Sex-Based Differences in Incidence of Inflammatory Bowel Diseases-Pooled Analysis of Population-Based Studies From Western Countries.

BACKGROUND & AIMS: Although the incidence of inflammatory bowel diseases (IBDs) varies with age, few studies have examined variations between the sexes. We therefore used population data from established cohorts to analyze sex differences in IBD incidence according to age at diagnosis. METHODS: We identified population-based cohorts of patients with IBD for which incidence and age data were available (17 distinct cohorts from 16 regions of Europe, North America, Australia, and New Zealand). We collected data through December 2016 on 95,605 incident cases of Crohn's disease (CD) (42,831 male and 52,774 female) and 112,004 incident cases of ulcerative colitis (UC) (61,672 male and 50,332 female). We pooled incidence rate ratios of CD and UC for the combined cohort and compared differences according to sex using random effects meta-analysis. RESULTS: Female patients had a lower risk of CD during childhood, until the age range of 10-14 years (incidence rate ratio, 0.70; 95% CI, 0.53-0.93), but they had a higher risk of CD thereafter, which was statistically significant for the age groups of 25-29 years and older than 35 years. The incidence of UC did not differ significantly for female vs male patients (except for the age group of 5-9 years) until age 45 years; thereafter, men had a significantly higher incidence of ulcerative colitis than women. CONCLUSIONS: In a pooled analysis of population-based studies, we found age at IBD onset to vary with sex. Further studies are needed to investigate mechanisms of sex differences in IBD incidence.

Trends in Epidemiology of Pediatric Inflammatory Bowel Disease in Canada: Distributed Network Analysis of Multiple Population-Based Provincial Health Administrative Databases.

OBJECTIVES: The incidence of pediatric-onset inflammatory bowel disease (IBD) is increasing worldwide. We used population-based health administrative data to determine national Canadian IBD incidence, prevalence, and trends over time of childhood-onset IBD. METHODS: We identified children <16 years (y) diagnosed with IBD 1999-2010 from health administrative data in five provinces (Alberta, Manitoba, Nova Scotia, Ontario, Quebec), comprising 79.2% of the Canadian population. Standardized incidence and prevalence were calculated per 100,000 children. Annual percentage change (APC) in incidence and prevalence were determined using Poisson regression analysis. Provincial estimates were meta-analyzed using random-effects models to produce national estimates. RESULTS: 5,214 incident cases were diagnosed during the study period (3,462 Crohn's disease, 1,382 ulcerative colitis, 279 type unclassifiable). The incidence in Canada was 9.68 (95% CI 9.11 to 10.25) per 100,000 children. Incidence was similar amongst most provinces, but higher in Nova Scotia. APC in incidence did not significantly change over the study period in the overall cohort (+2.06%, 95% CI -0.64% to +4.76%). However, incidence significantly increased in children aged 0-5y (+7.19%, 95% +2.82% to +11.56%). Prevalence at the end of the study period in Canada was 38.25 (95% CI 35.78 to 40.73) per 100,000 children. Prevalence increased significantly over time, APC +4.56% (95% CI +3.71% to +5.42%). CONCLUSIONS: Canada has amongst the highest incidence of childhood-onset IBD in the world. Prevalence significantly increased over time. Incidence was not statistically changed with the exception of a rapid increase in incidence in the youngest group of children.

Rural and Urban Residence During Early Life is Associated with Risk of Inflammatory Bowel Disease: A Population-Based Inception and Birth Cohort Study

OBJECTIVES: To determine the association between inflammatory bowel disease (IBD) and rural/urban household at the time of diagnosis, or within the first 5 years (y) of life. METHODS: Population-based cohorts of residents of four Canadian provinces were created using health administrative data. Rural/urban status was derived from postal codes based on population density and distance to metropolitan areas. Validated algorithms identified all incident IBD cases from administrative data (Alberta: 1999-2008, Manitoba and Ontario: 1999-2010, and Nova Scotia: 2000-2008). We determined sex-standardized incidence (per 100,000 patient-years) and incident rate ratios (IRR) using Poisson regression. A birth cohort was created of children in whom full administrative data were available from birth (Alberta 1996-2010, Manitoba 1988-2010, and Ontario 1991-2010). IRR was calculated for residents who lived continuously in rural/urban households during each of the first 5 years of life. RESULTS: There were 6,662 rural residents and 38,905 urban residents with IBD. Incidence of IBD per 100,000 was 33.16 (95% CI 27.24-39.08) in urban residents, and 30.72 (95% CI 23.81-37.64) in rural residents (IRR 0.90, 95% CI 0.81-0.99). The protective association was strongest in children <10 years (IRR 0.58, 95% CI 0.43-0.73) and 10-17.9 years (IRR 0.72, 95% CI 0.64-0.81). In the birth cohort, comprising 331 rural and 2,302 urban residents, rurality in the first 1-5 years of life was associated with lower risk of IBD (IRR 0.75-0.78). CONCLUSIONS: People living in rural households had lower risk of developing IBD. This association is strongest in young children and adolescents, and in children exposed to the rural environment early in life.

Corrigendum: Rural and Urban Residence During Early Life Is Associated with a Lower Risk of Inflammatory Bowel Disease: A Population-Based Inception and Birth Cohort Study.

This corrects the article DOI: 10.1038/ajg.2017.208.

Inflammatory bowel disease and risk of mortality in COPD.

Patients with chronic obstructive pulmonary disease (COPD) have higher incidence and prevalence of other chronic inflammatory diseases, including inflammatory bowel disease (IBD). We assessed whether IBD onset increases mortality risk in patients with COPD or asthma-associated COPD.Two population-based cohorts of COPD and asthma-COPD subjects were identified using the administrative health databases in Québec, Canada, 1990-2007. Death records were retrieved from the death certificate registry. Cox proportional hazards models were used to assess the impact of newly developed IBD on mortality risk.The COPD and asthma-COPD cohorts included 273 208 and 26 575 patients, respectively, of which 697 and 119 developed IBD. IBD increased the risk of all-cause mortality in both COPD (hazard ratio 1.23, 95% CI 1.09-1.4) and asthma-COPD (hazard ratio 1.65, 95% CI 1.23-2.22). In asthma-COPD patients, IBD increased the risk of mortality from respiratory conditions (hazard ratio 2.18, 95% CI 1.31-3.64); in COPD patients, IBD increased the risk of death from digestive conditions (hazard ratio 4.45, 95% CI 2.39-8.30).IBD is a risk factor for mortality in patients with pre-existing COPD or asthma-COPD. IBD increased mortality by respiratory and digestive conditions in patients with asthma-COPD and COPD, respectively.

Increased incidence of inflammatory bowel disease in Québec residents with airway diseases.

The objective of the study was to assess whether the incidences of Crohn's disease and ulcerative colitis are increased in patients with asthma and chronic obstructive pulmonary disease (COPD) compared to the general population. A population-based retrospective cohort study was conducted using the administrative health databases of Québec, Canada. Incidences of Crohn's disease and ulcerative colitis among patients with asthma and COPD were assessed for the 2001-2006 period. In total, 136 178 subjects with asthma and 143 904 subjects with COPD were identified. The average incidence of Crohn's disease and ulcerative colitis was 23.1 and 8.8 per 100 000 person-years among asthmatic patients; in the COPD cohort there were 26.2 Crohn's disease cases and 17 ulcerative colitis cases per 100 000 person-years. The incidence of Crohn's disease in asthma and COPD patients was 27% and 55% higher than in the general population of Québec; the incidence of ulcerative colitis was 30% higher among COPD patients compared to the general population. Incidence of inflammatory bowel disease was significantly increased in asthma and COPD patients compared to the general population of Québec. Incidence rates were particularly high in patients with COPD. Awareness of an association between airway diseases and inflammatory bowel disease in older age groups may play an important role in earlier detection of bowel disease and in the therapeutic management of such patients.

Effects of diurnal variations in temperature on non-accidental mortality among the elderly population of Montreal, Québec, 1984-2007.

The association between ambient temperature and mortality has been studied extensively. Recent data suggest an independent role of diurnal temperature variations in increasing daily mortality. Elderly adults-a growing subgroup of the population in developed countries-may be more susceptible to the effects of temperature variations. The aim of this study was to determine whether variations in diurnal temperature were associated with daily non-accidental mortality among residents of Montreal, Québec, who were 65 years of age and over during the period between 1984 and 2007. We used distributed lag non-linear Poisson models constrained over a 30-day lag period, adjusted for temporal trends, mean daily temperature, and mean daily concentrations of nitrogen dioxide and ozone to estimate changes in daily mortality with diurnal temperature. We found, over the 30 day lag period, a cumulative increase in daily mortality of 5.12% [95% confidence interval (CI): 0.02-10.49%] for a change from 5.9 °C to 11.1 °C (25th to 75th percentiles) in diurnal temperature, and a 11.27% (95%CI: 2.08-21.29%) increase in mortality associated with an increase of diurnal temperature from 11.1 to 17.5 °C (75th to 99th percentiles). The results were relatively robust to adjustment for daily mean temperature. We found that, in Montreal, diurnal variations in temperature are associated with a small increase in non-accidental mortality among the elderly population. More studies are needed in different geographical locations to confirm this effect.

Anti-TNF Therapy and the Risk of Herpes Zoster Among Patients With Inflammatory Bowel Disease.

BACKGROUND: The specific contribution of anti-TNF therapy to the onset of herpes zoster (HZ) in patients with inflammatory bowel disease (IBD) remains uncertain. Thus, the purpose of this nested case-control study was to explore whether the use of anti-TNF therapy is associated with an increased risk of HZ. METHODS: Using the Regie de l'Assurance Maladie du Québec, we identified incident cases of IBD between 1998 and 2015. We matched IBD cases of HZ with up to 10 IBD HZ-free controls on year of cohort entry and follow-up. Current use was defined as a prescription for anti-TNF therapy 60 days before the index date, with nonuse as the comparator. We conducted conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs), adjusting for potential confounders. RESULTS: The cohort consisted of 15,454 incident IBD patients. Over an average follow-up of 5.0 years, 824 patients were diagnosed with HZ (incidence of 9.3 per 1000 person-years). Relative to nonuse, current use of anti-TNF therapy was associated with an overall increased risk of HZ (OR, 1.5; 95% CI, 1.1-2.1). The risk was increased among those older than 50 years (OR, 2.1; 95% CI, 1.2-3.6) and those additionally using steroids and immunosuppressants (OR, 4.1; 95% CI, 2.3-7.2). CONCLUSIONS: Use of anti-TNF therapy was associated with an increased risk of HZ among patients with IBD, particularly among those older than 50 years and those on combination therapy. Prevention strategies for HZ ought to be considered for younger IBD patients commencing treatment.

Patient Perspectives of IBD Care and Services: An Integral Part of a Pan-Canadian Quality Improvement Initiative.

BACKGROUND: As beneficiaries of health service improvement initiatives, patients should have their perspectives of and gaps in care elicited to inform and guide the development of quality indicators to assess health care services. The purpose of this study was to identify patient perspectives amenable for conversion into measurable inflammatory bowel disease (IBD) care quality indicators. METHODS: Crohn's and Colitis Canada's Promoting Access and Care through Centres of Excellence (PACE) program organized four patient focus groups in three Canadian provinces in 2016 to capture the perspective of patients on IBD care services. The RQDA package in R was used for transcript analysis, theme identification and for building a theme hierarchy based on the number of citations. The main themes were converted into patient-derived quality indicators. RESULTS: Several perceived unmet needs were elicited from participants that could be converted into measurable quality indicators. These unmet needs addressed the need for information, access to multidisciplinary services and specialized care, and access to psychological support. Patient unmet needs informed the selection of nine quality indicators that were included in the final list of PACE indicators to assess IBD care services across Canada. CONCLUSIONS: Our study provides a detailed description of patient perspectives on IBD care services that were an integral part of the development of measurable indicators of the quality of care in the context of a universal health care system.

No Change in Surgical and Hospitalization Trends Despite Higher Exposure to Anti-Tumor Necrosis Factor in Inflammatory Bowel Disease in the Québec Provincial Database From 1996 to 2015.

BACKGROUND: Crohn disease (CD) and ulcerative colitis (UC) have high health care expenditures because of medications, hospitalizations, and surgeries. We evaluated disease outcomes and treatment algorithms of patients with inflammatory bowel disease (IBD) in Québec, comparing periods before and after 2010. METHODS: The province of Québec's public health administrative database was used to identify newly diagnosed patients with IBD between 1996 and 2015. The primary and secondary outcomes included time to and probability of first and second IBD-related hospitalizations, first and second major surgery, and medication exposures. Medication prescriptions were collected from the public prescription database. RESULTS: We identified 34,644 newly diagnosed patients with IBD (CD = 59.5%). The probability of the first major surgery increased after 2010 in patients with CD (5 years postdiagnosis before and after 2010: 8% [SD = 0.2%] vs 15% [SD = 0.6%]; P < 0.0001) and patients with UC (6% [SD = 0.2%] vs 10% [SD = 0.6%] ;P < 0.0001). The probability of the second major surgery was unchanged in patients with CD. Hospitalization rates remained unchanged. Patients on anti-tumor necrosis factor (anti-TNF) medications had the lowest probability of hospitalizations (overall 5-year probability in patients with IBD stratified by maximal therapeutic step: 5-aminosalicylic acids 37% [SD = 0.6%]; anti-TNFs 31% [SD = 1.8%]; P < 0.0001). Anti-TNFs were more commonly prescribed for patients with CD after 2010 (4% [SD = 0.2%] vs 16% [SD = 0.6%]; P < 0.0001) in the public health insurance plan, especially younger patients. Corticosteroid exposure was unchanged before and after 2010. Immunosuppressant use was low but increased after 2010. The use of 5-ASAs was stable in patients with UC but decreased in patients with CD. CONCLUSIONS: The probability of first and second hospitalizations remained unchanged in Québec and the probability of major surgery was low overall but did increase despite the higher and earlier use of anti-TNFs.

Risk of Malignant Cancers in Inflammatory Bowel Disease.

OBJECTIVES: To explore the trends and the predictors of incident malignant cancer among patients with inflammatory bowel disease [IBD]. METHODS: We identified a cohort of all patients with incident IBD in Quebec, Canada, from 1998 to 2015, using provincial administrative health-care databases [RAMQ and Med-Echo]. Annual incidence rates [IRs] of cancer were calculated using Poisson regression and were compared with those of the Quebec population using standardized incidence ratios [SIRs ]. Temporal trends in these rates were evaluated by fitting generalized linear models. Conditional logistic regression was used to estimate odds ratios [ORs] for predictors associated with cancer development. RESULTS: The cohort included 35 985 patients with IBD, of which 2275 developed cancers over a mean follow-up of 8 years (IR 785.6 per 100 000 persons per year; 95% confidence interval [CI] 754.0-818.5). The rate of colorectal cancer decreased significantly from 1998 to 2015 [p < 0.05 for linear trend], but the incidence remained higher than expected, compared with the Quebec population [SIR 1.39; 95% CI 1.19-1.60]. Rates of extraintestinal cancers increased non-significantly over time [p = 0.11 for linear trend]. In the IBD cohort, chronic kidney disease [OR 1.29; 95% CI 1.17-1.43], respiratory diseases [OR 1.07; 95% CI 1.02-1.12], and diabetes mellitus [OR 1.06; 95% CI 1.01-1.11] were associated with an increase in the incidence of cancer. CONCLUSIONS: The decreasing rates of colorectal cancer suggest improved management and care in IBD. Further studies are needed to explore the impact of comorbid conditions on the risk of cancer in IBD.

Selection of Quality Indicators in IBD: Integrating Physician and Patient Perspectives.

Background: Variation in clinical practice exists in many aspects of inflammatory bowel disease (IBD) care. Our aim was to develop a comprehensive set of quality indicators (QIs) to be measured in view of improving the quality of IBD care provided in clinical practice. This initiative was part of a global Canadian quality initiative PACE (Promoting Access and Care through Centres of Excellence). Methods: A modified RAND appropriateness method was used to identify and rate structure, process, outcome, and patient-derived QIs of IBD care. The process included a comprehensive literature search yielding a broad list of QIs, the online selection of QIs by a core expert panel, the selection of patient-derived QIs from 4 patient focus groups, and the subsequent selection of QIs by a multidisciplinary panel, followed by a moderated in-person multidisciplinary meeting during which each indicator was rated for importance and feasibility of measurement. Predetermined cutoffs for mean score and degree of disagreement were used to select the final list of QIs. Results: Forty-five QIs, including 6 that were patient-derived, were selected. Nine structure QIs addressed aspects related to the services and specialist care offered at an IBD unit or clinic. Thirty process indicators included administrative and workflow processes, features related to IBD therapy, surveillance, vaccination, and risk management. Six outcome QIs included measures of healthcare utilization, steroid use, and patient satisfaction. Conclusions: Forty-five QIs including patient-derived indicators were selected through an iterative process. These indicators can be used to measure and improve the quality of care provided to IBD patients. 10.1093/ibd/izy259_video1izy259.video15828250213001.

Inflammatory bowel disease and airway diseases.

Airway diseases are the most commonly described lung manifestations of inflammatory bowel disease (IBD). However, the similarities in disease pathogenesis and the sharing of important environmental risk factors and genetic susceptibility suggest that there is a complex interplay between IBD and airway diseases. Recent evidence of IBD occurrence among patients with airway diseases and the higher than estimated prevalence of subclinical airway injuries among IBD patients support the hypothesis of a two-way association. Future research efforts should be directed toward further exploration of this association, as airway diseases are highly prevalent conditions with a substantial public health impact.

Mortality Trends in Crohn's Disease and Ulcerative Colitis: A Population-based Study in Québec, Canada.

BACKGROUND: Mortality rates greater than in the general population have been reported in the population with Crohn's disease (CD), but reports for ulcerative colitis (UC) are conflicting. Trends with time were rarely described. We aimed to assess whether CD and UC mortality in Québec differs from that in the general population and to describe the trends over a 10-year observation period. METHODS: This is a population-based cohort study using the Québec administrative health databases and death certificates registry. All-cause and cause-specific standardized mortality ratios (SMRs) were computed for 1999 to 2008. A time trend analysis was used to assess changes in the SMR with the calendar year. RESULTS: All-cause mortality was significantly increased in CD and UC compared to the general population: SMR: CD 1.45 (95% confidence interval: 1.34-1.58), UC 1.21 (95% confidence interval: 1.12-1.32). In CD, mortality from digestive conditions, all neoplasms, digestive neoplasms, and colorectal, lymphatic, and lung cancer was significantly higher than in the general population. In UC, mortality from digestive, respiratory, and infectious conditions was also significantly increased. In both CD and UC, there was a decrease with time in all-cause SMRs and in digestive conditions, digestive neoplasms, colorectal cancer, and infectious diseases. SMRs for lung cancer and respiratory conditions increased over time in CD. CONCLUSIONS: All-cause mortality was significantly higher in CD and UC populations than in the general population. However, a decreasing trend with time was observed in all-cause and some cause-specific SMRs. In CD, SMRs for lung cancer and respiratory conditions increased during the observation period.

Risk of Lymphoma, Colorectal and Skin Cancer in Patients with IBD Treated with Immunomodulators and Biologics: A Quebec Claims Database Study.

BACKGROUND: Immunomodulatory medications in patients with inflammatory bowel disease (IBD) have been associated with an increased risk of developing certain malignancies. The aim of this study was to evaluate the risk of melanoma, nonmelanoma skin cancer, colorectal cancer and lymphoma associated with immunomodulators and biologics in patients with IBD. METHODS: A nested case-control study was carried out using the provincial health insurance database of Québec, Canada (RAMQ/MedECHO). RESULTS: A total of 41,176 patients with IBD were identified of whom 19,582 patients were eligible for inclusion in the study. Treatment with thiopurine for more than 5 years was associated with a significantly increased risk of nonmelanoma skin cancer (odds ratio: 1.78; 95% confidence interval, 1.25-2.54). Immunomodulator treatment was not associated with an increased risk of non-Hodgkin's lymphoma (odds ratio: 0.87; 95% confidence interval, 0.53-1.41). Neither immunomodulators nor anti-TNF-α agents were associated with an increased risk of melanoma or colorectal cancer. CONCLUSIONS: In a large provincial IBD cohort, treatment with immunomodulators for more than 5 years was associated with an increased risk of non-melanoma skin cancer, whereas the risk of lymphoma, melanoma, and colorectal cancer was not increased. No association was found between the risk of the evaluated malignancies and anti-TNF-α medications.

Epidemiology of inflammatory bowel disease in Québec: recent trends.

BACKGROUND: Among 10 provinces in Canada, Québec has the second highest incidence of Crohn's disease (CD), based on data collected more than a decade ago. To date, there are no reports on the occurrence of ulcerative colitis (UC) and no updates on the occurrence of CD in Québec. We sought to describe trends in the annual incidence and prevalence of inflammatory bowel disease in Québec during 2001 to 2008. METHODS: A population-based retrospective cohort study was conducted using the administrative health databases of Québec. IBD cases were identified using a validated case definition requiring at least 1 hospitalization or 4 physician claims within a 2-year period. Incident cases were defined as individuals who had been free of inflammatory bowel disease for at least 2 years before the 2-year time span of the case definition. RESULTS: We identified 24,377 CD and 15,346 UC cases. The mean age at diagnosis was 39 and 46 years for CD and UC, respectively. There was a significant decline in the annual incidence from 2001 to 2008 for both CD (P < 0.003) and UC (P < 0.001). No significant change with time was found in pediatric cases. The point prevalence in 2008 was 277 CD and 164 UC cases per 100,000 population. The average incidence was 17.4 CD cases per 100,000 person-years and 10.1 UC cases per 100,000 person-years. There was no predominance of urban or rural cases for either CD or UC. CONCLUSIONS: During 2001 to 2008, annual incidence for both CD and UC declined in Québec. There was no significant change with time in incidence for pediatric cases.