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Background and aims: Several methods are available to diagnose Helicobacter pylori infection. Our objective was to evaluate the tests used for both the initial diagnosis and the confirmation of eradication after treatment in Europe. Methods: The European Registry on the management of Helicobacter pylori infection is an international, multicentre, prospective, non-interventional registry aiming to evaluate the management of Helicobacter pylori-infected patients in Europe. Countries with at least 100 cases registered from June 2013 to April 2021, and with a validated diagnostic method were analysed. Data were quality reviewed. Results: A total of 34,920 adult patients from 20 countries were included (mean age 51 years; 61% women). To establish the initial diagnosis, invasive tests were performed in 19,801 (71%) patients, non-invasive in 11,369 (41%), and both in 3437 (12%). The most frequent were histology (n = 11,885; 43%), a rapid urease test (n = 10,636; 38%) and an urea breath test (n = 7577; 27%). According to the age, invasive tests were indicated in 11,179 (77%) ≥50 years, and in 8603 (65%)

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

Randomized clinical trials and meta-analyses, primarily from Asian countries, have reported good effectiveness with high-dose dual therapy (HDDT) including a proton pump inhibitor (PPI) and amoxicillin when prescribed asAn international, multicenter, prospective non-interventional Registry (Hp-EuReg) aimed to evaluate the decisions and outcomes ofOverall HDDT effectiveness was 52% (per-protocol) and 51% (modified intention-to-treat). First-line and rescue treatment lines were equally effective, but the effectiveness was worse when patients had previously received metronidazole, tetracycline, or rifabutin. Adding bismuth to HDDT in rescue treatment did not yield better results. The incidence of adverse events was 30%, diarrhea being the most common (20% of patients); no serious adverse events were reported.Although HDDT is safe and has good compliance, it is not a good option in European first-line or rescue

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

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

Abstract: Introduction: The Pan-European Registry on Helicobacter pylori management was conceived in 2013 to monitor eradication practices in Europe for 10 years. Aim: To assess the efficacy of different eradication regimens in a single outpatient clinic of gastroenterology. Method: Between 2013 and 2019, 247 patients were registered in a prospective non-interventional study. The infection was diagnosed either by endoscopy, histology, rapid urease test or 13C-urea breath test. As first-line treatment, the patients received either a 7-day triple regimen (any of PPI + amoxicillin + clarithromycin or tinidazole), 10-day modified sequential treatment (PPI + amoxicillin for 5 days + tinidazole and levofloxacin for 5 days), 10-day quadruple concomitant treatment (PPI + amoxicillin + tetracycline or doxycycline + metronidazole or tinidazole) or bismuth-based quadruple treatment. Bismuth or non-bismuth based quadruple or alternative regimens were given as second- or third-line treatment. Results: The eradication rates on per protocol basis were: 82.7% (95% confidence interval: 68.1–97.4) (first-line regimens), 85.2% (75.4–94.9) (sequential treatment), 95.1% (89.6–100) (concomitant treatment) and 82.6% (69.7–95.9) (bismuth-based quadruple regimen). Second-line regimens achieved 65.2% (48.2–83.0) and third-line therapy 54.5% (19.4–86.6), respectively. Conclusion: The first-line concomitant regimen was superior to triple and not significantly better than the sequential or bismuth-based treatment. Second- and third-line regimens achieved largely suboptimal results. Orv Hetil. 2019; 160(47): 1856–1863.

The antibiotic resistance profile of Helicobacter pylori (H. pylori) is constantly changing. Up-to-date and reliable data for the effectiveness of first-line H. pylori treatment protocols are necessary to provide evidence-based best-practice guidelines.To determine the effectiveness, compliance and safety of first-line treatment for H. pylori in Israel.An observational, prospective, multicenter study was conducted in tertiary referral centers in Israel, as part of the European registry on H. pylori management (Hp-EuReg). H. pylori-infected patients were included from 2013 to March 2020. Data collected included demographics, clinical data, diagnostic tests, previous eradication attempts, current treatment, compliance, adverse events, and treatment outcome result.In total, 242 patients were registered, including 121 (50%) who received first-line therapy, 41% of these individuals received clarithromycin based triple therapy and 58.9% received a four-drug regimen. The overall effectiveness of first-line therapy was 85% and 86% by modified intention-to-treat and per protocol analyses, respectively. The effectiveness of both sequential and concomitant therapies was 100% while clarithromycin-based triple therapy achieved an eradication rate of 79%. Treatment eradication was higher among patients who received high dose proton pump inhibitor (PPI) compared to those treated with low dose PPI (100% vs. 81.5% respectively, P0.01). No difference in treatment effectiveness was found between 7-, 10-, and 14-day treatment.The effectiveness of clarithromycin-based triple therapy is suboptimal. First-line treatment of H. pylori infection should consist of four drugs, including high dose PPI, according to international guidelines.

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.

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.To evaluate the efficacy and safety of third-line treatments with bismuth, metronidazole, and either tetracycline or doxycycline.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.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).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.

International audience; Background and aims: Inflammatory bowel diseases (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), are chronic and disabling disorders. Prospective disease-modification trials to prevent disease progression are eagerly awaited. However, disease progression is not clearly defined. The objective of the Selecting End PoInts foR Disease-ModIfication Trials (SPIRIT) initiative was to achieve international expert consensus on the endpoints to be used in future IBD-disease modification trials.Methods: This initiative under the auspices of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) began with a systematic literature search to evaluate the current evidence on the definition of disease progression in IBD. On October 22, 2019, a consensus meeting took place during the United European Gastroenterology Week (UEGW) Congress in Barcelona, during which predefined proposed statements were discussed in a plenary session and voted on anonymously. Agreement was defined as at least 75% of participants voting for any one statement.Results: The group agreed that the ultimate therapeutic goal in both CD and UC is to prevent disease impact on patient's life (health-related quality of life, disability, fecal incontinence), midterm complications (encompass bowel damage in CD, IBD-related surgery and hospitalizations, disease extension in UC, extraintestinal manifestations, permanent stoma, short bowel syndrome), and long-term complications (gastrointestinal and extraintestinal dysplasia or cancer, mortality).Conclusions: Recommendations on which goals to achieve in disease-modification trials for preventing disease progression in patients with IBD are proposed by the SPIRIT consensus. However, these recommendations will require validation in actual clinical studies before implementation in disease-modification trials.

Many interesting articles have been published from different parts of the world over the last year assessing various issues around Helicobacter pylori eradication therapy. This article will address the published literature over the last year pertaining to the topic of treatment of H. pylori infection. The main themes that emerge are assessing the efficacy of standard triple therapy, as well as exploring new first-line treatments, mainly optimized nonbismuth-containing and bismuth-containing quadruple therapies with some promising data also emerging on dual therapy. There was also considerable progress in investigating antibiotic resistance rates with much more data emerging from varied parts of the world compared to recent years. Advances in the use of adjunctive therapies, especially probiotic therapies have also been made. Undoubtedly, the eradication of H. pylori remains a worthwhile goal to alleviate the burden of diseases caused by the complications of this infection, including dyspepsia, peptic ulcer disease, and gastric cancer.

The International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) is the only global organization devoted to the study of and management of the inflammatory bowel diseases (IBDs), namely, Crohn?s disease and ulcerative colitis. Membership is composed of physician-scientists who have established expertise in these diseases. The organization hosts an annual meeting and a number of working groups addressing issues of the epidemiology of IBD, diet and nutrition, and the development and use of treatments for IBD. There are currently 89 members of IOIBD representing 26 different countries. The organization has taken particular interest in the coronavirus disease-2019 (COVID-19) pandemic and how it may affect the IBD patient population. This document summarizes the results of 2 recent virtual meetings of the group and subsequent expert guidance for patients and providers.

Coeliac disease (CD) is a chronic immune-mediated disease triggered by the ingestion of gluten. It has an estimated prevalence of approximately 1% in European populations. Specific HLA-DQA1 and HLA-DQB1 alleles are established coeliac susceptibility genes and are required for the presentation of gliadin to the immune system resulting in damage to the intestinal mucosa. In the largest association analysis of CD to date, 39 non-HLA risk loci were identified, 13 of which were new, in a sample of 12 014 individuals with CD and 12 228 controls using the Immunochip genotyping platform. Including the HLA, this brings the total number of known CD loci to 40. We have replicated this study in an independent Irish CD case-control population of 425 CD and 453 controls using the Immunochip platform. Using a binomial sign test, we show that the direction of the effects of previously described risk alleles were highly correlated with those reported in the Irish population, (P= 2.2 x 10(-16)). Using the Polygene Risk Score (PRS) approach, we estimated that up to 35% of the genetic variance could be explained by loci present on the Immunochip (P = 9 x 10(-75)). When this is limited to non-HLA loci, we explain a maximum of 4.5% of the genetic variance (P= 3.6 x 10(-18)). Finally, we performed a meta-analysis of our data with the previous reports, identifying two further loci harbouring the ZNF335 and NIFA genes which now exceed genome-wide significance, taking the total number of CD susceptibility loci to 42.

Vitamin D, as potential immune modulator, has been implicated as an environmental risk factor for Crohn’s disease (CD). Vitamin D status may be associated with disease risk, severity, activity, and progression. While associations between circulating 25OHD and markers of disease activity and inflammation in CD have been reported, the results are inconsistent. To determine the association between vitamin D status and markers of disease activity and inflammation in CD. One hundred and nineteen CD patients’ active and inactive diseases were enrolled in the cross-sectional study. Subject demographics and clinical data were collected. A serum sample was collected for 25OHD and CRP analysis, and a stool sample was collected for fecal calprotectin (FC) measurement. The mean serum 25OHD concentration of the group was 59.8 (24.9) nmol/L. After controlling for confounding variables, serum 25OHD inversely correlated with FC (r = −0.207, P = 0.030), particularly among those in clinical remission (r = −0.242, P = 0.022). The association between FC and 25OHD was further confirmed by linear regression (r = 31.3 %, P

Infliximab has been shown to have beneficial effects on bone metabolism in patients with Crohn’s disease (CD) although as yet the exact mechanisms have not been fully elucidated. To evaluate the impact of adalimumab therapy on bone metabolism using a combined in vivo and in vitro model. Parathyroid hormone, vitamin D, bone formation markers, bone resorption marker, pro-inflammatory cytokines, anti-inflammatory cytokines, osteoprotegerin, and sRANKL were measured in control patients and pre- and post-treatment with adalimumab in CD patients. The effect of control patients’ and pre- and post-treatment CD patients’ sera on human osteoblasts (hFOB 1.19) in vitro cell viability and differentiation was also analyzed. There was a significant increase in bone formation markers osteocalcin (P

Background and aims: Anaemia is an important complication of inflammatory bowel disease [IBD]. The aim of this study was to determine the prevalence of anaemia and the practice of anaemia screening during the first year following diagnosis, in a European prospective population-based inception cohort.Methods: Newly diagnosed IBD patients were included and followed prospectively for 1 year in 29 European and one Australian centre. Clinical data including demographics, medical therapy, surgery and blood samples were collected. Anaemia was defined according to the World Health Organization criteria.Results: A total of 1871 patients (Crohn's disease [CD]: 686, 88%; ulcerative colitis [UC]: 1,021, 87%; IBD unclassified [IBDU] 164. 81%) were included in the study. The prevalence of anaemia was higher in CD than in UC patients and, overall, 49% of CD and 39% of UC patients experienced at least one instance of anaemia during the first 12 months after diagnosis. UC patients with more extensive disease and those from Eastern European countries, and CD patients with penetrating disease or colonic disease location, had higher risks of anaemia. CD and UC patients in need of none or only mild anti-inflammatory treatment had a lower risk of anaemia. In a significant proportion of patients, anaemia was not assessed until several months after diagnosis, and in almost half of all cases of anaemia a thorough work-up was not performed.Conclusions: Overall, 42% of patients had at least one instance of anaemia during the first year following diagnosis. Most patients were assessed for anaemia regularly; however, a full anaemia work-up was frequently neglected in this community setting.

Background and Aims: The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe possibly due to changes in environmental factors towards a more "westernised" standard of living. The aim of this study was to investigate differences in exposure to environmental factors prior to diagnosis in Eastern and Western European IBD patients. Methods: The EpiCom cohort is a population-based, prospective inception cohort of 1560 unselected IBD patients from 31 European countries covering a background population of 10.1. million. At the time of diagnosis patients were asked to complete an 87-item questionnaire concerning environmental factors. Results: A total of 1182 patients (76%) answered the questionnaire, 444 (38%) had Crohn's disease (CD), 627 (53%) ulcerative colitis (UC), and 111 (9%) IBD unclassified. No geographic differences regarding smoking status, caffeine intake, use of oral contraceptives, or number of first-degree relatives with IBD were found. Sugar intake was higher in CD and UC patients from Eastern Europe than in Western Europe while fibre intake was lower (p.

There is a commonly held perception that Helicobacter pylori related diseases are declining, however these are still associated with a high risk of morbidity and mortality. In recent years worrying themes have emerged such as increasing levels of antibiotic resistance and falling cure rates which illustrate there is no room for complacency with respect to H. pylori. In addition there are many significant issues which have not been elucidated regarding the role played by H. pylori in very serious pathologies such as gastric and esophageal cancer and other more benign disorders common in the developed world such as gastroesophageal reflux disease, functional dyspepsia and perhaps obesity which carry a significant impact both economically and as regards to symptoms. Future guidelines aimed at European practitioners and patients will need to address the questions raised by these issues as well as the more familiar areas such as constituents and duration of therapy.

Helicobacter pylori resistance rates to antibiotics vary in different countries and even in different regions of the same country. Choice of treatment is strongly dependent on antibiotic resistance rates. In some countries, triple therapy with a proton-pump inhibitor, amoxicillin, and clarithromycin is still the best option, but eradication results fall short of what would be desired (90–95%) in countries with clarithromycin resistance >20%, bismuth-containing quadruple therapy, or nonbismuth sequential or concomitant therapies may then be the preferred option. Newer antibiotic regimens are awaited. Vaccination would be the best option, especially for developing countries, but little progress has been made in designing a vaccine.

Colorectal cancer (CRC) screening has been shown to be effective in reducing CRC incidence and mortality. There are currently a number of screening modalities available for implementation into a population-based CRC screening program. Each screening method offers different strengths but also possesses its own limitations as a population-based screening strategy. We review the current evidence base for accepted CRC screening tools and evaluate their merits alongside their challenges in fulfilling their role in the detection of CRC. We also aim to provide an outlook on the demands of a low-risk population-based CRC screening program with a view to providing insight as to which modality would best suit current and future needs.

Vitamin D deficiency impacts on bone health and has potential new roles in inflammation. We aimed to determine the prevalence of and risk factors for vitamin D deficiency and to explore vitamin D supplement usage in patients with Crohn's disease (CD) in an outpatient setting, compared with controls.Serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured by radioimmunoassay in 151 participants, comprising 81 CD patients and 70 age-, sex- and socio-economic status-matched healthy controls. Levels of 25(OH)D50 nmol/L were classed as deficient. Data on vitamin supplement usage were recorded for all participants at interview.Vitamin D deficiency was common in patients with CD (63%) and significantly higher in winter than summer (68% v 50%; p0.001, χ(2)). Notably, the deficiency rate remained high even in summer (50%). On regression analysis, 25(OH)D levels were inversely associated with winter season. Disease-specific factors for lower serum 25(OH)D levels were longer disease duration and smoking. Overall, 43% of patients reported using a vitamin D-containing supplement, primarily at low dosages (200-400 IU/d); however, this level of supplement did not prevent deficiency. For the majority of CD patients, 25(OH)D remained below optimal levels proposed to confer bone and immune health benefits.Vitamin D deficiency was common in patients with CD and associated with longstanding disease, smoking and winter. While over 40% of patients used a vitamin D-containing supplement, the dosages were inadequate to prevent deficiency. Appropriate vitamin D screening and supplementation should be considered in the context of health promotion of outpatients with CD.

This article reviews the literature published pertaining to Helicobacter pylori eradication over the last year. The general perception among clinicians and academics engaged in research on H. pylori has been that eradication rates for first-line therapies are falling, although some data published this year have cast doubt on this. The studies published this year have therefore focussed on developing alternative strategies for the first-line eradication of H. pylori. In this regard, clear evidence now exists that both levofloxacin and bismuth are viable options for first-line therapy. The sequential and "concomitant" regimes have also been studied in new settings and may have a role in future algorithms also. In addition, data have emerged that the probiotic Saccharomyces boulardii may be a useful adjunct to antibiotic therapy. Other studies promote individualized therapies based on host polymorphisms, age, and other such demographic factors.

BACKGROUND: There is no international agreement on scoring systems used to measure disease activity in ulcerative colitis, nor is there a validated definition for disease remission. AIM: To review the principles and components for defining remission in ulcerative colitis and propose a definition that will help improve patient outcomes. METHODS: A review of current standards of remission from the perspective of clinical trials, guidelines, clinical practice and patients was conducted by the authors. Selected literature focused on the components of a definition of remission, the utility of a definition and treatment strategies, based on current definitions. RESULTS: Different definitions of remission affect the assessment of outcome and make it difficult to compare trials. In the clinic, endoscopy is rarely used to confirm remission, because mucosal healing has only recently begun to be related to the duration of subsequent remission in a way that will affect clinical practice. Histopathology may be the ultimate arbiter of mucosal healing. There is no agreement on the definition of remission in current guidelines. Patient-defined remission may predict endoscopic remission, but has yet to be shown to predict duration of remission. CONCLUSIONS: A standard based on clinical symptoms and endoscopy is proposed. Histopathology is a third dimension of remission that may have prognostic value. The definition of remission should help predict long-term outcome. The expectations of patients and their physicians need to be raised, as the goal of treatment of active ulcerative colitis should be to induce remission.

Summary Background Patients with inflammatory bowel disease (IBD) are at increased risk of osteoporosis. A number of studies have emerged in recent years indicating that tumour necrosis factor (TNF) blockade appears to have a beneficial effect on bone mineral density (BMD) in IBD patients. Aims To provide a review of the available data regarding the effect of the currently licensed anti-TNF-α therapies on bone metabolism and BMD in IBD patients. Methods A Medline search was performed using the search terms ‘infliximab’, ‘bone metabolism’, ‘IBD’, ‘BMD’, ‘bone markers’, ‘adalimumab’, ‘bone disease’, ‘Crohn’s disease’ and ‘ulcerative colitis’. Results Infliximab has a beneficial effect on bone turnover markers in Crohn’s disease (CD) patients in the short term. The longest study to date comprising 24 CD patients showed an overall improvement in two bone formation markers – b-alkaline phosphatase (P = 0.022) and osteocalcin (P = 0.008) at 4 months post-treatment. Moreover, the largest study to date comprising 71 CD patients showed significant improvement in sCTx, a bone resorption marker (P = 0.04) at week-8 post-treatment. There is little data looking at the effect of anti-TNF-α therapy on bone metabolism in ulcerative colitis. Moreover, the long-term effects of anti-TNF-α therapy on bone structure and fracture risk in IBD patients are currently not known. The effect of cessation of anti-TNF-α therapy on bone metabolism is also unknown. Conclusion Properly controlled long-term trials are needed to fully evaluate the impact of TNF blockade on bone mineral density.

Epidemiologic shift with rising incidence of Crohn’s disease (CD) has been reported in recent studies. To determine disease behaviour and therapeutic interventions undertaken in newly diagnosed patients with CD. Patients diagnosed with CD between January 2006 and June 2008 were included. Disease type, location, degree of involvement and type of therapeutic interventions were recorded. A total of 78 patients were included. Colonic, ileo-colonic, terminal ileal and isolated small bowel disease were present in 37, 27, 9 and 5 patients, respectively. Disease phenotype was inflammatory, stenosing and fistulising in 42, 30 and 6 patients, respectively. Surgery was required in 22 patients, including right hemicolectomy (n = 8), subtotal colectomy (n = 4), segmental colonic resection (n = 2), segmental small bowel resection (n = 2), appendectomy (n = 2) and perianal surgery (n = 4). Fourteen patients underwent surgery at the time of diagnosis. Laparoscopic surgery was performed in 14 patients. A significant proportion of newly diagnosed patients with CD underwent surgical intervention on their first admission to hospital. This may signify a changing trend in the management approach.

Colorectal polyps are usually asymptomatic and are found opportunistically. Individuals with adenomata are at increased risk for cancer and therefore guidelines exist for surveillance of these lesions including those of the British Society of Gastroenterology (BSG). Deviation from these guidelines is common and increases the workload of endoscopy. We examined those individuals waiting for endoscopy for polyp surveillance to see whether strict adherence to BSG guidelines could facilitate opportunities for screening. A total of 413 patients with earlier colonic polyps were examined, of whom 50 patients were excluded based on having alternative indications for surveillance, 179 (49.3%) were appropriately scheduled for surveillance and 184 patients (55.9%) were scheduled incorrectly. Seventy-nine patients (30%) could have been discharged; of these, 59 had hyperplastic polyps. Of the remaining 105 inappropriate triages under surveillance at the wrong interval, seven patients were scheduled for too infrequent surveillance and 98 were too frequent. A total of 284 patients with adenomatous polyps were under surveillance of whom 11 patients (3.8%) were in the high-risk category and all were appropriately scheduled, and 75 patients (26.4%) were in the intermediate-risk category, of whom 48 were appropriately scheduled, 20 were incorrectly triaged as high risk and seven were triaged as low risk. A total of 198 (69.7%) patients were in the low-risk category, 117 of these were correctly triaged, 15 were incorrectly triaged as high risk and 66 were classified as intermediate risk. Over a five-year period, 318 unnecessary colonoscopies are being performed. On the basis of the data obtained from a population-based colorectal screening programme using immunohistochemical-faecal occult blood testing in our department another 1516 patients could be screened annually without requiring any additional endoscopy resources, if strict adherence to guidelines was assured.

It is accepted that the success of Helicobacter pylori eradication treatment using standard triple therapy is declining. Resistance, particularly to clarithromycin, has been shown in numerous countries to be rising to a level where the use of standard triple therapy in its current form may no longer be justified. The two major factors influencing resistance are prior exposure to the antibiotic and compliance with therapy. Regimes based on bismuth and levofloxacin, which had previously been mainly second-line options, are now emerging as superior first-line options. Trials of sequential and concomitant therapies are also showing the usefulness of these treatments in different populations. Options for third and subsequent line therapies include furazolidone and rifabutin-based regimes. Susceptibility testing should be performed to maintain accurate data on resistance levels, and has also clinical utility in difficult to eradicate cases. None of these, however, will be successful unless compliance is improved upon. If compliance is assured and eradication confirmation pursued, it has been repeatedly illustrated that near full eradication is achievable.

Summary Background Helicobacter pylori infection is eradicated with antimicrobial agents and drug-resistant strains make successful treatment difficult. Geographical variations in virulence-factor genotype also exist. Aim To evaluate prevalence of drug resistance and virulence-factor genotype in Irish H. pylori strains and to investigate if there is any relationship between drug resistance and genotype. Methods Helicobacter pylori strains isolated from 103 patients were examined. Antimicrobial susceptibilities were tested by Etest. The virulence-factor genotypes were determined using PCR. Frequencies of spontaneous metronidazole-resistance were measured in vitro. Results Metronidazole resistance was present in 37.9% of strains examined. 16.5% of strains were clarithromycin-resistant and resistance to both agents observed was found in 12.6% of strains. 68% of strains were cagA+. The dominant vacA type was s1/m2, followed by s1/m1 and s2/m2. The metronidazole resistance rate in cagA− group was significantly higher than in cagA+ (P = 0.0089). Spontaneous resistance to metronidazole in cagA− occurred in higher frequency when compared with cagA+. Conclusions cagA+ and vacAs1/m2 type was the dominant genotype in Irish H. pylori strains. Significant rates of metronidazole resistance were observed in cagA− group. cagA− strains tend to acquire metronidazole resistance in vitro. Absence of cagA might be a risk factor in development of metronidazole resistance.

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

Background and aims Communication to patients of information about their disease has become increasingly important in modern medicine, and particularly with chronic nonfatal disorders like inflammatory bowel disease (IBD), but the subject is not adequately researched or understood. Methods We studied the media and preferences for communication of information in a multi-national community-based inception cohort of European and Israeli patients with IBD and 10 years follow-up, using structured questionnaires categorizing demographics, disease status, current and preferred sources of information, use of electronic media, role of patients' associations, and satisfaction level. Results The 917 patients completing the questionnaire were derived from northern (60%) and southern (40%) countries. The mean age was 48.3 years (62% under 50 years); 51% were males; 67% had ulcerative colitis, 33% Crohn's disease. Sixty-six percent of patients designated the specialist as their primary source of information, 77% indicated satisfaction with their current information, and 65% reported not receiving information about medical treatment in the past year. Patient concerns were about new research into their illness (64%), medical treatments (58%), risks and complications (51%) and genetics (42%). Preferred sources of information were paper bulletin (76%), electronic media (30%) and international organization (79%). Diagnosis (ulcerative colitis or Crohn's disease), gender, education level and country impacted significantly on patients' choices. Conclusions In providing health care information to patients with IBD their individual attitudes and preferences must be considered. There should be greater roles for IBD patients' associations and international IBD-research organizations, and an increasing use of electronic media.

Since the discovery of Helicobacter pylori in the early 1980s several treatment regimens have been developed to effectively treat this infection. International guidelines have allowed consensus on the best management and improved eradication rates. In recent years increasing antimicrobial resistance and falling eradication rates highlight the need for updated guidelines. In this article we review the most recent European management guidelines and in view of the unavailability of some drugs consider new treatment regimens for the management of H. pylori in Ireland.

PUBLISHED, * Joint Senior Authors, We acknowledge funding from Coeliac UK (to DAvH); the Coeliac Disease Consortium (an innovative cluster approved by the Netherlands Genomics Initiative and partly funded by the Dutch Government, grant BSIK03009 to CW); the European Union (STREP 036383); the Netherlands Organization for Scientific Research (VICI grant 918.66.620 to CW); the Science Foundation Ireland; the Irish Health Research Board; Hitachi Europe Ltd.; and the Wellcome Trust (GR068094MA Clinician Scientist Fellowship to DAvH; New Blood Fellowship to RMcM; support for the work of RMcG and PD). We thank the Barts and The London Genome Centre for genotyping support; J Swift, P. Kumar, D.P. Jewell, S.P.L. Travis, K. Moriarty for collection of UKGWAS and additional samples. We acknowledge use of DNA from the British 1958 Birth Cohort collection, funded by the UK Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02.. We thank A. Monsuur for patient recruitment, G. Meijer and J. Meijer for histology review, K. Duran for DNA extraction, H. van Someren and F. Mulder for clinical database management, M. Plateel and the Genotyping facilities at UMCG and UMC Utrecht for technical assistance (the Netherlands). We thank M. Abuzakouk, R. McLoughlin, K. Brophy, C. Feighery, J. McPartlin for sample collection. Irish Control DNA was supplied by Irish Blood Transfusion Service/Trinity College Dublin Biobank. We thank the Wellcome Trust Centre for Human Genetics, University of Oxford for provision of computing facilities and G. McVean for recombination rate data. We thank all celiac and control individuals for participating in this study.

OBJECTIVES: There is no clear evidence that dietary proteins aggravate Crohn’s disease (CD). We aimed to clarify the antibody response to dietary proteins in CD. METHODS: Antibody to porcine pancreatic amylase (PPA) a protease-resistant dietary protein (anti-PPA), was examined in CD patients (N = 104), ulcerative colitis (UC) patients (N = 85), and healthy controls (N = 83), and its relationship with the clinical characteristics of CD was investigated. Antibodies to casein and ovalbumin, anti-Saccharomyces cerevisiae antibodies (ASCA), and antibodies to I2 from Pseudomonas fluorescens (anti-I2) were also examined. RESULTS: Thirty-eight percent (39/104) of the CD patients expressed anti-PPA antibodies, and this percentage was significantly higher as compared with the control group (5%, 4/83) and the UC group (9%, 8/85) (P < 0.001). A significantly higher level of anti-PPA antibodies was detected in patients with “small bowel disease-dominant” CD than in those with “colitis-dominant” CD (P < 0.05). Antibodies to casein and ovalbumin were not specifically expressed in CD patients. As ASCA was detected in 33% and anti-I2 in 46% of the CD patients, 72% of the CD patients were found positive for at least one of the three antibodies including anti-PPA antibodies. CONCLUSIONS: CD patients showed a specific antibody response to PPA, as compared with UC patients and controls. There was a significantly higher level of anti-PPA antibody in patients with “small bowel disease-dominant” CD, suggesting that dietary proteins could play a role in the inflammatory response in CD patients with small bowel disease. Anti-PPA antibodies combined with ASCA/anti-I2 may be useful for the diagnosis of CD. (Am J Gastroenterol 2008;103:656‐664)

Summary Background One of the most frequently asked questions during consultation with those affected by inflammatory bowel disease is what are its effects on pregnancy, and how the treatment will impact on conception and pregnancy outcomes. Aim To review available data regarding the safety of biological therapies during pregnancy, primarily in woman with inflammatory bowel disease. Methods A Medline search was performed and available original research and review articles relating to the use of biological (antitumour necrosis factor-α) therapies in inflammatory bowel disease were reviewed. Where information regarding the use of a drug in inflammatory bowel disease during pregnancy was limited, articles referring to its use for other indications, such as rheumatoid arthritis, were reviewed. Conclusions Based on available data, biological therapies appear to be safe in pregnancy. Most studies looking at the effects of any one medication on pregnancy in inflammatory bowel disease are confounded by the fact that most patients are on multiple medications and have varying levels of disease activity. Stopping therapy in the third trimester should be considered. Large registries with longer follow-up periods will be necessary before firm conclusions about the safety of antitumour necrosis factor-α therapies during conception and pregnancy can be drawn.

Crohn's disease (CD) is a chronic inflammation of the gastrointestinal tract associated with life-long high health care costs. We aimed to determine the effect of disease phenotype on cost.Clinical and economic data of a community-based CD cohort with 10-year follow-up were analyzed retrospectively in relation to Montreal classification phenotypes.In 418 patients, mean total costs of health care for the behavior phenotypes were: nonstricturing-nonpenetrating 1690, stricturing 2081, penetrating 3133 and penetrating-with-perianal-fistula 3356 €/patient-phenotype-year (P0.001), and mean costs of surgical hospitalization 215, 751, 1293 and 1275 €/patient-phenotype-year respectively (P0.001). Penetrating-with-perianal-fistula patients incurred significantly greater expenses than penetrating patients for total care, diagnosis and drugs, but not surgical hospitalization. Total costs were similar in the location phenotypes: ileum 1893, colon 1748, ileo-colonic 2010 and upper gastrointestinal tract 1758 €/patient-phenotype-year, but surgical hospitalization costs differed significantly, 558, 209, 492 and 542 €/patient-phenotype-year respectively (P0.001). By multivariate analysis, the behavior phenotype significantly impacted total, medical and surgical hospitalization costs, whereas the location phenotype affected only surgical costs. Younger age at diagnosis predicted greater surgical expenses.Behavior is the dominant phenotype driving health care cost. Use of the Montreal classification permits detection of cost differences caused by perianal fistula.

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