Shaw, S, Blanchard JF, Bernstein CN. Association between the use of antibiotics in the first year of life and pediatric inflammatory bowel disease. American Journal of Gastroenterology 2010; 105: 2687-2692.

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The development of commensal flora in infants has been shown to be sensitive to antibiotic use.  Altered intestinal flora is thought to contribute to the etiology of IBD, an idiopathic chronic condition.  We aimed to determine if early use of antibiotics was associated with development of IBD in childhood. We accessed the population-based University of Manitoba Inflammatory Bowel Disease Epidemiologic Database. IBD status was determined from a validated administrative database definition.  A total of 36 subjects diagnosed between 1996 and 2008 were matched to 360 controls, based on age, sex and geographic region. Antibiotic data were drawn from the Manitoba Drug Program Information Network, a comprehensive population-based database of all prescription drugs for all Manitobans dating back to 1995.  Antibiotic use in the first year of life was compared for IBD cases versus controls. The mean age at IBD diagnosis was 8.4 years. Twenty one cases (58%) had one or more antibiotic dispensations in their first year of life, versus 39% of controls.  Crohn’s disease was diagnosed in 75% of IBD cases. Those receiving one or more dispensations of antibiotics were 3 times more likely of being an IBD case than a control.  We concluded that subjects diagnosed with IBD in childhood are more likely to have used antibiotics in their first year of life.

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Nugent Z, Blanchard JF, Bernstein CN. A population based study of health care resource use among infliximab users. American Journal of Gastroenterology 2010; 105: 2009-2016.

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There has been some evidence from clinical trials that persons who received infliximab (Remicade) or adalimumab (Humira) would be less likely to require hospitalization or surgery over the course of 1 year follow up than persons who got placebo within the course of the clinical trial. Hence we wanted to study the “real world” experience of hospitalization surgery and doctor visits among infliximab users compared with those who didn’t use infliximab. As comparison groups to infliximab users we included a group of patients who were prescribed azathioprine (Immuran), or 6-mercaptopurine (Purinthol) for the first time, a group who were prescribed at least 30 days of steroids (prednisone) and a group who were prescribed none of prednisone, azathioprine, 6-mercaptopurne, methotrexate, or infliximab. IBD-associated doctor visits were consistently higher for infliximab users; both pre- and post- initial dosing, although overall physician visits were similar between those who used infliximab, those who used azathioprine or 6-mercaptopurine, and those who had a new course of steroids. There was a steep rise in hospitalizations in the 6 months prior to initial prescription of infliximab, azathioprine (or 6-mercapotopurine) or steroids and hospitalizations were higher in the infliximab group until 18-24 months after the first prescription at which point levels fell to those evident 2-5 years prior to initiating infliximab and to levels in the other drug groups. The likelihood of surgery post dosing was greater in the infliximab users than in the group using azathioprine (or 6-mercapotopurine) or the group using none of these immune drugs for up to 36 months but the surgery rate was not different than the group newly prescribed steroids.

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We concluded that in a “step-up” approach to infliximab use (where only more ill patient get prescribed this medication) it takes 2 years for doctor visits to reduce to 2 year pre dosing rates and 18-24 months to reach hospitalization rates at 2 years pre dosing and hospitalization rates of other groups using azathioprine (or 6-mercapotopurine) or steroids. Surgical rates to 3 years post dosing were still higher than in other groups using azathioprine (or 6-mercapotopurine) or steroids.

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One argument for expending the high cost of infliximab is that it could reduce or even eliminate the high cost of hospitalization or surgery. We could not show that infliximab use decreased health care utilization to levels below pre-infliximab therapy or levels below the other Crohn’s disease patient groups. Considering the high expense of infliximab it may be difficult to prove cost effectiveness in a “step-up” approach to initiating the drug where it is reserved for the most ill patients unless indirect costs (the costs of missing work or school) and quality of life are accounted for.

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Krause DO, Dowd SE, Little AC, Bernstein CN. Complete genome sequence of adherent invasive Escherichia coli UM146 isolated from ileal Crohn’s disease biopsy tissue. Journal of Bacteriology 2010; 193(2):583.

 

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Sepehri S, Kotlowski R, Bernstein CN, Krause DO. Phylogenetic analysis of inflammatory bowel disease associated Escherichia coli and the fimH virulence determinant. Inflammatory Bowel Diseases 2009; 15:1737-45.

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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.

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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.

 

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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.

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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.

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Bernstein CN, Nugent Z, Longobardi T, Blanchard JF. Isotretinoin is not associated with inflammatory bowel disease: A population based case control study. American Journal of Gastroenterology 2009; 104: 2774-2778.

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There has been some discussion in the medical literature whether persons using isotretinoin (Accutane or its generic forms)  to treat acne are at increased risk of getting IBD. In this study we assessed the use of isotretinoin prior to diagnosis of IBD and in comparison with a matched control group who did not get IBD. We found that 1.2% of IBD cases used isotretinoin prior to IBD diagnosis which was statistically similar to controls (1.1% users). This was also similar to the number of IBD patients who used isotretinoin after a diagnosis of IBD was made (1.1%). There was no difference between isotretinoin use prior to Crohn’s disease compared with use prior to ulcerative colitis. We concluded that patients with IBD were no more likely to have used isotretinoin prior to diagnosis than controls matched by sex, age and area of residence. While there may be anecdotes of isotretinoin causing acute colitis our data suggest that isotretinoin is not likely to cause chronic IBD.

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Shanahan F, Bernstein CN. The evolving epidemiology of inflammatory bowel disease. Current Opinion in Gastroenterology 2009; 25:301-305.

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Bernstein CN, Shanahan F. Disorders of a modern lifestyle– reconciling the epidemiology of inflammatory bowel diseases. Gut 2008; 57:1185-1191.

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These reports update current trends in the epidemiology of IBD including the emergence of IBD in developing countries. The emergence in developing nations may provide important clues to the causes of IBD.

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Bernstein CN (on behalf of organizing committee). Assessing environmental risk factors affecting the inflammatory bowel diseases: A joint workshop of the Crohn’s & Colitis Foundations of Canada and the USA. Inflammatory Bowel Diseases 2008; 14: 1139-1146.

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This was a report of a meeting sponsored by the CCFC and CCFA bringing together experts on studying the environment in IB D and other diseases.

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Tang L, Nabalamba A, Graff LA. Bernstein CN. A comparison of self-perceived health status in IBD and IBS from a Canadian national population survey. Canadian Journal of Gastroenterology 2008; 22: 475-483.

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In this study we used data from the 2005 Canadian Community Health Survey which had a sample size of 132,947 Canadians to determine whether differences exist in perceptions of physical health, mental health and stress levels between patients with IBD and patients with irritable bowel syndrome (IBS). Information on 4441 participants aged 19 years or older who reported that they had been diagnosed with Crohn’s disease (n=474), ulcerative colitis (n=637) or IBS (n=3330) was analyzed. We found that people with IBD were more likely to experience fair or poor general health. IBS patients reported higher levels of stress and poorer mental health than IBD patients.

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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.

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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.

 

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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 Disease 2008; 14: 1575-84.

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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.

 

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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.

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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.

 

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

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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.

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Longobardi T, Bernstein CN. Utilization of health-care resources by patients with IBD in Manitoba: a profile of time since diagnosis. American Journal of Gastroenterology 2007; 102(8): 1683-1691.

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Administrative databases were used to report resource use in 2000/1. We found that within the first 2 years from disease diagnosis, the most costly resources were employed. Independent of disease duration, in general, outpatient utilization was over twice as likely among IBD cases compared with controls whether or not the contact was made for IBD-specific reasons. The likelihood of health care utilization was greatest among newly diagnosed cases for outpatient visits with an internist (an increase by 6-fold over non-IBD controls) and surgical visits (an increase by 3-fold over non-IBD controls). Inpatient stays for IBD-specific reasons in general were considered dependent on disease duration; in particular, there was a 4-fold higher likelihood for the incident (new) cases relative to their controls. For non-IBD-specific reasons, IBD cases were 1.5 times as likely to have inpatient stays, regardless of disease duration. We concluded that we can likely measure the greatest proportion of treatment effects on resource use within a relatively short period. Hence, even if some therapies are very expensive it is possible that their use could limit other expenses that would be incurred otherwise.

 

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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.

 

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Kotlowski R, Bernstein CN, Sepehri S, Krause DO. High prevalence of Escherichia coli belonging to the B2+D phylogenetic group in inflammatory bowel disease. Gut 2007; 56: 669-75.

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Vagianos K, Bector S, McConnell J, Bernstein C. Nutrition assessment of patient with inflammatory bowel disease. Journal of Parenteral and Enteral Nutrition 2007; 31:311-319.

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Sepehri S, Kotlowski R, Bernstein CN, Krause DO. Microbial diversity of inflamed and non-inflamed gut biopsy tissues in inflammatory bowel disease.  Inflammatory Bowel Diseases 2007:13: 675-683.

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Bernstein CN, Rawsthorne P, Blanchard JF. A population-based case control study of measles, mumps and rubella and inflammatory bowel disease. Inflammatory Bowel Diseases 2007;13:759-762.

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Bernstein CN, Wang MH, Sargent M, Brant SR, Collins MT. Testing the interaction between NOD-2 status and serological response to Mycobacterium paratuberculosis in IBD. Journal of Clinical Microbiology 2007; 45: 968-71.

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Longobardi T, Bernstein CN. Health care resource utilization in IBD. Clinical Gastroenterology and Hepatology 2006; 4: 731-743.

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Our Centre is fortunate to have one of the few health economists in the world devoted to studying the economics of IBD. Dr. Teresa Longobardi has been exploring how often persons with Crohn’s disease and ulcerative colitis visit their physicians, get hospitalized or undergo surgery. We found that persons with either Crohn’s disease or ulcerative colitis do have more outpatient visits and more hospitalizations than persons without IBD. Persons with Crohn’s disease have more outpatient visits and more hospitalizations than persons with ulcerative colitis. However, persons with ulcerative colitis are more likely to undergo surgery than persons with Crohn’s disease. Of persons with newly diagnosed Crohns’ disease and ulcerative colitis, over 15 years, there is a 50% chance of being hospitalized and 30% chance of undergoing surgery. In this newly diagnosed group followed over 15 years persons with Crohn’s disease were 4x more likely to be hospitalized and more likely to have surgery than persons with ulcerative colitis.

 

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Bernstein CN, Wajda A, Svenson LW, MacKenzie A, Koehoorn M, Jackson M, Fedorak R, Israel D, Blanchard JF. The epidemiology of inflammatory bowel disease in Canada: a population-based study. American Journal of Gastroenterology 2006; 101: 1559-1568.

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In our initial report the incidence rate of Crohn’s disease of 15/100,000 and the prevalence rate of nearly 200/100,000 were the highest yet to be reported in the world. Manitoba got branded as the Crohn’s disease hotspot in the world. In 2004 with funding from the Crohn’s and Colitis Foundation of Canada ($200000) we established collaboration with researchers in BC, Alberta, Saskatchewan, and Nova Scotia. Using the administrative definition for a diagnosis of IBD, applied to the provincial health databases of these other provinces, we estimated that the incidence rate of Crohn’s disease was 13.5/100,000 in 1998-2000 and the prevalence in 2000 of both Crohn’s disease and ulcerative colitis was 155000. We further estimated that in 2005 there would be approximately 170,000 Canadians with IBD. This study also found that rates in Manitoba were similar in Alberta and Saskatchewan, and rates in Nova Scotia were slightly higher than those of the Prairie Provinces. Hence Manitoba was not the Crohn’s disease hotspot but rather Canada was a hotspot. Rates in BC, particularly of Crohn’s disease were significantly lower. This raises the possibility that there is something environmentally different about BC than elsewhere in the country, or that the large immigrant population of BC (with a lower likelihood of having IBD) contributed to lowering the incidence rates of IBD.

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Bernstein CN, Rawsthorne P, Cheang M, Blanchard JF. A population-based case control study of potential risk factors for IBD. American Journal of Gastroenterology 2006; 101: 993-1002.

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Burgmann T, Clara I, Graff L, Walker J, Lix L, Rawsthorne P, McPhail C, Rogala L, Miller N, Bernstein CN. The Manitoba IBD Cohort study: Prolonged symptoms before diagnosis-How much is IBS? Clinical Gastroenterology and Hepatology 2006; 4: 614-20.

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Graff LA, Walker JR, Lix L, Clara I, Rawsthorne P, Rogala L, Miller N, Jakul L, McPhail C, Ediger J, Bernstein CN. The relationship of inflammatory bowel disease type and activity to psychological functioning and quality of life. Clinical Gastroenterology and Hepatology 2006; 4:1491-1501.

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Mackalski BA, Bernstein CN. New diagnostic imaging tools for inflammatory bowel disease. Gut 2006 May; 55(5):733-41.

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Eckburg P, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson K, Relman DA. Diversity of the human intestinal microbial flora. Science 2005; 308:1635-1638.

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Together with researchers at Stanford University in California, we were the first to report on the normal human gut microbiome. The human gut microbiome refers to the bacteria or ‘gut bugs’ that normally reside within the bowel. All humans have millions of bugs of different varieties in their bowels that help keep the bowels working properly.

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Bernstein CN, Blanchard JF, Rawsthorne P, Collins MT. A population-based case control study of seroprevalence of Mycobacterium paratuberculosis in patients with Crohn's disease and ulcerative colitis. Journal of Clinical Microbiology 2004; 42:1129-1135.

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