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Introduction: A new clinician-administered inflammatory bowel disease (IBD) Disability Index (IBDDI) was recently developed and validated among a population in France. We aimed to validate the IBDDI in a North American setting and adapt for use as a self-report tool. Methods: Persons 18-65 years old from the population-based University of Manitoba IBD Research Registry were mailed a self-administered survey. This survey included the IBDDI and several scales that should correlate with a disability measure- the World Health Organization (WHO) Disability Assessment Scale (WHODAS) 2.0, Work and Social Adjustment Scale (WSAS), the Inflammatory Bowel Disease Questionnaire (IBDQ), and the K6-Kessler Emotional Distress Scale. We used Pearson correlation coefficients to assess construct validity, Cronbach's alpha to assess internal consistency, and Factor analysis to assess which of the IBDDI items likely belonged to a single IBD-related disability factor. Results: In response to the survey request,1143 (46% of those contacted) participated (61% female, mean age 51, 52% with Crohn's disease). On an index scale from 0-100, 14% had a score ≥50 (extreme disability, 18% of those with Crohn's disease; 10% of those with ulcerative colitis). There were strong correlations between IBDDI and WSAS (0.76), WHODAS (0.76), K6 (0.73), and an inverse correlation with IBDQ (-0.86). The Cronbach's alpha was high (0.88). All but 2 items (number of liquid stools in the past week and arthritis/arthralgia) of the 14 identified for IBDDI loaded highly onto a single factor (factor loading > 0.40). Conclusions: The findings support the validity of this new self-report version of the IBDDI as a sound measure of disability in IBD.

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BACKGROUND: Proton pump inhibitor (PPI) use is associated with an increased risk of Clostridium difficile infection (CDI), though the mechanism is unclear. PPI induced alterations to the gut microbiome may facilitate the emergence of CDI, though the effects of PPIs on gut microbiota are not well characterised. [Correction added on 10 March 2016, after first online publication: microflora has been changed to microbiota throughout the article.] AIM: To compare the faecal microbiomes of long-term PPI users to those with no history of PPI use. METHODS: We used a population-based database to identify individuals with ≥5 years of continuous PPI use along with non-PPI using controls. Stool samples were subjected to microbiological analysis, with hierarchical clustering at genus level, along with alpha and beta diversity measures comparing the two groups. Metadata was accounted for using quantile regression to eliminate potential confounding variables in taxonomic abundance comparisons. RESULTS: Sixty-one subjects (32 PPI, 29 controls) were analysed. While no significant differences in alpha diversity were found between the PPI users and controls, a moderate shift of the PPI users away from the non-PPI user cluster in the beta diversity was observed. After controlling for pertinent confounders, we discovered a decrease in Bacteroidetes and an increase in Firmicutes at the phylum level. We also performed species classifications and found Holdemania filiformis and Pseudoflavonifractor capillosus to be increased and decreased in the PPI cohort, respectively. CONCLUSIONS: Long-term PPIs use has an effect on the gut microbiome. The alteration in the ratio of Firmicutes to Bacteroidetes may pre-dispose to the development of CDI.

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BACKGROUND: Predictors of complicated Crohn's disease (CD), defined as stricturing or penetrating behaviour, and surgery have largely been derived from referral centre populations. AIM: To investigate whether serological markers, susceptibility genes or psychological characteristics are associated with complicated CD or surgery in a population-based cohort. METHODS: One hundred and eighty-two members of the Manitoba IBD Cohort with CD phenotyped using the Montreal classification underwent genetic and serological analysis at enrolment and after 5 years. One hundred and twenty-seven had paired sera at baseline and 5 years later and their data were used to predict outcomes at a median of 9.3 years. Serological analysis consisted of a seven antibody panel, and DNA was tested for CD-associated NOD2 variants (rs2066845,rs2076756,rs2066847), ATG16L1 (rs3828309, rs2241880) and IL23R (rs11465804). Psychological characteristics were assessed using semi-structured interviews and validated survey measures. RESULTS: Sixty-five per cent had complicated CD and 42% underwent surgery. Multivariate analysis indicated that only ASCA IgG-positive serology was predictive of stricturing/penetrating behaviour (OR = 3.01; 95% CI: 1.28-7.09; P = 0.01) and ileal CD (OR = 2.2; 95% CI: 1.07-4.54, P = 0.03). Complicated CD behaviour was strongly associated with surgery (OR = 5.6; 95% CI: 2.43-12.91; P < 0.0001), whereas in multivariate analysis, only ASCA IgG was associated (OR = 2.66; 95% CI, 1.40-5.06, P = 0.003). ASCA titre results were similar at baseline and follow-up. Psychological characteristics were not significantly associated with disease behaviour, serological profile or genotype. CONCLUSIONS: ASCA IgG at baseline was significantly associated with stricturing/penetrating disease at 9-10 years from diagnosis. Stricturing/penetrating disease was significantly associated with surgery. In a model including serology, the genotypes assessed did not significantly associate with complicated disease or surgery.

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UNLABELLED: A large Canadian cohort was studied over 10 years to see if proton pump inhibitor (PPI) use increased the risk of sustaining a fragility fracture. We found an increased risk of fracture in individuals who used PPIs. The risk remained after controlling for other known fracture risk factors. INTRODUCTION: Multiple retrospective studies have linked proton pump inhibitor use with increased risk of fragility fracture. We prospectively studied the association between PPI use and fracture in a large cohort over a 10-year period while controlling for known fracture risk factors. METHODS: We studied 9,423 participants in the Canadian Multicenter Osteoporosis Study. The cohort was formed in 1995-1997 and followed for 10 years with monitoring for incident nontraumatic fracture and PPI use. Cox regression analyses were used to assess the association between PPI use and incident fracture risk. RESULTS: PPI use, coded as a time-dependent variable, was associated with a shorter time to first nontraumatic fracture, hazard ratio (HR)=1.75 (95% confidence interval (CI) 1.41-2.17, p<0.001). After controlling for multiple risk factors, including femoral neck bone density, the association remained significant, HR=1.40 (95% CI 1.11-1.77, p=0.004). Similar results were obtained after controlling for bisphosphonate use, using PPI "ever" use, or when the outcome was restricted to hip fracture. CONCLUSIONS: In this large prospective population-based cohort study, we found an association between PPI use and increased risk of fragility fracture. Although the increased risk found was modest, this finding is important, given the high prevalence of PPI use and the excess morbidity and mortality associated with osteoporosis-related fractures.

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BACKGROUND: It is believed that women with inflammatory bowel disease (IBD) have heightened symptoms around their menses. However, there is little information regarding normative changes and which symptoms emerge in relation to menses. AIM: To determine the relationship between gastrointestinal and other symptoms and menses in a population-based cohort of women with IBD vs. healthy women. METHODS: Women enrolled in the University of Manitoba IBD Research Registry who were between 18 and 65 years were mailed a survey. A control group of adult women were recruited through out-patient gynaecology clinics. Participants were asked to consider their menstrual periods in the recent several months and report on symptoms 1-5 days prior to and during the days of their menses. RESULTS: There were 151 premenopausal women with Crohn's disease (CD), 87 with ulcerative colitis (UC) and 156 premenopausal controls. Mean age of menses onset was similar in all three cohorts and the percentage in each group with regular menstrual periods was similar. Premenstrually, abdominal pain was less commonly reported in UC (36.8%) than CD (51%, P = 0.034) and controls (57.6%, P = 0.002). Premenstrually, and during menses diarrhoea was more commonly reported in CD (47.7% and 59.6% respectively) than UC (26.4% P = 0.001 and 42.5%, P = 0.01 respectively) and controls (24.4%, P < 0.0001 and 28.2%, P < 0.0001 respectively). Premenstrually, women with CD (46%) vs. UC (26%) were more likely to report worsening of their IBD symptoms (P = 0.0007), but there was no difference between CD (47%) and UC (39%) for reporting worsening during menses (P = 0.24). CONCLUSIONS: Compared to healthy women, women with IBD had similar symptom experiences premenstrually, except that those with CD were more likely to have increased diarrhoea premenstrually. During menses, women with CD or UC were more likely to experience diarrhoea than healthy controls.

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BACKGROUND: Aspirin use is with an increased risk of upper gastrointestinal complications (UGICs). Proton pump inhibitors (PPIs) decrease the risk of UGICs among aspirin users. The distribution of risk factors for UGIC and PPI utilization among aspirin users remains uncharacterized. AIM: To determine the prevalence and predictors of PPI use in high-risk aspirin users. METHODS: Using questionnaires and administrative records, we collected information on aspirin and PPI utilization and risk factors for UGICs from a stratified random sample of subjects with established cardiovascular disease. We calculated the proportion of aspirin users with UGIC risk factors and determined the prevalence of PPI use among aspirin users with risk factors. Regression analysis was used to determine predictors of PPI use among aspirin users. RESULTS: Overall response rate was 35%, of whom 86% were regular aspirin users. Seventy-one per cent of aspirin users had at least one risk factor (in addition to cardiac disease) for the development of UGICs. Although a history of UGIC was predictive of PPI use, 44% of aspirin users with a prior history of UGICs did not receive a concomitant PPI, and only 23% of subjects with additional UGIC risk factors were prescribed a PPI. CONCLUSION: There is a high prevalence of UGIC risk factors among aspirin users, and many are not prescribed PPIs as a gastroprotective strategy.

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BACKGROUND: When faced with the same set of facts, healthcare providers often make different diagnoses, employ different tests and prescribe disparate therapies. AIM: To perform a national survey to measure process of care and variations in decision-making in Crohn's disease, and the compared results between experts and community providers. METHODS: We constructed a survey with five vignettes to elicit provider beliefs regarding the appropriateness of diagnostic tests and therapies in Crohn's disease. We measured agreement between community gastroenterologists and Crohn's disease experts, and measured variation within each group using the RAND Disagreement Index (DI), which is a validated measure of provider variation. RESULTS: We received 186 responses (42% response rate). Experts and community providers generally agreed on diagnostic testing decisions in Crohn's disease. However, there was a significant disagreement between groups for several decisions (use of 5-aminosalicylate in particular), and there was evidence of 'extreme variation' (defined as DI > 1.0) within groups across a range of decisions. CONCLUSIONS: Although experts and community providers are in general consensus about diagnostic decision-making in Crohn's disease, extreme variation exists both between and within groups for key therapeutic decisions in Crohn's disease. We must understand and decrease this variation prior to future efforts of creating explicit quality indicators in Crohn's disease.

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BACKGROUND: Several therapies have been demonstrated to be beneficial in the management of acute variceal bleeding (AVB). The aim of the present study was to characterize the use of these therapies at a Canadian tertiary care centre. PATIENTS AND METHODS: A comprehensive chart review was performed to assess the management of all adult cirrhotic patients with AVB who were admitted to a university-affiliated, tertiary care centre between April 2001 and March 2004. RESULTS: A total of 81 AVB patients were identified with a mean age of 53.7+/-13.2 years and a median model for end-stage liver disease score of 14. Endoscopy was performed within 8.2+/-7.6 h of admission. Variceal banding was performed for 87% of patients with esophageal varices, which were the most common source of bleeding (80%). Octreotide was used in 82% of patients for a mean duration of 74.3+/-35.4 h; prophylactic antibiotics were used in 25% of patients and beta-blockers were used in 24% of patients without any contraindications. Follow-up endoscopy was arranged for 46 of 71 (65%) survivors. Prophylactic antibiotic use was associated with the presence of ascites, while beta-blockers were used more often in the last year of the study. CONCLUSIONS: There is a disconnection between the use of evidence-based recommendations and routine clinical practices in the management of AVB. Deficiencies identified include the lack of use of prophylactic antibiotics and beta-blockers, variable use of octreotide and inadequate follow-up recommendations. There is a need to identify measures to improve the process of care for patients with AVB which would ensure optimal management of these patients.

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BACKGROUND: Proton pump inhibitors (PPIs) following endoscopic haemostasis reduce rebleeding rates in patients with high-risk acute non-variceal upper gastrointestinal bleeding. Many advocate the use of PPIs prior to endoscopy, although its incremental benefit is unproven. AIM: To determine if providing PPIs before endoscopy reduces adverse gastrointestinal outcomes in acute non-variceal upper gastrointestinal bleeding patients. METHODS: We performed a retrospective review to identify patients presenting to two tertiary care centres with acute non-variceal upper gastrointestinal bleeding between 1999 and 2004. Subjects receiving PPI therapy before endoscopy were compared with those not receiving pre-endoscopic PPI therapy. The primary outcome measure was the development of any adverse bleeding outcome (rebleeding, surgery for control of bleeding, in-hospital mortality, readmission within 30 days for acute non-variceal upper gastrointestinal bleeding). RESULTS: 385 patients were included in our study [132 (12 intravenous/120 po) pre-endoscopic PPI vs. 253 no pre-endoscopic PPI]. Patients receiving pre-endoscopic PPI therapy were significantly less likely to develop adverse outcomes compared with those not given pre-endoscopic PPIs (25% vs. 13%, P = 0.005). Rebleeding, upper gastrointestinal surgery, mortality and length of hospital stay were also significantly lower in patients receiving pre-endoscopic PPI. CONCLUSIONS: The use of PPIs before endoscopy significantly reduces the risk of developing adverse gastrointestinal outcomes in patients with acute non-variceal upper gastrointestinal bleeding. Future studies are required to better characterize this relationship.

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BACKGROUND: Many doctors unnecessarily prescribe gastroprotective strategies to non-steroidal anti-inflammatory drugs users at low risk of non-steroidal anti-inflammatory drug-related gastrointestinal complications. AIM: To identify factors that predict the overuse of gastroprotective strategies in low-risk non-steroidal anti-inflammatory drug users. METHODS: We distributed a questionnaire to family doctors and general internists consisting of a clinical vignette describing a low-risk hypothetical patient with osteoarthritis who was a candidate for non-steroidal anti-inflammatory drug therapy. Respondents were asked whether they would prescribe this patient a gastroprotective strategy and to estimate the annual risk of that patient developing a gastrointestinal complication with non-steroidal anti-inflammatory drug use. Respondents inappropriately recommending a gastroprotective strategy were compared with respondents who opted not to use gastroprotection. RESULTS: We received 340 responses (response rate of 28.3%), of which 278 supplied analysable data. Thirty-five percent of respondents inappropriately recommended a gastroprotective strategy for the low-risk subject. Inappropriate prescribers were significantly more likely to overestimate the risk of gastrointestinal complications with traditional non-steroidal anti-inflammatory drugs and this was strongly predictive of gastroprotective strategy recommendation in logistic regression. CONCLUSIONS: Many doctors inappropriately recommend gastroprotective strategies in low-risk non-steroidal anti-inflammatory drug users. Improving doctors' awareness of non-steroidal anti-inflammatory drug-associated gastrointestinal risks may lead to a decrease in inappropriate utilization of gastroprotective strategies in low-risk patients.

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BACKGROUND: Aspirin is often used in patients with cardiovascular disease, but it can also cause gastrointestinal complications. Proton pump inhibitors reduce the risk of gastrointestinal complications in aspirin users with a history of gastrointestinal complications. AIM: To determine the prevalence of gastrointestinal risk factors in aspirin users and the prevalence of proton pump inhibitor utilization in high-risk patients. METHODS: We reviewed all patients admitted to hospital between April and October 2004 with a diagnosis of cardiovascular disease. We collected data on demographics, medication use, comorbid illnesses, previous gastrointestinal complications, and medication use on admission and discharge. RESULTS: A total of 324 patients were admitted with cardiovascular disease of whom 94% were discharged on aspirin. Seventy-eight per cent of patients admitted had at least one gastrointestinal risk factor in addition to having cardiovascular disease, and 15% had three or more additional gastrointestinal risk factors. Patients with additional gastrointestinal risk factors were more likely to be prescribed proton pump inhibitor therapy (27% vs. 10%, P < 0.001). Only 10% of proton pump inhibitor-naíve high-risk aspirin users were prescribed a proton pump inhibitor upon discharge. CONCLUSIONS: The majority of high-risk aspirin users are not receiving proton pump inhibitors for gastroprotection. Further work is required to encourage providers to consider the use of gastroprotective strategies in appropriate patients.

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