Forbes J, Van Domselaar G, Bernstein CN. The gut microbiota in immune-mediated inflammatory diseases. Frontiers in Microbiology 2016; 7:1081.

 

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Forbes J, Van Domselaar G, Bernstein CN. Microbiome survey of the inflamed and non-inflamed gut at different compartments within the gastrointestinal tract of inflammatory bowel disease patients. Inflammatory Bowel Diseases 2016; 22:817-25.

 

We compared the bacterial communities of inflamed and noninflamed bowel lining of patients with IBD and by analysis of the microbiota composition at distinct areas of the ileum and colon. There was no variation in any bacteria comparing inflamed to non-inflamed areas of the bowel within Crohn’s disease or within ulcerative colitis. The main differences were in comparing the non-inflamed mucosa between Crohn’s disease and ulcerative colitis: Groups (phyla) of organisms known as Bacteroidetesand Fusobacteria were detected more frequently in inflamed Crohn’s disease areas than in inflamed ulcerative colitis mucosa. Conversely, Proteobacteria and Firmicutes were more frequently observed in the inflamed ulcerative colitis mucosa. At the genus level (a smaller group of bacteria than phyla) the abundance of 13 groups were significantly different within the non-inflamed mucosa between Crohn’s disease and ulcerative colitis.

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Forbes J, Van Domselaar G, Sargent M, Green C, Springthorpe S, Krause D, Bernstein CN. Microbiome profiling of drinking water in relation to incidence of inflammatory bowel disease. Canadian Journal of Microbiology 2016; 18:1-13.

 

For one year we collected water from firehalls and community centres from over 20 communities in Winnipeg and in rural Manitoba. We aimed for areas that were known to have either high or low incidence of IBD. We wanted to determine if there were bacteria in the water that were unique to high or low incidence areas or missing from high or low incidence areas so as to potentially target those bacteria for treatment of IBD. This work lays out a basis for further studies exploring water as a potential environmental source for IBD triggers. 

 

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Bernstein CN, Nugent ZN, Targownik LE, Singh H, Lix L. Predictors and risks for death in a population based study of persons with IBD in Manitoba. Gut 2015; 64: 1403-1411.

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We aimed to determine the predictors and risk for death among persons with either Crohn’s disease (CD) or ulcerative colitis (UC) compared to the general population.  We used the population based University of Manitoba IBD Epidemiology Database to calculate mortality rates in persons with IBD in relation to the general population. There were 10,788 prevalent cases of CD and UC and 101,860 matched controls.  Persons with CD had a 26% higher mortality rate than the general population but there was no difference in mortality for prevalent UC cases compared to matched controls. CD cases were more likely to die of colorectal cancer, non-Hodgkin lymphoma, digestive diseases, pulmonary embolism and sepsis and UC cases were more likely to die from colorectal cancer, digestive diseases, and respiratory diseases.  For incident cases there were significant effects on mortality by socioeconomic status, comorbidity score and surgery. The greatest risk for death in both CD and UC was within the first 30 days following gastrointestinal  surgery. The first year from diagnosis was also associated with increased risk of death in both CD and UC, but persisted after the 1st year only in CD. We concluded that there is a significantly increased risk of mortality in CD compared to controls while in UC an increased risk for death was only evident in the first year from diagnosis. Surgery poses an increased risk for death in both CD and UC for up to 1 year.

 

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Mayo NE, Scott SC, Bernstein CN, Lix LM. How are you? Do people with inflammatory bowel disease experience response shift on this question? Health and Quality of Life Outcomes 2015; May 6: 13: 52.

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As individuals experience changes in their health, they may alter the way they evaluate health and quality of life. The purpose of this study was to estimate the extent to which individuals with IBD change their rating of health over time because of response shift especially in relation to a single question on self-rated health. Disease activity, vitality, pain, somatization, and physical and social function explained 51% of the variation in general health over two years with no evidence of response shift in the majority of the sample. Negative response shift was found for 8%, who initially rated health better than predicted; positive response shift was found for 6%. The positive response shift group was younger and had better baseline scores on measures of general health, hostility, pain, mental health and social and role function. Less pain and better social function scores at baseline were predictors of negative response shift. In conclusion, the majority of people with IBD did not demonstrate a response shift indicating that the health rating over time was stable in relation to that predicted by known time varying clinical variables. This adds to the evidence that the single question on self-rated health is useful for monitoring individuals over time.

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Bernstein CN, Banerjee A, Targownik LE, Singh H, Ghia JE, Burchill C, Chateau D, Roos LL. Cesarean Section Delivery Is Not a Risk Factor for Development of Inflammatory Bowel Disease: A Population-based Analysis. Clinical Gastroenterology and Hepatology 2016;14(1):50-7.

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We aimed to determine if mode of delivery (Cesarean section  versus vaginal delivery) impacted on the future risk of inflammatory bowel disease (IBD). The University of Manitoba IBD Epidemiology Database contains records on all Manitobans diagnosed with IBD between 1984-2010. From 1970, 6-digit family health registration numbers were used in Manitoba which allows linkage of mothers to their offspring. Maternal health records including dates and modes of delivery and siblings of individuals with IBD were identified.  1671 individuals with IBD and 10488 controls matched by age, gender, area of residence (at IBD diagnosis) could be linked to their mother’s obstetrical records. Urban versus rural residency was associated with higher likelihood of caesarean section for both IBD cases (12.8% vs. 9.7%) and for controls (13.3% vs 9.4%). In Crohn’s disease, males were more likely than females to have caesarean section (13.5% vs.8.4%). Overall, there was no difference in caesarean section for IBD (11.6%) versus controls (11.7%). In multivariate analysis, being born by caesarean section was not associated with an increased risk of subsequent IBD, controlling for age, sex, urban residence, and income. Persons with IBD were no more likely to have been born by caesarean section  than their unaffected siblings (1740 siblings from 1615 families) (11.6% vs.11.3%). We concluded that caesarean section  is not more common in IBD than in controls or in their siblings.

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Bhasin S, Singh H, Targownik LE, Israeli E, Bernstein CN. Rates and reasons for nonuse of prescription medication for inflammatory bowel disease in a referral clinic. Inflammatory Bowel Disease 2016;22(4):919-24.

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We aimed to determine the rates and reasons for nonuse of IBD-specific medication in a referral clinic. Consecutive persons with Crohn’s disease  (n=426) and UC (n=344) were followed in a single clinic over 2 years. At each patient visit it was determined whether and what type of IBD-specific medications were used at that visit. If medications were not used the reason for nonuse was recorded. Deep remission was considered a reason for nonuse if the attending physician believed the person was in deep remission and agreed for them to be off medications.  Nonuse of IBD-specific medication was seen in 126 persons with Crohn’s disease  (30%) and 65 persons with UC (19%). In Crohn’s disease increased age and disease duration were associated with nonuse; disease phenotype did not predict nonuse. In UC disease duration was associated with nonuse but age was not. In Crohn’s disease, the most common reason for medication nonuse was deep remission (51.6%), followed by not having seen a gastroenterologist for a lengthy period (17%), and nonadherence (16%). In UC 51.3% of nonuse was attributed to deep remission, followed by nonadherence (26.3%) and not having seen a gastroenterologist for a lengthy period (9.2%). We concluded that over a quarter of persons with IBD attending at a tertiary care practice do not use IBD-specific medications with a higher rate in CD than UC. The decision not to use medications was deemed to be appropriate in approximately one-half of all nonusers.​​

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Nugent Z, Singh H, Targownik LE, Strome T, Snider C, Bernstein CN. Predictors of emergency department use by persons with IBD: A population based study. Inflammatory Bowel Diseases 2016; 22: 2907-2916.

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We aimed to describe the patterns and predictors of Emergency Department (ED) attendance and post ED hospitalization by persons with inflammatory bowel disease (IBD). We linked the University of Manitoba IBD Epidemiology Database with the Emergency Department Information System of the Winnipeg Regional Health Authority to determine the rates of presentation to the ED by persons with IBD from 01/01/09 to 03/31/12. Incident cases were diagnosed during the study period and all others were considered prevalent cases. We determined predictors of attendance in the ED and for hospitalization within 2 days of ED attendance. The study population included 300 incident and 3394 prevalent cases, of whom 76% and 49%, respectively, attended the ED at least once during the study period. Incident cases with CD (as opposed to UC) or with a history of opioid use were more likely to attend the ED. Those who had seen a gastroenterologist within the preceding year were less likely to visit the ED. Among prevalent cases higher comorbidity, opioid or corticosteroid use, and recent hospital admission were predictive of ED attendance and those who saw only one physician in the preceding year had lower ED attendance. Presenting to the ED with a primary GI complaint was the strongest predictor of subsequent hospital admission.  We concluded that ED attendance by both incident and prevalent cases of IBD is high. We identified predictors of ED attendance and post ED hospitalization. This could guide the optimization of outpatient IBD care to limit ED attendance and potentially post ED hospitalization.

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Marrie RA, Walker JR, Graff LA, Lix LM, Bolton JM, Nugent Z, Targownik LE, Bernstein CN. Performance of administrative case definitions for depression and anxiety in inflammatory bowel disease. Journal of Psychosomatic Research 2016; 89: 107-113.

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Comorbid depression and anxiety are common in IBD, but few population-based estimates of the burden of depression and anxiety exist. Methods to support population-based studies are needed. We aimed to test the performance of administrative case definitions (that are extracted from Manitoba Health administrative data) for depression and anxiety in IBD and to understand what the prevalence of these conditions are in IBD.  We linked administrative (health claims) data from the province of Manitoba, Canada with clinical data for 266 persons in the Manitoba IBD Cohort Study. We compared the performance of administrative case definitions for depression and anxiety with (a) diagnoses of depression and anxiety as identified based on the Composite International Diagnostic Interview (CIDI), which identifies disorders meeting formal diagnostic criteria, and (b) participant report of physician-diagnosed depression or anxiety. Administrative definitions for depression showed moderate agreement with the CIDI. Agreement was higher with participant report of physician-diagnosed depression. The lifetime prevalence of depression was 29.3% based on the CIDI, 17.7% based on participant report of physician-diagnosed depression, and 21.8-22.5% based on administrative data. Compared to the CIDI, administrative definitions for anxiety showed onlyfair agreement. The lifetime prevalence of anxiety was 31.2% based on the CIDI, 9.7% based on participant report of physician-diagnosed anxiety, and 24.4-31.9% based on administrative data. We concluded that administrative data may be used for population-level surveillance of depression and anxiety in IBD, although they will not capture undiagnosed or untreated cases.

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Melesse DY, Targownik LE, Singh H, Blanchard JF, Bernstein CN. Patterns and predictors of long term nonuse of medical therapy among persons with inflammatory bowel disease. Inflammatory Bowel Diseases 2015; 21: 1615-1622.

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We aimed to describe the pattern and determine predictors of delayed initiation and long-term nonuse of IBD-specific medications among persons with IBD.  All incident cases of IBD diagnosed between1987-2012 were identified from the population-based University of Manitoba IBD Epidemiology Database. Point prevalence of long-term medication nonuse (defined as no receipt of IBD-specific medications for a year or longer) was determined over calendar time and the course of disease. Among 6451 persons with IBD followed since 1987 (46.8% male, 47.8% with Crohn’s disease (CD)), approximately 11.7% were not dispensed an IBD-specific medication within the first year. Within 5 years from diagnosis 6.2% were not dispensed an IBD-specific medication. Factors associated with delayed initiation included having CD, urban living at the time at diagnosis, lower socio-economic status (SES), age over 65 and having any medical comorbidity. The prevalence of long-term nonuse consistently remained between 40-50% of persons with IBD across the study years. Persons with CD, lower SES, IBD-associated surgery, or delayed initiation of first IBD medication were more likely to become long-term nonusers after initiation.  We concluded that at any given time, roughly half of all IBD patients have not used IBD specific medications in the previous year. We found that the majority of these persons did not have more than 2 visits within the past year for IBD and hence we concluded that it was likely that the majority of these nonusers of IBD-specific medications were in remission and not in need of an IBD-specific medication.

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Bernstein CN, Garland A, Peschken CA, Hitchon CA, Chen H, Fransoo R, Marrie RA. Predictors of ICU admission and outcomes one year post admission in persons with IBD: A population based study. Inflammatory Bowel Diseases 2015; 21: 1341-1347.

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We aimed to determine predictors of intensive care unit (ICU) admission and to assess health care utilization post-ICU admission among persons with IBD. We matched a population-based database of Manitobans with IBD to a general population cohort by age, sex and region of residence and linked these cohorts to a population-based ICU database. We compared the incidence rates of ICU admission among prevalent IBD cases according to health care utilization (HCU) in the year prior to admission adjusting for age, sex, socioeconomic status, region, and comorbidity. Among incident cases of IBD who survived their first ICU admission we compared HCU to matched controls who survived ICU admission. Risk factors for ICU admission from the year prior to admission included cumulative corticosteroid use and IBD-related surgery. Use of immunomodulatory therapies (azathioprine, 6-mercaptopurine, and methotrexate) within one year, or surgery for IBD beyond one year prior, were not associated with ICU admission. In those who used corticosteroids and immunomodulatory medications in the year prior to ICU admission, the use of immunomodulatory medications conferred a 30% risk reduction in ICU admission. Persons with IBD who survived ICU admission had higher health care utilization in the year following ICU discharge than controls. We concluded that corticosteroid use and surgery within the year are associated with ICU admission in IBD while immunomodulatory therapy is not. Surviving ICU admission is associated with high health care utilization in the year post-ICU discharge.

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Bernstein CN, Nugent ZN, Targownik LE, Singh H, Lix L. Predictors and risks for death in a population based study of persons with IBD in Manitoba. Gut 2015; 64: 1403-1411.

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We aimed to determine the predictors and risk for death among persons with either Crohn’s disease (CD) or ulcerative colitis (UC) compared to the general population.  We used the population based University of Manitoba IBD Epidemiology Database to calculate mortality rates in persons with IBD in relation to the general population. There were 10,788 prevalent cases of CD and UC and 101,860 matched controls.  Persons with CD had a 26% higher mortality rate than the general population but there was no difference in mortality for prevalent UC cases compared to matched controls. CD cases were more likely to die of colorectal cancer, non-Hodgkin lymphoma, digestive diseases, pulmonary embolism and sepsis and UC cases were more likely to die from colorectal cancer, digestive diseases, and respiratory diseases.  For incident cases there were significant effects on mortality by socioeconomic status, comorbidity score and surgery. The greatest risk for death in both CD and UC was within the first 30 days following gastrointestinal  surgery. The first year from diagnosis was also associated with increased risk of death in both CD and UC, but persisted after the 1st year only in CD. We concluded that there is a significantly increased risk of mortality in CD compared to controls while in UC an increased risk for death was only evident in the first year from diagnosis. Surgery poses an increased risk for death in both CD and UC for up to 1 year.

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Singh H, Nugent Z, Brownell M, Targownik L, Roos L, Bernstein CN. Academic performance among children with inflammatory bowel disease: A population based study. Journal of Pediatrics 2015; 166: 1128-33.

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We aimed to determine grade 12 academic performance (and potential predictors) for children with IBD compared to population controls. Children diagnosed with IBD under age 17 years were identified from the population-based University of Manitoba IBD Epidemiology Database and were matched by age-, sex- and area of residence to 10 randomly selected controls. Grade 12 educational outcomes (scores on the provincial grade 12 language arts, mathematics standards tests and enrollment in grade12 by age 17) were determined by linkage to the province wide Manitoba Education Database. Grade 12 educational outcomes among 337 children with IBD were compared with 3093 without IBD. There were no significant differences among the two groups in the standardized scores for language arts and mathematics or enrollment in grade 12 by age 17. Lower socioeconomic status and diagnosis with mental health problems 6 months prior to 6 months post IBD diagnosis were independent predictors of worse educational outcomes.  There was no significant effect of age of diagnosis of IBD, type of IBD (UC vs. CD), use of corticosteroids or immunomodulator agents, hospitalizations or surgery for IBD.  It is reassuring that children with IBD on average achieve similar levels of academic achievement in grade 12 as those without IBD. This study identified the educational impact of mental health conditions at IBD diagnosis among children.

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Singh H, Nugent Z, Targownik LE, El Matary W, Brownell M, Bernstein CN. Health care utilization among a population based cohort of children with inflammatory bowel disease. Clinical Gastroenterology and Hepatology 2015; 13: 1302-09.

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We explored health care use by children with IBD. We identified all children with IBD in the population-based University of Manitoba IBD Epidemiology Database; 651 children with IBD were matched for age, sex, and area of residence with 5950 children without IBD (controls), and followed up for a total of 6419 and 53,875 person-years, respectively. We extracted and analyzed data on IBD type (Crohn's disease vs ulcerative colitis), diagnosis before or after 2002 (era of diagnosis), age, sex, ambulatory care visits and hospitalizations before and after diagnosis, comorbidities, exposure to IBD drugs, and surgeries. We found that children with IBD were more likely to have visits for gastrointestinal symptoms in each of the 4 years before IBD diagnosis than controls, with no significant effect of era of diagnosis. Children with IBD had more physician encounters for psychosocial diagnoses in the 6 months before or after the IBD diagnosis, as well as in the second year after IBD diagnosis, than controls; 56% of children with IBD were exposed to corticosteroids within the year after their diagnosis, with no decrease over eras of follow-up evaluation. Among children diagnosed from 2002 through 2010, the 8-year actuarial rate of colectomy for those with ulcerative colitis was 8%, and the rate of resective surgery for Crohn's disease was 10%; both of these values were lower than for children diagnosed from 1987 through 2001. We concluded that in a population-based study from Canada, children with IBD were more likely to have visits for gastrointestinal symptoms in each of the 4 years before IBD diagnosis than children without IBD, indicating a potential delay in diagnosis of this disease. Rates of surgery are decreasing among children with IBD.

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Shaw S, Blanchard JF, Bernstein CN. Early Childhood Measles Vaccinations Are Not Associated With Pediatric IBD: A Population-Based Analysis. Journal of Crohn’s and Colitis 2015; 9: 334-8.

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Early childhood vaccinations have been hypothesized to contribute to the emergence of paediatric IBD in developed countries. Using linked population-based administrative databases, we aimed to explore the association between vaccination with measles-containing vaccines and the risk for IBD. This was a case-control study using the University of Manitoba IBD Epidemiology Database. The database was linked to the Manitoba Immunization Monitoring System [MIMS], a population-based database of immunizations administered in Manitoba. All paediatric IBD cases in Manitoba, born after 1989 and diagnosed before March 31, 2008, were included. Controls were matched to cases on the basis of age, sex, and region of residence at time of diagnosis. Measles-containing vaccinations received in the first 2 years of life were documented, with vaccinations categorized as 'None' or 'Complete', with completeness defined according to Manitoba's vaccination schedule. A total of 951 individuals [117 cases and 834 controls] met eligibility criteria, with average age of diagnosis among cases at 11 years. The proportion of IBD cases with completed vaccinations was 97%, compared with 94% of controls. In models adjusted for physician visits and area-level socioeconomic status, no statistically significant association was detected between completed measles vaccinations and the risk of IBD  We concluded that no significant association between completed measles-containing vaccination in the first 2 years of life and paediatric IBD could be demonstrated in this population-based study.

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Vagianos K, Clara, I, Carr, R, Graff LA, Walker JR, Targownik LE, Lix LM, Rogala, L, Miller, N, Bernstein CN. What are adults with IBD eating? A closer look at the dietary habits of a population-based Canadian IBD cohort. Journal of Enteral and Parenteral Nutrition 2016; 40: 405-411.

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Abej E, El Matary W, Singh H, Bernstein CN. The utility of fecal calprotectin in the real-world clinical care of patients with inflammatory bowel disease. Canadian Journal of Gastroenterology and Hepatology 2016; Article ID 2483261, 6 pages.

 

We aimed to  determine the relationship between fecal calprotectin (FCAL) and imaging studies and other biochemical inflammatory markers and the impact of FCAL measurements on decision-making in IBD patient management in usual clinical practice. 240 persons with IBD were enrolled. The correlation between FCAL values and other markers for disease activity such as serum albumin (alb), hemoglobin (Hg), and C-reactive protein (CRP) and diagnostic imaging or colonoscopy was examined. FCAL greater than 250 mcg/g of stool was considered a positive result indicating active IBD. 183 stool samples (76.3%) were returned. The return rate in the pediatric and adult cohorts was 91% (n = 82) and 67.3% (n = 101), respectively. Positive FCAL was associated with colonoscopy findings of active IBD, low albumin, anemia, and elevated CRP. There was no significant difference for FCAL results by outcomes on small bowel evaluation among the 21 persons with small bowel CD. Most persons (87.5%) with normal FCAL and no change in therapy remained in remission during subsequent 3 months. We concluded that  FCAL is a useful marker of disease activity and a valuable tool in managing persons with IBD in clinical practice. Clinicians have to be cautious in interpreting FCAL results in small bowel.

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Graff LA, Sexton KA, Walker JR, Clara I, Targownik LE. Validating a measure of patient self-efficacy in disease self-management using a population-based IBD cohort: the IBD Self-Efficacy Scale. Inflammatory Bowel Diseases 2016; 22: 2165-72.

 

Self-efficacy describes a person's confidence in their ability to manage demands, and is predictive of health outcomes in chronic disease such as hospitalization and health status. However, meaningful measurement must be disease specific. This study aims to provide validation of the Inflammatory Bowel Disease Self-Efficacy scale (IBD-SE), using a population-based IBD sample. Manitoba IBD Cohort Study participants completed a survey and clinical interview at a mean of 12 years after diagnosis (121 with Crohn's disease; 108 with ulcerative colitis), which included validated measures of psychological functioning, disability, disease-specific quality of life, perceived health, and current and recent disease activity, in addition to the IBD-SE. The IBD-SE had high internal consistency (Cronbach's α = 0.97), and a 4-factor structure was confirmed. The IBD-SE was strongly correlated with mastery, measures of psychological well-being, stress, distress, disability, disease-specific quality of life, and overall perceived health. Those with currently inactive disease had higher self-efficacy than the active disease group with similar findings for recent symptomatic disease activity. We concluded that the IBD-SE is a reliable, valid, and sensitive measure as demonstrated in this population-based sample, supporting its utility in IBD. Because self-efficacy is a modifiable psychological characteristic that can contribute to positive health outcomes, the IBD-SE may prove to be a valuable instrument for research and in targeted intervention with IBD patients.

 

 

Restall G, Simms A, Walker JR, Graff LA, Sexton KA, Rogala L, Miller N, Haviva C, Targownik LE, Bernstein CN. Understanding work experiences of people with inflammatory bowel disease. Inflammatory Bowel Diseases 2016; 22:1688-97.

 

People with IBD are at increased risk for unemployment and work absenteeism over the course of their adult lives. However, little is known about the first hand experiences of people living with the disease regarding perceived barriers, facilitators, and strategies for navigating work roles. In this qualitative study, participants were purposefully recruited from 2 existing IBD cohort study samples. Recruitment strategies aimed for diversity in age, sex, and disease type, duration, and symptom activity. In-depth interviews sought perspectives of living with IBD.  45 people currently or previously in the workforce participated; 51% were female. The average age was 45 years and the average IBD duration was 11 years. Participants had a broad range of experiences in adapting to work roles. Experiences were shaped by: (1) personal health and well-being, (2) personal values, beliefs, and knowledge, (3) job characteristics, (4) workplace physical environment, (5) workplace culture, and (6) financial factors. Participants identified personal strategies and environmental supports that assisted them to navigate their work roles. In summary, the perspectives of people with IBD provided in-depth understanding of contextual factors that influence work roles. They identified personal strategies to manage health and choices about work, environmental supports that promote timely workplace accommodations, and appropriate social insurance benefits as facilitators of work retention for people.