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Background: Bismuth quadruple therapies (BQTs) including bismuth, a proton pump inhibitor (PPI) and two antibiotics have been shown to be highly effective for treating Helicobacter pylori infection even in areas of high bacterial antibiotic resistance., Objective: To describe the time trends of use, effectiveness and safety of BQT in Europe using the European Registry on Helicobacter pylori Management (Hp-EuReg)., Design: Patients registered in the Hp-EuReg from 2013 to 2021 who had received BQT were included. The regimens prescribed, the number of eradication attempts, effectiveness, adherence and safety were analysed. The effectiveness was assessed by modified intention to treat (mITT). Time-trend and multivariate analyses were performed to determine variables that predicted treatment success., Results: Of the 49 690 patients included in the Hp-EuReg, 15 582 (31%) had received BQT. BQT use increased from 8.6% of all treatments in 2013 to 39% in 2021. Single-capsule BQT-containing bismuth, metronidazole and tetracycline-plus a PPI (single-capsule BQT, ScBQT) was the most frequent treatment mode (43%). Schemes that obtained an effectiveness above 90% were the 10-day ScBQT and 14-day BQT using tetracycline plus metronidazole, or amoxicillin plus either clarithromycin or metronidazole. Only ScBQT achieved above 90% cure rates in all the geographical areas studied. Using the ScBQT scheme, adherence, the use of standard or high-dose PPIs, 14-day prescriptions and the use of BQT as first-line treatment were significantly associated with higher mITT effectiveness., Conclusion: The use of BQT increased notably in Europe over the study period. A 10-day ScBQT was the scheme that most consistently achieved optimal effectiveness., Trial Registration Number: NCT02328131., Competing Interests: Competing interests: XC has received research grants and fees for lectures from Allergan. JPG has served as speaker, consultant and advisory member for or has received research funding from Mayoly Spindler, Allergan, Diasorin, Richen, Biocodex and Juvisé. OPN received research funding from Allergan, Mayoly Spindler, Richen, Biocodex and Juvisé. DSB served as a lecturer for Astellas, AstraZeneca, KRKA and Abbott. FM is a consultant for PHATHOM, DaVoltera and has received grants from Allergan, bioMerieux and Mobidiag. The remaining authors declare no conflict of interest., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Background: The recommended schedule for single capsule bismuth quadruple therapy (scBQT, Pylera) includes a proton pump inhibitor (PPI) two times a day and three scBQT capsules four times a day. Four times a day treatments are inconvenient and reduce adherence. In contrast, adherence improves with three times a day schedules. In clinical practice, many gastroenterologists use four capsule scBQT three times a day. However, the effectiveness and safety of this latter approach remain uncertain., Aim: To assess the effectiveness and safety of scBQT administered three times a day in the patients included in the European Registry on Helicobacter pylori Management (Hp-EuReg)., Methods: All Spanish adult patients registered in the Asociación Española de Gastroenterología Research Electronic Data Capture (REDCap) database from June 2013 to March 2021 receiving 10-day scBQT were analysed. Modified intention-to-treat effectiveness, adherence and the safety of scBQT given three times a day were calculated and compared with the four times a day schedule. A multivariate analysis was performed to determine independent factors predicting cure of the infection., Results: Of the 3712 cases, 2516 (68%) were four times a day and 1196 (32%) three times a day. Mean age was 51 years, 63% were women and 15% had a peptic ulcer. The three times a day schedule showed significantly better overall cure rates than four times a day (1047/1112, 94%; 95% CI 92.7 to 95.6 vs 2207/2423, 91%; 95% CI 89.9 to 92.2, respectively, p=0.002). Adherence and safety data were similar for both regimens. In the multivariate analysis, three times a day dosage, first-line therapy, use of standard or high-dose PPIs and adherence over 90% were significantly associated with cure of the infection., Conclusions: ScBQT prescribed three times a day was more effective than the traditional four times a day schedule. No differences were observed in treatment adherence or safety., Competing Interests: Competing interests: XC has received research grants and fees for lectures from Allergan. JPG has served as speaker, consultant and advisory member for or has received research funding from Mayoly Spindler, Allergan, Diasorin, Gebro Pharma and Richen. OPN received research funding from Allergan and Mayoly Spindler. Dr Bordin served as a lecturer for Astellas, AstraZeneca, KRKA, and Abbott. FM is a consultant for PHATHOM and DaVoltera and has received grants from Allergan, bioMerieux and Mobidiag. The remaining authors declare no conflict of interest., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Peptic ulcer disease is a frequent pathology; although the incidence has decreased in recent years, it continues to be an important cause of morbidity and mortality associated with high healthcare costs. The most important risk factors are Helicobacter pylori(H. pylori) infection and the use of non-steroidal anti-inflammatory drugs. Most patients with peptic ulcer disease remain asymptomatic, with dyspepsia being the most frequent and often characteristic symptom. It can also debut with complications such as upper gastrointestinal bleeding, perforation or stenosis. The diagnostic technique of choice is upper gastrointestinal endoscopy. Treatment with proton pump inhibitors, eradication of H. pylori and avoiding the use of non-steroidal anti-inflammatory drugs are the basis of treatment. However, prevention is the best strategy, it includes an adequate indication of proton pump inhibitors, investigation and treatment of H. pylori, avoiding non-steroidal anti-inflammatory drugs or using those that are less gastrolesive., (Copyright © 2023. Published by Elsevier España, S.L.U.)

Background: Helicobacter pylori infection is the most important risk factor for gastric cancer (GC). Human gastric adenocarcinoma develops after long-term H. pylori infection via the Correa cascade. This carcinogenic pathway describes the progression from gastritis to atrophy, intestinal metaplasia (IM), dysplasia and GC. Patients with atrophy and intestinal metaplasia are considered to have precancerous lesions of GC (PLGC). H. pylori eradication and endoscopy surveillance are currently the only interventions for preventing GC. Better knowledge of the biology of human PLGC may help find stratification markers and contribute to better understanding of biological mechanisms. One way to achieve this is by using co-expression network analysis. Weighted gene co-expression network analysis (WGCNA) is often used to identify modules from co-expression networks and relate them to clinical traits. It also allows identification of driver genes that may be critical for PLGC., Aim: The purpose of this study was to identify co-expression modules and differential gene expression in dyspeptic patients at different stages of the Correa pathway., Methods: We studied 96 gastric biopsies from 78 patients that were clinically classified as: non-active (n = 10) and chronic-active gastritis (n = 20), atrophy (n = 12), and IM (n = 36). Gene expression of coding RNAs was determined by microarrays and non-coding RNAs by RNA-seq. The WGCNA package was used for network construction, module detection, module preservation and hub and driver gene selection., Results: WGCNA identified 20 modules for coding RNAs and 4 for each miRNA and small RNA class. Modules were associated with antrum and corpus gastric locations, chronic gastritis and IM. Notably, coding RNA modules correlated with the Correa cascade. One was associated with the presence of H. pylori. In three modules, the module eigengene (ME) gradually increased in the stages toward IM, while in three others the inverse relationship was found. One miRNA module was negatively correlated to IM and was used for a mRNA-miRNA integration analysis. WGCNA also uncovered driver genes. Driver genes show both high connectivity within a module and are significantly associated with clinical traits. Some of those genes have been previously involved in H. pylori carcinogenesis, but others are new. Lastly, using similar external transcriptomic data, we confirmed that the discovered mRNA modules were highly preserved., Conclusion: Our analysis captured co-expression modules that provide valuable information to understand the pathogenesis of the progression of PLGC., Competing Interests: Declaration of Competing Interest The authors declare no competing interest., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Helicobacter pylori infection is very common in the Spanish population and represents the main cause of chronic gastritis, peptic ulcer, and gastric cancer. The last iteration of Spanish consensus guidelines on H. pylori infection was conducted in 2016. Recent changes in therapeutic schemes along with increasing supporting evidence were key for developing the V Spanish Consensus Conference (May 2021). Fourteen experts performed a systematic review of the scientific evidence and developed a series of recommendations that were subjected to an anonymous Delphi process of iterative voting. Scientific evidence and the strength of the recommendation were classified using GRADE guidelines. An eradication therapy, when prescribed empirically, is considered acceptable when it reliably achieves, or preferably surpass, 90% cure rates. Currently, only quadruple therapies (with or without bismuth) and generally lasting 14 days, accomplish this goal in first- and second-line therapies. A non-bismuth quadruple concomitant regimen (proton pump inhibitor, clarithromycin, amoxicillin, and metronidazole) or a quadruple bismuth-based combination (proton pump inhibitor, bismuth, tetracycline, and metronidazole), are recommended as first-line regimens. Rescue therapies after eradication failure and management of H. pylori infection in peptic ulcer disease were also reviewed., (Copyright © 2021 Elsevier España, S.L.U. All rights reserved.)

Introduction: Gastric premalignant conditions (GPC) surveillance has been proposed to improve the prognosis of gastric cancer (GC), but the early GC detection rate remaining low, and missing GC during an esophago-gastro-duodenoscopy is still a problem. We aimed to explore the gastroenterologists' attitudes on the detection and management of GPC., Methods: A cross-sectional study was designed based on a survey among gastroenterologists from Asociación Española de Gastroenterología., Results: The participation rate was 12% (146/1243). Eighty-one percent worked at secondary or tertiary-care hospitals with the capability to perform mucosectomy (80%), but with a lesser availability of endoscopic submucosal dissection (35%). Most respondents had high-definition endoscopes (88%), and virtual chromoendoscopy (86%), but during performing an upper endoscopy, 34% never or rarely use chromoendoscopy, and 73% apply a biopsy protocol often/very often when atrophy or intestinal metaplasia (IM) is suspected. Half of the respondents self-reported their ability to recognize atrophy or IM ≤7 (on a scale from 0 to 10), whereas ≤6 for dysplasia or early GC. Helicobacter pylori infection is eradicated and verified by ≥90%. Endoscopic surveillance of atrophy/IM is performed by 62%. An immediate endoscopy for dysplasia is not always performed. For low-grade dysplasia, 97.6% consider endoscopic management, but for high-grade dysplasia, 23% regard gastric surgery., Conclusion: There is a wide variability in the detection and management of GPC among Spanish gastroenterologists, and compliance with guidelines and biopsy protocols could be improved. Performance of high-quality gastroscopies including use of virtual chromoendoscopy, that might allow an improvement in the GPC detection, needs also to be generalized., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Helicobacter pylori infection is very common in the Spanish population and represents the main cause of chronic gastritis, peptic ulcer, and gastric cancer. The last iteration of Spanish consensus guidelines on H. pylori infection was conducted in 2016. Recent changes in therapeutic schemes along with increasing supporting evidence were key for developing the V Spanish Consensus Conference (May 2021). Fourteen experts performed a systematic review of the scientific evidence and developed a series of recommendations that were subjected to an anonymous Delphi process of iterative voting. Scientific evidence and the strength of the recommendation were classified using GRADE guidelines. An eradication therapy, when prescribed empirically, is considered acceptable when it reliably achieves, or preferably surpass, 90% cure rates. Currently, only quadruple therapies (with or without bismuth) and generally lasting 14 days, accomplish this goal in first- and second-line therapies. A non-bismuth quadruple concomitant regimen (proton pump inhibitor, clarithromycin, amoxicillin, and metronidazole) or a quadruple bismuth-based combination (proton pump inhibitor, bismuth, tetracycline, and metronidazole), are recommended as first-line regimens. Rescue therapies after eradication failure and management of H. pylori infection in peptic ulcer disease were also reviewed.

Introduction: Helicobacter pylori-infected individuals may present low-density infection, undetectable by conventional tests such as histology, rapid urease test, or urea breath test. Droplet digital polymerase chain reaction (ddPCR) is more sensitive than other polymerase chain reaction methods. We aimed to evaluate the ability of ddPCR to detect H. pylori infection in patients diagnosed as negative by conventional tests., Methods: Dyspeptic patients (n = 236) were tested for H. pylori by histology, urea breath test, and rapid urease test. Patients were classified as having 3 positive (n = 25, control group), 2 positive (n = 12), one positive (n = 41), or zero positive (n = 158) diagnostic tests. DNA was extracted from gastric biopsies. Triplicate ddPCR testing for each of the 16S rDNA, ureA, and vacA(s) genes was performed using a QX200 ddPCR system (Bio-Rad). A gene was considered positive when detected by at least 2 of 3 repeated ddPCRs. H. pylori positivity was defined as having 2 or more positive genes., Results: All the biopsies of the control patients were positive for all 3 16S rDNA, ureA, and vacA(s) genes. H. pylori infection was detected in 57 (36%), 22 (54%), and 9 (75%) patients with zero, 1, and 2 positive diagnostic tests, respectively. The density of infection was 5, 121, 599, and 3,133 copies of H. pylori genome equivalents for patients with zero, 1, and 2 of 3 positive test results and for the control group, respectively., Discussion: ddPCR detected low-density "occult" H. pylori infection in a significant proportion (36%) of patients diagnosed as negative by conventional methods. The number of conventional positive tests was related to the density of infection.

Background: At present only monoclonal EIA (enzyme-immunoassay) stool antigen-tests have obtained optimal accuracy in the diagnosis of Helicobacter pylori. Our aim was to evaluate the accuracy of two stool antigen-tests, the validated Premier Platinum HpSA PLUS (EIA test) and the newly available ImmunoCard STAT! HpSA HD (rapid test) for the initial diagnosis and the confirmation of eradication of H. pylori infection., Patients and Methods: Patients with indication of H. pylori diagnosis, or confirmation after treatment were included. Data were coded to protect personal data and ensure blindness between tests. Accuracy was considered as coincident diagnosis with the gold standard ( 13 C-urea breath test, UBT). The EIA was used as a bench standard. All stool tests were performed in duplicate., Results: 264 patients completed the protocol (100 naïve, 164 post-eradication). Average age was 52 years, 61% women, 11% ulcer. Positive diagnoses by UBT were 41% for naïve and 17% for post-eradication. Overall ImmunoCard and EIA accuracies were respectively 91% (95%C.I.=88-94%) and 89% (86-93%), sensitivities 72% (67-78%) and 72% (67-78%), and specificities 98% (96-100%), and 95% (92-97%). Concordance between ImmunoCard and EIA was 95% (93-98%)., Discussion: Our results indicate that the newly available ImmunoCard rapid stool antigen-test achieves 90% accuracy, with high specificity but suboptimal sensitivity. The ImmunoCard attained equivalent accuracies as the EIA bench standard, with 95% concordance., (Copyright © 2019 Elsevier España, S.L.U. All rights reserved.)

Background: Susceptibility-guided treatment has been proposed as a way to improve Helicobacter pylori eradication rates. Evidence on its efficacy for rescue therapy is very scarce. The aim of this study was to indirectly assess the applicability and effectiveness of susceptibility-guided treatment by evaluating (a) the rate of acceptance of endoscopy, (b) its success in detecting resistances, and (c) infection cure rates in patients harboring strains found to be susceptible to the antibiotics administered in clinical trials in which the efficacy of second-line treatments was reported., Methods: A systematic review of studies evaluating second-line H pylori treatment was carried out in multiple databases. Studies reporting antibiotic susceptibility evaluation and/or cure rates in patients harboring sensitive and resistant strains were selected. Data were extracted in duplicate., Results: The systematic review identified 36 eligible studies. Acceptance was evaluated in only one study of 60 patients, of whom only 38 agreed to endoscopy. Among the 2890 patients who received endoscopy and culture, resistances were finally determined in 86.5%. Cure rate was 72.5% in the 113 patients harboring a clarithromycin-susceptible strain after previous clarithromycin treatment, 93.5% in the 765 patients harboring a metronidazole-susceptible strain, and 83.8% in the 192 patients harboring a levofloxacin-susceptible strain. No studies with repeated administration of levofloxacin or metronidazole were found., Conclusion: Even if the culture shows a clarithromycin-sensitive strain, repeating clarithromycin after a first failure should be discouraged. Susceptibility-guided treatment alone did not achieve adequate cure rates for rescue therapies. Additional measures are needed to design rescue treatments that consistently achieve excellent cure rates., (© 2019 John Wiley & Sons Ltd.)

There are no systematic data on the rates of antibiotic resistance after the failure of a first eradication treatment. The objective of this study was to determine the prevalence of secondary resistance to antibiotics by conducting a systematic review of studies evaluating the secondary resistance of Helicobacter pylori. We identified 31 studies (2,787 patients). Resistance was determined in 1,764 patients. A percentage of 99.1 of patients received clarithromycin as first-line treatment and 58.7% developed resistance. A percentage of 24.3 received metronidazole and 89.7% developed resistance. Secondary resistance to amoxicillin was extremely rare. Secondary resistance after first-line treatment was very common. These findings support the recommendation not to repeat clarithromycin or metronidazole after the failure of a first eradication treatment., (Copyright © 2018 Elsevier España, S.L.U. All rights reserved.)

More than 30 years after its discovery, Helicobacter pylori (H. pylori) infection remains the most common cause of gastric and duodenal diseases. H. pylori is the leading cause of chronic gastritis, peptic ulcer, gastric MALT lymphoma and gastric adenocarcinoma. Several consensuses have recently been published on the management of H. pylori infection. The general guidelines of the Spanish consensus, the Toronto Consensus and the Maastricht V Consensus of 2016 are similar but concrete recommendations can vary significantly. In addition, the recommendations of some of these consensuses are decidedly complex. This position paper from the Catalan Society of Digestology is an update of evidence-based recommendations on the management and treatment of H. pylori infection. The aim of this document is to review this information in order to make recommendations for routine clinical practice that are simple, specific and easily applied to our setting., (Copyright © 2018 Elsevier España, S.L.U. All rights reserved.)

Introduction: The efficacy of currently recommended third-line therapies for Helicobacter pylori is suboptimal, even that of culture-guided treatments. Resistance to multiple antibiotics is the major factor related to treatment failure. The aim of this study was to evaluate the effectiveness and safety of a 14-day therapy using high-dose of amoxicillin, metronidazole and esomeprazole., Material and Methods: Multicenter open-label study as a register in routine clinical practice in patients with two previous failures of eradication therapy. A triple therapy with esomeprazole 40 mg b.d., amoxicillin 1 g t.d.s and metronidazole 500 mg t.d.s for 2 weeks was administered as a third-line therapy after a first treatment including clarithromycin and a second treatment including a quinolone. Helicobacter pylori status was determined by either histology or 13 C-UBT both before and after treatment., Results: A total of 68 patients were included in this study. An interim analysis showed that only three out of eight patients who had received metronidazole in previous eradication regimens were cured (37%, 95% CI 8-75); as a result, after this interim analysis only metronidazole-naïve patients were included. The ITT eradication rate in metronidazole-naive patients was 64% (95% CI 51-76). Adverse events occurred in 58% of patients, all of them mild-to-moderate. Two patients (3%) did not complete >90% of the treatment because of side effects. No severe adverse events occurred., Conclusion: Cure rates of this 14-day schedule using high-dose esomeprazole, amoxicillin and metronidazole as a third-line eradication regimen were suboptimal, especially in patients who had received metronidazole in previous failed eradication regimens., (© 2017 John Wiley & Sons Ltd.)

Helicobacter pylori approximately infect 50% of Spanish population and causes chronic gastritis, peptic ulcer and gastric cancer. Until now, three consensus meetings on H.pylori infection had been performed in Spain (the last in 2012). The changes in the treatment schemes, and the increasing available evidence, have justified organizing the IVSpanish Consensus Conference (March 2016), focused on the treatment of this infection. Nineteen experts participated, who performed a systematic review of the scientific evidence and developed a series of recommendation that were subjected to an anonymous Delphi process of iterative voting. Scientific evidence and the strength of the recommendation were classified using GRADE guidelines. As starting point, this consensus increased the minimum acceptable efficacy of recommended treatments that should reach, or preferably surpass, the 90% cure rate when prescribed empirically. Therefore, only quadruple therapies (with or without bismuth), and generally lasting 14 days, are recommended both for first and second line treatments. Non-bismuth quadruple concomitant regimen, including a proton pump inhibitor, clarithromycin, amoxicillin and metronidazole, is recommended as first line. In the present consensus, other first line alternatives and rescue treatments are also reviewed and recommended., (Copyright © 2016 Elsevier España, S.L.U., AEEH y AEG. All rights reserved.)

Background: Helicobacter pylori infects human stomachs of over half the world's population, evades the immune response and establishes a chronic infection. Although most people remains asymptomatic, duodenal and gastric ulcers, MALT lymphoma and progression to gastric cancer could be developed. Several virulence factors such as flagella, lipopolysaccharide, adhesins and especially the vacuolating cytotoxin VacA and the oncoprotein CagA have been described for H. pylori. Despite the extensive published data on H. pylori, more research is needed to determine new virulence markers, the exact mode of transmission or the role of multiple infection., Materials and Methods: Amplification and sequencing of six housekeeping genes (amiA, cgt, cpn60, cpn70, dnaJ, and luxS) related to H. pylori pathogenesis have been performed in order to evaluate their usefulness for the specific detection of H. pylori, the genetic discrimination at strain level and the detection of multiple infection. A total of 52 H. pylori clones, isolated from 14 gastric biopsies from 11 patients, were analyzed for this purpose., Results: All genes were specifically amplified for H. pylori and all clones isolated from different patients were discriminated, with gene distances ranged from 0.9 to 7.8%. Although most clones isolated from the same patient showed identical gene sequences, an event of multiple infection was detected in all the genes and microevolution events were showed for amiA and cpn60 genes., Conclusions: These results suggested that housekeeping genes could be useful for H. pylori detection and to elucidate the mode of transmission and the relevance of the multiple infection., (© 2016 John Wiley & Sons Ltd.)

Background: Due to clarithromycin resistance, the current efficacy of Helicobacter pylori first-line triple therapies including clarithromycin is low. It seems reasonable to explore alternative clarithromycin-free therapies., Objectives: The objective of this study was to evaluate the efficacy of triple therapy including a proton-pump inhibitor (PPI), amoxicillin and metronidazole (PAM) as first-line H. pylori therapy by systematic review and meta-analysis., Methods: Studies evaluating PAM in adult patients were included. Meta-analyses comparing PAM with other treatments were performed. The primary endpoint was the ITT eradication rate for H. pylori first-line treatment. In addition, sensitivity analyses ascertained the effects of treatment schedule, dosage and duration on cure rates., Results: Ninety-four studies (8061 patients) were included. Meta-analyses comparing PAM versus clarithromycin-including triple therapies showed a significant difference in favour of PPI, amoxicillin and clarithromycin (PAC) (70% versus 77.1%; OR = 0.70, 95% CI = 0.56-0.88) and PPI, metronidazole and clarithromycin (PMC) therapy (66.4% versus 77.7%; OR = 0.55, 95% CI = 0.39-0.76). Sensitivity analyses showed a similar efficacy of PAM versus PAC when drugs were administered for 14 days (80% versus 84%; OR = 0.70, 95% CI = 0.44-1.12). There were not enough studies to perform further comparisons. Number of antibiotic doses (P = 0.012), length of treatment (P < 0.001) and use of high metronidazole doses (P = 0.021) were related to higher cure rates in the sensitivity analysis including observational studies., Conclusions: PAM was less efficacious than clarithromycin-including triple therapies. However, its efficacy was similar to that of PAC when drugs were administered for 14 days, although ITT cure rates did not reach 90%. Use of 14 day, thrice daily and high-metronidazole-dose PAM treatments markedly increased the cure rate., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Immunochromatographic tests need to be improved in order to enhance their reliability. Recently, several new kits have appeared on the market. The objective was to evaluate the diagnostic accuracy of three monoclonal rapid stool tests - the new Uni-Gold™ H.pylori Antigen (Trinity Biotech, Ireland), the RAPID Hp StAR (Oxoid Ltd., UK) and the ImmunoCard STAT! HpSA (Meridian Diagnostics, USA) - for detecting H. pylori infection prior to eradication treatment., Design and Methods: Diagnostic accuracy (sensitivity and specificity) and reliability (concordance between observers) were evaluated in 250 untreated consecutive dyspeptic patients. The gold standard for diagnosing H. pylori infection was defined as the concordance of two or more of rapid urease test (RUT), histopathology and urease breath test (UBT) or positive culture in isolation. Readings of immunochromatographic tests were performed by two different observers. Sensitivity, specificity, positive and negative predictive values and 95% confidence intervals were calculated. Sensitivity and specificity were compared using the McNemar test., Results: The three tests showed a good correlation, with Kappa values>0.9. RAPID Hp StAR had a sensitivity of 91%-92% and a specificity ranging from 77% to 85%. Its sensitivity was higher than that of Uni-Gold™ H.pylori Antigen and ImmunoCard STAT! HpSA (p<0.01). Uni-Gold™ H.pylori Antigen kit showed a sensitivity of 83%, similar to ImmunoCard STAT! HpSA. Specificity of Uni-Gold™ H.pylori Antigen approached 90% (87-89%) and was superior to that of RAPID Hp StAR (p<0.01)., Conclusions: Uni-Gold™ H.pylori Antigen and ImmunoCard STAT! HpSA present similar levels of diagnostic accuracy. RAPID Hp StAR was the most sensitive but less reliable of the three immunochromatographic stool tests. None are as accurate and reliable as UBT, RUT and histology., (Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Laboratory-based chemiluminescence immunoassays (CLIA) are widely used in clinical laboratories. Some years ago, a CLIA test was developed for the detection of Helicobacter pylori in stool samples, known as LIAISON H. pylori SA, but little information on its use has been reported. To evaluate the accuracy of the LIAISON H. pylori SA assay for diagnosing H. pylori infection prior to eradication treatment. Diagnostic reliability was evaluated in 252 untreated consecutive patients with dyspepsia. The gold standard for diagnosing H. pylori infection was defined as the concordance of the rapid urease test (RUT), histopathology and urea breath test (UBT). The CLIA assay was performed according to the manufacturer's instructions. Sensitivity, specificity, positive and negative predictive values, and 95% CIs were calculated. According to the gold standard selected, 121 patients were positive for H. pylori infection and 131 negative. LIAISON H. pylori SA had a sensitivity of 90.1% and a specificity of 92.4%, with positive and negative predictive values of 91.6% and 90.1%, respectively. The accuracy of the LIAISON H. pylori SA chemiluminescent diagnostic assay seems comparable to that of ELISA or the best-performing LFIAs. Its sensitivity and specificity, however, seem slightly lower than those of histology, RUT or UBT. The advantages of the assay are that it is cheap, automated, and minimally labor-intensive., (Copyright © 2016 American Federation for Medical Research.)

Background: The cure rate of standard triple therapy for Helicobacter pylori infection is unacceptably low. Susceptibility-guided therapies (SGTs) have been proposed as an alternative to standard empirical treatments. The aim of this study was to perform a systematic review and meta-analysis evaluating the efficacy of SGTs., Methods: A systematic search was performed in multiple databases. Randomized controlled trials comparing cure rates of SGTs versus those of empirical therapy were selected and analysed separately for first- and second-line treatments. A meta-analysis was performed using risk ratio (RR) and number needed to treat (NNT) to measure the effect., Results: Twelve studies were included in the meta-analysis. In first-line treatment, SGT was more efficacious than empirical 7-10 day triple therapy (RR 1.16, 95% CI 1.10-1.23, I (2) = 33%; NNT = 8). Most studies used a 7-10 day triple therapy and randomized the patients after endoscopy and/or culture, thus precluding the comparison of SGT versus non-invasive testing and empirical treatment in clinical practice. For second-line therapy, only four studies were found. Results were highly heterogeneous and no significant differences were found (RR 1.11, 95% CI 0.82-1.51, I (2) = 87%)., Conclusions: Once endoscopy and culture have been performed, SGT is superior to empirical 7 or 10 day triple therapy for first-line treatment. Further studies are needed to evaluate the effectiveness of SGT in clinical practice, especially when compared with currently recommended first-line quadruple therapies., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Proton pump inhibitors (PPI) are a major cause of false-negative Helicobacter pylori test results. Detecting PPI use and stopping it 2 weeks before testing is the preferred approach to improve the reliability of H pylori diagnostic tests. Immunoblot and molecular methods may be useful for the detection of H pylori infection in difficult cases. When conventional tests are negative and eradication is strongly indicated, empirical H pylori treatment should be considered. In this article, an updated critical review of the usefulness of the various invasive and noninvasive tests in the context of extensive PPI use is provided., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: No trial has compared non-bismuth quadruple 'sequential' and 'concomitant' regimens in settings with increasing clarithromycin rates. The study aims to compare the effectiveness and safety of these therapies for Helicobacter pylori treatment., Design: Prospective randomised clinical trial in 11 Spanish hospitals. Patients naïve to eradication therapy with non-investigated/functional dyspepsia or peptic ulcer disease were included. Randomised (1:1) to sequential (omeprazole (20 mg/12 h) and amoxicillin (1 g/12 h) for 5 days, followed by 5 days of omeprazole (20 mg/12 h), clarithromycin (500 mg/12 h) and metronidazole (500 mg/12 h)), or concomitant treatment (same drugs taken concomitantly for 10 days). Eradication was confirmed with (13)C-urea breath test or histology 4 weeks after treatment. Adverse events (AEs) and compliance were evaluated with questionnaires and residual medication count., Results: 338 consecutive patients were randomised. Mean age was 47 years, 60% were women, 22% smokers and 20% had peptic ulcer. Concomitant and sequential eradication rates were, respectively, 87% vs 81% by intention-to-treat (p=0.15) and 91% vs 86% (p=0.131) per protocol. Respective compliances were 83% vs 82%. Treatment-emergent AEs were reported in 59% of patients (no differences found between treatments). AEs were mostly mild (60%), and average length was 6.1 days, causing discontinuation only in 12 patients. Multivariate analysis: 'concomitant' treatment showed an OR of 1.5 towards better eradication rate in a borderline significance CI (95% CI 0.9 to 2.8)., Conclusions: Concomitant therapy led to a non-statistically significant advantage (5%) over sequential therapy, coming closer to 90% cure rates. Both therapies showed an acceptable safety profile. ClincialTrials.gov: NCT01273441.

Background: The optimal duration for Helicobacter pylori (H. pylori) eradication therapy is controversial, with recommendations ranging from 7 to 14 days. Several systematic reviews have attempted to address this issue but have given conflicting results and limited their analysis to proton pump inhibitor (PPI), two antibiotics (PPI triple) therapy. We performed a systematic review and meta-analysis to investigate the optimal duration of multiple H. pylori eradication regimens., Objectives: The primary objective was to assess the relative effectiveness of different durations (7, 10 or 14 days) of a variety of regimens for eradicating H. pylori. The primary outcome was H. pylori persistence. The secondary outcome was adverse events., Search Methods: The Cochrane Library, MEDLINE, EMBASE, and CINAHL were searched up to December 2011 to identify eligible randomised controlled trials (RCTs). We also searched the proceedings of six conferences from 1995 to 2011, dissertations and theses, and grey literature. There were no language restrictions applied to any search., Selection Criteria: Only parallel group RCTs assessing the efficacy of one to two weeks duration of first line H. pylori eradication regimens in adults were eligible. Within each regimen, the same combinations of drugs at the same dose were compared over different durations. Studies with at least two arms comparing 7, 10, or 14 days were eligible. Enrolled participants needed to be diagnosed with at least one positive test for H. pylori on the basis of a rapid urease test (RUT), histology, culture, urea breath test (UBT), or a stool antigen test (HpSA) before treatment. Eligible trials needed to confirm eradication of H. pylori as their primary outcome at least 28 days after completion of eradication treatment. Trials using only serology or a polymerase chain reaction (PCR) to determine H. pylori infection or eradication were excluded., Data Collection and Analysis: Study eligibility and data extraction were performed by two independent review authors. Data analyses were performed within each type of intervention, for both primary and secondary outcomes. The relative risk (RR) and number needed to treat (NNT)/number needed to harm (NNTH) according to duration of therapy were calculated using the outcomes of H. pylori persistence and adverse events. A random-effects model was used. Subgroup analyses and sensitivity analyses were planned a priori., Main Results: In total, 75 studies met the inclusion criteria. Eight types of regimens were reported with at least two comparative eligible durations. They included: PPI + two antibiotics triple therapy (n = 59), PPI bismuth-based quadruple therapy (n = 6), PPI + three antibiotics quadruple therapy (n = 1), PPI dual therapy (n = 2), histamine H2-receptor antagonist (H₂RA) bismuth quadruple therapy (n = 3), H₂RA bismuth-based triple therapy (n = 2), H₂RA + two antibiotics triple therapy (n = 3), and bismuth + two antibiotics triple therapy (n = 2). Some studies provided data for more than one regimen or more than two durations.For the PPI triple therapy, 59 studies with five regimens were reported: PPI + clarithromycin + amoxicillin (PCA); PPI + clarithromycin + a nitroimidazole (PCN); PPI + amoxicillin + nitroimidazole (PAN); PPI + amoxicillin + a quinolone (PAQ); and PPI + amoxicillin + a nitrofuran (PANi). Regardless of type and dose of antibiotics, increased duration of PPI triple therapy from 7 to 14 days significantly increased the H. pylori eradication rate (45 studies, 72.9% versus 81.9%), the RR for H. pylori persistence was 0.66 (95% CI 0.60 to 0.74), NNT was 11 (95% CI 9 to 14). Significant effects were seen in the subgroup of PCA (34 studies, RR 0.65, 95% CI 0.57 to 0.75; NNT 12, 95% CI 9 to 16); PAN (10 studies, RR 0.67, 95% CI 0.52 to 0.86; NNT = 11, 95% CI 8 to 25); and in PAQ (2 studies, RR 0.37, 95% CI 0.16 to 0.83; NNT 3, 95% CI 2 to 10); but not in PCN triple therapy (4 studies, RR 0.87, 95% CI 0.71 to 1.07). Significantly increased eradication rates were also seen for PPI triple therapy with 10 versus 7 days (24 studies, 79.9% versus 75.7%; RR 0.80, 95% CI 0.72 to 0.89; NNT 21, 95% CI 15 to 38) and 14 versus 10 days (12 studies, 84.4% versus 78.5%; RR 0.72, 95% CI 0.58 to 0.90; NNT 17, 95% CI 11 to 46); especially in the subgroup of PAC for 10 versus 7 days (17 studies, RR 0.80, 95% CI 0.70 to 0.91) and for 14 versus 10 days (10 studies, RR 0.69, 95% CI 0.52 to 0.91). A trend towards increased H. pylori eradication rates was seen with increased duration of PCN for 10 versus 7 days, and of PAN for 10 versus 7 days and 14 versus 10 days, though this was not statistical significant. The proportion of patients with adverse events, defined by authors, was marginally significantly increased only between 7 days and 14 days (15.5% versus 19.4%; RR 1.21, 95% CI 1.06 to 1.37; NNTH 31, 95% CI 18 to 104) but not for other duration comparisons. The proportion of patients discontinuing treatment due to adverse events was not significantly different between treatment durations.Only limited data were reported for different durations of regimens other than PPI triple therapy. No significant difference of the eradication rate was seen for all regimens according to different durations except for H₂RA bismuth quadruple therapy, where a significantly higher eradication rate was seen for 14 days versus 7 days, however only one study reported outcome data., Authors' Conclusions: Increasing the duration of PPI-based triple therapy increases H. pylori eradication rates. For PCA, prolonging treatment duration from 7 to 10 or from 10 to 14 days is associated with a significantly higher eradication rate. The optimal duration of therapy for PCA and PAN is at least 14 days. More data are needed to confirm if there is any benefit of increasing the duration of therapy for PCN therapy. Information is limited for regimens other than PPI triple therapy; more studies are needed to draw meaningful conclusions for optimal duration of other H. pylori eradication regimens.

About half of the world's population is currently infected with Helicobacter pylori, which is involved in the development of several gastro-duodenal pathologies. The increasing number of antibiotic resistance reduces the effectiveness of the first-line therapy, so new strategies to improve the H. pylori eradication rates are needed. Antimicrobial Photodynamic Therapy (APDT) benefits from photogenerated reactive oxygen species, such as singlet oxygen, which inactivate microorganisms by means of photosensitising dyes and visible light. Therefore, it could be a suitable alternative for H. pylori eradication in the gastro-duodenal tract, particularly in patients infected with antibiotic resistant strains. We evaluated APDT against H. pylori, in vitro, using a new photosensitising material (PSM) based on a ruthenium(II) complex covalently bound to micrometric glass beads. Five H. pylori isolates (classified according to cagA genotype, and metronidazole-clarithromycin resistance) were used. Bacteria were mixed with the PSM and incubated in the dark or illuminated by blue light. Aliquots (min 1', 2', 5', 15' and 30') were cultured and colonies were counted after 2-3 days. A 99.99999% decrease was detected in the number of colonies in the irradiated wells where the bacterium was mixed with the PSM, compared to non-illuminated wells or with irradiated wells without PSM. It was also confirmed that DNA is a molecular target for oxidant species released during APDT (evaluated by alkaline gel electrophoresis after endonuclease III incubation, ureC and cagA RT-PCR, and bacterial fingerprint). Results were independent of cagA gene and antibiotic resistances., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

A limited amount of new information was published in the field of diagnosis and epidemiology of Helicobacter pylori this last year. Besides some improvement in current tests, it is interesting to note the attempts to identify severe disease, for example gastric cancer, by breath analysis using nanomaterial-based sensors. In contrast, the predictive value for gastric cancer and atrophy of pepsinogen determinations was found inadequate. Prevalence studies of H. pylori infection have been carried out in adults and children around the world in the general population but also in specific communities. The usual risk factors were found. In addition, a Japanese study highlighted the role of grandmothers in the familial transmission of H. pylori. A study showed that the infection may not always readily establish itself in children, given the number of transient infections observed. It was also noted that after eradication, a first-year relapse is likely to be a recurrence of the previous infection, while later on it is probably a reinfection with a new strain., (© 2013 John Wiley & Sons Ltd.)

Background: Second-line bismuth-containing quadruple therapy is complex and frequently induces adverse effects. A triple rescue regimen containing levofloxacin is a potential alternative; however, resistance to quinolones is rapidly increasing., Aim: To evaluate the efficacy and tolerability of a second-line triple-regimen-containing levofloxacin in patients whose Helicobacter pylori eradication treatment failed and to assess whether the efficacy of the regimen decreases with time., Design: Prospective multicenter study., Patients: In whom treatment with a regimen comprising a proton-pump inhibitor, clarithromycin, and amoxicillin had failed., Intervention: Levofloxacin (500 mg bid), amoxicillin (1 g bid), and omeprazole (20 mg bid) for 10 days., Outcome: Eradication was confirmed using the C-urea breath test 4 to 8 weeks after therapy. Compliance/tolerance: Compliance was determined through questioning and recovery of empty medication envelopes. Incidence of adverse effects was evaluated by means of a questionnaire., Results: The study sample comprised 1000 consecutive patients (mean age, 49 ± 15 y, 42% men, 33% peptic ulcer) of whom 97% took all medications correctly. Per-protocol and intention-to-treat eradication rates were 75.1% (95% confidence interval, 72%-78%) and 73.8% (95% confidence interval, 71%-77%). Efficacy (intention-to-treat) was 76% in the year 2006, 68% in 2007, 70% in 2008, 76% in 2009, 74% in 2010, and 81% in 2011. In the multivariate analysis, none of the studied variables (including diagnosis and year of treatment) were associated with success of eradication. Adverse effects were reported in 20% of patients, most commonly nausea (7.9%), metallic taste (3.9%), myalgia (3.1%), and abdominal pain (2.9%)., Conclusions: Ten-day levofloxacin-containing therapy is an encouraging second-line strategy, providing a safe and simple alternative to quadruple therapy in patients whose previous standard triple therapy has failed. The efficacy of this regimen remains stable with time.

Although the connection of microRNAs (miRNAs) to some diseases is well established, their involvement in chronic infections such as Helicobacter pylori has received less attention. The aim was to compare miRNA expression profiling in patients with duodenal ulcer (DU) due to H. pylori infection with that in infected patients without DU and in uninfected patients. The miRNA expression profile was determined by microarrays in antral mucosal samples from well-characterized dyspeptic patients (n = 46). The most significant set of miRNAs was subsequently analysed in an independent validation group of patients (n = 42). Transcripts for IL8, IL12p40, IL12p35 and IL23p19, the signalling molecules MYD88, GATA6, SOCS2 and STAT6 and H. pylori virulence factors cagA and VacA were analysed. Microarray experiments showed that 17 miRNAs were deregulated in the mucosa of H. pylori-infected patients. No significant differences were observed between normal and DU patients. PCR confirmed the up-regulation of miR-9, miR-146a, miR-155 and miR-650 and the down-regulation of miR-96 and miR-204 in the independent validation set of patients. Importantly, miR-9, miR-96, miR-146a and miR-650 expression was specific to chronic-active gastritis. H. pylori-infected patients showed higher levels of IL8 and IL12p40 mRNAs and lower levels of GATA6 and SOCS2 mRNAs. The antral mucosa of patients with non-active or chronic-active gastritis showed significantly lower levels of GATA6, MYD88, SOCS2 and STAT6 mRNAs compared with patients without gastritis. The down-regulation of these factors was not correlated with the expression of any of the validated miRNAs. The exact role of the miRNA changes observed will require further study., (© 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.)

Objectives: To evaluate the effect of Helicobacter pylori (H. pylori) eradication on ulcer bleeding recurrence in a prospective, long-term study including 1,000 patients., Methods: Patients with peptic ulcer bleeding were prospectively included. Prior non-steroidal anti-inflammatory drug (NSAID) use was not considered exclusion criteria. H. pylori infection was confirmed by rapid urease test, histology, or (13)C-urea breath test. Several eradication therapies were used. Subsequently, ranitidine 150 mg o.d. was administered until eradication was confirmed by (13)C-urea breath test 8 weeks after completing therapy. Patients with therapy failure received a second, third, or fourth course of eradication therapy. Patients with eradication success did not receive maintenance anti-ulcer therapy and were controlled yearly with a repeat breath test. NSAID use was not permitted during follow-up., Results: Thousand patients were followed up for at least 12 months, with a total of 3,253 patient-years of follow-up. Mean age 56 years, 75% males, 41% previous NSAID users. In all, 69% had duodenal ulcer, 27% gastric ulcer, and 4% pyloric ulcer. Recurrence of bleeding was demonstrated in three patients at 1 year (which occurred after NSAID use in two cases, and after H. pylori reinfection in another one), and in two more patients at 2 years (one after NSAID use and another after H. pylori reinfection). The cumulative incidence of rebleeding was 0.5% (95% confidence interval, 0.16-1.16%), and the incidence rate of rebleeding was 0.15% (0.05-0.36%) per patient-year of follow up., Conclusion: Peptic ulcer rebleeding virtually does not occur in patients with complicated ulcers after H. pylori eradication. Maintenance anti-ulcer (antisecretory) therapy is not necessary if eradication is achieved. However, NSAID intake or H. pylori reinfection may exceptionally cause rebleeding in H. pylori-eradicated patients.

Background: Strong acid inhibition using esomeprazole increases cure rates with triple therapy and 10-day treatments are more effective than 7-day ones. The combination of amoxicillin plus metronidazole at full doses, and using a physiologically-correct schedule three times a day, and has been shown to overcome metronidazole resistance and to achieve good eradication rates., Aims: To assess the eradication rate of a new first-line treatment regimen associating strong acid inhibition, amoxicillin and metronidazole and to evaluate tolerance., Methods: Patients from eight hospitals were included. Helicobacter pylori status was assessed by at least one of the following: histology, culture, rapid urease test or urea breath test (UBT). Ten-day treatment was prescribed comprising esomeprazole 40 mg twice a day plus amoxicillin 1 g and metronidazol 500 mg both three times a day. Helicobacter pylori cure was assessed by UBT., Results: A hundred and thirty-six patients were enrolled. Mean age was 52.6 ± 16 years and 59.6% of patients were men. Main indications for treatment were: uninvestigated dyspepsia (13.6%); functional dyspepsia (18.2%); gastric ulcer (21.8%); and duodenal ulcer (39.8%). Helicobacter pylori eradication was achieved in 112 of the 127 patients who returned for follow-up. Eradication rates were 82.4% (95% CI: 74.7-88.1) by intention-to-treat analysis and 88.2% (95% CI: 81.2-92.8) by per protocol. Treatment was well tolerated and no major side effects were reported. Nine patients complained of mild side effects., Conclusions: Cure rates of the combination of esomeprazole, amoxicillin and metronidazole are high and the treatment was well tolerated. This pilot study warrants the comparison of this schedule with current standards., (© 2012 Blackwell Publishing Ltd.)

Background: In some cases, Helicobacter pylori infection persists even after three eradication treatments., Aim: To evaluate the efficacy of an empirical fourth-line rescue regimen with rifabutin in patients with three eradication failures., Design: Multicentre, prospective study., Patients: In whom the following three treatments had consecutively failed: first (PPI + clarithromycin + amoxicillin); second (PPI + bismuth + tetracycline + metronidazole); third (PPI + amoxicillin + levofloxacin)., Intervention: A fourth regimen with rifabutin (150 mg b.d.), amoxicillin (1 g b.d.) and a PPI (standard dose b.d.) was prescribed for 10 days., Outcome: Eradication was confirmed by (13) C-urea breath test 4-8 weeks after therapy. Compliance and tolerance: Compliance was determined through questioning and recovery of empty medication envelopes. Adverse effects were evaluated using a questionnaire., Results: One-hundred patients (mean age 50 years, 39% men, 31% peptic ulcer/69% functional dyspepsia) were included. Eight patients did not take the medication correctly (in six cases due to adverse effects). Per-protocol and intention-to-treat eradication rates were 52% (95% CI = 41-63%) and 50% (40-60%). Adverse effects were reported in 30 (30%) patients: nausea/vomiting (13 patients), asthenia/anorexia (8), abdominal pain (7), diarrhoea (5), fever (4), metallic taste (4), myalgia (4), hypertransaminasemia (2), leucopenia (<1,500 neutrophils) (2), thrombopenia (<150,000 platelets) (2), headache (1) and aphthous stomatitis (1). Myelotoxicity resolved spontaneously in all cases., Conclusions: Even after three previous H. pylori eradication failures, an empirical fourth-line rescue treatment with rifabutin may be effective in approximately 50% of the cases. Therefore, rifabutin-based rescue therapy constitutes a valid strategy after multiple previous eradication failures with key antibiotics, such as clarithromycin, metronidazole, tetracycline and levofloxacin., (© 2012 Blackwell Publishing Ltd.)

Background: Helicobacter pylori infection is the main cause of gastric mucosa-associated lymphoid tissue (MALT) lymphoma., Aim: To review several common misconceptions in the management of H. pylori-associated gastric MALT-lymphoma., Methods: Bibliographical searches were performed in MEDLINE up to June 2011., Results: If adequate diagnostic methods are used, and if only low-grade lymphomas are considered, the prevalence of H. pylori infection is very high (almost 90%). H. pylori eradication is effective in treating approximately 80% of patients with early stage lymphoma. In H. pylori-positive gastric high-grade lymphomas, antibiotic therapy should always be prescribed, as approximately 50% of them regress after H. pylori eradication. Patients with early stage MALT lymphoma negative for H. pylori might still benefit from antibiotic treatment as the sole treatment. Complete remission of gastric MALT lymphoma after H. pylori eradication can take even >12 months. PCR assay for the detection of monoclonal B cells remains positive in many cases after complete remission has been reached. Patients with a persistent clonal band should not be treated unless the lymphoma can be histologically demonstrated. Synchronous occurrence of gastric adenocarcinoma and MALT lymphoma has been repeatedly reported. In some patients in complete remission, eradication of H. pylori does not prevent later development of early gastric cancer. Gastric lymphoma recurrence occurs in some patients after both bacterial and lymphoma regression. H. pylori reinfection does not constitute a prerequisite for lymphoma recurrence., Conclusions: The present article states several misconceptions in the management of H. pylori-associated gastric MALT-lymphoma in clinical practice, reviews the related scientific evidence and proposes the adequate attitude in each case., (© 2011 Blackwell Publishing Ltd.)

Background & Objectives: The aim of this document is to provide a methodological framework and to review key aspects for adequately designing trials to evaluate new treatments for Helicobacter pylori infection., Methods: Non-systematic literature review., Results & Conclusions: Regarding the design of the article, we suggest selecting for future trials drugs to which H. pylori has no significant primary resistances and evaluating therapies with pilot studies before engaging in randomized trials. The manuscript defines how the number and type of H. pylori diagnostic tests necessary before and after the trial depend on the setting and reliability of the tests. It recommends the best methods and timing for H. pylori testing before and after therapy. Other recommendations are using current standard treatments as comparators of new therapies, determining antibiotic sensitivity - whenever useful and possible - using adequate randomization and allocation concealment but not necessarily blinding, and performing an intention-to-treat and a per-protocol analysis. In addition, we give basic tips for reporting and discussing study results., (© 2011 Blackwell Publishing Ltd.)

Background: Traditional standard triple therapy for Helicobacter pylori infection (PPI-clarithromycin-amoxicillin) can easily be converted to non-bismuth quadruple (concomitant) therapy by the addition of a nitroimidazole twice daily., Aim: To critically review evidence on the role of non-bismuth quadruple therapy (PPI-clarithromycin-amoxicillin-nitroimidazole) in the treatment of H. pylori infection., Methods: Bibliographical searches were performed in MEDLINE and relevant congresses., Results: The first randomised comparison of the non-bismuth quadruple therapy and the sequential (PPI-amoxicillin 5days plus PPI-clarithromycin-nitroimidazole 5days) regimens recently concluded that both were similar in terms of efficacy and safety and that the sequential administration protocol may be unnecessarily complex. Several randomised controlled trials (and one meta-analysis) have demonstrated that non-bismuth quadruple therapy is more effective than and is equally well tolerated as standard triple therapy. A meta-analysis of 15 studies (1723 patients) revealed a mean H. pylori cure rate (intention-to-treat) of 90% for non-bismuth quadruple therapy. A tendency towards better results with longer treatments (7-10days vs. 3-5days) has been observed, so it seems reasonable to recommend the length of treatment by achieving maximal cure rates (10days). Clarithromycin resistance may reduce the efficacy of non-bismuth quadruple therapy, although the decrease in eradication rates seems to be far lower than in standard triple therapy. Experience with the non-bismuth quadruple therapy in patients with metronidazole-resistant strains is still very limited., Conclusions: Non-bismuth quadruple (concomitant) therapy appears to be an effective, safe, and well-tolerated alternative to triple therapy and is less complex than sequential therapy. Therefore, this regimen appears well suited for use in settings where the efficacy of triple therapy is unacceptably low., (© 2011 Blackwell Publishing Ltd.)

Objectives: It has been suggested that prevalence of Helicobacter pylori (Hp) in peptic ulcer bleeding (PUB) is lower than that in non-complicated ulcers. As Hp infection is elusive in PUB, we hypothesized that this low prevalence could be related to an insufficiently intensive search for the bacteria. The aim of the study was to evaluate whether the prevalence of Hp in PUB depends on the diagnostic methods used in a given study., Methods: A systematic review was performed of studies assessing the prevalence of Hp infection in patients with PUB. Data were extracted in duplicate. Univariate and multivariate random-effects meta-regression analyses were performed to determine the factors that explained the differences in Hp prevalence between studies., Results: The review retrieved 71 articles, including 8,496 patients. The mean prevalence of Hp infection in PUB was 72%. The meta-regression analysis showed that the most significant variables associated with a high prevalence of Hp infection were the use of a diagnostic test delayed until at least 4 weeks after the PUB episode-odds ratio: 2.08, 95% confidence interval: 1.10-3.93, P=0.024-and a lower mean age of patients-odds ratio: 0.95 per additional year, 95% confidence interval: 0.92-0.99, P=0.008., Conclusions: Studies that performed a delayed test and those including younger patients found a higher prevalence of Hp, approaching that recorded in cases of non-bleeding ulcers. These results suggest that the low prevalence of Hp infection described in PUB may be related to the methodology of the studies and to patients' characteristics, and that the true prevalence of Hp in PUB is still to be determined. Our data also support the recent recommendations of the International Consensus on Non-Variceal Upper Gastrointestinal Bleeding regarding the performance of a delayed diagnostic test when Hp tests carried out during the acute PUB episode are negative.

Background and Aims: Histological and rapid urease tests to detect H. pylori in biopsy specimens obtained during peptic ulcer bleeding episodes (PUB) often produce false-negative results. We aimed to examine whether immunohistochemistry and real-time PCR can improve the sensitivity of these biopsies., Patients and Methods: We selected 52 histology-negative formalin-fixed paraffin-embedded biopsy specimens obtained during PUB episodes. Additional tests showed 10 were true negatives and 42 were false negatives. We also selected 17 histology-positive biopsy specimens obtained during PUB to use as controls. We performed immunohistochemistry staining and real-time PCR for 16S rRNA, ureA, and 23S rRNA for H. pylori genes on all specimens., Results: All controls were positive for H. pylori on all PCR assays and immunohistochemical staining. Regarding the 52 initially negative biopsies, all PCR tests were significantly more sensitive than immunohistochemical staining (p<0.01). Sensitivity and specificity were 55% and 80% for 16S rRNA PCR, 43% and 90% for ureA PCR, 41% and 80% for 23S rRNA PCR, and 7% and 100% for immunohistochemical staining, respectively. Combined analysis of PCR assays for two genes were significantly more sensitive than ureA or 23S rRNA PCR tests alone (p<0.05) and marginally better than 16S rRNA PCR alone. The best combination was 16S rRNA+ureA, with a sensitivity of 64% and a specificity of 80%., Conclusions: Real-time PCR improves the detection of H. pylori infection in histology-negative formalin-fixed paraffin-embedded biopsy samples obtained during PUB episodes. The low reported prevalence of H. pylori in PUB may be due to the failure of conventional tests to detect infection.

Background: Few data are available on the prevalence of erosive and severe esophagitis in Western countries., Objective: To retrospectively determine the prevalence and the factors predicting erosive esophagitis and severe esophagitis in a large series of endoscopies in Spain., Design: Retrospective observational study. A multivariate analysis was performed to determine variables predicting severe esophagitis., Setting: Databases of 29 Spanish endoscopy units., Patients: Patients submitted to a diagnostic endoscopy during the year 2005., Interventions: Retrospective review of the databases., Main Outcome Measurements: Esophagitis severity (graded according to the Los Angeles classification) and associated endoscopic findings., Results: Esophagitis was observed in 8.7% of the 93,699 endoscopies reviewed. Severe esophagitis (LA grade C or D) accounted for 22.5% of cases of the disease and was found in 1.9% of all endoscopies. Incidences of esophagitis and those of severe esophagitis were 86.2 and 18.7 cases per 100,000 inhabitants per year respectively. Male sex (OR 1.89) and advanced age (OR 4.2 for patients in the fourth age quartile) were the only variables associated with severe esophagitis. Associated peptic ulcer was present in 8.8% of cases., Limitations: Retrospective study, no data on individual proton pump inhibitors use., Conclusions: Severe esophagitis is an infrequent finding in Spain. It occurs predominantly in males and in older individuals. Peptic ulcer disease is frequently associated with erosive esophagitis.

If we had to give a general view of the articles published in the year 2010, we should conclude that the evidence in the year 2010 suggests that, also in Helicobacter pylori diagnosis, "the devil is in the details". In this sense, different studies suggested that skipping citric acid pretreatment or local validation or reducing the (13) C-urea dose markedly decreases the accuracy of the urea breath test. The studies also implied that, even between monoclonal stool tests, there are large differences between the marketed tests. Finally, even histology does not work adequately in patients with gastric cancer or extensive areas of intestinal metaplasia. In these cases, specific gastric sites should be biopsied to improve the reliability of histology., (© 2010 Blackwell Publishing Ltd.)

Background: Studies comparing new monoclonal fecal tests for evaluating cure of Helicobacter pylori infection after treatment are scarce. The objective was to compare the diagnostic accuracy of three monoclonal stool tests: two rapid in-office tools -RAPID Hp StAR and ImmunoCard STAT! HpSA - and an EIA test - Amplified IDEIA Hp StAR., Materials and Methods: Diagnostic reliability of the three tests was evaluated in 88 patients at least 8 weeks after H. pylori treatment. Readings of immunochromatographic tests were performed by two different observers. Sensitivity, specificity, positive and negative predictive values and 95% confidence intervals were calculated., Results: All tests presented similar performance for post-eradication testing. Sensitivity for detecting persistent infection was 100% for both Amplified IDEIA and RAPID Hp StAR and 90% for ImmunoCard STAT! HpSA. Respective specificities were 94.9%, 92.3-93.6% and 94.9%. Negative predictive values were very high (100%, 100% and 98.7% respectively). But positive predictive values were lower, ranging from 62.5 to 71.4%., Conclusion: All monoclonal fecal tests in this series presented similar performance in the post-treatment setting. A negative test after treatment adequately predicted cure of the infection. However, nearly a third of tests were false positive, showing a poor predictive yield for persistent infection.

Background: Alternative treatment regimens for standard triple therapy are urgently needed., Aim: To critically review the evidence on the role of "sequential" regimen for the treatment of Helicobacter pylori infection., Methods: Bibliographical searches were performed in MEDLINE and international congresses., Results: Several pooled-data analyses and meta-analyses have demonstrated that sequential regimen is more effective than standard triple therapy. Sequential therapy is not affected by bacterial (CagA status, infection density) and host factors (underlying disease, smoking). Clarithromycin resistance seems to be the only factor reducing their efficacy. However, even in these patients, an acceptable >75% eradication rate can be achieved. Unfortunately, almost all the studies have been performed in Italy. Whether it is necessary to provide the drugs sequentially or if the 4 components of sequential therapy can be given concurrently is unclear. Nonbismuth quadruple therapy seems to be an effective and safe alternative to triple therapy and is less complex than sequential therapy., Conclusions: Sequential therapy is a novel promising treatment approach that deserves consideration as a treatment strategy for H. pylori infection. However, further robust assessment across a much broader range of patients is required before sequential therapy could supplant existing treatment regimens and be generally recommended in clinical practice.

Importance of the Field: Standard triple therapy (STT) is the most used treatment for Helicobater pylori infection. The prevalence of antibiotic resistance has increased substantially in recent years and there has been a corresponding decrease in efficacy., Areas Covered in This Review: Bibliographical searches were performed in MEDLINE and international congresses up to 2009 for 'Helicobacter pylori' AND 'sequential regimen/therapy'., What the Reader Will Gain: Several meta-analyses have demonstrated that sequential therapy (SQT) is more effective than STT. SQT is not affected by bacterial and host factors that have, until now, predicted the outcome of STT. Primary clarithromycin resistance is the only factor reducing the efficacy of SQT; however, even in these patients an acceptable > 75% eradication can be achieved. So far, almost all the studies have been performed in Italy. The advantages of SQT over STT should be confirmed in different countries. Whether it is necessary to provide the drugs sequentially or if the four components of SQT can be given concurrently is unclear., Take Home Message: SQT is a promising new treatment approach that deserves consideration as a treatment strategy for H. pylori infection. However, further robust assessment across a much broader range of patients is required before SQT could supplant existing treatment regimens and be generally recommended in clinical practice.

Background: Well-devised studies comparing new but different monoclonal fecal tests for diagnosing Helicobacter pylori infection are scarce. The objective of this study was to compare the diagnostic accuracy of 3 monoclonal stool tests: 2 rapid in-office tools-RAPID Hp StAR and ImmunoCard STAT! HpSA-and an enzyme immunoassay test-Amplified IDEIA Hp StAR-for diagnosing H. pylori infection prior to eradication treatment., Methods: Diagnostic reliability was evaluated in 199 untreated consecutive patients with dyspeptic symptoms. The gold standard for diagnosing H. pylori infection was defined as the concordance of the rapid urease test, histopathology, and urea breath test. Readings of immunochromatographic tests were performed by 2 different observers. Sensitivity, specificity, positive and negative predictive values, and 95% confidence intervals were calculated. Sensitivity and specificity were compared using the McNemar test., Results: The sensitivity and specificity of Amplified IDEIA Hp StAR were 90% and 89%, respectively. This enzyme immunoassay test was significantly more sensitive than ImmunoCard STAT! HpSA and more specific than RAPID Hp StAR. The sensitivity and specificity of RAPID Hp StAR were 91% and 80%, respectively, according to observer 1, and 92% and 76%, respectively, according to observer 2. It was significantly more sensitive and less specific than ImmunoCard STAT! HpSA. The sensitivity and specificity of ImmunoCard STAT! HpSA were 69% and 90%, respectively, according to observer 1, and 74% and 89%, respectively, according to observer 2., Conclusions: Amplified IDEIA Hp StAR seems to be the most accurate stool test for diagnosing H. pylori for patients with dyspeptic symptoms. The currently available in-office tests obtain slightly less reliable results.

Monoclonal gammopathy of unknown significance (MGUS) is a chronic haematological alteration that carries a 1% risk per year of malignant evolution. The origin of this disturbance remains unknown. Previous reports have suggested that a subgroup of patients presenting MGUS might cure after Helicobacter pylori eradication. This study evaluates the effect of H. pylori eradication in a cohort of 30 patients with MGUS. A 7-day clarithromycin-based triple treatment was prescribed to patients with MGUS infected with H. pylori. Quantification of the monoclonal component was performed at inclusion and at least 12 months after treatment. The monoclonal component persisted unchanged in all patients who cured the H. pylori infection.

Background: Clinical trials provide evidence of the high effectiveness of Helicobacter pylori eradication for preventing recurrent ulcer-related gastrointestinal hemorrhage. The best strategy for curing the infection in this setting is, however, still under debate., Objective: To evaluate four different strategies for prevention of rebleeding in patients with peptic ulcer hemorrhage: 1) test for H. pylori and treatment, if positive; 2) proton pump inhibitor maintenance; 3) no preventive treatment; 4) empirical H. pylori eradication immediately after bleeding., Methods: A decision analysis model was used, with a time horizon of 2 years and a third-party payer perspective. Costs were estimated for two different settings: a low-cost-for-care area (Spain) and a high-cost area (USA). Main outcome measure was incremental cost-effectiveness ratio for each upper gastrointestinal hemorrhage avoided., Results: Empirical H. pylori eradication was the dominant strategy: its estimated rate of recurrent bleeding was lower (6.1%) than those of strategies 1 (7.4%), 2 (11.1%), and 3 (18.4%) and it was the least expensive strategy. The results remained stable when variables were changed inside a wide range of plausible values. Sensitivity analysis also showed that the prevalence of H. pylori in bleeding ulcer was the variable that most influenced the results: when it was below 45% in Spain or below 51% in the United States, empirical eradication was not a dominant strategy although it remained cost-effective., Conclusion: In patients with bleeding peptic ulcer, empirical treatment of H. pylori infection immediately after feeding is restarted is the most cost-effective strategy for preventing recurrent hemorrhage.

Background: Despite many changes, no large studies comparing the different diagnostic tests for Helicobacter pylori have been performed in the past 10 years. In this time, monoclonal stool antigen immunoassays and in-office 13C-urea breath tests (UBTs) have appeared. The aim of this study was to evaluate the accuracy of invasive and noninvasive tests in a large series of dyspeptic patients., Methods: A total of 199 dyspeptic patients who had not previously been treated for H. pylori infection were prospectively enrolled. Noninvasive analyses included a commercial infrared-based UBT and a commercially available stool test. Biopsy-based tests included histological examination and a rapid urease test. A patient was considered to be infected when at least 2 test results were positive. Sensitivity, specificity, positive and negative predictive values, and 95% confidence intervals were calculated. The test results were compared using the McNemar test., Results: Rates of positive test results were similar (54%) for the rapid urease test, histopathological examination, and the stool test. By contrast, 75% of UBT results were positive, and the UBT was associated with a very low specificity (60%). For this reason, the delta cutoff value for the UBT was recalculated as 8.5%. Sensitivities and specificities with this new cutoff value were 95% and 100%, respectively, for the rapid urease test; 94% and 99%, respectively, for histopathological examination; 90% and 93%, respectively, for the stool test; and 90% and 90%, respectively, for the UBT., Conclusions: Histological examination and rapid urease testing showed excellent diagnostic reliability. The stool test seems to be a good, noninvasive alternative to endoscopy-based tests. By contrast, the infrared-based UBT evaluated in our study showed a lower than expected performance, which was partially corrected when the cutoff value for the test was recalculated.

Background: The evidence on whether high-dose proton pump inhibitors (PPIs) increase cure rates of Helicobacter pylori treatment has not been previously assessed., Aim: To evaluate the evidence on the usefulness of high-dose PPI in standard triple therapy by performing a systematic review and a meta-analysis., Methods: A systematic search was performed in multiple databases and in the abstracts submitted to the Digestive Diseases Week, the European Helicobacter Study Group congress and the United European Gastroenterology Week. Randomized trials comparing a standard dose of a PPI with high-dose PPI both twice a day in triple therapy combining a PPI plus clarithromycin and either amoxicillin or metronidazole were selected. Relative risk (RR) and 95% confidence intervals (95% CIs) for all comparisons were calculated using Review Manager., Results: Six studies fulfilled the inclusion criteria. All used triple therapy for 7 days. A mean intention-to-treat cure rate of 82% was achieved with high-dose PPI and one of 74% with standard dose (RR: 1.09; 95% CI: 1.01-1.17). Subgroup analysis showed that the maximum increase was observed when the PPI compared were omeprazole 20 mg or pantoprazole 40 mg vs. esomeprazole 40 mg., Conclusion: High-dose PPI seems more effective than standard-dose for curing H. pylori infection in 7-day triple therapy.

Background: Cure rates of Helicobacter pylori infection with standard triple therapy are disappointingly low. A very effective, new sequential treatment schedule has recently been described. However, all studies published to date were performed in Italy; it is mandatory to confirm these results in other settings., Aim: To assess the cure rate and the acceptability of a new sequential treatment regimen through a pilot study., Methods: A hundred and thirty-nine patients (60% men, mean age 49.6 +/- 15.7 yr) were recruited from six centers. H. pylori status was assessed by histology, urease test or urea breath test. Sequential regime consisted of a 10-day treatment including a proton pump inhibitor (PPI) b.d. plus amoxicillin 1 g b.d. for the first 5 days, followed by a PPI b.d. clarithromycin 500 mg b.d. and metronidazole 500 mg b.d for the next 5 days. Eradication was determined 8 wk after the end of treatment by urea breath test or histology. Eradication rates were calculated both per protocol and by intention-to-treat., Results: Eradication was achieved in 117 out of 129 patients who returned for a follow-up test. The intention-to-treat eradication rate was thus 84.2% (95%CI: 77%-90%) and the per-protocol cure rate 90.7% (95%CI: 84%-95%). The treatment was well tolerated. Only 14 patients complained of mild side effects., Conclusions: Sequential treatment seems highly effective for eradicating H. pylori.