogeneous, and a clear definition of postoperative recurrence remains to be determined. Our Endpoints Working Group of the International Organization for the study of Inflammatory Bowel Disease [IOIBD] aimed to standardise postoperative outcomes, to discuss which endpoints should be used for postoperative clinical trials, and to define those which could be used in trials or registries. METHODS: Based on a systematic review of the literature, recommendations and statements were drafted and sent to all IOIBD members for a first round of voting. Recommendations and statements were revised based on the voters' comments during a consensus hybrid conference open to all IOIBD members. If no agreement was reached after two rounds of voting, the statement was excluded. RESULTS: In the systematic review, 3071 manuscripts were screened of which 434 were included. Sixteen recommendations were identified, of which 11 were endorsed. Recommendations and statements include that endoscopy remains the gold standard and should be used as a short-term primary endpoint in both observational cohorts and randomised controlled trials. Clinical symptoms classically used in clinical trials for luminal CD are not reliable in this specific situation. For that reason, longer-term endpoints should be based on the evidence of macroscopic inflammation assessed by imaging techniques, endoscopy, or as reflected by the presence of complications. CONCLUSIONS: Agencies recommend the use of clinical evaluations, as in the case of luminal CD, and do not recognise primary endpoints based solely on endoscopy. This consensus has led to agreement on the need to define postoperative endoscopy-based and/or imaging-based endpoints.
Subject(s)
Crohn Disease , Recurrence , Crohn Disease/surgery , Humans , Ileum/surgery , Ileum/pathologyABSTRACT
The prevalence of Helicobacter pylori remains high in the older population. Specific age-related peculiarities may impact the outcomes of H. pylori treatment. The aim of the study was to evaluate the diagnostics and effectiveness of H. pylori eradication between the younger and older European populations. "European Registry on H. pylori Management (Hp-EuReg)" data from 2013 to 2022 were analyzed. Patients were divided into older (≥ 60 years) and younger (18-59 years) groups. Modified intention-to-treat (mITT) and per-protocol (PP) analysis was performed. 49,461 patients included of which 14,467 (29%) were older-aged. Concomitant medications and penicillin allergy were more frequent among the older patients. Differences between younger and older populations were observed in treatment duration in first-line treatment and in proton pump inhibitors (PPIs) doses in second-line treatment. The overall incidence of adverse events was lower in the older adults group. The overall first-line treatment mITT effectiveness was 88% in younger and 90% in the older patients (p < 0.05). The overall second-line mITT treatment effectiveness was 84% in both groups. The effectiveness of the most frequent first- and second-line triple therapies was suboptimal (< 90%) in both groups. Optimal efficacy (≥ 90%) was achieved by using bismuth and non-bismuth-based quadruple therapies. In conclusion, the approach to the diagnostics and treatment of H. pylori infection did not generally differ between younger and older patients. Main differences were reported in the concurrent medications, allergy to penicillin and adverse events both in first- and second-line treatment. Optimal effectiveness rates were mostly achieved by using bismuth and non-bismuth-based quadruple therapies. No clinically relevant differences in the effectiveness between the age groups were observed.
Subject(s)
Helicobacter Infections , Helicobacter pylori , Hypersensitivity , Humans , Aged , Helicobacter Infections/drug therapy , Helicobacter Infections/epidemiology , Anti-Bacterial Agents/adverse effects , Bismuth/therapeutic use , Drug Therapy, Combination , Proton Pump Inhibitors/adverse effects , Penicillins/therapeutic use , Treatment Outcome , Hypersensitivity/drug therapyABSTRACT
The segmentation of patients into homogeneous groups could help to improve eradication therapy effectiveness. Our aim was to determine the most important treatment strategies used in Europe, to evaluate first-line treatment effectiveness according to year and country. Data collection: All first-line empirical treatments registered at AEGREDCap in the European Registry on Helicobacter pylori management (Hp-EuReg) from June 2013 to November 2022. A Boruta method determined the "most important" variables related to treatment effectiveness. Data clustering was performed through multi-correspondence analysis of the resulting six most important variables for every year in the 2013-2022 period. Based on 35,852 patients, the average overall treatment effectiveness increased from 87% in 2013 to 93% in 2022. The lowest effectiveness (80%) was obtained in 2016 in cluster #3 encompassing Slovenia, Lithuania, Latvia, and Russia, treated with 7-day triple therapy with amoxicillin-clarithromycin (92% of cases). The highest effectiveness (95%) was achieved in 2022, mostly in Spain (81%), with the bismuth-quadruple therapy, including the single-capsule (64%) and the concomitant treatment with clarithromycin-amoxicillin-metronidazole/tinidazole (34%) with 10 (69%) and 14 (32%) days. Cluster analysis allowed for the identification of patients in homogeneous treatment groups assessing the effectiveness of different first-line treatments depending on therapy scheme, adherence, country, and prescription year.
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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.
Subject(s)
Colorectal Neoplasms , Mass Screening , Humans , Prospective Studies , Early Detection of Cancer , Colorectal Neoplasms/epidemiology , Colonoscopy , Occult Blood , FecesABSTRACT
BACKGROUND AND AIMS: Several methods are available to diagnose Helicobacter pylori infection. Our objective was to evaluate the tests used for both the initial diagnosis and the confirmation of eradication after treatment in Europe. METHODS: The European Registry on the management of Helicobacter pylori infection is an international, multicentre, prospective, non-interventional registry aiming to evaluate the management of Helicobacter pylori-infected patients in Europe. Countries with at least 100 cases registered from June 2013 to April 2021, and with a validated diagnostic method were analysed. Data were quality reviewed. RESULTS: A total of 34,920 adult patients from 20 countries were included (mean age 51 years; 61% women). To establish the initial diagnosis, invasive tests were performed in 19,801 (71%) patients, non-invasive in 11,369 (41%), and both in 3437 (12%). The most frequent were histology (n = 11,885; 43%), a rapid urease test (n = 10,636; 38%) and an urea breath test (n = 7577; 27%). According to the age, invasive tests were indicated in 11,179 (77%) ≥50 years, and in 8603 (65%) <50 years. Depending on the country, the use of invasive tests ranged from 29-99% in <50 years to 60-99% in ≥50. Most of the tests used to confirm eradication were non-invasive (n = 32,540; 93%), with the urea breath test being the most frequent (n = 32,540; 78%). In 2983 (9%) post-treatment tests, histology (n = 1887; 5%) or a rapid urease test (n = 1223; 4%) were performed. CONCLUSION: A great heterogeneity was observed for the initial diagnosis and confirmation of the eradication. The reasons for the apparent lack of adherence to the clinical guidelines should be further explored.
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Many patients with inflammatory bowel disease (IBD) have persistent symptoms and disease activity despite the best available medical or surgical treatments. These patients are commonly referred to as having difficult-to-treat IBD and need additional therapeutic strategies. However, the absence of standard definitions has impeded clinical research efforts and comparisons of data. Under the guidance of the endpoints cluster of the International Organization for the Study of Inflammatory Bowel Disease, we held a consensus meeting to propose a common operative definition for difficult-to-treat IBD. 16 participants from 12 countries voted on 20 statements covering various elements of difficult-to-treat IBD, such as failure of medical and surgical treatments, disease phenotypes, and specific complaints from patients. "Agreement" was defined as at least 75% consensus. The group agreed that difficult-to-treat IBD is defined by the failure of biologics and advanced small molecules with at least two different mechanisms of action, or postoperative recurrence of Crohn's disease after two surgical resections in adults, or one in children. In addition, chronic antibiotic-refractory pouchitis, complex perianal disease, and comorbid psychosocial complications that impair disease management also qualified as difficult-to-treat IBD. Adoption of these criteria could serve to standardise reporting, guide enrolment in clinical trials, and help identify candidates for enhanced treatment strategies.
Subject(s)
Crohn Disease , Inflammatory Bowel Diseases , Humans , Consensus , Inflammatory Bowel Diseases/drug therapy , Crohn Disease/therapy , Crohn Disease/diagnosisABSTRACT
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.
Subject(s)
Anti-Infective Agents , Helicobacter Infections , Helicobacter pylori , Quinolones , Humans , Adult , Middle Aged , Aged , Helicobacter Infections/diagnosis , Helicobacter Infections/drug therapy , Helicobacter Infections/epidemiology , Clarithromycin/therapeutic use , Anti-Bacterial Agents , Prospective Studies , Serbia/epidemiology , Proton Pump Inhibitors/therapeutic use , Amoxicillin/therapeutic use , Metronidazole/therapeutic use , Tetracycline/therapeutic use , Anti-Infective Agents/therapeutic use , Treatment Outcome , Quinolones/therapeutic use , Drug Therapy, Combination , RegistriesABSTRACT
BACKGROUND AND AIMS: Patients with inflammatory bowel disease [IBD] have an attenuated response to initial COVID-19 vaccination. We sought to characterize the impact of IBD and its treatment on responses after the third vaccine against SARS-CoV-2. METHODS: This was a prospective multicentre observational study of patients with IBD [nâ =â 202] and healthy controls [HC, nâ =â 92]. Serological response to vaccination was assessed by quantification of anti-spike protein [SP] immunoglobulin [Ig]G levels [anti-SPIgG] and in vitro neutralization of binding to angiotensin-converting enzyme 2 [ACE2]. Peripheral blood B-cell phenotype populations were assessed by flow cytometry. SARS-CoV-2 antigen-specific B-cell responses were assessed in ex vivo culture. RESULTS: Median anti-SP IgG post-third vaccination in our IBD cohort was significantly lower than HCs [7862 vs 19 622 AU/mL, pâ <â 0.001] as was ACE2 binding inhibition [pâ <â 0.001]. IBD patients previously infected with COVID-19 [30%] had similar quantitative antibody response as HCs previously infected with COVID-19 [pâ =â 0.12]. Lowest anti-SP IgG titres and neutralization were seen in IBD patients on anti-tumour necrosis factor [anti-TNF] agents, without prior COVID-19 infection, but all IBD patients show an attenuated vaccine response compared to HCs. Patients with IBD have reduced memory B-cell populations and attenuated B-cell responses to SARS-CoV-2 antigens if not previously infected with COVID-19 [pâ =â 0.01]. Higher anti-TNF drug levels and zinc levels <65 ng/ml were associated with significantly lower serological responses. CONCLUSIONS: Patients with IBD have an attenuated response to three doses of SARS-CoV-2 vaccine. Physicians should consider patients with higher anti-TNF drug levels and/or zinc deficiency as potentially at higher risk of attenuated response to vaccination.
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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.
Subject(s)
Colorectal Neoplasms , Early Detection of Cancer , Humans , United States , Cross-Sectional Studies , Surveys and Questionnaires , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/prevention & control , Mass Screening , Occult Blood , ColonoscopyABSTRACT
BACKGROUND AND AIMS: The optimal management of naïve and not naïve Helicobacter pylori patients remains unclear. Therefore, it is essential to evaluate whether the actual clinical practice mirrors the indications suggested by the guidelines. This study aimed to assess the effectiveness and the safety of the empirical first- and second-line treatments prescribed to patients enroled at Italian centres participating in the European Registry on H. pylori Management (Hp-EuReg). METHODS: The Hp-EuReg is an international multicentre prospective non-interventional registry starting in 2013 aiming to evaluate the management of H. pylori infection by European gastroenterologists. Patients were registered in an e-CRF by AEG-REDCap. Variables assessed included demographics, previous eradication attempts, treatment regimen, effectiveness, and tolerance. RESULTS: Overall, 3723 patients from 2013 to February 2021 were included: 2996 and 727 received an empirical first- and second-line treatment, respectively. According to the modified ITT analysis, among the first-line regimens, only the bismuth quadruple therapy with three-in-one-single capsule (BQT-TSC), the concomitant, and the sequential treatment - all lasting 10 days - achieved an eradication rate >90%. Among the second-line regimens, only the 10-day BQT-TSC reported an effectiveness >90%. High-dose PPI twice daily also significantly increased the effectiveness of some therapies. The BQT-TSC was the regimen with the highest incidence of adverse events. CONCLUSIONS: Only quadruple therapies lasting at least 10 days achieved over 90% eradication rates among the empirical first- and second-line regimens. It remains unclear whether high-dose PPI twice daily can improve the efficacy of quadruple treatment.
Subject(s)
Helicobacter Infections , Helicobacter pylori , Humans , Anti-Bacterial Agents/therapeutic use , Prospective Studies , Proton Pump Inhibitors/therapeutic use , Drug Therapy, Combination , Helicobacter Infections/diagnosis , Helicobacter Infections/drug therapy , Helicobacter Infections/epidemiology , Bismuth/therapeutic use , Italy/epidemiology , RegistriesABSTRACT
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.