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Epidemiology Publications // 2011-2012

Wong S, Walker JR, Graff LA, Carr R, Clara I, Promislow S, Miller N, Rogala L, Bernstein CN. The information needs and preferences of persons with longstanding IBD. Canadian Journal of Gastroenterology 2012; 26: 525-531.

Understanding the information needs and preferred vehicles of information delivery to patients with inflammatory bowel disease (IBD) will enhance their care. We surveyed persons with longstanding IBD as to their information needs and preferred vehicles of information delivery. 271 persons in the Manitoba IBD Cohort Study at a mean disease duration of 11 years were surveyed to assess its information needs across 23 issues, both retrospectively at the time of diagnosis and currently. Most participants (64%) were initially diagnosed by a gastroenterologist, or otherwise by a family physician (19%) or surgeon (12%). Recalling time of diagnosis, at least 80% rated as very important information about common symptoms of IBD, possible complications, long-term prognosis, medication side effects, self management of symptoms and when to involve the doctor, yet only 10% to 36% believed they received the right amount of information about these issues. Dietary guidance was also regarded as important by 80% to 89%, yet only 8% to 16% received the correct amount of information. Regarding current needs, a large proportion believed it would be very helpful to have more information about long-term prognosis (66%) and diet considerations (60% to 68%). The following information sources were regarded as very acceptable: medical specialist (81%); brochure (79%); family doctor (64%); and website (64%), with 51% ranking the medical specialist as the first choice. In a comparison of the responses of this cohort to those of a recently diagnosed sample, there was remarkable consistency in the information needs and most desired sources of information. In the present population-based cohort with longstanding disease, dietary information was regarded as the least adequately addressed. There was clear openness to receiving information through other routes than just the medical specialist, suggesting that optimizing brochures and websites would be an important adjunct source of information. We concluded that approximately 10 years after diagnosis, only a small percentage of persons with IBD believed they received the correct amount of information about the issues they regarded as most important to have discussed at diagnosis.

 

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: 356-361.

Persons with IBD 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. Eighty-six persons, stratified by age, were enrolled from a population-based longitudinal IBD cohort study to undergo 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 above 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 greater than 50 years, decreasing body mass index, and corticosteroid use were most notably correlated with BMD loss. Subjects aged less than 50 years did not have significant declines in BMD. IBD symptom activity scores correlated poorly with BMD loss. Vertebral fractures were uncommon, with only two subjects out of 41 greater than 50 years old developing a definite radiographic fracture over the course of follow-up. No major nonvertebral fractures were observed. Patients with IBD do not appear to have significantly accelerated BMD loss. Older age, decreasing body mass index, and corticosteroid use may identify IBD patients at greater risk for BMD loss.

 

Bernstein CN, Longobardi T, Finlayson G, Blanchard JF. The direct medical cost of managing IBD patients: A Canadian population based study. Inflammatory Bowel Diseases 2012; 18: 1498-1508.

This study aimed to quantify the direct medical cost of treating IBD in Manitoba in 2005/2006. In all, 7375 individuals with IBD recorded in the University of Manitoba IBD Epidemiology Database were matched on age, gender, and geography to up to 10 non-IBD controls. Data for cases and controls were extracted from Manitoba Health databases in fiscal 2005/2006 for pharmaceutical, physician claims, and hospital abstracts. The average expenditure were computed for the annual cost of pharmaceuticals, hospitalizations (day surgery and inpatient), and physician office visits. We assessed costs based on age, sex, type of IBD, disease duration, and level of care provided. In 2005/2006 the average direct cost of an IBD case was $3896 which was twice that of controls (P < 0.05). Crohn's disease (n = 3735) was significantly more costly on average than ulcerative colitis (UC; n = 3640) ($4232 and $3552, respectively, P < 0.001). The most costly cases included those within 1 year of diagnosis ($6611; SE = $593), those hospitalized overnight (15%) ($13,495, maximum  costing  case= $130,332), those who had a surgical stay (2% of IBD cases) ($18,749, range = $13,413-$125,912), and those using infliximab (0.7%) ($31,440; maximum costing case= $96,328). For individuals using infliximab their direct annual average healthcare cost was $9683 (maximum costing case = $55,208) prior to using infliximab. We concluded that in Manitoba the direct average annual healthcare cost of Crohn’s disease is greater than UC and that of a patient using infliximab tends to be greater than one incurring a surgical stay.

 

Targownik LE, Nugent Z, Singh H, Bernstein CN. The epidemiology of colectomy in ulcerative colitis: Results from a population-based cohort. American Journal of Gastroenterology 2012; 107: 1228-1235.

Previous studies have reported colectomy rates of over 50% in ulcerative colitis, though changes in management may have influenced the rates of colectomy in the modern era. We sought to determine the incidence of colectomy in ulcerative colitis and identify risk factors associated with early colectomy and late colectomy. We tracked the occurrence of total colectomy in all patients with known ulcerative colitis, subdivided into early colectomy (≤90 days from diagnosis date), and late colectomy (>90 days from diagnosis). Among 3752 patients with ulcerative colitis, 367 underwent colectomy. The 5-, 10- and 20-year actuarial risk of requiring colectomy was 7.5%, 10.4%, and 14.8% respectively. Male sex (hazard ratio [HR] 2.63, 95%CI: 1.58–4.36), and being initially diagnosed during a hospitalization (HR 12.46 95%CI: 7.40–21.0) were predictive of early colectomy after adjustment for confounders. In-hospital diagnosis was predictive of late colectomy, whereas being diagnosed more recently was protective against late colectomy (HR 0.96, 95%CI 0.93-0.98). We concluded that the cumulative incidence of colectomy in ulcerative colitis is lower than previously reported, and appears to be decreasing further among more recently diagnosed cohorts of patients. Male sex and hospitalization at the time of diagnosis are major risk factors for early colectomy and late colectomy.

 

Shaw S, Blanchard JF, Bernstein CN. Association between early childhood otitis media and pediatric inflammatory bowel disease: an exploratory population-based analysis. Journal of Pediatrics 2012; 162: 510-514.

Antibiotic use in childhood may alter intestinal flora predisposing to IBD. The most common disease for which antibiotics are used in childhood is otitis media. We aimed to determine if a diagnosis of otitis media in the first five years of childhood was associated with development of pediatric IBD. A total of 294 pediatric IBD cases diagnosed between 1989 and 2008 were matched to 2,377 controls, based on age, sex and geographic region (Total N=2,671). Otitis media diagnoses were based on physician claims. IBD status was determined from a validated administrative database definition. Approximately 5% of IBD cases and 12% of controls had no otitis media diagnoses prior to IBD case date. By age of 5, 89% of IBD cases had at least one diagnosis of otitis media, compared to 82% of controls. In multivariable analyses, compared to cases and controls with no otitis media diagnoses, individuals with an otitis media otitis media diagnosis by the age of 5 were at 2.8 times the odds of being an IBD case (95%CI: 1.5-5.2, p=.001). This association was detected in stratified models examining Crohn’s disease and ulcerative colitis separately. We concluded that compared to controls, subjects diagnosed with IBD were more likely to have had at least one early childhood episode of otitis media prior to their diagnosis. We suspect otitis media serves as a proxy measure of antibiotic use.

Nguyen G, Gulamhusein A, Bernstein CN. 5-Aminosalicylic acid is not protective against colorectal cancer in inflammatory bowel disease: A meta-analysis of non-referral populations. American Journal of Gastroenterology 2012; 107: 1298-1304.

Some studies have demonstrated that 5-aminosalicylic acid (5-ASA) is associated with a reduced risk of colorectal cancer in IBD. However, as noted in our study above and in other population-based studies no protective association has been found. We conducted a systematic review that focused on non-referral studies to reassess the role of 5-ASA for prevetion of colorectal cancer in. We searched MEDLINE, EMBASE, and the Cochrane databases for studies of non-referral populations that assessed the association between 5-ASA use for at least 1 year and colorectal neoplasia between 1966 and 2011 and conducted a quantitative meta-analysis.

Four observational studies fulfilled inclusion criteria. While there was moderate heterogeneity between studies the overall pooled likelihood of 5ASA preventing colorectal cancer was not met. A series of sensitivity analyses in which each of the four studies was excluded one at a time did not show any significant change in the overall pooled odds ratio or likelihood that 5ASA was protective against colorectal cancer. We conducted a separate meta-analysis of nine clinic-based studies, which, in contrast, yielded  protection of 5ASA against colorectal cancer by almost half the rate. We concluded that our meta-analysis yielded inconsistent results that were dependent on the inclusion of either non-referral or clinic-based populations. Based on non-referral studies, there does not seem to be a protective effect of 5-ASA on development of colorectal cancer in IBD. However, heterogeneity among these studies limits their interpretation.

Nguyen GC, Nugent Z, Shaw S, Bernstein CN. Outcomes of patients with Crohn’s disease have improved since 1996 and are associated with increased specialist care. Gastroenterology 2011; 141: 90-97.

In this study we investigated the long term outcomes of Crohn’s disease in terms of surgeries over 25 years f the University of Manitoba IBD Epidemiology Database. While a well placed surgery can sometimes allow a patients to markedly improve their quality of life an overall reduction in surgery rates might be considered to be a sign of either less severe disease or improved overall management. We investigated factors that affect long-term outcomes in Crohn’s disease. We performed a retrospective study of 3403 patients with Crohn’s disease, diagnosed between 1988 and 2008 in Manitoba, Canada. Subjects were assigned to cohorts based on diagnosis year: cohort I (before 1996), cohort II (1996-2000), or cohort III (2001 and after). We compared risks for surgery and hospitalization among the cohorts and assessed use of immunomodulators and specialists. The 5-year risks of first surgery were 30%, 22%, and 18% for cohorts I, II, and III, respectively. The adjusted hazard ratios for first surgery in cohorts II and III, compared with cohort I, were 0.72 (95% confidence interval [CI], 0.62-0.84) and 0.57 (95% CI, 0.48-0.68), respectively. The adjusted hazard ratio for cohort III, compared with cohort II, was 0.79 (95% CI, 0.65-0.97). There was a higher prevalence of visits to a gastroenterologist within the first year of diagnosis among cohorts II and III (cohort I, 53%; cohort II, 72%; and cohort III, 88%; P<.0001), which was associated with a reduced need for surgery (hazard ratio, 0.83; 95% CI, 0.71-0.98) and contributed to differences in surgery rates among the cohorts. The association between early gastroenterology care and lower risk for surgery was most evident 2 years after diagnosis (hazard ratio, 0.66; 95% CI, 0.53-0.82). Use of immunomodulators within the first year of diagnosis was higher in cohort III than in cohort II (20% vs 11%; P<.0001). We concluded that risk of surgery decreased among patients with Crohn’s disease diagnosed after 1996, compared with before, 1996, and was associated with specialist care. Specialist care within 1 year of diagnosis might improve outcomes in Crohn’s disease. Overall surgical rates in Crohn’s disease have reduced between 1988 and 2008 which suggests that either the natural history of the disease reflects a milder disease course over time or that medical management has improved such that surgery rates have reduced.

 

Shaw SY, Blanchard JF, Bernstein CN. Association Between the Use of Antibiotics and New Diagnoses of Crohn’s Disease and Ulcerative Colitis. American Journal of Gastroenterology 2011; 106; 2133-2142.

We aimed to determine if use of antibiotics 2-5 years prior to diagnosis in adults was associated with development of IBD. We assessed the population-based University of Manitoba Inflammatory Bowel Disease Epidemiologic Database.  A total of 2,234 subjects diagnosed with IBD between 2001 and 2008 were matched to 22,346 controls, based on age, sex and geographic region. Antibiotic data were drawn from the Manitoba Drug Program Information Network, a comprehensive database of all prescription drugs for all Manitobans dating back to 1995.

The mean age at diagnosis was 43.4 years. 12% of cases had at least 3 prescriptions two years prior to the case date, compared to 7% of controls.  The likelihood for those receiving at least 3 dispensations 2 years prior to their study inclusion was 50% higher in IBD cases than controls. This difference in at least 3 dispensations between cases and controls was fairly consistent at 3, 4 and 5 years prior to IBD case date.  Antibiotic dispensations were associated with both Crohn's disease and UC, with the association nominally stronger in Crohn's disease cases for at least 1 and at least 2 dispensations, while the association was stronger in UC cases for at least 3 dispensations. A dose-dependent relationship between number of antibiotic dispensations, and the risk of IBD was observed across all years investigated. We concluded that subjects diagnosed with IBD were more likely to have been prescribed antibiotics 2-5 years prior to their diagnosis. This possibly implicates antibiotic use as a predisposing factor in IBD etiology.

Bernstein CN, Nugent Z, Blanchard JF. 5-aminosalicylate is not chemoprophylactic for colorectal cancer in IBD: a population based study. American Journal of Gastroenterology 2011; 106: 731-6.

People with UC or Crohn’s colitis are at increased risk of developing colorectal ancer compared to the general population. We aimed to determine if use of 5-aminosalicylates (5-ASA) was associated with a reduced risk of colorectal cancer (CRC) in people with IBD. We used the population-based University of Manitoba IBD Epidemiology Database from 1984 to 2008 and which includes all prescription medication use since 1995. In 2008, there were 8,744 subjects with IBD (ulcerative colitis 4,325, Crohn's disease 4,419, females 4,851, males 3,893). In study I, we assessed the incidence of colorectal cancer among 5-ASA users (at least 1 year, and at least 5 years of cumulative use) compared with nonusers. In study II, we assessed a cohort of those with colorectal cancer (n=101) diagnosed in 1995-2008, matched to a control cohort by age, sex, disease duration, and disease diagnosis without CRC (n=303) to assess use of 5ASA prior to colorectal cancer diagnosis. For study I, the risk for colorectal cancer among 5-ASA users was nearly identical to non users for persons with at least 1 year of use and was actually increased 2-fold for those with at least 5 years of use with no difference when assessing by diagnosis. Males, but not females, using 5-ASA for at least 5 years had an increased risk of colorectal cancer. In study II, colorectal cancer cases had similar use of any 5-ASA compared with controls for at least 1 year of use at least 5 years and a similar average number of 5-ASA prescriptions at 10 vs. 11  and a similar average number of dose days at 330 vs. 410 . We concluded that 5-ASA use does not prevent colorectal cancer in IBD.

Publications // from the Manitoba IBD Epidemiology Database