The Manitoba IBD Cohort Study

This study was initiated in 2002 with funding from the Canadian Institutes of Health Research ($1.2 million). It is a population-based study where 388 subjects who were within 7 years of diagnosis of their IBD were enrolled. The participating persons have been followed annually with in-person interviews and with semi-annual mail-in surveys. The study was initiated to be a 5 year study and remarkably by the end of 5 years 353 persons were still participating (a loss of 1.8%/year). In January, 2008 the Canadian Institutes of Health Research announced that the study was being funded again ($1.5 million) to pursue another 5 years. The goal of the Manitoba IBD Cohort is to determine predictors of outcomes as well as to optimize management of various aspects of IBD.

The Manitoba IBD Cohort Study has been enormously successful. Participants range in age from 18-83 years old and 60% are females. Approximately two thirds live in Winnipeg and the rest live throughout Manitoba including Brandon, Dauphin, Swan River, Flin Flon, Thompson, Winkler and Steinbach. Some subjects live elsewhere in Canada, yet still maintain their participation. Linda Rogala and Norine Miller are our two research nurses who keep in close contact with the participants. We are grateful to the participants who continue with us and are helping to provide a wealth of research information. We continue to follow 270 subjects in this study which is now in its 9th year The Manitoba IBD Cohort Study has become internationally renowned and is one of the few follow up studies in the world conducted over several years of patients with IBD. The following are some of the findings from this study have been reported to date:


Back row – left to right are:Dr. Lesley Graff, Dr. John Walker, Dr. Charles Bernstein, Dr. Jason Ediger, Ian Clara Front row – left to right are: Norine Miller, RN, Dr. Teresa Longobardi, Trish Rawsthorne, RN, BA, Rachel Carr, Kylie Bernstein, Linda Rogala, BN Missing: Dr. William Leslie, Dr. Lisa Lix ,Dr Laura Targownik, Dr. Jamie Blanchard and Kathy Vagianos.




New Studies for 2012

Targownik LE, Leslie WD, Carr R, Clara I, Miller N, Rogala L, Graff LA, Walker JR, Bernstein CN. Longitudinal change in bone mineral density in a population-based cohort of patients with inflammatory bowel disease.Calcific Tissue International 2012; 91: 356-61

Persons with inflammatory bowel disease are reported to have a high prevalence of osteoporosis and reduced bone mineral density (BMD) and to be at higher risk of fracture. The course of BMD loss over time is poorly characterized in persons with IBD. 86 persons, from the Manitoba IBD Cohort Study underwent BMD testing at baseline, with final BMD testing a mean of 4.3 years later. The proportion of subjects with significant change in BMD at the lumbar spine, total hip, and femoral neck was assessed, as were clinical, biochemical, and anthropomorphic changes. Vertebral radiographs were also obtained at baseline and at the end of follow-up in those aged 50 years and older to detect vertebral fractures. The change in BMD seen in this cohort of IBD patients was similar to the expected rate of BMD loss in the general population. Age >50 years, decreasing body mass index (BMI), and corticosteroid use were most notably correlated with BMD loss. Subjects younger than 50 years did not have statistically significant declines in BMD. IBD symptom activity scores correlated poorly with BMD loss. Vertebral fractures were uncommon, with only two subjects out of 41 older than 50 years who developed a definite radiographic fracture over the course of follow-up. No major nonvertebral fractures were observed. We concluded that patients with IBD do not appear to have significantly accelerated BMD loss. Older age, decreasing BMI, and corticosteroid use may identify IBD patients at greater risk for BMD loss.

Rawsthorne P, Clara I, Graff LA, Bernstein KI, Carr R, Walker JR, Ediger J, Miller N, Rogala L, Bernstein CN. The Manitoba IBD Cohort Study: A prospective longitudinal evaluation of the use of complementary and alternative medicine and services. Gut 2012; 61:521-7.

Complementary and alternative medicine (CAM) are used by 40-50%of the population and similarly amongst persons with IBD. We have the opportunity with the Manitoba IBD Cohort Study to determine: a) the prevalence of CAM use in a population based sample of IBD subjects, b) the persistence of use over time (4.5 years), c) how much CAM used is an ingested product versus a service, d) how much CAM used is specifically for IBD reasons, e) personal variables that are associated with CAM use

Persons participating in the Manitoba IBD Cohort Study completed surveys on their use of CAM products and services. 330 subjects completed all 4 surveys at 0, 12, 30 and 54 months. The questionnaires inquired about the use of 13 CAM service providers and 10 CAM products in the 12 months prior to the survey and whether the CAM use was specifically in relation to their IBD or not. Additional services or products were captured under the “Other” category.

Over a 4.5 year period 77% of IBD subjects in a population-based cohort try CAM services or products at some time and approximately 40% use CAM at any one time. However only 14% are consistent users. Of note, at most 10% are using CAM Products for their IBD (~40% of all CAM product users) and 6% are using CAM Services for their IBD (~12% of all CAM Service users). Females and persons with university degrees are more likely to use CAM, but disease diagnosis or activity did not predict CAM use. Immunosuppressant users were significantly less likely to use CAM. We concluded that clinicians need to make a bigger effort in understanding why patients choose CAM, how it benefits them, and consider any interactions in relation to conventional treatment.

We are in the process of analyzing data on fatigue in IBD, patients perceptions of what causes their IBD, determinants of patients adherence to therapy over time, and dietary intake among IBD patients compared to persons without IBD in the community.


2011 Studies

Graff LA, Vincent N, Walker JR, Clara I, Carr R, Ediger J, Miller N, Rogala L, Rawsthorne P, Lix L, Bernstein CN. A population-based study of fatigue and sleep difficulties in inflammatory bowel disease. Inflammatory Bowel Diseases 2011; Sep;17(9):1882-9.

There has been little investigation of fatigue, a common symptom in IBD. The aim of this study was to evaluate fatigue more comprehensively, considering relationships with psychological and biological factors simultaneously in our Manitoba IBD Cohort. 318 participants ( 51% Crohn’s disease ) were assessed by survey, interview, and blood sample. Fatigue, sleep quality, daytime drowsiness, stress, psychological distress, and quality of life were measured with validated scales. Hemoglobin and C-reactive protein (CRP) levels (a nonspecific blood test that reflects active inflammation) were also obtained. Differences were tested for those with Crohn’s disease versus ulcerative coltis and whether persons reported active disease symptoms or inactive disease. Data for this study were collected at 24 months after enrollment into the Manitoba IBD Cohort. We found that elevated CRP was found for 23% of the sample and 12% were anemic (had a low hemoglobin level); 46% had active disease. Overall, 72% of those with active and 30% with inactive disease reached clinical thresholds for fatigue (Multidimensional Fatigue Inventory; P < 0.001); 77% and 49% of those with active or inactive disease, respectively, experienced poor sleep (P < 0.001). There were few differences between those with Crohn’s disease and ulcerative colitis on the factors assessed, except for higher CRP levels in Crohn’s disease. Multiple logistic regression analyses found that elevated fatigue was associated with active disease (odds ratio [OR] 4.2, 95% confidence interval [CI] 2.2-7.8), poor sleep quality (OR 4.0, 95% CI 1.9-8.6), and perceived stress (OR 4.2, 95% CI 2.2-8.1), but not with hours of sleep, Hg, or CRP. This means that persons with IBD with characteristics of active disease, poor sleep, or higher perceived stress were about 4 times more likely to have fatigue than persons with IBD without those characteristics. We concluded that fatigue and poor sleep are not only highly prevalent in active disease, but both are still significant concerns for many with inactive disease. Psychological factors are associated with fatigue in IBD in addition to disease and sleep considerations.

Longobardi T, Walker JR, Graff LA, Bernstein CN. Health service utilization in IBD: comparison of self-report and administrative data. BMC Health Serv Res. 2011 May 31;11:137.

In understanding how often persons with IBD need to use health services (either doctor visits or hospitalizations) studies can be done either by asking persons directly (self-report) which has the hazard of the person’s ability to recall events over past time or by reviewing administrative data, such like that collected by Manitoba Health (administrative data). The problem with relying on administrative data is that there remains the possibility that data input into the record was erroneous (ie the person doing the coding had the wrong diagnosis) Hence we compared the reporting of 352 subjects within the Manitoba IBD Cohort of their visits over the past year to a doctor and as to their hospitalizations in the past year. Reports of recent antibiotic use were also recorded.
According to the administrative data, in the previous year, 15% of respondents had an overnight hospitalization, while 10% had an IBD-related hospitalization. Self-report concordance was highly sensitive (92%; 82%) and specific (96%; 97%, respectively). 97% of participants had contact with a physician in the previous year, and 69% had IBD-related visits. Physician visits were significantly under-reported and there was a trend to over-report the number of nights in hospital. We concluded that self-report data can be helpful in evaluating health service utilization, provided that the researcher is aware of the systematic sources of bias. Outpatient visits are well identified by self-report. The discordance for the type of outpatient visit (whether it was related to IBD or not) may be either a weakness of self-report or a flaw in diagnosis coding of the administrative data. If administrative data are not available, self-report information may be a cost-effective alternative, particularly for hospitalizations.

Sajobi TT, Lix LM, Clara I, Walker J, Graff LA, Rawsthorne P, Miller N, Rogala L, Carr R, Bernstein CN.Measures of relative importance for health-related quality of life. Quality of Life Research 2011 Apr 24. [Epub ahead of print]

This paper was undertaken to help us understand the optimal methods for doing health-related quality of life (HRQOL) studies in IBD. HRQOL data are often collected on multiple domains for two or more groups of study participants. Quantitative measures of relative importance, which are used to rank order the domains based on their ability to discriminate between groups, are an alternative to multiple tests of significance on the group differences. This study describes relative importance measures based on logistic regression and multivariate analysis of variance (MANOVA) models. Study participants with self-reported active (n = 244) and inactive (n = 105) disease were compared on 12 HRQOL domains from the Inflammatory Bowel Disease Questionnaire (IBDQ) and Medical Outcomes Study 36-item Short-Form (SF-36) Questionnaire. We found that all but two relative importance measures ranked the IBDQ bowel symptoms and emotional health domains as most important. We concluded that MANOVA-based importance measures are recommended for multivariate normal data and when group covariances are equal, while logistic regression measures are recommended for non-normal data and when the correlations among the domains are small. Relative importance measures can be used in exploratory studies to identify a small set of domains for further research.


2009 Studies

Graff LA, Walker JR, Bernstein CN. Depression and anxiety in inflammatory bowel disease: A review of comorbidity and management. Inflammatory Bowel Diseases 2009; 15:1105-18.

Graff LA, Walker JR, Clara I, Lix L, Miller N, Rogala L, Rawsthorne P, Bernstein CN. Stress coping, distress, and health perceptions in inflammatory bowel disease and community controls. American Journal of Gastroenterology 2009; 104: 2959-69.

Clara I, Lix LM, Walker JR, Graff LA, Miller N, Rogala L, Rawsthorne P, Bernstein CN. The Manitoba IBD Index: Evidence for a New and Simple Indicator of IBD Activity. American Journal of Gastroenterology 2009; 104(7):1754-63.

Leslie WD, Miller N, Rogala L, Bernstein CN. Body mass and composition affect bone density in recently diagnosed inflammatory bowel disease: The Manitoba IBD Cohort Study. Inflammatory Bowel Diseases 2009; 15: 39-46

A subgroup of 101 subjects from the overall study participated in a study examining bone outcomes. In this substudy we aimed to clarify the role of weight and body composition as a determinant of bone mineral density (BMD) in recently diagnosed IBD. Baseline BMD and body composition were measured and repeated 2.3 ± 0.3 y later. The greater the weight, height and body mass measurements the higher the bone density at all sites. While both fat tissue and lean tissue showed positive relationships with BMD, lean tissue showed a much stronger correlation than fat tissue especially for total hip. Increase (or decrease) in hip bone density was strongly associated with an increase (or decrease) in all body mass variables. We concluded that measures of body mass are important determinants of baseline BMD in recently diagnosed IBD patients. Furthermore, change in body mass correlated with change in BMD, especially at total hip. Early optimization and maintenance of nutrition and body weight, particularly toward lean tissue mass, may play an important role in preventing IBD-related bone disease. In other words it is important that with weight gain it is not any weight gain (i.e. fat tissue) but better that it is lean body mass.


2008 Studies

Rogala L, Miller N, Graff LA, Rawsthorne P, Clara I, Walker JR, Lix L, Ediger JP, McPhail C, Bernstein CN. A population-based controlled study of social support, self-perceived stress, activity and work issues and access to health care in IBD. Inflammatory Bowel Diseases 2008; 14: 526-35.

In this study we compared IBD participants’ levels of social supports, self-perceived daily stress, disability and access to health care with those of a matched community sample. Compared to the community sample, those with IBD received more tangible, affective or emotional support in the prior year, and were more likely to have experienced a positive interaction, although support levels were generally high across both groups. Those with IBD were as likely to be employed as those in the community sample. However they reported greater rates of reduced activity and days missed. Work was not identified as a significant source of stress, but physical health was more likely to be identified as a main stressor by those with active IBD compared to the non IBD sample. Individuals with IBD were twice as likely to report unmet healthcare needs than the community sample. There was agreement across both groups regarding common barriers including long waits and availability. These direct comparisons highlight that in some areas those with IBD manage similarly to the general community. These data also lend support to the IBD community that they are no less likely to be unemployed which could positively impact on their interaction with the insurance industry. However, we need to further explore the areas in which IBD patients feel they have unmet health care needs.

Lix LM, Graff LA, Walker JR, Clara I, Rawsthorne P, Rogala L, Miller N, Ediger J, Pretorius T, Bernstein CN. Longitudinal study of quality of life and psychological functioning for active, fluctuating, and inactive disease patterns in inflammatory bowel disease.Inflammatory Bowel Disease2008; 14: 1575-84

This study assesses quality of life and psychological functioning in IBD as related to patterns of disease activity over time. Based on their two-year pattern of self-reported disease activity, participants were assigned to one of three groups: consistently active, fluctuating, or consistently inactive disease. Half of the participants had fluctuating disease activity, while almost one-third of participants reported consistent active disease. Participants with the fluctuating activity pattern showed significant improvement in disease-specific quality of life compared to participants with consistent activity. Perceived stress, health anxiety, and pain anxiety decreased while pain catastrophizing and mastery increased over time, although the amount of change was not significantly different among disease activity patterns. However, when the data were averaged over time there were significant differences among disease activity patterns on most outcomes. We concluded that 1) change in IBD quality of life was influenced by one’s longitudinal profile of disease activity (whether it was always active, always inactive or fluctuating between active and inactive), but change in psychological functioning was not and 2) there were modest improvements in positive and negative psychological functioning suggesting that disease has an impact even when patients are not experiencing active symptoms.

Walker JR, Ediger JP, Graff LA, Greenfeld JM, Clara I, Lix L, Rawsthorne P, Miller N, Rogala L, McPhail C, Bernstein CN. The Manitoba IBD Cohort Study: A population-based study of the prevalence of lifetime and twelve-month anxiety and mood disorders. American Journal of Gastroenterology 2008; 103: 1989-97.

We aimed to determine if mood and anxiety disorders (current and lifetime) are more common in IBD than in a gender and age matched comparison sample from the same population. Much disability and functional impairment occuring in chronic health problems is associated with comorbidity with psychiatric disorders. For our study, Cohort participants were assessed using the Comprehensive International Diagnostic Interview (CIDI), the structured psychiatric interview used most extensively in research around the world, allowing comparison to recently published prevalence rates from community epidemiological studies. A comparison of lifetime prevalence suggests higher rates of panic, generalized anxiety, and obsessive-compulsive disorders and major depression and lower rates of social anxiety and bipolar disorders in the IBD sample than in national samples in the US and New Zealand. Direct comparisons with matched controls (with data available for three anxiety disorders) found lifetime prevalence of panic disorder higher in IBD vs. controls; 8.0% vs. 4.7%, of social anxiety disorder lower in IBD vs controls; and of major depression higher in IBD vs controls (27.2% vs. 12.3%). Comparing IBD respondents with and without lifetime anxiety or mood disorder, those with a disorder reported earlier onset of IBD symptoms and there was a trend toward earlier IBD diagnosis. Hence, clinicians should be aware of the increased prevalence of depression and panic disorder and possibly other anxiety disorders in persons living with IBD as these disorders may influence response to treatment and quality of life.

Bone substudies:

Our group has previously conducted a number of studies exploring the increased risk of bone fractures and osteoporosis in IBD. Our goal is to determine the magnitude of changes in bone mineral density and to identify predictors of loss/gain of bone mass and fracture over time.

Leslie WD, Miller N, Rogala L, Bernstein CN. Vitamin D status and bone density in recently diagnosed inflammatory bowel disease: The Manitoba IBD Cohort StudyAmerican Journal of Gastroenterology 2008; 103: 1451-9.

BMD is usually normal at the time of IBD diagnosis. This study’s objective was to clarify the role of vitamin D metabolism in recently diagnosed IBD. Baseline BMD and serum 25-hydroxy vitamin D (25OHD) were measured in the subgroup of 101 subjects who participated in the bone assessment substudy at baseline and at 2 years later. Only a minority (21.8%) of recently diagnosed IBD participants had optimal serum 25OHD levels (≥75 nmol/L). Serum 25OHD was positively correlated with baseline BMD at all sites. Gain in total body BMD between the baseline and follow up BMD was positively correlated with 25OHD. Poorer vitamin D status correlated with lower baseline BMD and better vitamin D status was correlated with a gain in total body BMD. Patients with IBD should take vitamin D supplements.


2007 Studies

Adherence to medication regimens

Our goal is to determine the level of adherence with medication treatment over time and to determine predictors associated with high adherence rates.

Ediger JP, Walker JR, Graff L, Lix L, Clara I, Rawsthorne P, Rogala L, Miller N, McPhail C, Deering K, Bernstein CN. Predictors of medication adherence in inflammatory bowel disease. American Journal of Gastroenterology 2007;102: 1417-26.

Medication has become a major component of health care costs and adherence to treatment is an important issue. Despite widespread interest there is limited understanding of issues related to adherence and few data on the topic in IBD. Using a validated multi-item self-report measure, adherence was assessed as a continuous variable and then categorized as high or low. High adherence was reported by 73% of males and 63% of females. For males, predictors of low adherence included ulcerative colitis diagnosis (as opposed to Crohn’s disease) and being employed. For females, predictors of low adherence included younger age (<40). High scores on the Obstacles to Medication Use Scale (a scale designed to measure a number of possible obstacles to adherence to medications) strongly related to low adherence for both men and women. 5-ASA use was not related to adherence. For women, immunosuppressant use was associated with high adherence. A personality measure termed low trait agreeableness was associated with low adherence. Predictors of adherence differed markedly between genders, although obstacles such as medication cost were relevant for both men and women. We plan to study what factors impact on medication adherence over time and whether they change over time.