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Background: Ustekinumab is approved for ulcerative colitis (UC)., Aims: To assess the durability of ustekinumab in patients with UC and its short-term effectiveness, durability and tolerability in clinical practice., Methods: Retrospective, multicentre study of patients who had received their first ustekinumab dose at least 16 weeks before inclusion. Patients were followed until treatment discontinuation or last visit. Only patients with active disease at the start of ustekinumab treatment were considered in the effectiveness analysis. Patients who stopped ustekinumab before their last visit were considered not to be in subsequent remission., Results: We included 620 patients; 155 (25%) discontinued ustekinumab during follow-up (median 12 months). Rate of discontinuation was 20% per patient-year of follow-up. Anaemia at baseline (hazard ratio, HR 1.5; 95% confidence interval [CI] 1.1-2.1), steroids at baseline (HR 1.5; 95% CI 1.06-2.08) and more severe clinical activity at baseline (HR 1.5; 95% CI 1.09-2.06) were associated with higher risk of discontinuation. At the end of induction, 226 (40%) patients were in steroid-free clinical remission. Moderate-severe vs mild disease activity at baseline (odds ratio [OR] 0.3; 95% CI 0.2-0.5), male sex (OR 0.5; 95% CI 0.4-0.8), and increased number of previous biologics (OR 0.6; 95% CI 0.6-0.8) were associated with lower likelihood of steroid-free clinical remission at week 16. One hundred and seventy-six patients (28%) had at least one adverse event. We observed no negative impact of ustekinumab on extraintestinal manifestations and/or immune-mediated diseases., Conclusions: Ustekinumab durability in UC was relatively high, and treatment was effective in highly refractory patients. The safety profile was consistent with previous studies., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Background: Ulcerative proctitis (UP) can have a milder, less aggressive course than left-sided colitis or extensive colitis. Therefore, immunosuppressants tend to be used less in patients with this condition. Evidence, however, is scarce because these patients are excluded from randomised controlled clinical trials. Our aim was to describe the characteristics of patients with refractory UP and their disease-related complications, and to identify the need for immunosuppressive therapies., Methods: We identified patients with UP from the prospective ENEIDA registry sponsored by the GETECCU. We evaluated socio-demographic data and complications associated with immunosuppression. We defined immunosuppression as the use of immunomodulators, biologics and/or small molecules. We used logistic regression to identify factors associated with immunosuppressive therapy., Results: From a total of 34,716 patients with ulcerative colitis, we identified 6281 (18.1%) with UP; mean ± SD age 53 ± 15 years, average disease duration of 12 ± 9 years. Immunosuppression was prescribed in 11% of patients, 4.2% needed one biologic agent and 1% needed two; 2% of patients required hospitalisation, and 0.5% underwent panproctocolectomy or subtotal colectomy. We identified 0.2% colorectal tumours and 5% extracolonic tumours. Patients with polyarthritis (OR 3.56, 95% CI 1.86-6.69; p < 0.001) required immunosuppressants., Conclusions: Among patients with refractory UP, 11% required immunosuppressant therapy, and 4.2% required at least one biologic agent., (© 2024 John Wiley & Sons Ltd.)

Background: The advent of new therapeutic agents and the improvement of supporting care might change the management of acute severe ulcerative colitis (ASUC) and avoid colectomy., Aims: To evaluate the colectomy-free survival and safety of a third-line treatment in patients with ASUC refractory to intravenous steroids and who failed either infliximab or ciclosporin., Methods: Multicentre retrospective cohort study of patients with ASUC refractory to intravenous steroids who had failed infliximab or ciclosporin and received a third-line treatment during the same hospitalisation. Patients who stopped second-line treatment due to disease activity or adverse events (AEs) were eligible. We assessed short-term colectomy-free survival by logistic regression analysis. Kaplan-Meier curves and Cox regression models were used for long-term assessment., Results: Among 78 patients, 32 received infliximab and 46 ciclosporin as second-line rescue treatment. Third-line treatment was infliximab in 45 (58%), ciclosporin in 17 (22%), tofacitinib in 13 (17%) and ustekinumab in 3 (3.8%). Colectomy was performed in 29 patients (37%) during follow-up (median 21 weeks). Of the 78 patients, 32 and 18 were in clinical remission at, respectively, 12 and 52 weeks. At the last visit, 25 patients were still on third-line rescue treatment, while 12 had stopped it due to clinical remission. AEs were reported in 26 (33%) patients. Two patients died (2.6%), including one following colectomy., Conclusion: Third-line rescue treatment avoided colectomy in over half of the patients with ASUC and may be considered a therapeutic strategy., (© 2024 John Wiley & Sons Ltd.)

Background: Methotrexate can be used to maintain remission in Crohn's disease patients who are intolerant to thiopurines. Data on its use as monotherapy in other scenarios are limited., Aim: To assess the effectiveness of methotrexate monotherapy in Crohn's disease patients after previous failure to anti-tumour necrosis factor (anti-TNFα) drugs., Methods: A retrospective, observational multicentre study of data from the Spanish ENEIDA registry. Participants were patients with active Crohn's disease and previous failure to anti-TNFα started on methotrexate monotherapy. Short-term effectiveness was assessed at 12-16 weeks based on Harvey-Bradshaw index (HBI): clinical remission as HBI ≤ 3 points and clinical response as HBI drop of ≥ 3 points over baseline. Long-term effectiveness was defined as steroid-free methotrexate persistence from 12 to 16 weeks until maximum follow up. Adverse events were recorded., Results: Data were compiled for 110 patients treated with methotrexate after a failed response to one (39%) or two (55.6%) anti-TNFα agents. Short-term clinical response and remission rates were 60% and 30.9% respectively. Of 74 patients who continued after week 16, long-term effectiveness was achieved in 82% and 74% at 12 and 24 months respectively. In the multivariate analysis, non-remission at short term (vs remission) was associated with long-term failure (HR 2.58, 95%CI 1.95-3.68, P = 0.028). Adverse events (evaluated in 100 patients) were recorded in 44%, and in 30.4% of these patients, they led to methotrexate discontinuation., Conclusions: The benefits observed suggest methotrexate monotherapy could be a valid option in Crohn's disease patients with previous failure to anti-TNFα., (© 2021 John Wiley & Sons Ltd.)

Background: Different bismuth quadruple therapies containing proton-pump inhibitors, bismuth salts, metronidazole, and a tetracycline have been recommended as third-line Helicobacter pylori eradication treatment after failure with clarithromycin and levofloxacin., Aim: To evaluate the efficacy and safety of third-line treatments with bismuth, metronidazole, and either tetracycline or doxycycline., Methods: Sub-study with Spanish data of the "European Registry on H pylori Management" (Hp-EuReg), international multicenter prospective non-interventional Registry of the routine clinical practice of gastroenterologists. After previous failure with clarithromycin- and levofloxacin-containing therapies, patients receiving a third-line regimen with 10/14-day bismuth salts, metronidazole, and either tetracycline (BQT-Tet) or doxycycline (BQT-Dox), or single capsule (BQT-three-in-one) were included. Data were registered at AEG-REDCap database. Univariate and multivariate analyses were performed., Results: Four-hundred and fifty-four patients have been treated so far: 85 with BQT-Tet, 94 with BQT-Dox, and 275 with BQT-three-in-one. Average age was 53 years, 68% were women. Overall modified intention-to-treat and per-protocol eradication rates were 81% (BQT-Dox: 65%, BQT-Tet: 76%, BQT-three-in-one: 88%) and 82% (BQT-Dox: 66%, BQT-Tet: 77%, BQT-three-in-one: 88%), respectively. By logistic regression, higher eradication rates were associated with compliance (OR = 2.96; 95% CI = 1.01-8.84) and no prior metronidazole use (OR = 1.96; 95% CI = 1.15-3.33); BQT-three-in-one was superior to BQT-Dox (OR = 4.46; 95% CI = 2.51-8.27), and BQT-Tet was marginally superior to BQT-Dox (OR = 1.67; 95% CI = 0.85-3.29)., Conclusion: Third-line H pylori eradication with bismuth quadruple treatment (after failure with clarithromycin and levofloxacin) offers acceptable efficacy and safety. Highest efficacy was found in compliant patients and those taking 10-day BQT-three-in-one or 14-day BQT-Tet. Doxycycline seems to be less effective and therefore should not be recommended., (© 2020 John Wiley & Sons Ltd.)

Background: Data on the long-term administration of ustekinumab in recommended doses are limited., Aim: To assess the real-world, long-term effectiveness of ustekinumab in refractory Crohn's disease (CD)., Methods: Multi-centre study of CD patients starting ustekinumab at the recommended dose, followed for 1 year. Values for the Harvey-Bradshaw Index (HBI), endoscopic activity, C-reactive protein (CRP), and faecal calprotectin (FC) were recorded at baseline and at weeks 26 and 52. Demographic and clinical data, previous treatments, adverse events (AEs) and hospitalisations were documented. Potential predictors of remission were examined., Results: A total of 407 patients were analysed. The initial maintenance dose of 90 mg SC was administered every 12, 8 and 4 weeks in 56 (14%), 347 (85%) and 4 (1%) patients, respectively. After 52 weeks, treatment was discontinued in 112 patients (27.5%). At baseline, 295 (72%) had an HBI >4 points. Of these, 169 (57%) and 190 (64%) achieved clinical remission at weeks 26 and 52, respectively. FC levels returned to normal in 44% and 54% of patients at weeks 26 and 52, and CRP returned to normal in 36% and 37% of patients at weeks 26 and 52, respectively. AEs were recorded in 60 patients. The use of fewer previous anti-TNFα agents and ileal localisation were associated with clinical remission, and endoscopic severity was associated with poor response. No factors correlated with endoscopic remission., Conclusion: After 52 weeks, ustekinumab demonstrated effectiveness in inducing clinical and endoscopic remission in patients with refractory CD., (© 2020 John Wiley & Sons Ltd.)

Background: Thiopurines are the most widely used immunosuppressants in IBD although drug-related adverse events (AE) occur in 20%-30% of cases., Aim: To evaluate the safety of thiopurines in elderly IBD patients METHODS: Cohort study including all adult patients in the ENEIDA registry who received thiopurines. Patients were grouped in terms of age at the beginning of thiopurine treatment, specifically in those who started thiopurines over 60 years or between 18 and 50 years of age. Thiopurine-related AEs registered in the ENEIDA database were compared., Results: Out of 48 752 patients, 1888 started thiopurines when over 60 years of age and 15 477 under 50 years of age. Median treatment duration was significantly shorter for those who started thiopurines >60 years (13 [IQR 2-55] vs 32 [IQR 5-82] months; P < .001). Patients starting >60 years had higher rates of all types of myelotoxicity, digestive intolerance and hepatotoxicity. Thiopurines were discontinued due to AEs (excluding malignancies and infections) in more patients starting >60 years (67.2% vs 63.1%; P < .001). Elderly age and female sex were independent risk factors for most AEs., Conclusion: In elderly IBD patients, thiopurines are associated with an increased risk of non-infectious, non-neoplastic, AEs., (© 2019 John Wiley & Sons Ltd.)

Introduction: Dyspepsia and Helicobacter pylori are two of the most relevant digestive conditions in primary care. Several consensuses on the subject have been published, but the assimilation/implementation of these guidelines is uncertain., Aims and Methods: To evaluate the attitudes, perceptions, limitations, and adherence to recommendations of Spanish primary care physicians using an open online survey. Responses were anonymously codified. Estimated margin of error was 3.4%. Responses were weighted by province, gender, age, and type of practice. Survey was performed using the AEG-REDCap platform., Results: A total of 1445 responses, received between December 2017 and April 2018, were analyzed. Women represented 54%, and the average age was 48 years; 59% were from urban context, 20% from semi-urban, and 21% from rural; 93% provided public practice. Over 40% had read at least one Maastricht consensus (24% Maastricht V), and 34% had attended a course related to H. pylori. 16% reported no direct access to any validated diagnostic method, only 44% to urea breath test, and 33% did not systematically refer to eradication confirmation test. The first-line treatment of choice was standard triple therapy in 56%, followed by concomitant therapy (28%). Only 20% of physicians had optimal adherence to recommendations., Conclusion: Even though some improvements from guidelines have been partially incorporated, the level of penetration of recommendations is still poor and delayed. To provide optimal primary care, the barriers for implementation, access to diagnostic tests and to continuous medical education, should be removed. Rigorous dissemination, implementation, and evaluation programs are desired in future consensuses., (© 2019 John Wiley & Sons Ltd.)

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.)

Background: Multiple Helicobacter pylori second-line schedules have been described as potentially useful. It remains unclear, however, which are the best combinations, and which features of second-line treatments are related to better cure rates. The aim of this study was to determine that second-line treatments achieved excellent (>90%) cure rates by performing a systematic review and when possible a meta-analysis. A meta-regression was planned to determine the characteristics of treatments achieving excellent cure rates., Methods: A systematic review for studies evaluating second-line Helicobacter pylori treatment was carried out in multiple databases. A formal meta-analysis was performed when an adequate number of comparative studies was found, using RevMan5.3. A meta-regression for evaluating factors predicting cure rates >90% was performed using Stata Statistical Software., Results: The systematic review identified 115 eligible studies, including 203 evaluable treatment arms. The results were extremely heterogeneous, with 61 treatment arms (30%) achieving optimal (>90%) cure rates. The meta-analysis favored quadruple therapies over triple (83.2% vs 76.1%, OR: 0.59:0.38-0.93; P = .02) and 14-day quadruple treatments over 7-day treatments (91.2% vs 81.5%, OR; 95% CI: 0.42:0.24-0.73; P = .002), although the differences were significant only in the per-protocol analysis. The meta-regression did not find any particular characteristics of the studies to be associated with excellent cure rates., Conclusion: Second-line Helicobacter pylori treatments achieving>90% cure rates are extremely heterogeneous. Quadruple therapy and 14-day treatments seem better than triple therapies and 7-day ones. No single characteristic of the treatments was related to excellent cure rates. Future approaches suitable for infectious diseases-thus considering antibiotic resistances-are needed to design rescue treatments that consistently achieve excellent cure rates., (© 2018 John Wiley & Sons Ltd.)

Background: Onset during old age has been reported in upto 10% of total cases of inflammatory bowel disease (IBD)., Aim: To evaluate phenotypic characteristics and the use of therapeutic resources in patients with elderly onset IBD., Methods: Case-control study including all those patients diagnosed with IBD over the age of 60 years since 2000 who were followed-up for >12 months, identified from the IBD databases. Elderly onset cases were compared with IBD patients aged 18 to 40 years at diagnosis, matched by year of diagnosis, gender and type of IBD (adult-onset)., Results: One thousand three hundred and seventy-four elderly onset and 1374 adult-onset cases were included (62% ulcerative colitis (UC), 38% Crohn's disease (CD)). Among UC patients, elderly onset cases had a lower proportion of extensive disease (33% vs 39%; P < 0.0001). In CD, elderly onset cases showed an increased rate of stenosing pattern (24% vs 13%; P < 0.0001) and exclusive colonic location (28% vs 16%; P < 0.0001), whereas penetrating pattern (12% vs 19%; P < 0.0001) was significantly less frequent. Regarding the use of therapeutic resources, there was a significantly lower use of corticosteroids (P < 0.0001), immunosuppressants (P < 0.0001) and anti-TNFs agents (P < 0.0001) in elderly onset cases. Regarding surgery, we found a significantly higher surgery rate among elderly onset UC cases (8.3% vs 5.1%; P < 0.009). Finally, elderly onset cases were characterised by a higher rate of hospitalisations (66% vs 49%; P < 0.0001) and neoplasms (14% vs 0.5%; P < 0.0001)., Conclusions: Elderly onset IBD shows specific characteristics and they are managed differently, with a lower use of immunosuppressants and a higher rate of surgery in UC., (© 2018 John Wiley & Sons Ltd.)

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.)

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: The decreasing efficacy of H. pylori eradication treatments over time makes the search for better regimens and adjuvant medications a priority., Aim: To conduct a meta-analysis of studies comparing rabeprazole or esomeprazole with other proton pump inhibitors (PPI) or with each other in H. pylori eradication treatment., Selection of Studies: Randomised clinical trials comparing esomeprazole or rabeprazole with first-generation PPIs (omeprazole-lansoprazole-pantoprazole) or with each other., Results: The meta-analysis (35 studies, 5998 patients) showed higher eradication rates for esomeprazole than for first-generation PPIs: 82.3% vs. 77.6%; OR = 1.32(1.01-1.73); NNT = 21. Rabeprazole also showed better results than first-generation PPIs: 80.5% vs. 76.2%; OR = 1.21(1.02-1.42); NNT = 23. PPI dosage sub-analysis: only esomeprazole 40 mg b.d. improved results [83.5% esomeprazole vs. 72.4% first generation; OR = 2.27(1.07-4.82); NNT = 9]. Whereas rabeprazole 10 and 20 mg b.d. maintained results, esomeprazole 20 mg b.d. obtained lower efficacy. Esomeprazole vs. rabeprazole sub-analysis (five studies): no significant differences were found: 78.7% vs. 76.7%; OR = 0.90(0.70-1.17). CYP2C19 sub-analysis: Genotype did not significantly affect eradication either in first [OR = 1.76(0.99-3.12)] or new generation [OR = 1.19(0.73-1.95)] PPIs. However, sub-analysis considering only extensive metaboliser patients showed higher eradication with new-generation PPIs [OR = 1.37(1.02-1.84)]., Conclusions: Esomeprazole and rabeprazole show better overall H. pylori eradication rates than first-generation PPIs. This clinical benefit is more pronounced in esomeprazole 40 mg b.d. regimens. In CYP2C19 extensive metabolisers, new-generation PPIs are more effective than first-generation PPIs for H. pylori eradication. However, a general recommendation of using new-generation PPIs in all scenarios remains unclear., (© 2012 Blackwell Publishing Ltd.)

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: Ciclosporin has proven to be effective in patients with corticosteroid-refractory ulcerative colitis (UC). When therapy with this drug fails, infliximab can be considered to avoid colectomy. The efficacy and safety of this sequential approach remain unknown., Aim: To assess the efficacy and safety profile of treatment with infliximab after failure of ciclosporin in patients with a corticosteroid-refractory flare of UC., Methods: Retrospective review of medical records of patients with a corticosteroid-refractory flare of UC who did not respond to ciclosporin and received salvage therapy with infliximab within a month of discontinuing ciclosporin. The severity of the flare and response to the treatment were graded using the Lichtiger index. Cumulative rates of colectomy were calculated using Kaplan-Meier analysis. Cox regression analysis was performed to identify predictors of colectomy. To evaluate the safety profile of this treatment strategy, any adverse event occurring after the first infusion of infliximab was considered., Results: The study population comprised 47 patients with corticosteroid-refractory UC treated with infliximab after failure of ciclosporin. The median baseline Lichtiger index was 13. The mean time from the last ciclosporin dose to the first infliximab infusion was 6 days. After the first infliximab infusion, 13% of patients achieved remission, and 74% partial response. Of the 35 patients who received the third infliximab infusion, 60% achieved remission, and 37% partial response. Fourteen patients (30%) underwent colectomy. The rate of adverse events was 23%. One death occurred in a 40-year-old man who failed ciclosporin and infliximab and underwent surgery 10 days after the first infliximab infusion; he died of nosocomial pneumonia., Conclusions: Treatment with infliximab makes it possible to avoid colectomy in two-thirds of corticosteroid-refractory UC patients in whom ciclosporin fails. However, the rates of adverse events and mortality mean that the decision to administer sequential therapy (ciclosporin-infliximab) should be taken on an individual basis., (© 2011 Blackwell Publishing Ltd.)

Background: Even with the current most effective treatment regimens, a relevant proportion of patients will fail to eradicate Helicobacter pylori infection., Aim: To evaluate the role of rifabutin in the treatment of H. pylori infection., Methods: Bibliographical searches were performed in MEDLINE. Data on the efficacy of rifabutin-containing regimens on H. pylori eradication were combined and meta-analysed using the generic inverse variance method., Results: Rifabutin shows good in vitro activity against H. pylori. Mean H. pylori rifabutin resistance rate (calculated from 11 studies including 2982 patients) was 1.3% (95% confidence interval = 0.9-1.7%). When only studies including patients naïve to H. pylori eradication treatment were considered, this figure was even lower (0.6%). On the other hand, higher values of rifabutin resistance were calculated (1.59%) when only post-treatment patients were considered. Overall, mean H. pylori eradication rate (intention-to-treat analysis) with rifabutin-containing regimens (1008 patients) was 73% (67-79%). Respective cure rates for second-line (223 patients), third-line (342 patients) and fourth/fifth-line (95 patients) rifabutin therapies were 79% (67-92%), 66% (55-77%) and 70% (60-79%) respectively. For treating H. pylori infection, almost all studies have administered rifabutin 300 mg/day; this dose seems to be more effective than 150 mg/day. The ideal length of treatment remains unclear, but 10- to 12-day regimens are generally recommended. The mean rate of adverse effects was 22% (19-25%). Myelotoxicity is the most significant, although this complication was rare. Until now, all patients have recovered of leucopenia uneventfully in a few days, and there have been no reports of infection or other adverse outcomes related to it., Conclusion: Rifabutin-containing rescue therapy constitutes an encouraging strategy after multiple (usually three) previous eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole, tetracycline and levofloxacin., (© 2011 Blackwell Publishing Ltd.)

BACKGROUND  A decrease in the Helicobacter pylori eradication rate after standard triple therapy has been suggested in recent years. AIM  To assess the efficacy of standard triple therapy in the eradication of H. pylori through an epidemiological analysis of all published Spanish trials. A secondary aim was to review the prevalence of clarithromycin resistance in Spain. METHODS  Articles on H. pylori eradication in Spain published in peer-reviewed journals were identified through MEDLINE searches. Studies that included a triple therapy consisting of any proton pump inhibitor with clarithromycin (500 mg b.d.) and amoxicillin (1 g b.d.) for up to 14 days were selected. Spanish studies evaluating the prevalence of clarithromycin resistance were also reviewed. Meta-analysis was performed using the generic inverse variance method. RESULTS The pooled eradication rates by year from Spanish studies evaluating the efficacy of the standard triple regimen revealed a relatively constant rate over the years. Overall, the analysis of the 32 studies (4727 patients) showed a mean H. pylori cure rate of 80% (95% CI = 77-82%) by intention-to-treat and 83% (81-86%) by per-protocol. When only peptic ulcer disease or 7-day regimens were considered, results were similar. Based on 13 studies (3293 patients), mean clarithromycin resistance rate was 8% (5-10%). CONCLUSION Although a decrease in the H. pylori eradication rate after triple therapy has been suggested in recent years, cure rates with this regimen did not change in Spain between 1997 and 2008. However, this by no means indicates that the efficacy of standard triple therapy in Spain is acceptable, as it has been calculated to be around only 80%. Therefore, it is evident that new strategies to improve first-line treatment are urgently needed., (© 2011 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: Determining the risk of rebleeding after endoscopic therapy for peptic ulcer bleeding (PUB) may be useful for establishing additional haemostatic measures in very high-risk patients., Aim: To identify predictors of rebleeding after endoscopic therapy., Methods: Bibliographic database searches were performed to identify studies assessing rebleeding after endoscopic therapy for PUB. All searches and data abstraction were performed in duplicate. A parameter was considered to be an independent predictor of rebleeding when it was detected as prognostic by multivariate analyses in ≥2 studies. Pooled odds ratios (pOR) were calculated for prognostic variables., Results: Fourteen studies met the prespecified inclusion criteria. Pre-endoscopic predictors of rebleeding were: (i) Haemodynamic instability: significant in 9 of 13 studies evaluating the variable (pOR: 3.30, 95% CI: 2.57-4.24); (ii) Haemoglobin value: significant in 2 of 10 (pOR: 1.73, 95% CI: 1.14-2.62) and (iii) Transfusion: significant in two of six (pOR not calculable). Endoscopic predictors of rebleeding were: (i) Active bleeding: significant in 6 of 12 studies (pOR: 1.70, 95% CI: 1.31-2.22); (ii) Large ulcer size: significant in 8 of 12 studies (pOR: 2.81, 95% CI: 1.98-4.00); (iii) Posterior duodenal ulcer location: significant in four of eight studies (pOR: 3.83, 95% CI: 1.38-10.66) and (iv) High lesser gastric curvature ulcer location: significant in three of eight studies (pOR: 2.86; 95% CI: 1.69-4.86)., Conclusions: Major predictors for rebleeding in patients receiving endoscopic therapy are haemodynamic instability, active bleeding at endoscopy, large ulcer size, ulcer location, haemoglobin value and the need for transfusion. These risk factors may be useful for guiding clinical management in patients with PUB., (© 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.)

Background: Temporal changes in the incidence of cause-specific gastrointestinal (GI) complications may be one of the factors underlying changing medical practice patterns., Aim: To report temporal changes in the incidence of five major causes of specific gastrointestinal (GI) complication events., Methodology: Population-based study of patients hospitalised due to GI bleeding and perforation from 1996 to 2005 in Spain. We report crude rates, and estimate regression coefficients of temporal trends, severity and recorded drug use for five frequent GI events. GI hospitalisation charts were validated by independent review of large random samples., Results: The incidence per 100 000 person-years of hospitalisations due to upper GI ulcer bleeding and perforation decreased over time [from 54.6 and 3.9 in 1996 (R² = 0.944) to 25.8 and 2.9 in 2005 (R² = 0.410) respectively]. On the contrary, the incidence per 100 000 person-years of colonic diverticular and angiodysplasia bleeding increased over time [3.3 and 0.9 in 1996 (R² = 0.443) and 8.0 and 2.6 in 2005 (R² = 0.715) respectively]. A small increasing trend was observed for the incidence per 100 000 person-years of intestinal perforations (from 1.5 to 2.3 events). Based on data extracted from the validation process, recent recorded drug intake showed an increased frequency of anticoagulants with colonic diverticular and angiodysplasia bleeding, whereas NSAID and low-dose aspirin use were more prevalent in peptic ulcer bleeding and colonic diverticular bleeding respectively., Conclusions: From 1996 to 2005, hospitalisations due to peptic ulcer bleeding and perforation have decreased significantly, whereas the number of cases of colonic diverticular and angiodysplasia bleeding have increased., (© 2011 Blackwell Publishing Ltd.)

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: Helicobacter pylori infection rates in duodenal ulcer (DU) patients may be lower than previously estimated., Aim: To review the real prevalence of H. pylori-negative DUs and its possible causes., Methods: Bibliographical searches in MEDLINE looking for the terms 'H. pylori' and 'duodenal ulcer'., Results: Mean prevalence of H. pylori infection in DU disease, calculated from studies published during the last 10 years including a total of 16 080 patients, was 81%, and this figure was lower (77%) when only the last 5 years were considered. Associations with H. pylori-negative DU were: (1) False negative results of diagnostic methods, (2) NSAID use (21% in studies with <90% infection rate), (3) Complicated DU (bleeding, obstruction, perforation), (4) Smoking, (5) Isolated H. pylori duodenal colonization, (6) Older age, (7) Gastric hypersecretion, (8) Diseases of the duodenal mucosa, (9) Helicobacter'heilmanii' infection and (10) Concomitant diseases., Conclusion: In patients with H. pylori-negative DU disease, one should carefully confirm that the assessment of H. pylori status is reliable. In truly H. pylori-negative patients, the most common single cause of DU is, by far, the use of NSAIDs. Ulcers not associated with H. pylori, NSAIDs or other obvious causes should, for the present, be viewed as 'idiopathic'. True idiopathic DU disease only exceptionally exists.

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.

Aim: To evaluate the effect of Helicobacter pylori eradication on ulcer bleeding recurrence in a prospective, long-term study including more than 400 patients., Methods: Patients with peptic ulcer bleeding were prospectively included. H. pylori infection was confirmed by rapid urease test, histology or (13)C-urea breath test. Several eradication regimens were used. Ranitidine 150 mg was administered daily until eradication was confirmed by breath test 8 weeks after completing eradication therapy. Patients with therapy failure received a second or third course of therapy. Patients with eradication success did not receive maintenance anti-ulcer therapy, and were controlled yearly with a repeated breath test., Results: Four hundred and twenty-two patients were followed up for at least 12 months, with a total of 906 patient-years of follow up. Mean age was 59 years, and 35% were previous nonsteroidal anti-inflammatory drug (NSAID) users. Sixty-nine percent had duodenal, 24% gastric, and 7% pyloric ulcer. Recurrence of bleeding was demonstrated in two patients at 1 year (incidence: 0.22% per patient-year of follow up), which occurred after NSAID use in both cases., Conclusion: Peptic ulcer rebleeding does not occur in patients with complicated ulcers after H. pylori eradication. Maintenance anti-ulcer (antisecretory) therapy is not necessary if eradication is achieved.

Aim: To evaluate (i) the diagnostic usefulness of a delayed test in initially negative patients; and (ii) the reliability of the rapid urease test, histology or a combination of the two to diagnose Helicobacter pylori during emergency endoscopy in a large clinical practice series., Patients and Methods: Records of patients with ulcer bleeding from 1995 to 2000 were reviewed. Patients with initially negative tests were retested 4-8 weeks after the bleeding episode. Sensitivity of urease, histology or a combination of the two to detect H. pylori at initial endoscopy and the efficacy of delayed Urea Breath Test in detecting missed infection was determined., Results: The study included 429 patients. A delayed second test detected H. pylori infection in 57 out of 72 (79%) of initially negative patients. The sensitivity for detecting H. pylori was 76%, 78% and 86% for urease, histology and their combination, respectively. The prevalence of H. pylori was 95% in duodenal and 88% in gastric ulcer. In addition, only one test was performed in 17 of the 32 patients who were considered negative., Conclusion: Not even the combination of a negative urease and histology in the initial endoscopy is able to rule out infection in bleeding ulcer patients. A delayed test should be performed to rule out Helicobacter pylori infection completely.

Aim: To evaluate whether eradication of Helicobacter pylori prevents peptic ulcer in non-steroidal anti-inflammatory drug users by means of a meta-analysis., Material and Methods: A systematic search was performed in MEDLINE, EMBASE, the Cochrane Controlled Trials Register and the AGA congress. Randomized trials comparing H. pylori eradication vs. non-eradication or eradication vs. a proton pump inhibitor in patients receiving a non-steroidal anti-inflammatory drug were selected., Results: Five studies and 939 patients were included in the analysis; 34 of 459 (7.4%) patients developed a peptic ulcer in the eradicated group vs. 64 of 480 (13.3%) in the control group. The odds ratio was 0.43 (95% confidence interval: 0.20-0.93). Sub-analyses showed a significant reduction of risk for non-steroidal anti-inflammatory drug-naive (odds ratio = 0.26; 95% confidence interval: 0.14-0.49) but not for previously treated patients (odds ratio = 0.95, 95% confidence interval: 0.53-1.72). Two studies with a total of 385 patients compared eradication vs. a proton pump inhibitor; five of 196 (2.6%) developed a peptic ulcer in the eradicated group vs. zero of 189 (0%) in the proton pump inhibitor group (odds ratio = 7.43; 95% confidence interval: 1.27-43.6)., Conclusion: Helicobacter pylori eradication reduces the incidence of peptic ulcer in the overall population receiving non-steroidal anti-inflammatory drugs. It appears to be especially effective when performed in non-steroidal anti-inflammatory drug-naïve patients. Nonetheless, eradication seems less effective than treatment with a maintenance proton pump inhibitor for preventing non-steroidal anti-inflammatory drug-associated ulcers.

Objective: To systematically review the Helicobacter pylori eradication efficacy with ranitidine bismuth citrate (RBC) and two antibiotics, and to conduct a meta-analysis of randomized clinical trials comparing the efficacy of proton pump inhibitor (PPI) vs. RBC with two antibiotics for 1 week., Selection of Studies: Studies evaluating RBC plus two antibiotics were considered. For the meta-analysis, randomized controlled trials comparing PPI vs. RBC plus two antibiotics for 1 week were included., Search Strategy: Electronic and manual bibliographical searches. Assessment of study quality and data extraction: Independently done by two reviewers., Data Synthesis: 'Intention-to-treat' eradication rate. Meta-analysis was performed, combining the odds ratios (OR) of the individual studies. Subanalysis: Depending on the type of antibiotics and the quality of the studies., Results: Mean H. pylori eradication with 7-day RBC-clarithromycin-amoxicillin, RBC-clarithromycin-nitroimidazole, and RBC-amoxicillin-nitroimidazole was 83%, 86%, and 71%, respectively. The meta-analysis showed comparable efficacy with RBC and PPI when they were combined with clarithromycin and amoxicillin (OR = 1.11; 95% CI = 0.88-1.40), or with amoxicillin and metronidazole (OR = 0.92; 95%CI = 0.60-1.41). However, when comparing PPI vs. RBC plus clarithromycin and a nitroimidazole, higher cure rates with RBC than with PPI were demonstrated (OR = 1.65; 95% CI = 1.15-2.37)., Conclusion: The efficacy of RBC and PPI-based triple regimens were comparable when using the clarithromycin-amoxicillin or the amoxicillin-metronidazole combination. However, RBC seems to have a higher efficacy than PPI when clarithromycin and a nitroimidazole are the antibiotics prescribed. Therefore, if one prefers to use the clarithromycin-nitroimidazole regimen, RBC should be used instead of a PPI.

Background: Quadruple rescue therapy requires a complex scheme with four drugs., Aim: To evaluate the efficacy of ranitidine bismuth citrate-tetracycline-metronidazole rescue regimen, and to compare two different metronidazole dose schemes., Methods: Prospective multicentre study including proton-pump inhibitor + clarithromycin + amoxicillin failures. Rescue regimen included two 7-day treatment: (i) ranitidine bismuth citrate (400 mg b.d.)-tetracycline (500 mg q.d.s.)-metronidazole (500 mg t.d.s.; RTM1); or (ii) the same regimen but with metronidazole 250 mg q.d.s. (RTM2). Eradication was confirmed with (13)C-urea breath test., Results: A total of 150 patients were included (58 RTM1, 92 RTM2). All patients but two (one in each group) returned after treatment. About 86% in group RTM1 and 95% in RTM2 correctly took all the medications (P = 0.076). Per-protocol eradication rates with RTM1 and RTM2 were 74 (95% CI: 60-84) and 69% (59-78). The intention-to-treat eradication rates were 64 (51-75) and 70% (59-78; P > 0.05). The type of regimen was not associated with eradication in the multivariate analysis. Adverse effects were more frequent with RTM1 (41%) than with RTM2 (30%; P > 0.05)., Conclusion: Seven-day triple rescue therapy with ranitidine bismuth citrate-tetracycline-metronidazole is effective for Helicobacter pylori eradication, and represents an encouraging alternative to quadruple therapy, with the advantage of simplicity. The administration of metronidazole every 6 h (together with tetracycline), and at a low dose (250 mg), achieves similar efficacy and is probably associated with a better compliance and a lower incidence of adverse effects.

Background: First-line proton pump inhibitor-based triple and quadruple therapies for Helicobacter pylori eradication present similar levels of efficacy. Cross-over treatment (quadruple following triple failure, and triple following quadruple failure) seems the most sensible approach to treatment failures, but the two strategies -'quadruple first' versus 'triple first'- have not been previously compared. The aims of our study were to assess the usefulness and the cost-effectiveness of the two treatment strategies., Material and Methods: Forty-nine out of 344 patients included in a previous study comparing triple therapy - 7 days of omeprazole, amoxicillin and clarithromycin twice a day - with quadruple therapy - 7 days of omeprazole twice a day, plus tetracycline, metronidazole and bismuth subcitrate three times a day - failed initial treatment and were assigned to cross-over therapy. Cure was determined by urea breath test. A decision analysis was performed to compare the two eradication strategies., Results: Intention to treat cure rates were 46% (10/22 patients; 95% CI 24-68%) for second-line triple therapy and 63% (17/27 patients; 95% CI 42-81%) for second-line quadruple therapy. Per protocol cure rates were 71% and 85%, respectively. Intention to treat cure rates were 87% (95% CI 81-92%) for the 'triple first' versus 86% (95% CI 80-91%) for the 'quadruple first' strategy (p = .87). The 'quadruple first' strategy was more cost-effective. The incremental cost of 'triple first' strategy per person was 19 in the low-cost area and 65 US dollars in the high-cost area., Conclusions: The effectiveness of 'triple first' and 'quadruple first' strategies is similar, although the latter seems slightly more cost-effective.

Background: Helicobacter pylori infection in chronic renal failure patients has been linked to peptic ulcer and gastric neoplasia after kidney transplantation. It may also contribute to the accelerated arteriosclerosis that is usual in this population. Few data are available on the usefulness of noninvasive diagnostic tests for H. pylori infection in dialyzed patients, especially regarding the new fecal antigen detection tests. The objective of this study was to determine the efficacy of a noninvasive test for H. pylori infection in patients with chronic renal failure., Methods: Eighty-six patients were included in a cross-sectional study. Urea breath test, serology and three fecal tests--FemtoLab H. pylori (Connex, Germany), Premier Platinum HpSA (Meridian, USA) and Simple H. pylori (Operon SA, Spain) were performed. Helicobacter pylori status was determined by concordance of the tests. Sensitivity, specificity and positive and negative predictive values were calculated for each test., Results: Sensitivity, specificity, positive and negative predictive values were 94%, 96%, 94% and 96% for the urea breath test; 97%, 64%, 66% and 97% for serology; 86%, 100%, 100% and 91%, for FemtoLab H. pylori; 58%, 96%, 91% and 76% for Premier Platinum HpSA and 61%, 78%, 74% and 67% for Simple H. pylori., Conclusions: The urea breath test seems to be the most reliable diagnostic method for H. pylori infection in patients with chronic renal failure. Serology has a low specificity, and the results of the fecal tests vary widely.

Aim: To evaluate the accuracy of several methods aimed to detect Helicobacter pylori stool antigens in patients with upper gastrointestinal bleeding., Methods: Thirty-four patients with upper gastrointestinal bleeding because of peptic ulcer were included. The first stool sample during hospitalization was collected, and stool antigens were determined with: polyclonal enzyme-linked immunosorbent assay (Premier-Platinum-HpSA); monoclonal enzyme-linked immunosorbent assay (Amplified-IDEIA-HpStAR); and rapid monoclonal immunochromatographic test (ImmunoCard-STAT HpSA). A patient was considered infected when H. pylori was diagnosed with invasive tests (rapid urease test or histology) or with (13)C-urea breath test. When all tests were negative, a new breath test was repeated after stopping proton pump inhibitors., Results: All patients were infected and, therefore, only sensitivity of the tests could be calculated: polyclonal enzyme-linked immunosorbent assay (74%), monoclonal enzyme-linked immunosorbent assay (94%), and rapid monoclonal immunochromatographic test (60%; concordance between the two observers was high, kappa = 0.9). Neither the presence of maelena nor the delay in obtaining stool samples explained false negatives., Conclusions: Neither the polyclonal enzyme-linked immunosorbent assay stool antigen test nor the rapid immunochromatographic stool antigen test can be recommended to diagnose H. pylori infection in patients with upper gastrointestinal bleeding. However, the monoclonal enzyme-linked immunosorbent assay stool antigen test is highly sensitive for detecting the infection in patients with this complication, although more studies are necessary to evaluate the specificity of the method.

Aim: To perform a meta-analysis comparing the efficacy of Helicobacter pylori eradication therapy vs. antisecretory non-eradication therapy for the prevention of recurrent bleeding from peptic ulcer., Methods: A search was made of the Cochrane Controlled Trials Register, MEDLINE, EMBASE, CINAHL and several congresses for controlled clinical trials comparing the efficacy of H. pylori eradication therapy vs. antisecretory non-eradication therapy for the prevention of peptic ulcer re-bleeding. Studies with all patients taking non-steroidal anti-inflammatory drugs were excluded. Extraction and quality assessment of the studies were performed by two reviewers., Results: In the first meta-analysis, the mean percentage of re-bleeding in the H. pylori eradication therapy group was 4.5%, compared with 23.7% in the non-eradication therapy group without long-term antisecretory therapy [odds ratio, 0.18; 95% confidence interval (CI), 0.09-0.37; 'number needed to treat' (NNT), 5; 95% CI, 4-8]. In the second meta-analysis, the re-bleeding rate in the H. pylori eradication therapy group was 1.6%, compared with 5.6% in the non-eradication therapy group with maintenance antisecretory therapy (odds ratio, 0.25; 95% CI, 0.08-0.76; NNT, 20; 95% CI, 12-100). When only patients with successful H. pylori eradication were included, the re-bleeding rate was 1%., Conclusions: The treatment of H. pylori infection is more effective than antisecretory non-eradication therapy (with or without long-term maintenance antisecretory treatment) in the prevention of recurrent bleeding from peptic ulcer. Consequently, all patients with peptic ulcer bleeding should be tested for H. pylori, and eradication therapy should be prescribed to infected patients.

Background: It is unknown whether proton pump inhibitors are superior to H2-receptor antagonists in Helicobacter pylori eradication regimens., Aim: To perform a meta-analysis comparing the efficacy of both antisecretors when co-prescribed with antibiotics., Methods: Randomized clinical trials comparing proton pump inhibitors vs. H2-receptor antagonists with the same antibiotics were selected. Data sources included PubMed, the Cochrane Controlled Trials Register and abstracts from congresses up to January 2002. A meta-analysis was performed by combining the odds ratios., Results: Twenty studies fulfilled the inclusion criteria. In the intention-to-treat analysis, the mean eradication rates with proton pump inhibitors and H2-receptor antagonists plus antibiotics were 74% [95% confidence interval (CI), 71-76%] and 69% (95% CI, 66-71%), respectively. The odds ratio for this comparison was 1.31 (95% CI, 1.09-1.58). The number needed to treat with proton pump inhibitors to achieve eradication success, compared with H2-receptor antagonists, was 25. When studies prescribing very high doses of H2-receptor antagonists (two of the outliers) were excluded, the odds ratio (for proton pump inhibitors vs. H2-receptor antagonists) increased to 1.37, the number needed to treat decreased to 20 and the heterogeneity between the studies decreased., Conclusions: Overall, proton pump inhibitors are more effective than H2-receptor antagonists when prescribed at usual doses with antibiotics to eradicate H. pylori infection.

Background: It is not known whether certain proton-pump inhibitors are more efficacious than others when used in triple therapy for Helicobacter pylori eradication., Aim: To compare the efficacy of different proton-pump inhibitors in triple therapy by performing a meta-analysis., Methods: A MEDLINE search was performed. Abstracts of the European Helicobacter pylori Study Group and the American Gastroenterological Association congresses from 1996 to 2002 were also examined. Randomized studies with at least two branches of triple therapy that differed only in terms of type of proton-pump inhibitor were included in a meta-analysis using Review Manager 4.1., Results: Fourteen studies were included. Intention-to-treat cure rates were similar for omeprazole and lansoprazole: 74.7% vs. 76%, odds ratio (OR) 0.91 [95% confidence interval (CI) 0.69-1.21] in a total of 1085 patients; for omeprazole and rabeprazole: 77.9% vs. 81.2%, OR 0.81 (95% CI 0.58-1.15) in a total of 825 patients; for omeprazole and esomeprazole: 87.7% vs. 89%, OR 0.89 (95% CI 0.58-1.35) in 833 patients; and for lansoprazole and rabeprazole: 81% vs. 85.7%, OR 0.77 (95% CI 0.48-1.22) in 550 patients., Conclusion: The efficacy of various proton-pump inhibitors seems to be similar when used for H. pylori eradication in standard triple therapy.

Background: Triple therapy (proton pump inhibitor, clarithromycin and amoxicillin or an imidazole) is the first-line treatment for Helicobacter pylori infection. However, the effectiveness of triple therapy is decreasing due to the increase in antibiotic resistance. Quadruple therapy (proton pump inhibitor, tetracycline, metronidazole and a bismuth salt) is a very effective regimen even in areas of high prevalence of antibiotic resistance, and may be an alternative first-line treatment., Aim: To compare triple vs. quadruple therapy for the first-line treatment of H. pylori infection., Methods: An extensive literature search was performed to identify randomized trials comparing triple vs. quadruple therapy. Selected trials were included in a meta-analysis using Review Manager 4.1., Results: Four studies met the inclusion criteria. Eradication rates with quadruple therapy were slightly higher in both the intention-to-treat (81% vs. 78%; odds ratio, 0.83; 95% confidence interval, 0.61-1.14) and per protocol (88% vs. 85%; odds ratio, 0.81; 95% confidence interval, 0.55-1.20) analysis, although the differences were not statistically significant. Nor were there significant differences in compliance or adverse effects between the therapies., Conclusion: Triple and quadruple therapies seem to be roughly equivalent in terms of effectiveness, compliance and side-effects profile when administered as first-line treatment for H. pylori infection.

Aim: Eradication therapy with proton pump inhibitor, clarithromycin and amoxicillin is extensively used, although it fails in a considerable number of cases. A 'rescue' therapy with a quadruple combination of omeprazole, bismuth, tetracycline and metronidazole (or ranitidine bismuth citrate with these same antibiotics) has been recommended, but it still fails in approximately 20% of cases. Our aim was to evaluate the efficacy and tolerability of a rifabutin-based regimen in patients with two consecutive H. pylori eradication failures., Design: Prospective multicenter study., Patients: Consecutive patients in whom a first eradication trial with omeprazole, clarithromycin and amoxicillin and a second trial with omeprazole, bismuth, tetracycline and metronidazole (three patients) or ranitidine bismuth citrate with these same antibiotics (11 patients) had failed were included., Intervention: A third eradication regimen with rifabutin (150 mg bid), amoxicillin (1 g bid) and omeprazole (20 mg bid) was prescribed for 14 days. All drugs were administered together after breakfast and dinner. Compliance with therapy was determined from the interrogatory and the recovery of empty envelopes of medications., Outcome: H. pylori eradication was defined as a negative 13C-urea breath test 8 weeks after completing therapy., Results: Fourteen patients have been included. Mean age +/- SD was 42 +/- 11 years, 41% males, peptic ulcer (57%), functional dyspepsia (43%). All patients took all the medications and completed the study protocol. Per-protocol and intention-to-treat eradication was achieved in 11/14 patients (79%; 95% confidence interval = 49-95%). Adverse effects were reported in five patients (36%), and included: abdominal pain (three patients), nausea and vomiting (one patient), and oral candidiasis (one patient); no patient abandoned the treatment due to adverse effects., Conclusion: Rifabutin-based rescue therapy constitutes an encouraging strategy after multiple previous eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole and tetracycline.

Aim: To perform a systematic review of the efficacy of rabeprazole-based therapies in Helicobacter pylori eradication, and to conduct a meta-analysis comparing the efficacy of rabeprazole and other proton pump inhibitors when co-prescribed with antibiotics., Methods: Studies evaluating rabeprazole plus antibiotics were considered. Only randomized trials comparing rabeprazole and other proton pump inhibitors with antibiotics, and differing only in the proton pump inhibitor, were included in the meta-analysis. Electronic and manual bibliographic searches were conducted. The percentage (weighted mean) of successful eradication was calculated. Meta-analysis was performed by combining the odds ratios (OR) of the individual studies., Results: The eradication rates were as follows: 14-day rabeprazole-amoxicillin, 73%; rabeprazole-amoxicillin-clarithromycin for 3, 5, 7 and 10 days, 44%, 72%, 78% and 75%, respectively; low-dose rabeprazole (20 mg/day), amoxicillin and clarithromycin for 7 days, 81%; high-dose rabeprazole (40 mg/day), amoxicillin and clarithromycin for 7 days, 75%; 7-day rabeprazole-clarithromycin-nitroimidazole, 85%. Twelve comparative studies were included in the meta-analysis. The eradication rate with rabeprazole plus antibiotics was 79%; it was 77% with other proton pump inhibitors (OR = 1.15; 95% confidence interval, 0.93-1.42). Sub-analysis comparing rabeprazole at low doses (10 mg b.d.) with other proton pump inhibitors at standard doses (omeprazole 20 mg b.d. or lansoprazole 30 mg b.d.) showed no differences., Conclusions: Rabeprazole achieves similar H. pylori eradication rates to omeprazole and lansoprazole when co-prescribed with antibiotics. Low doses of rabeprazole (10 mg b.d.), when administered with two antibiotics, may be sufficient to eradicate H. pylori infection.

Background: Helicobacter pylori infection may lead to peptic ulcer disease, and causes significant morbidity in patients with cirrhosis. The measurement of H. pylori antigens in human stools has been proposed as a valuable, non-invasive, diagnostic tool. A number of tests have recently been commercialized. However, very few data are available on their reliability in patients with cirrhosis., Aim: To evaluate the usefulness of three new tests--HpSA (Meridian Diagnostics Inc., Cincinnati, OH, USA), Simple H. pyl (OPERON S.A., Zaragoza, Spain) and FemtoLab H. pylori (Connex, Martinsried, Germany)--in the diagnosis of H. pylori infection in cirrhotic patients., Methods: H. pylori infection was determined in 79 cirrhotic patients (48 men, 31 women; age range, 29-82 years; mean, 62 +/- 11 years) by concordance of histology and urea breath test. The sensitivity, specificity and positive and negative predictive values of each stool test were calculated., Results: According to the reference method, the sensitivities of HpSA, Simple H. pyl and FemtoLab H. pylori immunoassays were 76%, 87% and 78%, respectively, and their specificities were 93%, 62% and 79%, respectively., Conclusions: Faecal tests are non-invasive and easy-to-perform tools for the diagnosis of H. pylori infection. However, their sensitivity and specificity seem to be non-optimal in patients with cirrhosis.

Background: Helicobacter pylori-associated peptic ulcer is a frequent complication in cirrhotic patients and its morbidity rate is high. In spite of this, diagnostic methods for H. pylori infection have not been fully evaluated in these patients., Aim: To evaluate H. pylori diagnostic methods in patients with liver cirrhosis., Methods: One hundred and one cirrhotic patients were included in the study. Three antral and two corpus biopsies were obtained for rapid urease test of the antral mucosa, and Giemsa stain and immunohistochemistry were performed for both the corpus and antrum. Serology, 13C-urea breath test and faecal H. pylori antigen determination were also carried out., Results: Sixty-two patients were positive and 35 were negative for H. pylori infection; four were indeterminate. The sensitivity and specificity were 90.4% and 100%, respectively, for antral histology, 100% and 100% for gastric body histology, 90.4% and 100% for antral immunohistochemistry, 96.2% and 96.7% for body immunochemistry, 85.7% and 97% for rapid urease test, 83.6% and 55.9% for serology, 96.4% and 97.1% for 13C-urea breath test and 75.4% and 94.1% for faecal antigen., Conclusion: The most reliable tests for H. pylori infection in cirrhotic patients were the 13C-urea breath test and gastric body histology.

Background: Seven-day triple therapy including omeprazole, clarithromycin and amoxicillin has become the treatment of choice for Helicobacter pylori infection. However, 7 days of classical quadruple therapy combining omeprazole, tetracycline, metronidazole and bismuth may be an alternative to triple therapy., Aim: To compare triple vs. quadruple therapy for H.pylori eradication., Methods: Three hundred and thirty-nine patients with peptic ulcer and H. pylori infection were included in the study. Patients were randomized to receive omeprazole, 20 mg, amoxicillin, 1 g, and clarithromycin, 500 mg, all b.d., or omeprazole, 20 mg b.d., tetracycline chloride, 500 mg, metronidazole, 500 mg, and bismuth subcitrate, 120 mg, all t.d.s. Cure was defined as a negative urea breath test at least 2 months after treatment., Results: Per protocol and intention-to-treat cure rates were 86%[95% confidence interval (CI), 80-91%] and 77% (95% CI, 70-83%) for triple therapy, and 89% (95% CI, 82-93%) and 83% (95% CI, 76-88%) for quadruple therapy. No significant differences between the groups were found in the cure rates, compliance or side-effects., Conclusion: One-week triple and quadruple therapy show similar results when used as first-line eradication treatment.