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Background and Aims Thromboprophylaxis use in paediatric inflammatory bowel disease [IBD] is inconsistent. Current guidelines only support treating children with acute severe colitis with risk factors. We convened an international RAND panel to explore thromboprophylaxis in paediatric IBD inpatients in the context of new evidence. Methods We convened a geographically diverse 14-person panel of paediatric gastroenterologists alongside supporting experts. An online survey was sent before an online meeting. Panellists were asked to rate the appropriateness of thromboprophylaxis in hospitalised paediatric IBD patients via 27 scenarios of varying ages, gender, and phenotype, with and without thrombotic risk factors. Anonymised results were presented at the meeting. A second modified survey was distributed to all panellists present at the meeting. Results from the second survey constitute the RAND panel results. The validated RAND disagreement index defined disagreement when ≥ 1. Results The combined outcome of thromboprophylaxis being considered appropriate until discharge and inappropriate to withhold was seen in 20 of 27 scenarios, including: all patients with new-onset acute severe colitis; all flares of known ulcerative colitis, irrespective of risk factors except in pre-pubescent patients with limited disease and no risk factors; and all Crohn’s patients with risk factors. Disagreement was seen in five scenarios regarding Crohn’s without risk factors, where outcomes were already uncertain. Conclusions RAND panels are an established method to assess expert opinion in areas of limited evidence. This work therefore constitutes neither a guideline nor a consensus; however, the findings suggest a need to re-evaluate the role of thromboprophylaxis in future guidelines.

Coronavirus disease 2019 (COVID-19) in children with inflammatory bowel disease (IBD) typically results in a mild infection, similar to those without IBD. Children and adolescents have less severe manifestations of COVID-19 compared to older people, whether or not they have IBD. However, some IBD medications (in particular, corticosteroids) are associated with more severe COVID-19. During the first year of the global pandemic, more IBD care was provided with online technology, necessitated by efforts to reduce hospital and clinic visits. Additionally, non-endoscopic monitoring of inflammation has been required due to the cancellation of non-urgent procedures, resulting in longer endoscopy wait-times. In contrast, pregnant people (with and without IBD) who contract COVID-19 are at increased risk of severe manifestations, death and preterm delivery, making them a priority for severe acute respiratory syndrome coronavirus 2 protective measures and vaccination. Few studies have examined effect of COVID-19 on IBD-related disease activity in pregnant people with IBD. The pandemic has significantly affected the mental health and sense of well-being of children and their families, as well as pregnant people with IBD. These groups were much more likely to experience anxiety and depression compared with prior to the pandemic, even while concern has mostly abated regarding the effect of IBD medications and COVID-19 severity. Unfortunately, the availability of mental health care providers who specialize in people with IBD has not kept pace with the increasing demand.

The COVID-19 pandemic has ushered a globally focused vaccine development program that produced multiple successful vaccines within a year. Four SARS-CoV-2 vaccines have been approved for use in Canada, using two different technologies, all of which have shown excellent efficacy in reducing the rate of symptomatic COVID-19 infection and 100% efficacy in preventing death from COVID-19. People with inflammatory bowel disease (IBD), like many others with immune-mediated chronic diseases, were excluded from the pivotal trials of these vaccines, leading to early hesitancy by regulatory bodies to endorse administering the vaccines to these groups. However, recent data has shown that the adverse event rate to SARS-CoV-2 vaccine among people with IBD is similar to the general population. Early data has further shown that people with IBD are capable of mounting a robust immune response to SARS-CoV-2 vaccines, particularly following a second dose, whereas the response to the first dose is blunted in those receiving anti-TNF therapy or conventional immunosuppressants (azathioprine, 6-mercaptopurine, methotrexate). Based on these data and evidence from previous vaccine programs among people with IBD, multiple national and international expert panels have recommended that individuals with IBD receive complete vaccination against SARS-CoV-2 as soon as possible.

Jasbir Dhaliwal,1– 6 Meltem Tuna,1 Baiju R Shah,1,7,8 Sanjay Murthy,1,9,10 Emily Herrett,4 Anne M Griffiths,2,3 Eric I Benchimol1– 3,8 1ICES, Toronto, ON, Canada; 2SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, ON, Canada; 3Department of Paediatrics, University of Toronto, Toronto, ON, Canada; 4London School of Hygiene and Tropical Medicine, London, UK; 5Cincinnati Children’s Hospital Medical Center, Division of Gastroenterology, Hepatology and Nutrition, Cincinnati, OH, USA; 6Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA; 7Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; 8Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada; 9The Ottawa Hospital IBD Centre, The Ottawa Hospital and Ottawa Hospital Research Institute, Ottawa, ON, Canada; 10Department of Medicine and School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, CanadaCorrespondence: Jasbir DhaliwalPediatrics, University of Cincinnati, Cincinnati Children’s Hospital Medical Center, Division of Gastroenterology, Hepatology and Nutrition, Secondary Appointments in Division of Biomedical Informatics and James M Anderson Center for Health Systems Excellence, 3333 Burnet Avenue, Cincinnati, OH, 45229, USATel +15133789468Email Jasbir.dhaliwal@cchmc.orgBackground: Inflammatory bowel disease (IBD) is now a global disease with incidence increasing throughout Asia.Aim: To determine the incidence of IBD among South Asians and Chinese people residing in Ontario, Canada’s most populous province.Methods: All incident cases of IBD in children (1994– 2015) and adults (1999– 2015) were identified from population-based health administrative data. We classified South Asian and Chinese ethnicity using immigration records and surnames. We determined standardized incidence of IBD and adjusted incidence rate ratio (aIRR) in South Asians and Chinese compared to the general population.Results: Among 16,230,638 people living in Ontario, standardized incidence of IBD per 100,000 person-years was 24.7 (95% CI 24.4– 25.0), compared with 14.6 (95% CI 13.7– 15.5) in 982,472 South Asians and with 5.4 (95% CI 4.8– 5.9) in 764,397 Chinese. The risk of IBD in South Asians was comparable to the general population after adjusting for immigrant status and confounders (aIRR 1.03, 95% CI 0.96– 1.10). South Asians had a lower risk of Crohn’s disease (CD) (aIRR 0.66, 95% CI 0.60– 0.77), but a higher risk of ulcerative colitis (UC) (aIRR 1.47, 95% CI 1.34– 1.61). Chinese people had much lower rates of IBD (aIRR 0.24, 95% CI 0.20– 0.28), CD (aIRR 0.21, 95% CI 0.17– 0.26), and UC (aIRR 0.28, 95% CI 0.23– 0.25).Conclusion: Canadians of South Asian ethnicity had a similarly high risk of developing IBD compared to other Canadians, and a higher risk of developing UC, a finding distinct from the Chinese population. Our findings indicate the importance of genetic and environmental risk factors in people of Asian origin who live in the Western world.Keywords: inflammatory bowel disease, ulcerative colitis, Crohn’s disease, incidence, ethnicity, epidemiology, South Asian, Chinese

Background Modern, specialised care for children with inflammatory bowel disease [IBD] may have resulted in changes in health services use. We report trends over time in health services utilisation and surgery for children with IBD and children without IBD. Methods Children aged Results IBD-specific hospitalisation rates decreased by 2.5% [95% CI 1.8–3.2%] annually, and all-cause hospitalisation rates in children without IBD decreased by 4.3% [95% CI 3.5–5.1%] annually. Intestinal resection risk in CD decreased by 6.0% [95% CI 4.6–7.3%] annually and colectomy risk in UC decreased by 3.0% [95% CI 0.7–5.2%] annually. In contrast, IBD-specific outpatient visit rates increased after 2005 by 4.0% [95% CI 3.1–4.9%] annually. Similar trends in outpatient visits were not observed in children without IBD. Conclusions Hospitalisations and surgeries decreased over time while outpatient visits increased after 2005. Decreasing hospitalisations were mirrored in children without IBD, likely resulting from a combination of changes in disease management and health system factors.

Background & aims: The incidence of inflammatory bowel disease (IBD) is increasing internationally, particularly in nations with historically low rates. Previous reports of the epidemiology of pediatric-onset IBD identified a paucity of data. We systematically reviewed the global trends in incidence and prevalence of IBD diagnosed in individuals Methods: We systematically reviewed studies indexed in MEDLINE, EMBASE, Airiti Library, and SciELO from January 2010 to February 2020 to identify population-based studies reporting the incidence and/or prevalence of IBD, Crohn's disease, ulcerative colitis, and/or IBD-unclassified. Data from studies published before 2000 were derived from a previously published systematic review. We described the geographic distribution and trends in children of all ages and limiting to very early onset (VEO) IBD.Results: A total of 131 studies from 48 countries were included. The incidence and prevalence of pediatric-onset IBD is highest in Northern Europe and North America and lowest in Southern Europe, Asia, and the Middle East. Among studies evaluating trends over time, most (31 of 37, 84%) studies reported significant increases in incidence and all (7 of 7) reported significant increases in prevalence. Data on the incidence and prevalence of VEO-IBD are limited to countries with historically high rates of IBD. Time trends in the incidence of VEO-IBD were visually heterogeneous.Conclusions: Rates of pediatric-onset IBD continue to rise around the world and data are emerging from regions where it was not previously reported; however, there remains a paucity of data on VEO-IBD and on pediatric IBD from developing and recently developed countries.

Background Canadian-born children of South Asian [SA] ethnicity develop inflammatory bowel disease [IBD] at similar rates to those among Caucasian children. We evaluated the variation in phenotypic spectrum of IBD in SA and Caucasian children in a national paediatric inception cohort of new-onset IBD. Methods Patients aged Results Of 1156 children enrolled over 2014 to 2019, 623 were Caucasian [98% and 88% parents Canadian born] and 114 SA [79% Canadian born, 87% parents SA born]. Fewer SAs have a first-degree relative with IBD, 6% vs 19% in Caucasians, p = 0.002. SAs present at a younger age, median age 11.4 years (interquartile range [IQR] 9.2–14.3) vs 13 years [IQR 10.9-15 years], p = 0.03 and more commonly with a UC/IBD-U [ulcerative colitis/IBD-unclassified] subtype [ratio of UC/IBD-U to CD 1.2:1 vs 1:1.8 for Caucasians, p Conclusions The phenotypic spectrum of new-onset IBD in SA children differs from that of Caucasian children, but treatment and clinical course are similar within phenotypic subgroups.

The development of anti-tumour necrosis factor (TNF) therapies has transformed the care of patients with immune-mediated diseases such as inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, psoriasis and inflammatory arthropathies, including rheumatoid arthritis and ankylosing spondylitis. For IBD patients, these biologic therapies are effective at inducing and maintaining remission (1), reducing the need for surgery (2) and improving quality of life (3). Although anti-TNF therapies are effective in several different immune-mediated disorders, individual biologics are not, necessarily, equally effective in all disorders suggesting that their actions may differ between disorders. For example, the paradox that anti-TNF drugs used to treat rheumatoid arthritis (RA) and psoriasis may yet cause joint pains and skin reactions in IBD patients, emphasizes our imperfect understanding of the mechanism of action of these biologic therapies and the need to evaluate treatment outcomes separately for different disorders. The main factors that limit the use of anti-TNF drugs are adverse events and cost. Anti-TNF therapy is associated with joint pains, dermatological disorders and transfusion reactions (4). Transfusion reactions are associated with the development of antibodies to anti-TNF agents and this may also be associated with reduced treatment efficacy (5). Anti-TNF agents are also associated with an increased risk of infection (6) and risk of lymphoma although these risks may be exacerbated, to a greater or lesser extent, by the concomitant use of azathioprine or other immunosuppressive agents (7). Anti-TNF therapies are also expensive costing up to $20,000 per year for each patient in Canada. Canada spent more on biologic therapies for all indications than on any other class of drug in 2018 accounting for 8.2% of the $33.7 billion spent on prescription medications (8). While the cost of these therapies is significant, the cost of having IBD is also expensive to society. It is estimated that the indirect cost of IBD was $1.29 billion in Canada in 2018 (9,10). Anti-TNF therapies can improve quality of life and productivity and, accounting for these societal costs, biologics may offer value for money (11). In the Canadian setting, health care is mainly funded centrally by the tax payer and the government, understandably, focuses on how biologic therapy may reduce health care costs. This is less clear cut with research using health administrative data failing to demonstrate any significant decrease in hospitalizations or surgical resections in the anti-TNF era compared to what would be expected if these drugs had not been introduced (12). Given this perspective, it is understandable that approaches to reducing the cost of these drugs are being explored. The emergence of biosimilars, also known as subsequent entry biologics have provided an opportunity for third party payers to reduce anti-TNF therapy drug costs. A biosimilar is a biological medical product that is similar to the original but manufactured by a different company once the patent for that product has expired. They are typically less expensive than the original product and therefore an obvious target in attempts to reduce biologic drug costs. Biosimilars are distinct from usual generic drugs, which are simple small molecules that are relatively straightforward to reproduce and manufacture on a large scale, and identical to the original drug. Biologic therapies are more complex proteins and require replication in living cells. The product is dependent on the type of genetically modified cell being used, the production process and purification techniques (13). The manufacturing process is considerably more expensive than standard small molecules and therefore costs of biosimilars are higher than generically produced drugs. Furthermore, the variation from the originator is greater than would normally be seen with generics. However, it is important to emphasize that even with the original manufacturer there is potential for variability between each manufacturing run due to the complexity of living organisms. The Federal Drug Agency has released documents regarding the approval process for biosimilars (14) that other regulatory authorities have largely adopted (15). Essentially biosimilars must show a high degree of similarity to the original product and have no clinically meaningful differences in safety, purity and potency (14). This is a reasonable definition in principle but the definitions of ‘high degree of similarity’ as well as ‘clinically meaningful differences in safety and potency’ need further clarification in clinical practice. The Canadian Association of Gastroenterology has previously published a position statement on biosimilars (16) but this was 6 years ago, and more data are now available. Crohn’s and Colitis Canada has published a position statement more recently (17) but the two organizations felt it was of value to release a joint position statement after a full literature review. Several positions statements have been released by various organizations (Table 1) but none has provided an explicit literature search, nor have they assessed the quality of evidence of a defined clinical question according to GRADE criteria (18). Table 1. Position statements reached by other groups on the use of biosimilars

ObjectivesRandomised controlled trials conducted using cohorts and routinely collected data, including registries, electronic health records and administrative databases, are increasingly used in healthcare intervention research. A Consolidated Standards of Reporting Trials (CONSORT) statement extension for trials conducted using cohorts and routinely collected data (CONSORT-ROUTINE) has been developed with the goal of improving reporting quality. This article describes the processes and methods used to develop the extension and decisions made to arrive at the final checklist.MethodsThe development process involved five stages: (1) identification of the need for a reporting guideline and project launch; (2) conduct of a scoping review to identify possible modifications to CONSORT 2010 checklist items and possible new extension items; (3) a three-round modified Delphi study involving key stakeholders to gather feedback on the checklist; (4) a consensus meeting to finalise items to be included in the extension, followed by stakeholder piloting of the checklist; and (5) publication, dissemination and implementation of the final checklist.Results27 items were initially developed and rated in Delphi round 1, 13 items were rated in round 2 and 11 items were rated in round 3. Response rates for the Delphi study were 92 of 125 (74%) invited participants in round 1, 77 of 92 (84%) round 1 completers in round 2 and 62 of 77 (81%) round 2 completers in round 3. Twenty-seven members of the project team representing a variety of stakeholder groups attended the in-person consensus meeting. The final checklist includes five new items and eight modified items. The extension Explanation & Elaboration document further clarifies aspects that are important to report.ConclusionUptake of CONSORT-ROUTINE and accompanying Explanation & Elaboration document will improve conduct of trials, as well as the transparency and completeness of reporting of trials conducted using cohorts and routinely collected data.

Background The incidence of inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is increasing internationally, particularly in developing nations where rates were historically low. Previous reports of the incidence and prevalence of pediatric-onset IBD have identified a paucity of population-based studies. Aims We reviewed the global trends in incidence of pediatric IBD using evidence from population-based studies. Methods (PROSPERO CRD42019125193) We systematically reviewed studies indexed in MEDLINE, EMBASE, Airiti Library, and SciELO from 01/2010-02/2020 to identify population-based studies reporting the incidence of pediatric-onset IBD, CD, and UC. Included studies combined childhood and adolescent-onset IBD (onset Results Of 8096 abstracts screened, 74 studies described the incidence of IBD, CD, or UC in 33 countries (Figure panel A). The incidence of pediatric-onset IBD is highest in Northern Europe and North America, and lowest in Southern Europe, Asia, and the Middle East. This geographical distribution is similar in UC, while incidence of pediatric-onset CD is highest in North America and Northern Europe, followed by Australia. Trends in incidence over time, stratified by continent, are reported in Figure, panel B. Significantly increasing incidence of IBD, CD, and/or UC was reported in China, Bahrain, Canada, New Zealand, Australia, Singapore, Saudi Arabia, and most European countries. Very Early Onset (VEO) IBD significantly increased in Canada, however Saudi Arabia reported decreasing incidence of VEO-CD but stable incidence of VEO-UC. Conclusions Conclusion: Incidence of pediatric-onset IBD are highest in Northern Europe and North American and are increasing globally. There remains a paucity of studies from many parts of the world on the incidence pediatric IBD. Further research is needed to understand the pathogenesis of the rising incidence of pediatric IBD, including work to understand the genetic, environmental, immunological and microbiome alterations leading to the increasing rates in children. References: 1Benchimol, Fortinsky et al. Inflamm Bowel Dis 2011;17:423–39. Funding Agencies None

Background Inflammatory bowel disease (IBD) increases the risk of venous thromboembolism (VTE) in patients of all ages but the risk of VTE among Canadian children with IBD has not previously been investigated. Aims Report the incidence of VTE and subtypes pulmonary embolism (PE) and deep vein thrombosis (DVT) in children with and without IBD. Methods Children diagnosed with IBD Results 3127 children with IBD (1826 CD; 1045 UC) were matched to 15,635 children without IBD. The cumulative incidence of VTE within 5 years of IBD diagnosis was 2.8 (95% CI 2.1–3.8) per 1000 PYs compared to 0.13 (95% CI 0.07–0.24) per 1000 PYs in children without IBD (Table). The 5-year cumulative incidences of VTE, DVT, and PE were significantly higher in children with IBD than in children without IBD (VTE: IRR 21.44, 95% CI 10.73–42.82; DVT: IRR 25.15, 95% CI 11.12–56.89; PE: IRR 4.01, 95% CI 1.22–13.18). Compared to UC patients, children with CD were at lower risk of VTE (IRR 0.53, 95% CI 0.29–0.96) and numerically, but not statistically, lower risk of DVT (IRR 0.59, 95% CI 0.30–1.14). Conclusions Although VTEs are relatively rare among children with IBD, these children are at much greater risk than children without IBD. Gastroenterologists caring for these patients should be cognizant of VTE risk and provide appropriate prophylaxis to those at high risk of VTE. Funding Agencies CCC

Background Health services use in inflammatory bowel disease (IBD) patients cost the Canadian healthcare system $1.3 billion per year, but recent changes to care in children with IBD may have altered trends in health services use. Characterization of these trends would aid health policy makers plan for the healthcare needs of IBD children. Aims To quantify time trends in IBD health services use in children and all-cause health services use in children with and without IBD using a population-based cohort. Methods Using the Ontario Crohn’s and Colitis Cohort, children Results IBD-specific hospitalization rates decreased by 2.5% (95%CI 1.8–3.2%) per year, but all-cause hospitalization rates in children without IBD decreased faster (APC, 95%CI: 4.3%, 3.5–5.1%, difference in rates p-value=0.0028). The hazard of intestinal resection for CD decreased by 6.0% (95%CI 4.6–7.3%) per year and the hazard of colectomy for UC decreased by 3.0% (95%CI 0.7–5.2%) per year. IBD-specific outpatient visit rates increased after 2005 by 4.0% (95%CI 3.1–4.9%) per year. Similar trends were not observed in children without IBD. Conclusions Decreasing hazards of intestinal resection and colectomy in children with IBD suggest changes in disease management, including more care being provided on an outpatient basis. Decreased hospitalization rates in IBD were mirrored by similar decreases in non-IBD children, indicating universal care changes. Understanding why these trends are occurring may help us better understand how to provide optimal care to children with IBD. Funding Agencies CIHRCanGIEC

Background Respiratory syncytial virus (RSV) infection is a major cause of hospitalization in young children in Canada, despite routine immunoprophylaxis in those with medical risk factors. We aimed to determine if cold temperatures are associated with RSV hospitalization. Methods We conducted a population-based nested case–control study of children in Ontario, Canada, using health administrative data. We compared children hospitalized for RSV between September 1, 2011 and August 31, 2012 to age and sex matched controls. We used multivariable logistic regression to identify associations between minimum daily temperature and RSV hospitalizations with adjustment for sociodemographic and environmental factors. Results We identified 1670 children with RSV hospitalizations during the study period and 6680 matched controls. Warmer temperatures (OR = 0.94, 95%CI: 0.93, 0.95) were associated with lower odds of RSV hospitalization. Southern ecozone (OR = 1.6, 95%CI: 1.2, 2.1), increased ozone concentration (OR = 1.03, 95%CI: 1.01, 1.06) and living in a lower income neighbourhood (OR = 1.3, 95%CI: 1.1, 1.5) significantly increased the odds of RSV hospitalization, as did living in a household with a larger number of siblings in a sub-cohort of children (OR = 1.34, 95%CI: 1.26, 1.41). Conclusions In Ontario, the likelihood of having an RSV hospitalization is associated with colder temperature exposures and socioeconomic factors.

Background Inflammatory bowel disease (IBD) is rising rapidly in Canadian children. These children require consistent high-quality specialized care to prevent long-term complications. Aims Evaluate variation in health services utilization and surgery rates across pediatric IBD centres in Ontario. Methods Incident cases of IBD Results Of 2584 IBD cases, 73.4% were treated in a pediatric IBD centre. Between-centre differences accounted for 0.18% (MHR 1.06) and 0.41% (MHR 1.09) of variation in hospitalizations and ED visits, respectively. Children treated at centres where a higher proportion of children were cared for by GIs were more likely to be hospitalized (HR 2.09, 95% CI 1.26–3.45). Children treated at centres with a longer mean diagnostic lag were also more likely to be hospitalized (HR 1.01, 95% CI 1.003–1.02). ED visits were not associated with the proportion of children cared for by gastroenterologists or diagnostic lag. Among 1529 CD cases, 14.1% required intestinal resection; 1.79% of variation in the risk of surgery resulted from between-centre differences (MHR 1.20). Surgery was less common among patients at centres where more children were cared for by GIs (HR 0.24, 95% CI 0.07–0.84) and with a longer mean diagnostic lag (HR 0.98, 95% CI 0.97–0.99). After adjusting for these, between-centre differences accounted for 0.005% (MHR 1.01) of variation in care. Minimal variation was observed among the 11.0% of 872 UC cases requiring colectomy, with 0.37% of variation due to between-centre differences (MOR 1.09). Colectomy risk was not associated with GI care or diagnostic lag. Conclusions Variation in ED visits, hospitalizations, and surgery among children with IBD is small; however, centre-level differences in GI specialist care use and time to diagnosis were associated with hospitalization and surgery. It is essential to understand between-centre differences to reduce variation and ensure high-quality care. Funding Agencies CCC

Canada has among the highest incidence and prevalence of inflammatory bowel disease (IBD) in the world. After decades of rising incidence of IBD in Canada during the 20th Century, the prevalence of IBD in 2018 is 0.7% of the Canadian population. Forecasting models predict that prevalence of IBD will continue to rise to 1.0% of the population by 2030. In 2018, the number of Canadians living with IBD is approximately 270,000 and is predicted to rise to 403,000 Canadians in 2030. Inflammatory bowel disease affects all age groups with adolescents and young adults at highest risk of diagnosis. Canadians of all ethnicities are being diagnosed with IBD including known high-risk groups such as Ashkenazi Jews and offspring of South Asian immigrants who were previously thought to be low risk. Moreover, IBD has evolved into a global disease with rising incidence in newly industrialized countries in Asia and South America. The causes of IBD remain unsolved; however, the high rates of disease in Western countries and its emergence in newly industrialized countries suggest that environmental factors associated with urbanization, modernization, or Western diets may be pertinent to understanding the pathogenesis of the disease. Highlights 1. Canada continues to have among the highest prevalence of IBD in the world. 2. Today, approximately 270,000 Canadians live with IBD. By 2030 it is estimated that nearly 403,000 Canadians will have a diagnosis of IBD. 3. Inflammatory bowel disease has become a worldwide disease with increasing rates in Asia, Africa, and South America—continents where IBD was rarely diagnosed prior to 1990. 4. The causes of IBD are unknown, but the high rates of disease over the past 60 years in Western countries and the emergence of disease in developing countries suggest that factors associated with urbanization, modernization, or Western diets may be pertinent to understanding the pathogenesis of the disease. 5. Many of the leading hypotheses as to the causes of IBD tie in with alteration of the gut microbiome, the suite of organisms that reside in the bowel and maintain bowel health throughout life. Key Summary Points 1. The incidence (the number of new diagnoses annually) of IBD rose throughout the 20th century in Canada and then stabilized at the turn of the 21st century. 2. The prevalence (the total number of diagnosed persons in the population) of IBD in Canada is among the highest in the world. 3. Today, 270,000 (0.7%, or 7 in 1000) Canadians are estimated to live with IBD. By 2030, that number is expected to rise to 403,000 Canadians (1% or 1 in 100). 4. Inflammatory bowel disease can be diagnosed at any age. However, the age groups that are most likely to be diagnosed are adolescents and young adults from 20 to 30 years of age. 5. Inflammatory bowel disease in Canada affects the lives of Canadians of all ethnicities, including known high-risk groups such as Ashkenazi Jews, and those thought previously to be at low risk, such as first-generation offspring of South Asian immigrants. 6. Canadian health policy makers will need to prepare the Canadian health care system for the rising burden of IBD. 7. As newly industrialized countries in Asia, Africa, and South America are transitioning to a Westernized society, IBD has emerged and its incidence in these countries is rising rapidly. 8. The gut microbiome includes microorganisms that maintain digestive health. Thus, changes in the microbiome, which may change the immune system’s response to triggers, may be important in initiating and perpetuating IBD. 9. A number of factors can alter the gut microbiome and early childhood may be a particularly important time such that breastfeeding, early life diet, use of antibiotics, infections, and other environmental exposures may impact the gut microbiome in such a way that facilitates developing IBD. 10. Smoking is associated with an increased risk and worsening disease course of Crohn’s disease. Quitting smoking is associated with an increased risk of developing ulcerative colitis. Therefore, never initiating smoking can mitigate the risk for IBD. Educational programs aimed at those at-risk for IBD should emphasize the risk of starting to smoke tobacco. 11. Modifying exposure to environmental risk factors associated with the Westernization of society (e.g., Western diet and lifestyles) may provide an avenue for reducing the risk of IBD in Canada and worldwide. Gaps in Knowledge and Future Directions 1. While the incidence of IBD appears to be stabilizing in some regions in Canada, IBD may be occurring more frequently in certain populations such as in children, South Asians, Ashkenazi Jews, and immigrants. Future research should focus on the changing demographics of IBD in Canada. 2. The prevalence of IBD will rise steadily over the next decade. To enable better health care system planning and to respond adequately to the increasing burden of IBD, ongoing surveillance of the epidemiology and health services utilization of IBD in Canada is necessary. 3. Most studies have focused on the mortality associated with IBD. Future research is necessary to assess health-adjusted life expectancy and overall life expectancy for those living with IBD. 4. Analyses of resources, infrastructure, and personnel need to be modeled into the future in order to prepare our health care system for the rising burden of IBD. 5. Research on the interaction between genes, microbes, and our environment will inform our understanding of the pathogenesis of IBD, information necessary to prevent IBD in the future.

Canada has among the highest rates of childhood-onset IBD in the world. Over 7000 children and youth under 18 years old are living with IBD in Canada, and 600 to 650 children under 16 years old are diagnosed annually. While the peak age of onset of IBD is highest in the second and third decades of life, over the past two decades incidence has risen most rapidly in children under 5 years old. The treatment of children with IBD presents important challenges including therapeutic choices, risk of adverse events to medications, psychosocial impact on the child and family, increased cost of health care and the implications of the transition from pediatric to adult care. Despite the unique circumstances faced by children and their families, there is a lack of research to help understand the causes of the rising incidence and the best therapies for children with IBD. Scientific evidence—and specifically clinical trials of pharmaceuticals—are too often extrapolated from adult research. Health care providers must strive to understand the unique impact of childhood-onset IBD on patients and families, while researchers must expand work to address the important needs of this growing patient population. Highlights In 2018, there are over 7000 children and youth under 18 years old living with IBD in Canada, and 600 to 650 young children (under 16 years) diagnosed every year. The number of children in Canada living with IBD is growing rapidly, increasing 50% in the first decade of the 21st century. Inflammatory bowel disease is still rare in children younger than 5 years of age, but it is occurring in such young children more often than in the past. Children with IBD are different from adults. For example, delayed growth, extent of disease and difficulties encountered during adolescence are all unique to the pediatric experience. We must consider the psychosocial well-being of both children and their families, given that caring for a child with IBD can affect the global functioning of families. Treatment approaches in children sometimes differ from those in adults. However, to date, all effective therapies in adults have also been effective in children. There is great need for clinical trials of new therapies in children so that they have equal access to emerging treatments and optimal pediatric dosing can be established. Key Summary Points Rates of new diagnoses in children under 16 years old were increasing most rapidly in Ontario (increased 5.8% per year) and Quebec (increased 2.8% per year). Nova Scotia has the highest rate of pediatric IBD, with lower rates in Quebec and Ontario. However, even Ontario and Quebec have higher rates of pediatric IBD than most countries in the world. Inflammatory bowel disease is caused by the interaction between genes, environmental risk factors, the microbiome and the immune system. Since children experience shorter exposures and possibly fewer environmental risk factors, the interaction between these risk factors and genes may be stronger with childhood-onset IBD. The microbiome is mostly established in early childhood and is affected by a number of factors such as environment, diet, pregnancy/delivery factors and antibiotic use. Changing the microbiome to a healthier state may prevent the disease and may also be a novel therapeutic target to treat active inflammation in children with IBD. Children with IBD are different from adults. They are more likely to have extensive involvement of their intestines, especially in ulcerative colitis, and are at risk for growth impairment, osteoporosis, and psychosocial difficulties affecting their families. Children with IBD may incur more direct health costs for treatment of their IBD compared with adults. However, this is not universally true for all children because those who are very young at diagnosis (2 to 6 years old) may have milder disease or respond better to medications. This may result in decreased use of the health system, fewer hospitalizations and less risk of surgery than older children and adolescents. The choice of treatments for children with IBD may be different from that of adults. It is important to consider pediatric-specific disease considerations. Delayed growth, deficient bone development, psychosocial well-being of the child and family, disease extent, disease severity and risk of poor outcomes during transition from pediatric to adult health care are all important considerations when choosing the best treatment for children and adolescents. While the medications used are similar in children and adults with IBD, research to assess the effectiveness and safety of these medications in children (especially very young children) is sparse. Children with IBD may be more responsive to treatment than adults because they are more likely to have inflammatory (rather than stricturing) disease. Therefore, treating the inflammation earlier in the course of disease may prevent long-term complications such as strictures, obstruction, need for surgery and need for hospitalization. Some medications used in IBD have unique or more pronounced risks in children compared with adults. For example, chronic prednisone use is associated with growth impairment and stunting in children. Anti-TNF biologics are the only medications proven to improve growth in children with Crohn’s disease and should be considered early in the course of disease in patients with severe IBD or those with marked growth impairment at the time of diagnosis. Some medications are used differently, depending on the sex of the patient. For example, azathioprine (with or without biologics) is associated with hepatosplenic T cell lymphoma (and other forms of lymphoma) in adolescent and young adult males more often than females. Methotrexate is associated with birth defects in the growing fetus and therefore should be avoided in adolescent and adult women of child-bearing age who are not using two or more forms of birth control. A small group of children, typically presenting in the first two years of life, have single-gene mutations that cause an IBD-like bowel disease and also immune system dysfunction. These patients may not respond to traditional IBD medications and may require therapies such as bone marrow transplant. Canada is leading research efforts to investigate, diagnose and treat this small group of very vulnerable children. Inflammatory bowel disease (especially when it is active) can affect school attendance, social interactions, concentration and learning. Schools should be aware of the implications of IBD and make allowances for these factors in children with active inflammation and symptoms to optimize their chances of academic and social success. Gaps in Knowledge and Future Research Directions We have limited knowledge on what causes IBD in children and why rates are rising most rapidly in young children. We must better understand the interaction between genes, the environment, the immune system and the microbiome in order to better prevent and treat the disease. Treatment for infants with IBD-like illnesses and single-gene mutations is limited. Future research should work towards identifying these children and learning how best to treat them. There are few clinical trials for biologics in children, and most exclude very young children. Support for such trials is important to understand whether the treatments work, how they should optimally be given and whether they are safe for young children with IBD. Considering the effectiveness of dietary therapies for children with Crohn’s disease (exclusive enteral nutrition), we should work to understand how diet affects intestinal inflammation and the microbiome in order to better use dietary therapies to treat IBD. Health services researchers, health care providers and policy-makers should work together to understand why variation in the access to treatment and medical care of children with IBD exists. We must work together to improve the quality of care provided to these children and ensure they have the highest quality of care. Psychosocial implications of IBD in children and their families are of importance to long-term and overall well-being. Children with a chronic, incurable disease are at risk for mental illness associated with their disease. We should design interventions to improve the psychosocial status, mental health and quality of life of children with IBD and their families. While nonlive immunizations are safe for children with IBD, we must understand how to improve their effectiveness in children who are immunosuppressed. While the peak onset of IBD occurs in the second or third decades of life, the frequency of new diagnoses in younger children is rising rapidly. In Canada, the fastest growing group of newly diagnosed people with IBD are children aged under 5 years (termed ‘very early onset [VEO] IBD). These young children have not been included in clinical trials of new medications, resulting in a lack of scientific evidence of safety and effectiveness of treatments in this group, and clinical experience has shown that they do not respond to usual medications used for the majority of children with IBD. Providing children with IBD with high-quality care and social support also poses other challenges to care providers, families and the health system. This section will focus on the unique challenges facing Canadian children with IBD. A complete overview of the objectives, working committees and methodology of creating the report can be found in the supplemental file, Technical Document.

Eric I Benchimol,1–5 M Ellen Kuenzig,1,2,5 Charles N Bernstein,6,7 Geoffrey C Nguyen,5,8 Astrid Guttmann,5,9 Jennifer L Jones,10 Beth K Potter,4 Laura E Targownik,6,7 Christina A Catley,5 Zoann J Nugent,6,11 Divine Tanyingoh,12,13 Nassim Mojaverian,5 Fox E Underwood,12,13 Shabnaz Siddiq,1,2 Anthony R Otley,14 Alain Bitton,15 Matthew W Carroll,16 Jennifer C deBruyn,17 Trevor JB Dummer,18 Wael El-Matary,19 Anne M Griffiths,9 Kevan Jacobson,20,21 Desmond Leddin,10 Lisa M Lix,22 David R Mack,1–3 Sanjay K Murthy,4,23 Juan Nicolás Peña-Sánchez,24 Harminder Singh,6,7 Gilaad G Kaplan12,13 On behalf of the Canadian Gastro-Intestinal Epidemiology Consortium 1Children’s Hospital of Eastern Ontario IBD Centre, Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Eastern Ontario, Ottawa, Canada; 2Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Canada; 3Department of Pediatrics, University of Ottawa, Ottawa, Canada; 4School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada; 5ICES, Toronto, Canada; 6University of Manitoba IBD Clinical and Research Centre, University of Manitoba, Winnipeg, Canada; 7Department of Internal Medicine, University of Manitoba, Winnipeg, Canada; 8Department of Medicine, Mount Sinai Hospital Centre for Inflammatory Bowel Disease, University of Toronto, Toronto, Canada; 9Department of Paediatrics, University of Toronto, Toronto, Canada; 10Department of Medicine, Dalhousie University, Halifax, Canada; 11CancerCare Manitoba, Winnipeg, Canada; 12Department of Medicine, University of Calgary, Calgary, Alberta, Canada; 13Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada; 14Department of Pediatrics, Dalhousie University, Halifax, Canada; 15Division of Gastroenterology, McGill University Health Centre, Montreal, Canada; 16Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, University of Alberta, Edmonton, Canada; 17Division of Gastroenterology, Department of Pediatrics, University of Calgary, Calgary, Canada; 18School of Population and Public Health, University of British Columbia, British Columbia, Canada; 19Department of Pediatrics, University of Manitoba, Winnipeg, Canada; 20Department of Pediatrics, The University of British Columbia, British Columbia, Canada; 21Child and Family Research Institute, The University of British Columbia, British Columbia, Canada; 22Department of Community Health Sciences, University of Manitoba, Winnipeg, Canada; 23The Ottawa Hospital IBD Centre, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; 24Department of Community Health and Epidemiology, University of Saskatchewan, Saskatoon, Canada Background and aims: Canada’s large geographic area and low population density pose challenges in access to specialized health care for remote and rural residents. We compared health services use, surgical rate, and specialist gastroenterologist care in rural and urban inflammatory bowel disease (IBD) patients in Canada.Methods: We used validated algorithms that were applied to population-based health administrative data to identify all people living with the following three Canadian provinces: Alberta, Manitoba, and Ontario (ON). We compared rural residents with urban residents for time to diagnosis, hospitalizations, outpatient visits, emergency department (ED) use, surgical rate, and gastroenterologist care. Multivariable regression compared the outcomes in rural/urban patients, controlling for confounders. Provincial results were meta-analyzed using random-effects models to produce overall estimates.Results: A total of 36,656 urban and 5,223 rural residents with incident IBD were included. Outpatient physician visit rate was similar in rural and urban patients. IBD-specific and IBD-related hospitalization rates were higher in rural patients (incidence rate ratio [IRR] 1.17, 95% CI 1.02–1.34, and IRR 1.27, 95% CI 1.04–1.56, respectively). The rate of ED visits in ON were similarly elevated for rural patients (IRR 1.53, 95% CI 1.42–1.65, and IRR 1.33, 95% CI 1.25–1.40). There were no differences in surgical rates or prediagnosis lag time between rural and urban patients. Rural patients had fewer IBD-specific gastroenterologist visits (IRR 0.79, 95% CI 0.73–0.84) and a smaller proportion of their IBD-specific care was provided by gastroenterologists (28.3% vs 55.2%, P65years (33.0% vs 59.2%, P

Background Budesonide is an oral glucocorticoid designed for the treatment of inflammatory bowel disease (IBD) that may reduce systemic adverse events (AEs). This review examined the efficacy and safety of budesonide for the induction and maintenance of clinical remission in Crohn’s disease (CD). Methods MEDLINE, EMBASE, other electronic databases, reference lists and conference proceedings were searched to November 2017 to identify randomized controlled trials of budesonide. Outcomes were the induction and maintenance of remission at eight weeks and one year, respectively, as well as corticosteroid-related AEs and abnormal adrenocorticotropic hormone (ACTH) tests. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were estimated using random effects models. Results Thirteen induction and 10 maintenance trials were included. Budesonide 9 mg/day was more effective than placebo (RR 1.93; 95% CI, 1.37–2.73; GRADE: moderate) but less effective than conventional steroids (RR 0.85; 95% CI, 0.75–0.97; GRADE: moderate) to induce remission. Corticosteroid-related AEs occurred less often with induction doses of budesonide than steroids (RR 0.64; 95% CI, 0.54–0.76; GRADE: moderate); budesonide did not increase AEs relative to placebo (RR 0.97; 95% CI, 0.76–1.23; GRADE: moderate). Budesonide 6 mg/day was not different from placebo for maintaining remission (RR 1.13; 95% CI, 0.94–1.35; GRADE: moderate). Both induction (GRADE: low for 3 mg/day, moderate for 9 mg/day) and maintenance budesonide treatment (GRADE: very low for 3 mg/day, low for 6 mg/day) increased the risk of an abnormal ACTH test compared with placebo, but less than conventional steroids (GRADE: very low for both induction and maintenance). Conclusion For induction of clinical remission, budesonide was more effective than placebo, but less effective than conventional steroids. Budesonide was not effective for the maintenance of remission. Budesonide was safer than conventional steroids, but the long-term effects on the adrenal axis and bone health remain unknown.

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

Meranda Nakhla,1,2 Marc Simard,3 Marjolaine Dube,3 Isabelle Larocque,3 Céline Plante,3 Laurent Legault,1,2 Celine Huot,4 Nancy Gagné,5 Julie Gagné,6 Sarah Wafa,2 Eric I Benchimol,7–9 Elham Rahme10 1Department of Pediatrics, Division of Endocrinology, Montreal Children’s Hospital, Montreal, QC, Canada; 2Centre for Outcomes Research & Evaluation, Research Institute of the McGill University Health Centre, Montreal, QC, Canada; 3Institut National de Santé Publique du Québec, Québec, QC, Canada; 4Department of Pediatrics, Division of Endocrinology, Centre Hospitalier Universitaire Sainte-Justine, Montreal, QC, Canada; 5Department of Pediatrics, Division of Endocrinology, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada; 6Department of Pediatrics, Division of Endocrinology, Centre Hospitalier de l’Université Laval, Quebec City, QC, Canada; 7Children’s Hospital of Eastern Ontario IBD Centre, Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital of Eastern Ontario, Ottawa, Canada; 8Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Canada; 9Faculty of Medicine, School of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada; 10Department of Medicine, Division of Clinical Epidemiology, McGill University, Montreal, QC, CanadaCorrespondence: Meranda NakhlaCenter of Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, 5252 de Maisonneuve Blvd, W, 3rd floor, office E3.08, Montreal H4A 3S5, QC, CanadaEmail meranda.nakhla@mcgill.caBackground: Type 1 diabetes is one of the most common chronic diseases in childhood with a worldwide incidence that is increasing by 3–5% per year. The incidence of type 2 diabetes, traditionally viewed as an adult disease, is increasing at alarming rates in children, paralleling the rise in childhood obesity. As the rates of diabetes increase in children, accurate population-based assessment of disease burden is important for those implementing strategies for health services delivery. Health administrative data are a powerful tool that can be used to track disease burden, health services use, and health outcomes. Case validation is essential in ensuring accurate disease identification using administrative databases.Aim: The aim of our study was to define and validate a pediatric diabetes case ascertainment algorithm (including any form of childhood-onset diabetes) using health administrative data.Research design and methods: We conducted a two-stage method using linked health administrative data and data extracted from charts. In stage 1, we linked chart data from a large urban region to health administrative data and compared the diagnostic accuracy of various algorithms. We selected those that performed the best to be validated in stage 2. In stage 2, the most accurate algorithms were validated with chart data within two other geographic areas in the province of Quebec.Results: Accurate identification of diabetes in children (ages ≤15 years) required four physician claims or one hospitalization (with International Classification of Disease codes within 1 year (sensitivity 91.2%, 95% confidence interval [CI] 89.2–92.9]; positive predictive value [PPV] 93.5%, 95% CI 91.7–95.0) or using only four physician claims in 2 years (sensitivity 90.4%, 95% CI 88.3–92.2; PPV 93.2%, 95% CI 91.7–95.0). Separating the physician claims by 30 days increased the PPV of all algorithms tested.Conclusion: Patients with child-onset diabetes can be accurately identified within health administrative databases providing a valid source of information for health care resource planning and evaluation.Keywords: pediatric, validation, health administrative data, diabetes

BACKGROUND: Women with inflammatory bowel disease (IBD) may require surgery, which may result in higher risk of infertility. Restorative proctocolectomy with ileal anal pouch anastomosis (IPAA) may increase infertility, but the degree to which IPAA affects infertility remains unclear, and the impact of other surgical interventions on infertility is unknown. OBJECTIVES: Primary objective • To determine the effects of surgical interventions for IBD on female infertility. Secondary objectives • To evaluate the impact of surgical interventions on the need for assisted reproductive technology (ART), time to pregnancy, miscarriage, stillbirth, prematurity, mode of delivery (spontaneous vaginal, instrumental vaginal, or Caesarean section), infant requirement for resuscitation and neonatal intensive care, low and very low birth weight, small for gestational age, antenatal and postpartum hemorrhage, retained placenta, postpartum depression, gestational diabetes, and gestational hypertension/preeclampsia. SEARCH METHODS: We searched MEDLINE, Embase, CENTRAL, and the Cochrane IBD Group Specialized Register from inception to September 27, 2018, to identify relevant studies. We also searched references of relevant articles, conference abstracts, grey literature, and trials registers. SELECTION CRITERIA: We included observational studies that compared women of reproductive age (≥ 12 years of age) who underwent surgery to women with IBD who had a different type of surgery or no surgery (i.e. treated medically). We also included studies comparing women before and after surgery. Any type of IBD‐related surgery was permitted. Infertility was defined as an inability to become pregnant following 12 months of unprotected intercourse. Infertility at 6, 18, and 24 months was included as a secondary outcome. We excluded studies that included women without IBD and those comparing women with IBD to women without IBD.. DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies and extracted data. We used the Newcastle‐Ottawa Scale to assess bias and GRADE to assess the overall certainty of evidence. We calculated the pooled risk ratio (RR) and 95% confidence interval (CI) using random‐effects models. When individual studies reported odds ratios (ORs) and did not provide raw numbers, we pooled ORs instead. MAIN RESULTS: We identified 16 observational studies for inclusion. Ten studies were included in meta‐analyses, of which nine compared women with and without a previous IBD‐related surgery and the other compared women with open and laparoscopic IPAA. Of the ten studies included in meta‐analyses, four evaluated infertility, one evaluated ART, and seven reported on pregnancy‐related outcomes. Seven studies in which women were compared before and after colectomy and/or IPAA were summarized qualitatively, of which five included a comparison of infertility, three included the use of ART, and three included other pregnancy‐related outcomes. One study included a comparison of women with and without IPAA, as well as before and after IPAA, and was therefore included in both the meta‐analysis and the qualitative summary. All studies were at high risk of bias for at least two domains. We are very uncertain of the effect of IBD surgery on infertility at 12 months (RR 5.45, 95% CI 0.41 to 72.57; 114 participants; 2 studies) and at 24 months (RR 3.59, 95% CI 1.32 to 9.73; 190 participants; 1 study). Infertility was lower in women who received laparoscopic surgery compared to open restorative proctocolectomy at 12 months (RR 0.70, 95% CI 0.38 to 1.27; 37 participants; 1 study). We are very uncertain of the effect of IBD surgery on pregnancy‐related outcomes, including miscarriage (OR 2.03, 95% CI 1.14 to 3.60; 776 pregnancies; 5 studies), use of ART (RR 25.09, 95% CI 1.56 to 403.76; 106 participants; 1 study), delivery via Caesarean section (RR 2.23, 95% CI 1.00 to 4.95; 20 pregnancies; 1 study), stillbirth (RR 1.96, 95% CI 0.42 to 9.18; 246 pregnancies; 3 studies), preterm birth (RR 1.91, 95% CI 0.67 to 5.48; 194 pregnancies; 3 studies), low birth weight (RR 0.61, 95% CI 0.08 to 4.83), and small for gestational age (RR 2.54, 95% CI 0.80 to 8.01; 65 pregnancies; 1 study). Studies comparing infertility before and after IBD‐related surgery reported numerically higher rates of infertility at six months (before: 1/5, 20.0%; after: 9/15, 60.0%; 1 study), at 12 months (before: 68/327, 20.8%; after: 239/377, 63.4%; 5 studies), and at 24 months (before: 14/89, 15.7%; after: 115/164, 70.1%; 2 studies); use of ART (before: 5.3% to 42.2%; after: 30.3% to 34.3%; proportions varied across studies due to differences in which women were identified as at risk of using ART); and delivery via Caesarean section (before: 8/73, 11.0%; after: 36/75, 48.0%; 2 studies). In addition, women had a longer time to conception after surgery (two to five months; 2 studies) than before surgery (5 to 16 months; 2 studies). The proportions of women experiencing miscarriage (before: 19/123, 15.4%; after: 21/134, 15.7%; 3 studies) and stillbirth (before: 2/38, 5.3%; after: 3/80: 3.8%; 2 studies) were similar before and after surgery. Fewer women experienced gestational diabetes after surgery (before: 3/37, 8.1%; after: 0/37; 1 study), and the risk of preeclampsia was similar before and after surgery (before: 2/37, 5.4%; after: 0/37; 1 study). We are very uncertain of the effects of IBD‐related surgery on these outcomes due to poor quality evidence, including confounding bias due to increased age of women after surgery. We rated evidence for all outcomes and comparisons as very low quality due to the observational nature of the data, inclusion of small studies with imprecise estimates, and high risk of bias among included studies. AUTHORS' CONCLUSIONS: The effect of surgical therapy for IBD on female infertility is uncertain. It is also uncertain if there are any differences in infertility among those undergoing open versus laparoscopic procedures. Previous surgery was associated with higher risk of miscarriage, use of ART, Caesarean section delivery, and giving birth to a low birth weight infant, but was not associated with risk of stillbirth, preterm delivery, or delivery of a small for gestational age infant. These findings are based on very low‐quality evidence. As a result, definitive conclusions cannot be made, and future well‐designed studies are needed to fully understand the impact of surgery on infertility and pregnancy outcomes.

Background and AimsIncidence of paediatric inflammatory bowel disease [IBD] in Canada is among the highest worldwide, and age of onset may be decreasing. In a multicentre nationwide inception cohort study, we examined variation in phenotype of IBD throughout the paediatric age spectrum.MethodsChildren aged ≥2 years [y] and ResultsAmong 1092 children (70% Caucasian; 64% Crohn’s disease [CD], 36% ulcerative colitis/inflammatory bowel disease unclassified [UC/IBD-U]; median age 13 y, interquartile range [IQR] 11–15 y), 210 [19%] were diagnosed before the age of age 10 y [Paris A1a] and 43 [4%] before age 6 y (very-early-onset [VEO-IBD]). CD was less common in younger children [42%, 56%, 66%, respectively, of VEO-IBD, A1a; A1b]. Colon-only IBD [UC/IBDU or CD-colon] was present in 81% of VEO-IBD and 65% of A1a; ileal disease increased progressively, reaching plateau at age 10 y. CD location was ileocolonic [L3] in 53% overall. Ileitis [L1] increased with age [6% of VEO-IBD; 13% of A1a; 21% of A1b], as did stricturing/penetrating CD [4% of A1a; 11% of A1b]. At all ages UC was extensive [E3/E4] in >85%, and disease activity moderate to severe according to Physician’s Global Assessment [PGA] and weighted Paediatric Crohn’s Disease Activity Index/Paediatric Ulcerative Colitis Activity Index [wPCDAI/PUCAI] in >70%. Heights were modestly reduced in CD [mean height z score -0.30 ± 1.23], but normal in UC/IBD-U.ConclusionsParis classification of age at diagnosis is supported by age-related increases in ileal disease until age 10 years. Other phenotypic features, including severity, are similar across all ages. Linear growth is less impaired in CD than in historical cohorts, reflecting earlier diagnosis.

BACKGROUND: The prevalence of IBD in elderly people ≥65y is growing rapidly in Canada. This group presents unique clinical challenges due to their comorbidity burden and increased susceptibility to infection. AIMS: To compare the incidence of emergency department (ED) visits and hospitalizations for infectious diseases in people with elderly-onset IBD compared to people without IBD. METHODS: Incident cases of elderly IBD (≥65y at diagnosis) diagnosed between 2002–2013 were identified from health administrative data in Ontario using a validated algorithm. Cases were age- and sex-matched to five controls. ED visits and hospitalizations for infectious diseases were identified from the National Ambulatory Care Reporting System and the CIHI Discharge Abstract Database, respectively. Negative binomial models were used to compare the incidence of any infection, any gastrointestinal infection, Clostridium difficile, influenza/pneumonia, sepsis, skin infection, or urinary tract infection. Models were adjusted for rural/urban residence, income, and ADG comorbidity index. Results are presented as incidence rate ratios (IRR) and 95% confidence intervals (CI). RESULTS: Cases of IBD, CD, and UC were at increased risk of hospitalization for all types of infections studied (Table). Of all infections analyzed, the greatest increase in the relative incidence compared to controls was seen for C. difficile (IBD: IRR 13.38, 95% CI 9.50–18.84). Patients with IBD, CD, and UC had also increased incidence of infection-related ED visits (Table). The highest relative incidence of ED visit was similarly noted for C. difficile (IBD: IRR 8.95, 95% CI 5.69–14.09). The 5-year risk of hospitalization and ED visits for any serious infection in patients with IBD were 29% and 40%, respectively, compared to 5% and 17% in controls. CONCLUSIONS: Elderly patients with IBD are at significantly increased risk of infections requiring acute care and hospitalization. Treatment strategies to minimize infections in elderly patients should be considered. FUNDING AGENCIES: CAG, CCC, CIHR

BACKGROUND: Inflammatory bowel disease (IBD) is becoming increasingly common among elderly Canadians. The risk of venous thromboembolism (VTE) in IBD patients increases with age. AIMS: Compare the incidence of VTE-associated hospitalizations in patients with elderly-onset IBD and non-IBD controls. METHODS: Incident cases of elderly-onset IBD (≥65y) diagnosed between April 1, 2002 and March 31, 2014 were identified from health administrative data in Ontario using a validated algorithm. Cases were age- and sex-matched to five non-IBD controls. Hospitalizations for VTE were identified from the CIHI Discharge Abstract Database. VTE was defined as deep venous thrombosis (DVT) and/or pulmonary embolism (PE) and could either be the reason for hospitalization or a complication occurring during hospitalization for another reason. The cumulative 5-year risks of VTE, DVT, and PE were calculated for cases and controls. The incidence of VTE, DVT, and PE were compared in cases and controls using a negative binomial model adjusting for comorbidities, rural/urban residence, and income. Results are presented as incidence rate ratios (IRR) and 95% confidence intervals (CI). Analyses were conducted for all types of IBD combined and separately for Crohn’s disease (CD) and ulcerative colitis (UC). We additionally compared the risk of VTE by type of IBD, adjusting for age, sex, comorbidities, rural/urban residence, and income. RESULTS: The 5-year risk of VTE was 5.3% in cases compared to 0.56% in controls (IRR 5.78, 95% CI 4.58–7.30). The incidence of DVT (IRR 7.45, 95% CI 5.38–10.32) and PE (IRR 4.76, 95% CI 3.55–6.39) were similarly increased in IBD. The association persisted when stratifying by disease type (Table). VTE was significantly more common in patients with CD than UC (IRR 1.36, 95% CI 1.03–1.81). DVT and PE were slightly, but not significantly, more common in CD than UC (DVT: IRR 1.35, 95% CI 0.93–1.96; PE: IRR 1.44, 95% CI 0.99–2.08). CONCLUSIONS: Elderly patients with IBD are significantly more likely to develop a VTE than people without IBD. Gastroenterologists treating these patients should be aware of the increased risk and future research should seek to identify predictive factors for VTE so that physicians can treat patients with prophylactic measures, when appropriate. FUNDING AGENCIES: CAG, CCC, CIHR

BACKGROUND: The benefits of recent improvements in IBD care on life expectancy (LE) and health-adjusted life expectancy (HALE) are unknown. AIMS: To compare LE and HALE in people with and without IBD and evaluate the impact of narcotics and IBD medications on LE. METHODS: Cases of IBD and controls (matched on age, sex, rurality, and income) were identified from health administrative data in Ontario using validated algorithms. Five-year mortality rates and period life tables were used to calculate LE in 1996, 2000, 2008, and 2011. Health Utility Index (HUI) (from the National Population Health Study and Canadian Community Health Survey) is a utility-based measure of health-related quality of life which was combined with period life tables to estimate HALE in 1996, 2000, and 2008. Prescription records from Ontario Drug Benefits (for patients ≥65 y old) and Narcotic Monitoring System (all ages) were used to determine the effect of medications on LE. RESULTS: LE significantly increased from 75.5y to 78.4y (Δ2.9y, 95%CI 1.3 to 4.5) in females and from 72.2y to 75.5y (Δ3.2y, 95%CI 2.1 to 4.4) in males with IBD (Figure). HALE was stable over time in females (Δ2.0y, 95%CI -1.6 to 5.7; 1996: 62.3y; 2008: 64.3y) but decreased in males (Δ-3.9y, 95%CI -6.6 to -1.2; 1996: 67.0y; 2008: 63.1y) with IBD. Both LE and HALE were significantly lower in those with IBD than controls (LE: females Δ6.6–8.1y, males Δ5.0–6.1y; HALE: females Δ9.5–13.5y, males Δ2.6–6.7y). Opioid use reduced life expectancy (chronic vs. non-users: females Δ-22.1, 95%CI -25.0 to -19.2; males Δ-36.0y, 95%CI -62.4 to -9.7; non-chronic vs. non-users: females -4.7, 95%CI -6.4 to -3.0; males Δ-2.7y, 95%CI -3.8 to -1.6). Systemic steroids, opioids, and their combination shortened LE and mesalamine lengthened LE in IBD patients ≥65y (see Table). CONCLUSIONS: Although LE increased over time in patients with IBD, the gap in LE between those with and without IBD remained significant. Increases in LE were not accompanied by increased HALE. Use of steroids and opioids had very negative consequences on LE. Decisions with regard to treatment strategies for patients with IBD should incorporate data on the differences in LE for different treatment groups. FUNDING AGENCIES: CAG, CCC, CIHR

peer-reviewed BACKGROUND & AIMS: Inflammatory bowel diseases (IBDs) exist worldwide, with high prevalence in North America. IBD is complex and costly, and its increasing prevalence places a greater stress on health care systems. We aimed to determine the past current, and future prevalences of IBD in Canada. METHODS: We performed a retrospective cohort study using population-based health administrative data from Alberta (2002–2015), British Columbia (1997– 2014), Manitoba (1990–2013), Nova Scotia (1996–2009), Ontario (1999–2014), Quebec (2001–2008), and Saskatchewan (1998–2016). Autoregressive integrated moving average regression was applied, and prevalence, with 95% prediction intervals (PIs), was forecasted to 2030. Average annual percentage change, with 95% confidence intervals, was assessed with log binomial regression. RESULTS: In 2018, the prevalence of IBD in Canada was estimated at 725 per 100,000 (95% PI 716–735) and annual average percent change was estimated at 2.86% (95% confidence interval 2.80%–2.92%). The prevalence in 2030 was forecasted to be 981 per 100,000 (95% PI 963–999): 159 per 100,000 (95% PI 133–185) in children, 1118 per 100,000 (95% PI 1069–1168) in adults, and 1370 per 100,000 (95% PI 1312–1429) in the elderly. In 2018, 267,983 Canadians (95% PI 264,579–271,387) were estimated to be living with IBD, which was forecasted to increase to 402,853 (95% PI 395,466–410,240) by 2030. CONCLUSION: Forecasting prevalence will allow health policy makers to develop policy that is necessary to address the challenges faced by health systems in providing high-quality and cost-effective care.

Objective: There is no standardized endoscopic description of upper gastrointestinal [UGI] disease in Crohn's disease [CD]. We prospectively applied the Simple Endoscopic Score for CD [SES-CD] to the UGI tract as a planned sub-study of the multicentre prospective ImageKids study. We aimed to assess the utility of the UGI-SES-CD and its clinical significance in paediatric CD. Design: Patients underwent an oesophagogastroduodenoscopy [EGD], ileocolonoscopy, and magnetic resonance enterography [MRE] with explicit clinical data recorded. SES-CD was scored at each region [oesophagus, stomach body, antrum, and duodenum]. Half of the patients were followed for 18 months, when a repeat MRE was performed. Results: A total of 202 children were included 56% males, mean age 11.5 +/- 3.2 years, median weighted Paediatric Crohn's Disease Activity Index [wPCDAI 25]). UGI-SES-CD score ranged 0-17, with 95 [47%] having a UGI-SES-CD = 1; no narrowing was detected. UGI-SES-CD = 1 was associated with higher: wPCDAI [32.5 vs 20; p = 0.03]; Physician's Global Assessment [PGA] of inflammation (45 mm visual analogue score [VAS] vs 30 mm VAS; p = 0.04); ileocolonoscopic SES-CD [10 vs 7; p = 0.004], faecal calprotectin [717 mu g/g vs 654 mu/g; p= 0.046]; and radiological global assessment of damage by MRE [7 mm VAS vs 0; p = 0.04]. In all, 81 patients were followed for 18 months and no association was identified between initial UGI SES-CD and markers of disease course such as surgery, MRE assessment, or treatment escalation. Conclusion: UGI-SES-CD is an easily reported objective scoring system and is associated with a more severe disease phenotype but not with disease course.

IntroductionInflammatory bowel disease (IBD; subtypes: Crohn’s disease (CD) and ulcerative colitis (UC)) is a chronic disease of the gastrointestinal tract with rising prevalence among people ≥65y. Rural residents, especially those ≥65y, have decreased access to specialist care. Specialist care is associated with lower risk of hospitalization and surgery. Objectives and ApproachWe evaluated variation across physician networks in access to specialist care and surgery among incident patients ≥65y in Ontario health administrative data. Access to specialist care was defined as: ≥1 outpatient visit to gastroenterologists or the majority of IBD-specific outpatient care by gastroenterologists. Variation was assessed with multilevel logistic regression and median odds ratios (MOR), adjusting for age, sex, distance from IBD physician, comorbidities, neighbourhood income, and rural/urban. Models evaluating surgical risk also adjusted for specialist care use, emergency department visits, and hospitalization at diagnosis. Network-level variables included rurality (RIO score), population colonoscopy and gastroenterologist supply. ResultsThere was significant variation in having ≥1 gastroenterologist visit (CD p=0.0001, MOR 3.3; UC p

IntroductionRandomised controlled trials (RCTs) conducted using cohorts and routinely collected health data, including registries, electronic health records and administrative databases, are increasingly used in healthcare intervention research. The development of an extension of the CONsolidated Standards of Reporting Trials (CONSORT) statement for RCTs using cohorts and routinely collected health data is being undertaken with the goal of improving reporting quality by setting standards early in the process of uptake of these designs. To develop this extension to the CONSORT statement, a scoping review will be conducted to identify potential modifications or clarifications of existing reporting guideline items, as well as additional items needed for reporting RCTs using cohorts and routinely collected health data.Methods and analysisIn separate searches, we will seek publications on methods or reporting or that describe protocols or results from RCTs using cohorts, registries, electronic health records and administrative databases. Data sources will include Medline and the Cochrane Methodology Register. For each of the four main types of RCTs using cohorts and routinely collected health data, separately, two investigators will independently review included publications to extract potential checklist items. A potential item will either modify an existing CONSORT 2010, Strengthening the Reporting of Observational Studies in Epidemiology or REporting of studies Conducted using Observational Routinely collected health Data item or will be proposed as a new item. Additionally, we will identify examples of good reporting in RCTs using cohorts and routinely collected health data.Ethics and disseminationThe proposed scoping review will help guide the development of the CONSORT extension statement for RCTs conducted using cohorts and routinely collected health data.

BACKGROUND: Growing evidence suggests that asthma and Crohn’s disease (CD) commonly co-occur. The impact of asthma on the prognosis of CD is not known. Studies evaluating the risk of surgery in CD patients using health administrative data are limited by their inability to adjust for confounding variables not included in these data, such as smoking. AIMS: The aim of our study was to assess the impact of asthma on the need for intestinal resection in CD adjusting for smoking status, despite smoking status being unmeasured in health administrative data, using a secondary dataset and novel methodology. METHODS: Using population-based health administrative data from Alberta, we conducted a cohort study to assess the impact of asthma on the need for surgery in patients with CD diagnosed between April 1, 2002 and March 31, 2008 (n=2,113). Validated algorithms were used to identify incident CD cases, patients with co-occurring asthma, and intestinal resection surgeries. The association between asthma and intestinal resection was estimated using Cox proportional hazards regression. Smoking status was imputed using a method based on martingale residuals, leveraging information from a secondary dataset in which smoking status was measured. This second dataset included patients enrolled in the Alberta IBD Consortium between 2007 and 2014 who completed environmental questionnaires (n=485). All analyses were adjusted for age, sex, rural/urban status, and mean neighbourhood income quintile. RESULTS: Asthma did not increase the risk of surgery in either the health administrative data unadjusted for smoking status (HR 1.03, 95% CI 0.81 to 1.29) or in the secondary data adjusted for smoking status (HR 0.74, 95% CI 0.50 to 1.37). The association remained non-significant after using the secondary data to impute smoking status in the health administrative data (HR 0.92, 95% CI 0.75 to 1.15). CONCLUSIONS: Although asthma is associated with an increased risk of CD, co-occurring asthma was not associated with the risk of surgery in patients with CD. This null association persisted after adjusting for smoking status. This study also demonstrates a novel method to adjust for smoking status in research using health administrative data when it is measured in a smaller secondary dataset. FUNDING AGENCIES: CAG, CCC, CIHR

Contains fulltext : 197751.pdf (Publisher’s version ) (Open Access) Background: Randomized controlled trials (RCTs) are often complex and expensive to perform. Less than one third achieve planned recruitment targets, follow-up can be labor-intensive, and many have limited real-world generalizability. Designs for RCTs conducted using cohorts and routinely collected health data, including registries, electronic health records, and administrative databases, have been proposed to address these challenges and are being rapidly adopted. These designs, however, are relatively recent innovations, and published RCT reports often do not describe important aspects of their methodology in a standardized way. Our objective is to extend the Consolidated Standards of Reporting Trials (CONSORT) statement with a consensus-driven reporting guideline for RCTs using cohorts and routinely collected health data. Methods: The development of this CONSORT extension will consist of five phases. Phase 1 (completed) consisted of the project launch, including fundraising, the establishment of a research team, and development of a conceptual framework. In phase 2, a systematic review will be performed to identify publications (1) that describe methods or reporting considerations for RCTs conducted using cohorts and routinely collected health data or (2) that are protocols or report results from such RCTs. An initial "long list" of possible modifications to CONSORT checklist items and possible new items for the reporting guideline will be generated based on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) and The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statements. Additional possible modifications and new items will be identified based on the results of the systematic review. Phase 3 will consist of a three-round Delphi exercise with methods and content experts to evaluate the "long list" and generate a "short list" of key items. In phase 4, these items will serve as the basis for an in-person consensus meeting to finalize a core set of items to be included in the reporting guideline and checklist. Phase 5 will involve drafting the checklist and elaboration-explanation documents, and dissemination and implementation of the guideline. Discussion: Development of this CONSORT extension will contribute to more transparent reporting of RCTs conducted using cohorts and routinely collected health data. 9 p.

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.

Objectives: Temporal changes for intestinal resections for Crohn’s disease (CD) are controversial. We validated administrative database codes for CD diagnosis and surgery in hospitalized patients and then evaluated temporal trends in CD surgical resection rates. Methods: First, we validated International Classification of Disease (ICD)-10-CM coding for CD diagnosis in hospitalized patients and Canadian Classification of Health Intervention coding for surgical resections. Second, we used these validated codes to conduct population-based surveillance between fiscal years 2002 and 2010 to identify adult CD patients undergoing intestinal resection (n=981). Annual surgical rate was calculated by dividing incident surgeries by estimated CD prevalence. Time trend analysis was performed and annual percent change (APC) with 95% confidence intervals (CI) in surgical resection rates were calculated using a generalized linear model assuming a Poisson distribution. Results: In the validation cohort, 101/104 (97.1%) patients undergoing surgery and 191/200 (95.5%) patients admitted without surgery were confirmed to have CD on chart review. Among the 116 administrative database codes for surgical resection, 97.4% were confirmed intestinal resections on chart review. From 2002 to 2010, the overall CD surgical resection rate was 3.8 resections per 100 person-years. During the study period, rate of surgery decreased by 3.5% per year (95% CI: -1.1%, -5.8%), driven by decreasing emergent operations (-10.1% per year [95% CI: -13.4%, -6.7%]) whereas elective surgeries increased by 3.7% per year (95% CI: 0.1%, 7.3%). Conclusions: Overall surgical resection rates in CD are decreasing, but a paradigm shift has occurred whereby elective operations are now more commonly performed than emergent surgeries.