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New long-acting HIV treatment products have the potential to change the HIV epidemic in the United States and globally. Phase 3 clinical trials of HIV treatments tend to underrepresent populations bearing a disproportionate burden of the HIV epidemic—including women, racial minorities, trans and gender-diverse people, older adults, the unhoused, people who inject drugs, those in rural areas, individuals with mental illness, and other marginalized groups. These populations commonly face significant challenges in adhering to daily HIV treatment regimens. Conducting clinical trials of long-acting treatment targeting specific unmet medical needs of these populations can improve understanding of optimal care approaches, broaden the indication for use of long-acting products, and inform treatment guidelines, all of which can influence reimbursement and access policies. Innovative trial designs and programmatic implementation can improve inclusivity for long-acting therapy. This article summarizes discussions of a multistakeholder workshop on study designs for long-acting HIV treatments. [ABSTRACT FROM AUTHOR]

Disorders of white matter are some of the most commonly encountered conditions in the practice of child neurology. For a child presenting with evidence of neurological impairment, a magnetic resonance imaging (MRI) of the brain is usually performed and often proves informative in suggesting the diagnosis. Traditionally, primary white matter disorders characterized by progressive destruction of myelin sheaths and to some extent oligodendrocytes, while initially preserving other components of the central nervous system (CNS), have been termed "leukodystrophies" when a genetic etiology is determined or suspected. The last decade has seen the identification of leukodystrophies with distinct clinical, MRI, and molecular findings. This review focuses on two disorders, Alexander disease (AD) and Megalencephalic leukoencephalopathy with cysts (MLC), which are newly characterized leukodystrophies that point to an important role for astrocytes in maintaining normal myelination. Alexander disease is an autosomal dominant disorder resulting from mutations in the GFAP gene that encodes for an intermediate filament protein specific to astrocytes. MLC is an autosomal recessive disorder in which 70% of cases harbor a mutation in MLC1, a gene that encodes for a protein highly expressed in distal astroglial processes. The precise pathogenesis of leukodystrophy in these two disorders remains unresolved. (Contains 2 tables and 2 figures.)

Eukaryotic initiation factor 2B (eIF2B)-related disorders are heritable white matter disorders with a variable clinical phenotype (including vanishing white matter disease and ovarioleukodystrophy) and an equally heterogeneous genotype. We report 9 novel mutations in the EIF2B genes in our subject population, increasing the number of known mutations to more than 120. Using homology modeling, we have analyzed the impact of novel mutations on the 5 subunits of the eIF2B protein. Although recurrent mutations have been found at CpG dinucleotides in the EIF2B genes, the high incidence of private or low frequency mutations increases the challenge of providing rapid genetic confirmation of this disorder, and limits the application of EIF2B screening in cases of undiagnosed leukodystrophy. [ABSTRACT FROM AUTHOR]

De novo dominant mutations in the GFAP gene have recently been associated with nearly all cases of Alexander disease, a rare but devastating neurological disorder. These heterozygous mutations must occur very early in development and be present in nearly all cells in order to be detected by the sequencing methods used. To investigate whether the mutations may have arisen in the parental germ lines, we determined the parental chromosome bearing the mutations for 28 independent Alexander disease cases. These cases included 17 different missense mutations and one insertion mutation. To enable assignment of the chromosomal origin of the mutations, six new single nucleotide polymorphisms in the GFAP gene were identified, bringing the known total to 26. In 24 of the 28 cases analyzed, the paternal chromosome carried the GFAP mutation ( P<0.001), suggesting that they predominantly arose in the parental germ line, with most occurring during spermatogenesis. No effect of paternal age was observed. There has been considerable debate about the magnitude of the male to female germ line mutation rate; our ratio of 6:1 is consistent with indirect estimates based on the rate of evolution of the sex chromosome relative to the autosomic chromosomes. [ABSTRACT FROM AUTHOR]

Megalencephalic leukoencephalopathy with subcortical cysts is one of the newly described white-matter disorders for which recognition has been brought about by advances in imaging technology. The essential diagnostic features include megalencephaly noted in infancy, motor disability in the form of spasticity, ataxia, occasional seizures, mild cognitive decline, and slow progression. Magnetic resonance imaging (MRI) shows bilateral extensive white-matter changes with cysts in the temporal regions. Based on the clinical and MRI features, megalencephalic leukoencephalopathy with subcortical cysts can be distinguished from other conditions (ie, Alexander's disease, Canavan's disease, glutaricaciduria type I) that present in infancy with megalencephaly. Megalencephalic leukoencephalopathy with subcortical cysts is an autosomal recessive disorder, and mutations in the MLC1 gene have now been shown to cause this condition. Several genotypic and phenotypic variations have been described. In India, megalencephalic leukoencephalopathy with subcortical cysts occurs predominantly in the Agarwal community. A common mutation in the MLC1 gene has been seen in 31 Agarwal patients, which suggests a founder effect. [ABSTRACT FROM AUTHOR]

Basic fibroblast growth factor (bFGF) is a potent angiogenic factor produced by cells of mesodermal and neuroectodermal origin. Despite numerous advances, the precise mechanism of bFGF release from cells still remains unknown. Upon release from cells, the protein is stored and protected in the extracellular matrix by binding to heparan sulfate proteoglycans. A number of reports suggest that degrading enzymes secreted by mast cells may play a role in the release of bFGF from connective tissue stores. Additionally, mast cells are believed to play a role in the formation of new blood vessels. In this report, we studied the events involved in neovascularization using a well-characterized model of angiogenesis in rabbits where neovascularization is induced by transfer of a well-perfused rectus abdominis muscle flap to an ischemic limb. Using this model, we demonstrate that bFGF expression is induced in normal myofibers and bFGF is released in the wound fluid at the ischemic/nonischemic interface. The highest concentrations of bFGF were detected on days 14 and 21 postoperation. We also show that the number of mast cells and their degranulation correlate with the release of bFGF from adjacent muscle tissue and the appearance of the growth factor in the wound fluid. There appears to exist a temporal correlation between number of mast cells, their degranulation, and the release of bFGF during angiogenesis in vivo. [ABSTRACT FROM AUTHOR]

Embryonic zebrafish represent a useful test system to screen substances for their ability to perturb development. The exposure scenarios, endpoints captured, and data analysis vary among the laboratories who conduct screening. A lack of harmonization impedes the comparison of the substance potency and toxicity outcomes across laboratories and may hinder the broader adoption of this model for regulatory use. The Systematic Evaluation of the Application of Zebrafish in Toxicology (SEAZIT) initiative was developed to investigate the sources of variability in toxicity testing. This initiative involved an interlaboratory study to determine whether experimental parameters altered the developmental toxicity of a set of 42 substances (3 tested in duplicate) in three diverse laboratories. An initial dose-range-finding study using in-house protocols was followed by a definitive study using four experimental conditions: chorion-on and chorion-off using both static and static renewal exposures. We observed reasonable agreement across the three laboratories as 33 of 42 test substances (78.6%) had the same activity call. However, the differences in potency seen using variable in-house protocols emphasizes the importance of harmonization of the exposure variables under evaluation in the second phase of this study. The outcome of the Def will facilitate future practical discussions on harmonization within the zebrafish research community.

The COVID-19 pandemic had a monumental impact on the inflammatory bowel disease (IBD) community. At the beginning of the pandemic, knowledge on the effect of SARS-CoV-2 on IBD was lacking, especially in those with medication-suppressed immune systems. Throughout the pandemic, scientific literature exponentially expanded, resulting in clinical guidance and vaccine recommendations for individuals with IBD. Crohn's and Colitis Canada established the COVID-19 and IBD Taskforce to process and communicate rapidly transforming knowledge into guidance for individuals with IBD and their caregivers, healthcare providers, and policy makers. Recommendations at the onset of the pandemic were based on conjecture from experience of prior viruses, with a precautionary principle in mind. We now know that the risk of acquiring COVID-19 in those with IBD is the same as the general population. As with healthy populations, advanced age and comorbidities increase the risk for severe COVID-19. Individuals with IBD who are actively flaring and/or who require high doses of prednisone are susceptible to severe COVID-19 outcomes. Consequently, sustaining maintenance therapies (e.g., biologics) is recommended. A three-dose mRNA COVID-19 vaccine regimen in those with IBD produces a robust antibody response with a similar adverse event profile as the general population. Breakthrough infections following vaccine have been observed, particularly as the virus continues to evolve, which supports receiving a bivalent vaccine booster. Limited data exist on the impact of IBD and its therapies on long-term outcomes following COVID-19. Ongoing research is necessary to address new concerns manifesting in those with IBD throughout the evolving pandemic., Competing Interests: Gilaad Kaplan has received honoraria for speaking or consultancy from AbbVie, Janssen, Pfizer, and Takeda. He has received research support from Ferring, Janssen, AbbVie, GlaxoSmith Kline, Merck, and Shire. He has been a consultant for Gilead. He shares ownership of a patent: TREATMENT OF INFLAMMATORY DISORDERS, AUTOIMMUNE DISEASE, AND PBC. UTI Limited Partnership, assignee. Patent WO2019046959A1. PCT/CA2018/051098. 7 Sept. 2018. He is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Ellen Kuenzig is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Charles Bernstein is supported in part by the Bingham Chair in Gastroenterology. He is on Advisory Boards for AbbVie Canada, Amgen Canada, Bristol Myers Squibb, JAMP Pharmaceuticals, Lilly Canada, Janssen Canada, Pfizer Canada, Roche Canada, Sandoz Canada, Takeda Canada. He is a Consultant for Mylan Pharmaceuticals and Takeda. He has received educational grants from AbbVie Canada, Pfizer Canada, Takeda Canada, Janssen Canada, and Bristol Myers Squibb Canada. He is on the speaker’s panel for AbbVie Canada, Janssen Canada, Pfizer Canada, and Takeda Canada. Received research funding from AbbVie Canada, Amgen Canada, Pfizer Canada, Sandoz Canada. Alain Bitton has participated in advisory boards with AbbVie, Janssen, Takeda, McKesson, BioJamp, Bristol Myers Squibb Hoffman-LaRoche, Amgen. He has received research support from AbbVie. He is on the speaker’s panel for Janssen, Takeda, AbbVie and has participated in educational activities supported by Viatris, has received educational support from Fresenius Kabi, Amgen, and Takeda. Jennifer Jones has received honoraria for speaking and consulting for AbbVie, Janssen, Pfizer, Shire, and Takeda. She is the co-chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Kate Lee has received honoraria from AbbVie Corporation and Bristol Myers Squibb Canada. Sanjay Murthy has previously participated in advisory board meetings for AbbVie, Janssen, Takeda, Pfizer, Shire and Ferring and as a speaker at educational events sponsored by Janssen, AbbVie and Pfizer. Laura Targownik has received research funding from AbbVie Canada, Takeda Canada, Sandoz Canada, Amgen Canada, Gilead Canada, Roche Canada and Pfizer Canada, and has been on Advisory Boards for Janssen Canada, AbbVie Canada, Takeda Canada, Pfizer Canada, Merck Canada, Roche Canada, Sandoz Canada, Organon Canada, Fresesnius Kabi Canada, Eli Lilly Canada, and Amgen Canada. She is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Léa Caplan has received an AbbVie IBD scholarship. Eric Benchimol holds the Northbridge Financial Corporation Chair in Inflammatory Bowel Disease, a joint Hospital-University Chair between the University of Toronto, The Hospital for Sick Children, and the SickKids Foundation. He has acted as a consultant for the Dairy Farmers of Ontario and McKesson Canada for matters unrelated to medications used to treat inflammatory bowel disease. He is Past Chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada and Editor-in-Chief of the Journal of the Canadian Association of Gastroenterology (JCAG). None: Joseph Windsor, Stephanie Coward, Juan-Nicolás Peña-Sanchez, Sara Ghandeharian, Noelle Rohatinsky, Jake Weinstein, Tyrel Jones May, Mira Browne, Nazanin Jannati, Sahar Tabatabavakili, James Im, Saketh Meka, Quinn Goddard, Julia Gorospe, Taylor Stocks, Najla Kanaan, Daniel Stuart, Tesa Ramsay, Kelly Robinson, Diane Charron-Bishop., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology.)

Psychiatric disorders are 1.5 to 2 times more prevalent in persons with inflammatory bowel disease (IBD) than in the general population, with pooled prevalence estimates of 21% for clinical anxiety and 15% for depression. Rates are even higher when considering mental health symptoms, as nearly one-third of persons with IBD experience elevated anxiety symptoms and one-quarter experience depression symptoms. Rates of these symptoms were much higher during periods of disease activity, more common in women than men, and more common in Crohn's disease than ulcerative colitis. There is robust evidence of the detrimental effects of comorbid depression and anxiety on the subsequent course of IBD based on longitudinal studies tracking outcomes over time. However, psychiatric disorders and IBD have bidirectional effects, with each affecting risk of the other. Elevated mental health concerns have been consistently associated with greater healthcare utilization and costs related to IBD. There is some signal that low resilience in adolescence could be a risk factor for developing IBD and that enhancing resilience may improve mental health and intestinal disease outcomes in IBD. Psychological therapies used to treat anxiety and depression occurring in the context of IBD have been shown to significantly improve the quality of life for persons with IBD and reduce anxiety and depression. There is less evidence in regard to the impact of psychotropic medications on mental health or disease outcomes in persons with IBD. There is consensus, however, that mental health must be addressed as part of comprehensive IBD care for children and adults., Competing Interests: Lesley Graff has been a consultant with Roche Canada. Ellen Kuenzig is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Eric Benchimol holds the Northbridge Financial Corporation Chair in Inflammatory Bowel Disease, a joint Hospital-University Chair between the University of Toronto, The Hospital for Sick Children, and the SickKids Foundation. He has acted as a consultant for the Dairy Farmers of Ontario and McKesson Canada for matters unrelated to medications used to treat inflammatory bowel disease. He is Past Chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada and Editor-in-Chief of the Journal of the Canadian Association of Gastroenterology (JCAG). Gilaad Kaplan has received honoraria for speaking or consultancy from AbbVie, Janssen, Pfizer and Takeda. He has received research support from Ferring, Janssen, AbbVie, GlaxoSmith Kline, Merck and Shire. He has been a consultant for Gilead. He shares ownership of a patent: TREATMENT OF INFLAMMATORY DISORDERS, AUTOIMMUNE DISEASE, AND PBC. UTI Limited Partnership, assignee. Patent WO2019046959A1. PCT/CA2018/051098. 7 September 2018. He is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Alain Bitton has participated in advisory boards with AbbVie, Janssen, Takeda, McKesson, BioJamp, Bristol Myers Squibb Hoffman-LaRoche, Amgen. He has received research support from AbbVie. He is on the speaker’s panel for Janssen, Takeda, AbbVie and has participated in educational activities supported by Viatris, has received educational support from Fresenius Kabi, Amgen and Takeda. Jennifer Jones has received honoraria for speaking and consulting for AbbVie, Janssen, Pfizer, Shire and Takeda. She is the co-chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Kate Lee has received honoraria from AbbVie Corporation and Bristol Myers Squibb Canada. anjay Murthy has previously participated in advisory board meetings for AbbVie, Janssen, Takeda, Pfizer, Shire and Ferring and as a speaker at educational events sponsored by Janssen, AbbVie and Pfizer. Laura Targownik has received research funding from AbbVie Canada, Takeda Canada, Sandoz Canada, Amgen Canada, Gilead Canada, Roche Canada and Pfizer Canada, and has been on Advisory Boards for Janssen Canada, AbbVie Canada, Takeda Canada, Pfizer Canada, Merck Canada, Roche Canada, Sandoz Canada, Organon Canada, Fresesnius Kabi Canada, Eli Lilly Canada and Amgen Canada. She is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Charles Bernstein is supported in part by the Bingham Chair in Gastroenterology. He is on Advisory Boards for AbbVie Canada, Amgen Canada, Bristol Myers Squibb, JAMP Pharmaceuticals, Lilly Canada, Janssen Canada, Pfizer Canada, Roche Canada, Sandoz Canada, Takeda Canada. He is a Consultant for Mylan Pharmaceuticals and Takeda. He has received educational grants from AbbVie Canada, Pfizer Canada, Takeda Canada, Janssen Canada, and Bristol Myers Squibb Canada. He is on the speaker’s panel for AbbVie Canada, Janssen Canada, Pfizer Canada and Takeda Canada. Received research funding from AbbVie Canada, Amgen Canada, Pfizer Canada, Sandoz Canada. None: Joseph Windsor, Stephanie Coward, Rose Geist, Juan-Nicolás Peña-Sánchez, Nazanin Jannati, Tyrel Jones May, Tasbeen Akhtar Sheekha, Tal Davis, Jake Weinstein, Ghaida Dahlwi, James Im, Jessica Amankwah Osei, Noelle Rohatinsky, Sara Ghandeharian, Quinn Goddard, Julia Gorospe, Shira Gertsman, Michelle Louis, Richelle Wagner, Colten Brass, & Rhonda Sanderson., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology.)

Cancer is a major cause of morbidity and mortality among people with inflammatory bowel disease (IBD). Intestinal cancers may arise as a complication of IBD itself, while extra-intestinal cancers may arise due to some of the immunosuppressive therapies used to treat IBD. Colorectal cancer (CRC) and small bowel cancer risks remain elevated among persons with IBD as compared to age-and sex-matched members of the general population, and the lifetime risk of these cancers is strongly correlated to cumulative intestinal inflammatory burden. However, the cumulative risk of cancer, even among those with IBD is still low. Some studies suggest that IBD-CRC incidence has declined over the years, possibly owing to improved treatment standards and improved detection and management of early neoplastic lesions. Across studies of extra-intestinal cancers, there are generally higher incidences of melanoma, hepatobiliary cancer, and lung cancer and no higher incidences of breast cancer or prostate cancer, with equivocal risk of cervical cancer, among persons with IBD. While the relative risks of some extra-intestinal cancers are increased with treatment, the absolute risks of these cancers remain low and the decision to forego treatment in light of these risks should be carefully weighed against the increased risks of intestinal cancers and other disease-related complications with undertreated inflammatory disease. Quality improvement efforts should focus on optimized surveillance of cancers for which surveillance strategies exist (colorectal cancer, hepatobiliary cancer, cervical cancers, and skin cancers) and the development of cost-effective surveillance strategies for less common cancers associated with IBD., Competing Interests: Sanjay Murthy has previously participated in advisory board meetings for AbbVie, Janssen, Takeda, Pfizer, Shire and Ferring and as a speaker at educational events sponsored by Janssen, AbbVie and Pfizer. Ellen Kuenzig is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Eric Benchimol holds the Northbridge Financial Corporation Chair in Inflammatory Bowel Disease, a joint Hospital-University Chair between the University of Toronto, The Hospital for Sick Children, and the SickKids Foundation. He has acted as a consultant for the Dairy Farmers of Ontario and McKesson Canada for matters unrelated to medications used to treat inflammatory bowel disease. He is Past Chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada and Editor-in-Chief of the Journal of the Canadian Association of Gastroenterology (JCAG). Charles Bernstein is supported in part by the Bingham Chair in Gastroenterology. He is on Advisory Boards for AbbVie Canada, Amgen Canada, Bristol Myers Squibb, JAMP Pharmaceuticals, Lilly Canada, Janssen Canada, Pfizer Canada, Roche Canada, Sandoz Canada, Takeda Canada. He is a Consultant for Mylan Pharmaceuticals and Takeda. He has received educational grants from AbbVie Canada, Pfizer Canada, Takeda Canada, Janssen Canada, and Bristol Myers Squibb Canada. He is on the speaker’s panel for AbbVie Canada, Janssen Canada, Pfizer Canada, and Takeda Canada. Received research funding from AbbVie Canada, Amgen Canada, Pfizer Canada, Sandoz Canada. Alain Bitton has participated in advisory boards with AbbVie, Janssen, Takeda, McKesson, BioJamp, Bristol Myers Squibb Hoffman-LaRoche, Amgen. He has received research support from AbbVie. He is on the speaker’s panel for Janssen, Takeda, AbbVie and has participated in educational activities supported by Viatris, has received educational support from Fresenius Kabi, Amgen, and Takeda. Jennifer Jones has received honoraria for speaking and consulting for AbbVie, Janssen, Pfizer, Shire, and Takeda. She is the co-chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Gilaad Kaplan has received honoraria for speaking or consultancy from AbbVie, Janssen, Pfizer, and Takeda. He has received research support from Ferring, Janssen, AbbVie, GlaxoSmith Kline, Merck, and Shire. He has been a consultant for Gilead. He shares ownership of a patent: TREATMENT OF INFLAMMATORY DISORDERS, AUTOIMMUNE DISEASE, AND PBC. UTI Limited Partnership, assignee. Patent WO2019046959A1. PCT/CA2018/051098. 7 Sept. 2018. He is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Kate Lee has received honoraria from AbbVie Corporation and Bristol Myers Squibb Canada. Laura Targownik has received research funding from AbbVie Canada, Takeda Canada, Sandoz Canada, Amgen Canada, Gilead Canada, Roche Canada and Pfizer Canada, and has been on Advisory Boards for Janssen Canada, AbbVie Canada, Takeda Canada, Pfizer Canada, Merck Canada, Roche Canada, Sandoz Canada, Organon Canada, Fresesnius Kabi Canada, Eli Lilly Canada, and Amgen Canada. She is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Harminder Singh has been on advisory boards or consulted for Pendopharm, Amgen Canada, Roche Canada, Sandoz Canada, Takeda Canada, Bristol Myers Squibb, and Guardant Health Inc. and has received research funding for an investigator-initiated study from Pfizer. None: Joseph Windsor, Priscilla Matthews, Parul Tandon, Stephanie Coward, Juan-Nicolás Peña-Sánchez, Noelle Rohatinsky, Sara Ghandeharian, Saketh Meka, Roxana Chis, Sarang Gupta, Eric Cheah, Tal Davis, Jake Weinstein, James Im, Quinn Goddard, Julia Gorospe, Jennifer Loschiavo, Kaitlyn McQuaid, Joseph D’Addario, Ken Silver, & Robyn Oppenheim., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology.)

The therapeutic landscape for inflammatory bowel disease (IBD) has changed considerably over the past two decades, owing to the development and widespread penetration of targeted therapies, including biologics and small molecules. While some conventional treatments continue to have an important role in the management of IBD, treatment of IBD is increasingly moving towards targeted therapies given their greater efficacy and safety in comparison to conventional agents. Early introduction of these therapies-particularly in persons with Crohn's disease-combining targeted therapies with traditional anti-metabolite immunomodulators and targeting objective markers of disease activity (in addition to symptoms), have been shown to improve health outcomes and will be increasingly adopted over time. The substantially increased costs associated with targeted therapies has led to a ballooning of healthcare expenditure to treat IBD over the past 15 years. The introduction of less expensive biosimilar anti-tumour necrosis factor therapies may bend this cost curve downwards, potentially allowing for more widespread access to these medications. Newer therapies targeting different inflammatory pathways and complementary and alternative therapies (including novel diets) will continue to shape the IBD treatment landscape. More precise use of a growing number of targeted therapies in the right individuals at the right time will help minimize the development of expensive and disabling complications, which has the potential to further reduce costs and improve outcomes., Competing Interests: Sanjay K. Murthy has previously participated in advisory board meetings for AbbVie, Janssen, Takeda, Pfizer, Shire and Ferring and as a speaker at educational events sponsored by Janssen, AbbVie and Pfizer. Adam V. Weizman has been a speaker for AbbVie, Janssen, Viatris, Amgen and Pendopharm and is on the advisory boards for AbbVie, Takeda and Ferring. Ellen Kuenzig is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Gilaad G. Kaplan has received honoraria for speaking or consultancy from AbbVie, Janssen, Pfizer and Takeda. He has received research support from Ferring, Janssen, AbbVie, GlaxoSmith Kline, Merck and Shire. He has been a consultant for Gilead. He shares ownership of a patent: TREATMENT OF INFLAMMATORY DISORDERS, AUTOIMMUNE DISEASE, AND PBC. UTI Limited Partnership, assignee. Patent WO2019046959A1. PCT/CA2018/051098. September 7, 2018. He is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Eric I. Benchimol holds the Northbridge Financial Corporation Chair in Inflammatory Bowel Disease, a joint Hospital-University Chair between the University of Toronto, The Hospital for Sick Children and the SickKids Foundation. He has acted as a consultant for the Dairy Farmers of Ontario and McKesson Canada for matters unrelated to medications used to treat inflammatory bowel disease. He is Past Chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada and Editor-in-Chief of the Journal of the Canadian Association of Gastroenterology (JCAG). Charles N. Bernstein is supported in part by the Bingham Chair in Gastroenterology. He is on Advisory Boards for AbbVie Canada, Amgen Canada, Bristol Myers Squibb, JAMP Pharmaceuticals, Lilly Canada, Janssen Canada, Pfizer Canada, Roche Canada, Sandoz Canada, Takeda Canada. He is a Consultant for Mylan Pharmaceuticals and Takeda. He has received educational grants from AbbVie Canada, Pfizer Canada, Takeda Canada, Janssen Canada and Bristol Myers Squibb Canada. He is on the speaker’s panel for AbbVie Canada, Janssen Canada, Pfizer Canada and Takeda Canada. Received research funding from AbbVie Canada, Amgen Canada, Pfizer Canada, Sandoz Canada. Alain Bitton has participated in advisory boards with AbbVie, Janssen, Takeda, McKesson, BioJamp, Bristol Myers Squibb Hoffman-LaRoche, Amgen. He has received research support from AbbVie. He is on the speaker’s panel for Janssen, Takeda, AbbVie and has participated in educational activities supported by Viatris, has received educational support from Fresenius Kabi, Amgen and Takeda. Jennifer L. Jones has received honoraria for speaking and consulting for AbbVie, Janssen, Pfizer, Shire and Takeda. She is the co-chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Kate Lee has received honoraria from AbbVie Corporation and Bristol Myers Squibb Canada. Ashley Patel has received an AbbVie IBD scholarship. Sophia Russo has received an AbbVie IBD scholarship. Laura E. Targownik has received research funding from AbbVie Canada, Takeda Canada, Sandoz Canada, Amgen Canada, Gilead Canada, Roche Canada and Pfizer Canada, and has been on Advisory Boards for Janssen Canada, AbbVie Canada, Takeda Canada, Pfizer Canada, Merck Canada, Roche Canada, Sandoz Canada, Organon Canada, Fresesnius Kabi Canada, Eli Lilly Canada and Amgen Canada. She is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. None: Joseph W. Windsor, Stephanie Coward, Juan-Nicolás Peña-Sánchez, Noelle Rohatinsky, Sara Ghandeharian, Nasruddin Sabrie, Sarang Gupta, Gurmun Brar, Rabia Khan, James H. B. Im, Tal Davis, Jake Weinstein, Joëlle St-Pierre, Roxana Chis, Saketh Meka, Eric Cheah, Quinn Goddard, Julia Gorospe, Jack Kerr, Kayla D. Beaudoin, Jonathan Blyth, Stephanie Blyth, and Diane Charron-Bishop., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology.)

Rates of inflammatory bowel disease (IBD) in Canadian children and adolescents are among the highest in the world, and the incidence is rising most rapidly in children under five years of age. These young children may have either a typical form of IBD with multi-factorial aetiology, or they may have a monogenic form. Despite the growing number of children in Canada living with this important chronic disease, there are few available medical therapies approved by Health Canada due to the omission of children from most clinical trials of newly developed biologics. As a result, off-label use of medications is common, and physicians have learned to use existing therapies more effectively. In addition, most Canadian children are treated in multidisciplinary, specialty clinics by physicians with extra training or experience in IBD, as well as specialist nurses, dietitians, mental health care providers and other allied health professionals. This specialized clinic approach has facilitated cutting edge research, led by Canadian clinicians and scientists, to understand the causes of IBD, the optimal use of therapies, and the best ways to treat children from a biopsychosocial perspective. Canadians are engaged in work to understand the monogenic causes of IBD; the interaction between genes, the environment, and the microbiome; and how to address the mental health concerns and medical needs of adolescents and young adults transitioning from paediatric to adult care., Competing Interests: Matthew Carroll has received speaker fees from AbbVie. Anne Griffiths past holder of the Northbridge Financial Corporation Chair in Inflammatory Bowel Disease, a joint Hospital-University Chair between the University of Toronto, The Hospital for Sick Children, and the SickKids Foundation. She has received research support from AbbVie Canada. She is co-owner of copyright for the Pediatric Ulcerative Colitis Activity Index (PUCAI) and for the TUMMY-UC. She has been an advisory board member or consultant for AbbVie, Amgen, Bristol Myers Squibb, Janssen, Lilly, Merck, Pfizer, Takeda, and has received speaker fees from AbbVie, Janssen, Takeda. She is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Ellen Kuenzig is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. David Mack is co-owner of Biotagenics Inc. Eytan Wine has received honoraria for speaking or consultancy from AbbVie, Janssen, Pfizer, Nestle Health Sciences, Mead Johnson Nutrition, and Biojamp. Gilaad Kaplan has received honoraria for speaking or consultancy from AbbVie, Janssen, Pfizer, and Takeda. He has received research support from Ferring, Janssen, AbbVie, GlaxoSmith Kline, Merck, and Shire. He has been a consultant for Gilead. He shares ownership of a patent: TREATMENT OF INFLAMMATORY DISORDERS, AUTOIMMUNE DISEASE, AND PBC. UTI Limited Partnership, assignee. Patent WO2019046959A1. PCT/CA2018/051098. 7 Sept. 2018. He is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Charles Bernstein is supported in part by the Bingham Chair in Gastroenterology. He is on Advisory Boards for AbbVie Canada, Amgen Canada, Bristol Myers Squibb, JAMP Pharmaceuticals, Lilly Canada, Janssen Canada, Pfizer Canada, Roche Canada, Sandoz Canada, Takeda Canada. He is a Consultant for Mylan Pharmaceuticals and Takeda. He has received educational grants from AbbVie Canada, Pfizer Canada, Takeda Canada, Janssen Canada, and Bristol Myers Squibb Canada. He is on the speaker’s panel for AbbVie Canada, Janssen Canada, Pfizer Canada, and Takeda Canada. Received research funding from AbbVie Canada, Amgen Canada, Pfizer Canada, Sandoz Canada. Alain Bitton has participated in advisory boards with AbbVie, Janssen, Takeda, McKesson, BioJamp, Bristol Myers Squibb Hoffman-LaRoche, Amgen. He has received research support from AbbVie. He is on the speaker’s panel for Janssen, Takeda, AbbVie and has participated in educational activities supported by Viatris, has received educational support from Fresenius Kabi, Amgen, and Takeda. Jennifer Jones has received honoraria for speaking and consulting for AbbVie, Janssen, Pfizer, Shire, and Takeda. She is the co-chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Kate lee has received honoraria from AbbVie Corporation and Bristol Myers Squibb Canada. Sanjay Murthy has previously participated in advisory board meetings for AbbVie, Janssen, Takeda, Pfizer, Shire and Ferring and as a speaker at educational events sponsored by Janssen, AbbVie and Pfizer. Laura Targownik has received research funding from AbbVie Canada, Takeda Canada, Sandoz Canada, Amgen Canada, Gilead Canada, Roche Canada and Pfizer Canada, and has been on Advisory Boards for Janssen Canada, AbbVie Canada, Takeda Canada, Pfizer Canada, Merck Canada, Roche Canada, Sandoz Canada, Organon Canada, Fresesnius Kabi Canada, Eli Lilly Canada, and Amgen Canada. She is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Jules Verdugo has received an AbbVie IBD scholarship. Samantha Morin has received an AbbVie IBD scholarship. Taylor Morganstein has received an AbbVie IBD scholarship and is a member of the Patient Adboard of AbbVie Canada. Eric Benchimol holds the Northbridge Financial Corporation Chair in Inflammatory Bowel Disease, a joint Hospital-University Chair between the University of Toronto, The Hospital for Sick Children, and the SickKids Foundation. He has acted as a consultant for the Dairy Farmers of Ontario and McKesson Canada for matters unrelated to medications used to treat inflammatory bowel disease. He is Past Chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada and Editor-in-Chief of the Journal of the Canadian Association of Gastroenterology (JCAG). None: Wael El-Matary, Colette Deslandres, Rose Geist, Tal Davis, Jake Weinstein, Justin Chan, Rabia Khan, Priscilla Matthews, Joseph Windsor, Stephanie Coward, Juan-Nicolás Peña-Sánchez, Noelle Rohatinsky, Sara Ghandeharian, James Im, Quinn Goddard, Julia Gorospe, & Lisa Banning., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology.)

People living with inflammatory bowel disease (IBD) and their caregivers are faced with indirect and out-of-pocket costs that they would not otherwise experience. These costs impact one's ability to contribute to the economy to their fullest potential. The indirect costs of IBD in Canada are estimated to be at least $1.51 billion in 2023 and include costs associated with lost productivity resulting from a combination of missed work (absenteeism), decreased workplace productivity (presenteeism), unemployment, premature mortality, and caregiving costs. Unemployment is the largest contributor to indirect costs ($1.14 billion), followed by costs of absenteeism and presenteeism ($285 million). Caregiving costs for children with IBD are estimated to be nearly $58 million. Canadians with IBD also pay $536 million every year for care that is not covered by universal or supplemental private health insurance; this includes allied healthcare (e.g., care provided by psychologists), medication, and other supportive therapy. Combined, the indirect and out-of-pocket costs of IBD in Canada are estimated at more than $2 billion CAD in 2023. This is substantially higher than the estimate of $1.29 billion in Crohn's and Colitis Canada's 2018 Impact of IBD report with differences attributable to a combination of rising prevalence, inflation, and the addition of presenteeism and caregiving costs to the total indirect costs., Competing Interests: Ellen Kuenzig is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Gilaad Kaplan has received honoraria for speaking or consultancy from AbbVie, Janssen, Pfizer, and Takeda. He has received research support from Ferring, Janssen, AbbVie, GlaxoSmith Kline, Merck, and Shire. He has been a consultant for Gilead. He shares ownership of a patent: TREATMENT OF INFLAMMATORY DISORDERS, AUTOIMMUNE DISEASE, AND PBC. UTI Limited Partnership, assignee. Patent WO2019046959A1. PCT/CA2018/051098. 7 Sept. 2018. He is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Sanjay Murthy has previously participated in advisory board meetings for AbbVie, Janssen, Takeda, Pfizer, Shire and Ferring and as a speaker at educational events sponsored by Janssen, AbbVie and Pfizer. Eric Benchimol holds the Northbridge Financial Corporation Chair in Inflammatory Bowel Disease, a joint Hospital-University Chair between the University of Toronto, The Hospital for Sick Children, and the SickKids Foundation. He has acted as a consultant for the Dairy Farmers of Ontario and McKesson Canada for matters unrelated to medications used to treat inflammatory bowel disease. He is Past Chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada and Editor-in-Chief of the Journal of the Canadian Association of Gastroenterology (JCAG). Charles Bernstein is supported in part by the Bingham Chair in Gastroenterology. He is on Advisory Boards for AbbVie Canada, Amgen Canada, Bristol Myers Squibb, JAMP Pharmaceuticals, Janssen Canada, Pfizer Canada, Roche Canada, Sandoz Canada, Takeda Canada. He is a Consultant for Mylan Pharmaceuticals and Takeda. He has received educational grants from AbbVie Canada, Pfizer Canada, Takeda Canada, Janssen Canada, and Bristol Myers Squibb Canada. He is on the speaker’s panel for AbbVie Canada, Janssen Canada, Pfizer Canada, and Takeda Canada. Received research funding from AbbVie Canada, Pfizer Canada, Sandoz Canada. Alain Bitton has participated in advisory boards with AbbVie, Janssen, Takeda, McKesson, BioJamp, Bristol Myers Squibb Hoffman-LaRoche, Amgen. He has received research support from AbbVie. He is on the speaker’s panel for Janssen, Takeda, AbbVie and has participated in educational activities supported by Viatris, has received educational support from Fresenius Kabi, Amgen, and Takeda. Jennifer Jones has received honoraria for speaking and consulting for AbbVie, Janssen, Pfizer, Shire, and Takeda. She is the co-chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Kate Lee has received honoraria from AbbVie Corporation and Bristol Myers Squibb Canada. Kate Latos has received an AbbVie IBD scholarship. Kate Mason has received an AbbVie IBD scholarship. Naji Blache has received an AbbVie IBD scholarhip. Laura Targownik has received research funding from AbbVie Canada, Takeda Canada, Sandoz Canada, Amgen Canada, Gilead Canada, Roche Canada and Pfizer Canada, and has been on Advisory Boards for Janssen Canada, AbbVie Canada, Takeda Canada, Pfizer Canada, Merck Canada, Roche Canada, Sandoz Canada, Organon Canada, Fresesnius Kabi Canada, Eli Lilly Canada, and Amgen Canada. She is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. None: James Im, Stephanie Coward, Joseph Windsor, Sanjay Murthy, Juan-Nicolás Peña-Sánchez, Noelle Rohatinsky, Sara Ghandeharian, Tyrel Jones May, Sahar Tabatabavakili, Rohit Jogendran, Jake Weinstein, Rabia Khan, Elias Hazan, Mira Browne, Tal Davis, Quinn Goddard, Julia Gorospe, Jack Kerr, & Anna Sklar., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology.)

Approximately one out of every 88 seniors has inflammatory bowel disease (IBD), and this is expected to increase in the future. They are more likely to have left-sided disease in ulcerative colitis, and isolated colonic disease in Crohn's disease; perianal disease is less common. Other common diagnoses in the elderly must also be considered when they initially present to a healthcare provider. Treatment of the elderly is similar to younger persons with IBD, though considerations of the increased risk of infections and malignancy must be considered when using immune modulating drugs. Whether anti-TNF therapies increase the risk of infections is not definitive, though newer biologics, including vedolizumab and ustekinumab, are thought to be safer with lower risk of adverse events. Polypharmacy and frailty are other considerations in the elderly when choosing a treatment, as frailty is associated with worse outcomes. Costs for IBD-related hospitalizations are higher in the elderly compared with younger persons. When elderly persons with IBD are cared for by a gastroenterologist, their outcomes tend to be better. However, as elderly persons with IBD continue to age, they may not have access to the same care as younger people with IBD due to deficiencies in their ability to use or access technology., Competing Interests: Seth Shaffer has served on advisory boards or consulted with Takeda Canada, AbbVie Canada, Janssen Canada, and Pfizer Canada. Ellen Kuenzig is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Alain Bitton has participated in advisory boards with AbbVie, Janssen, Takeda, McKesson, BioJamp, Bristol Myers Squibb Hoffman-LaRoche, Amgen. He has received research support from AbbVie. He is on the speaker’s panel for Janssen, Takeda, AbbVie and has participated in educational activities supported by Viatris, has received educational support from Fresenius Kabi, Amgen, and Takeda. Jennifer Jones has received honoraria for speaking and consulting for AbbVie, Janssen, Pfizer, Shire, and Takeda. She is the co-chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Kate Lee has received honoraria from AbbVie Corporation and Bristol Myers Squibb Canada. Sanjay Murthy haspreviously participated in advisory board meetings for AbbVie, Janssen, Takeda, Pfizer, Shire and Ferring and as a speaker at educational events sponsored by Janssen, AbbVie and Pfizer. Laura Targownik has received research funding from AbbVie Canada, Takeda Canada, Sandoz Canada, Amgen Canada, Gilead Canada, Roche Canada and Pfizer Canada, and has been on Advisory Boards for Janssen Canada, AbbVie Canada, Takeda Canada, Pfizer Canada, Merck Canada, Roche Canada, Sandoz Canada, Organon Canada, Fresesnius Kabi Canada, Eli Lilly Canada, and Amgen Canada. She is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Eric Benchimol holds the Northbridge Financial Corporation Chair in Inflammatory Bowel Disease, a joint Hospital-University Chair between the University of Toronto, The Hospital for Sick Children, and the SickKids Foundation. He has acted as a consultant for the Dairy Farmers of Ontario and McKesson Canada for matters unrelated to medications used to treat inflammatory bowel disease. He is Past Chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada and Editor-in-Chief of the Journal of the Canadian Association of Gastroenterology (JCAG). Gilaad Kaplan has received honoraria for speaking or consultancy from AbbVie, Janssen, Pfizer, and Takeda. He has received research support from Ferring, Janssen, AbbVie, GlaxoSmith Kline, Merck, and Shire. He has been a consultant for Gilead. He shares ownership of a patent: TREATMENT OF INFLAMMATORY DISORDERS, AUTOIMMUNE DISEASE, AND PBC. UTI Limited Partnership, assignee. Patent WO2019046959A1. PCT/CA2018/051098. 7 Sept. 2018. He is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Charles Bernstein is supported in part by the Bingham Chair in Gastroenterology. He is on Advisory Boards for AbbVie Canada, Amgen Canada, Bristol Myers Squibb, JAMP Pharmaceuticals, Lilly Canada, Janssen Canada, Pfizer Canada, Roche Canada, Sandoz Canada, Takeda Canada. He is a Consultant for Mylan Pharmaceuticals and Takeda. He has received educational grants from AbbVie Canada, Pfizer Canada, Takeda Canada, Janssen Canada, and Bristol Myers Squibb Canada. He is on the speaker’s panel for AbbVie Canada, Janssen Canada, Pfizer Canada, and Takeda Canada. Received research funding from AbbVie Canada, Amgen Canada, Pfizer Canada, Sandoz Canada. None: Joseph Windsor, Juan-Nicolás Peña-Sánchez, Noelle Rohatinsky, Sara Ghandeharian, Parul Tandon, Joëlle St-Pierre, Navneet Natt, Tal Davis, Jake Weinstein, James Im, Quinn Goddard, Julia Gorospe, Maxime Bergevin, Ken Silver, Dawna Bowles, Margaret Stewart, Marsha Pearlstein, Elizabeth Dawson., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology.)

Sex (the physical and physiologic effects resulting from having specific combinations of sex chromosomes) and gender (sex-associated behaviours, expectations, identities, and roles) significantly affect the course of inflammatory bowel disease (IBD) and the experience of living with IBD. Sex-influenced physiologic states, like puberty, the menstrual cycle, pregnancy, and andropause/menopause may also impact and be impacted by IBD. While neither Crohn's disease nor ulcerative colitis is commonly considered sex-determined illnesses, the relative incidence of Crohn's disease and ulcerative colitis between males and females varies over the life cycle. In terms of gender, women tend to use healthcare resources at slightly higher rates than men and are more likely to have fragmented care. Women are more commonly prescribed opioid medications and are less likely than men to undergo colectomy. Women tend to report lower quality of life and have higher indirect costs due to higher rates of disability. Women are also more likely to take on caregiver roles for children with IBD. Women with IBD are more commonly burdened with adverse mental health concerns and having poor mental health has a more profound impact on women than men. Pregnant people with active IBD have higher rates of adverse outcomes in pregnancy, made worse in regions with poor access to IBD specialist care. The majority of individuals with IBD in Canada do not have access to a pregnancy-in-IBD specialist; access to this type of care has been shown to allay fears and increase knowledge among pregnant people with IBD., Competing Interests: Laura Targownik has received research funding from AbbVie Canada, Takeda Canada, Sandoz Canada, Amgen Canada, Gilead Canada, Roche Canada and Pfizer Canada and has been on Advisory Boards for Janssen Canada, AbbVie Canada, Takeda Canada, Pfizer Canada, Merck Canada, Roche Canada, Sandoz Canada, Organon Canada, Fresesnius Kabi Canada, Eli Lilly Canada and Amgen Canada. She is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Natasha Bollegala has consulted for Takeda, AbbVie, Janssen and Pfizer, and has received honoraria from Takeda, AbbVie and Janssen. Vivian Huang has received consulting fees from AbbVie, Amgen, BMS, Janssen, Sandoz, Roche and Takeda. She has received speaker fees from AbbVie, Amgen, BMS, Ferring, Janssen, Merck, Organon, Pfizer, Sandoz, Takeda and Viatris. Ellen Kuenzig is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Eric Benchimol holds the Northbridge Financial Corporation Chair in Inflammatory Bowel Disease, a joint Hospital-University Chair between the University of Toronto, The Hospital for Sick Children and the SickKids Foundation. He has acted as a consultant for the Dairy Farmers of Ontario and McKesson Canada for matters unrelated to medications used to treat inflammatory bowel disease. He is Past Chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada and Editor-in-Chief of the Journal of the Canadian Association of Gastroenterology (JCAG). Gilaad Kaplan has received honoraria for speaking or consultancy from AbbVie, Janssen, Pfizer and Takeda. He has received research support from Ferring, Janssen, AbbVie, GlaxoSmith Kline, Merck and Shire. He has been a consultant for Gilead. He shares ownership of a patent: TREATMENT OF INFLAMMATORY DISORDERS, AUTOIMMUNE DISEASE AND PBC. UTI Limited Partnership, assignee. Patent WO2019046959A1. PCT/CA2018/051098. 7 September, 2018. He is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Sanjay Murthy has previously participated in advisory board meetings for AbbVie, Janssen, Takeda, Pfizer, Shire and Ferring and as a speaker at educational events sponsored by Janssen, AbbVie and Pfizer. Alain Bitton has participated in advisory boards with AbbVie, Janssen, Takeda, McKesson, BioJamp, Bristol Myers Squibb Hoffman-LaRoche, Amgen. He has received research support from AbbVie. He is on the speaker’s panel for Janssen, Takeda, AbbVie and has participated in educational activities supported by Viatris, has received educational support from Fresenius Kabi, Amgen and Takeda. Charles Bernstein is supported in part by the Bingham Chair in Gastroenterology. He is on Advisory Boards for AbbVie Canada, Amgen Canada, Bristol Myers Squibb, JAMP Pharmaceuticals, Lilly Canada, Janssen Canada, Pfizer Canada, Roche Canada, Sandoz Canada, Takeda Canada. He is a Consultant for Mylan Pharmaceuticals and Takeda. He has received educational grants from AbbVie Canada, Pfizer Canada, Takeda Canada, Janssen Canada and Bristol Myers Squibb Canada. He is on the speaker’s panel for AbbVie Canada, Janssen Canada, Pfizer Canada and Takeda Canada. Received research funding from AbbVie Canada, Amgen Canada, Pfizer Canada, Sandoz Canada. Jennifer Jones has received honoraria for speaking and consulting for AbbVie, Janssen, Pfizer, Shire and Takeda. She is the co-chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Kate Lee has received honoraria from AbbVie Corporation and Bristol Myers Squibb Canada. James Sousa has received an AbbVie IBD scholarship. Taylor Morganstein has received an AbbVie IBD scholarship and is a member of the Patient Adboard of AbbVie Canada. Ann Weber has received an AbbVie IBD scholarship. Cynthia Seow has served on advisory boards for Janssen, AbbVie, Takeda, Pfizer, Fresenius Kabi and Bristol Myers Squibb. She has received speaker honoraria from Janssen, AbbVie, Takeda, Pfizer and Fresenius Kabi. She has received funding from Alberta Children’s Hospital Research Institute, Crohn’s and Colitis Canada, The Canadian Institutes of Health Research, Calgary Health Trust and New South Wales Government Health. None: Joseph Windsor, Juan-Nicolás Peña-Sánchez, Noelle Rohatinsky, Sara Ghandeharian, Tal Davis, Jake Weinstein, James Im, Nazanin Jannati, Rabia Khan, Priscilla Matthews, Tyrel Jones May, Sahar Tabatabavakili, Rohit Jogendran, Elias Hazan, Mira Browne, Saketh Meka, Sonya Vukovic, Manisha Jogendran, Malini Hu, Jessica Amankwah Osei, Grace Wang, Tasbeen Akhtar Sheekha, Ghaida Dahlwi, Quinn Goddard, Julia Gorospe, Cyanne Nisbett, Shira Gertsman, & Taylor Stocks., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology.)

Rising compounding prevalence of inflammatory bowel disease (IBD) (Kaplan GG, Windsor JW. The four epidemiological stages in the global evolution of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 2021;18:56-66.) and pandemic-exacerbated health system resource limitations have resulted in significant variability in access to high-quality, evidence-based, person-centered specialty care for Canadians living with IBD. Individuals with IBD have identified long wait times, gaps in biopsychosocial care, treatment and travel expenses, and geographic and provider variation in IBD specialty care and knowledge as some of the key barriers to access. Care delivered within integrated models of care (IMC) has shown promise related to impact on disease-related outcomes and quality of life. However, access to these models is limited within the Canadian healthcare systems and much remains to be learned about the most appropriate IMC team composition and roles. Although eHealth technologies have been leveraged to overcome some access challenges since COVID-19, more research is needed to understand how best to integrate eHealth modalities (i.e., video or telephone visits) into routine IBD care. Many individuals with IBD are satisfied with these eHealth modalities. However, not all disease assessment and monitoring can be achieved through virtual modalities. The need for access to person-centered, objective disease monitoring strategies, inclusive of point of care intestinal ultrasound, is more pressing than ever given pandemic-exacerbated restrictions in access to endoscopy and cross-sectional imaging. Supporting learning healthcare systems for IBD and research relating to the strategic use of innovative and integrative implementation strategies for evidence-based IBD care interventions are greatly needed. Data derived from this research will be essential to appropriately allocating scarce resources aimed at improving person-centred access to cost-effective IBD care., Competing Interests: S.M. has previously participated in advisory board meetings for AbbVie, Janssen, Takeda, Pfizer, Shire and Ferring and as a speaker at educational events sponsored by Janssen, AbbVie and Pfizer. K.N. reports advisory board fees from AbbVie, Janssen, Pfizer, Ferring, Takeda, Celltrion, Bristol Mysers Squibb, Fresnius Kabi; speaker’s fees from AbbVie, Takeda, Pfizer; and research support from AbbVie, Takeda, Pfizer and the Helmsley Trust. E.K. is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. S.F. has received honoraria for speaking or consultancy from AbbVie, Amgen, Bristol Myers Squibb, Janssen, Pendopharm, Pfizer, Roche, Sandoz and Takeda. E.B. holds the Northbridge Financial Corporation Chair in Inflammatory Bowel Disease, a joint Hospital-University Chair between the University of Toronto, The Hospital for Sick Children and the SickKids Foundation. He has acted as a consultant for the Dairy Farmers of Ontario and McKesson Canada for matters unrelated to medications used to treat inflammatory bowel disease. He is Past Chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada and Editor-in-Chief of the Journal of the Canadian Association of Gastroenterology (JCAG). G.K. has received honoraria for speaking or consultancy from AbbVie, Janssen, Pfizer and Takeda. He has received research support from Ferring, Janssen, AbbVie, GlaxoSmith Kline, Merck and Shire. He has been a consultant for Gilead. He shares ownership of a patent: TREATMENT OF INFLAMMATORY DISORDERS, AUTOIMMUNE DISEASE, AND PBC. UTI Limited Partnership, assignee. Patent WO2019046959A1. PCT/CA2018/051098. 7 Sept. 2018. He is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. C.B. is supported in part by the Bingham Chair in Gastroenterology. He is on Advisory Boards for AbbVie Canada, Amgen Canada, Bristol Myers Squibb, JAMP Pharmaceuticals, Lilly Canada, Janssen Canada, Pfizer Canada, Roche Canada, Sandoz Canada, Takeda Canada. He is a Consultant for Mylan Pharmaceuticals and Takeda. He has received educational grants from AbbVie Canada, Pfizer Canada, Takeda Canada, Janssen Canada and Bristol Myers Squibb Canada. He is on the speaker’s panel for AbbVie Canada, Janssen Canada, Pfizer Canada and Takeda Canada. Received research funding from AbbVie Canada, Amgen Canada, Pfizer Canada, Sandoz Canada. L.T. has received research funding from AbbVie Canada, Takeda Canada, Sandoz Canada, Amgen Canada, Gilead Canada, Roche Canada and Pfizer Canada, and has been on Advisory Boards for Janssen Canada, AbbVie Canada, Takeda Canada, Pfizer Canada, Merck Canada, Roche Canada, Sandoz Canada, Organon Canada, Fresesnius Kabi Canada, Eli Lilly Canada and Amgen Canada. She is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. K.L. has received honoraria from AbbVie Corporation and Bristol Myers Squibb Canada. K.L. has received an AbbVie IBD scholarship. N.B. has received an AbbVie IBD scholarship. P.D. has received an AbbVie IBD scholarship. A.P. has received an AbbVie IBD scholarship. A.B. has participated in advisory boards with AbbVie, Janssen, Takeda, McKesson, BioJamp, Bristol Myers Squibb Hoffman-LaRoche, Amgen. He has received research support from AbbVie. He is on the speaker’s panel for Janssen, Takeda, AbbVie and has participated in educational activities supported by Viatris, has received educational support from Fresenius Kabi, Amgen and Takeda. J.J. has received honoraria for speaking and consulting for AbbVie, Janssen, Pfizer, Shire and Takeda. She is the co-chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. The other authors declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology.)

Healthcare utilization among people living with inflammatory bowel disease (IBD) in Canada has shifted from inpatient management to outpatient management; fewer people with IBD are admitted to hospitals or undergo surgery, but outpatient visits have become more frequent. Although the frequency of emergency department (ED) visits among adults and seniors with IBD decreased, the frequency of ED visits among children with IBD increased. Additionally, there is variation in the utilization of IBD health services within and between provinces and across ethnocultural and sociodemographic groups. For example, First Nations individuals with IBD are more likely to be hospitalized than the general IBD population. South Asian children with Crohn's disease are hospitalized more often than their Caucasian peers at diagnosis, but not during follow-up. Immigrants to Canada who develop IBD have higher health services utilization, but a lower risk of surgery compared to individuals born in Canada. The total direct healthcare costs of IBD, including the cost of hospitalizations, ED visits, outpatient visits, endoscopy, cross-sectional imaging, and medications are rising rapidly. The direct health system and medication costs of IBD in Canada are estimated to be $3.33 billion in 2023, potentially ranging from $2.19 billion to $4.47 billion. This is an increase from an estimated $1.28 billion in 2018, likely due to sharp increases in the use of biologic therapy over the past two decades. In 2017, 50% of total direct healthcare costs can be attributed to biologic therapies; the proportion of total direct healthcare costs attributed to biologic therapies today is likely even greater., Competing Interests: Ellen Kuenzig is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Laura Targownik has received research funding from AbbVie Canada, Takeda Canada, Sandoz Canada, Amgen Canada, Gilead Canada, Roche Canada and Pfizer Canada and has been on Advisory Boards for Janssen Canada, AbbVie Canada, Takeda Canada, Pfizer Canada, Merck Canada, Roche Canada, Sandoz Canada, Organon Canada, Fresesnius Kabi Canada, Eli Lilly Canada and Amgen Canada. She is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Sanjay Murthy has previously participated in advisory board meetings for AbbVie, Janssen, Takeda, Pfizer, Shire and Ferring and as a speaker at educational events sponsored by Janssen, AbbVie and Pfizer. Eric Benchimol holds the Northbridge Financial Corporation Chair in Inflammatory Bowel Disease, a joint Hospital-University Chair between the University of Toronto, The Hospital for Sick Children, and the SickKids Foundation. He has acted as a consultant for the Dairy Farmers of Ontario and McKesson Canada for matters unrelated to medications used to treat inflammatory bowel disease. He is the Past Chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada and Editor-in-Chief of the Journal of the Canadian Association of Gastroenterology (JCAG). Charles Bernstein is supported in part by the Bingham Chair in Gastroenterology. He is on Advisory Boards for AbbVie Canada, Amgen Canada, Bristol Myers Squibb, JAMP Pharmaceuticals, Lilly Canada, Janssen Canada, Pfizer Canada, Roche Canada, Sandoz Canada, Takeda Canada. He is a Consultant for Mylan Pharmaceuticals and Takeda. He has received educational grants from AbbVie Canada, Pfizer Canada, Takeda Canada, Janssen Canada and Bristol Myers Squibb Canada. He is on the speaker’s panel for AbbVie Canada, Janssen Canada, Pfizer Canada and Takeda Canada. Received research funding from AbbVie Canada, Amgen Canada, Pfizer Canada, Sandoz Canada. Alain Bitton has participated in advisory boards with AbbVie, Janssen, Takeda, McKesson, BioJamp, Bristol Myers Squibb Hoffman-LaRoche, Amgen. He has received research support from AbbVie. He is on the speaker’s panel for Janssen, Takeda, AbbVie and has participated in educational activities supported by Viatris, and has received educational support from Fresenius Kabi, Amgen and Takeda. Jennifer Jones has received honoraria for speaking and consulting for AbbVie, Janssen, Pfizer, Shire and Takeda. She is the co-chair of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. Kate Lee has received honoraria from AbbVie Corporation and Bristol Myers Squibb Canada. Kate Latos has received an AbbVie IBD scholarship. Kate Mason has received an AbbVie IBD scholarship. Gilaad Kaplan has received honoraria for speaking or consultancy from AbbVie, Janssen, Pfizer and Takeda. He has received research support from Ferring, Janssen, AbbVie, GlaxoSmith Kline, Merck and Shire. He has been a consultant for Gilead. He shares ownership of a patent: TREATMENT OF INFLAMMATORY DISORDERS, AUTOIMMUNE DISEASE, AND PBC. UTI Limited Partnership, assignee. Patent WO2019046959A1. PCT/CA2018/051098. 7 Sept. 2018. He is a member of the Scientific and Medical Advisory Council of Crohn’s and Colitis Canada. None: Stephanie Coward, Joseph Windsor, Juan-Nicolás Peña-Sánchez, Noelle Rohatinsky, Sara Ghandeharian, James Im, Rohit Jogendran, Saketh Meka, Jake Weinstein, Tyrel Jones May, Manisha Jogendran, Sahar Tabatabavakili, Elias Hazan, Malini Hu, Jessica Amankwah Osei, Rabia Khan, Grace Wang, Mira Browne, Tal Davis, Quinn Goddard, Julia Gorospe, Jack Kerr, & Anna Sklar., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology.)

Introduction: We determined adverse events after 4 doses of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine in those with inflammatory bowel disease (IBD), associations between antibodies and injection site reactions (ISR), and risk of IBD flare., Methods: Individuals with IBD were interviewed for adverse events to SARS-CoV-2 vaccine. Multivariable linear regression assessed the association between antibody titers and ISR., Results: Severe adverse events occurred in 0.03%. ISR were significantly associated with antibody levels after the fourth dose (geometric mean ratio = 2.56; 95% confidence interval 1.18-5.57). No cases of IBD flare occurred., Discussion: SARS-CoV-2 vaccines are safe for those with IBD. ISR after the fourth dose may indicate increased antibodies., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Introduction: Among the objectives in treatments with yttrium-90 spheres, is to demonstrate that the tumoricidal dose is achieved and that hepatotoxic doses are avoided, as well as that there is no extrahepatic deposition., Material and Methods: We use different amounts of yttrium-90 resin micro-spheres and a NEMA NU2-2007 phantom to check if the scanner maintains a response that allows real dosimetric calculations., Results: The Gemini tomograph responds linearly in a wide range of activities with R 2  = 0.9983., Conclusion: The detection capacity of the PET equipment allows us to carry out standard body studies with dosimetric purposes with times of five minutes per bed. It also make possible to verify the absence of extrahepatic deposition of significant amounts of yttrium 90 spheres., (Copyright © 2022 Sociedad Española de Medicina Nuclear e Imagen Molecular. Published by Elsevier España, S.L.U. All rights reserved.)

Deep learning techniques are being increasingly used in the scientific community as a consequence of the high computational capacity of current systems and the increase in the amount of data available as a result of the digitalisation of society in general and the industrial world in particular. In addition, the immersion of the field of edge computing, which focuses on integrating artificial intelligence as close as possible to the client, makes it possible to implement systems that act in real time without the need to transfer all of the data to centralised servers. The combination of these two concepts can lead to systems with the capacity to make correct decisions and act based on them immediately and in situ. Despite this, the low capacity of embedded systems greatly hinders this integration, so the possibility of being able to integrate them into a wide range of micro-controllers can be a great advantage. This paper contributes with the generation of an environment based on Mbed OS and TensorFlow Lite to be embedded in any general purpose embedded system, allowing the introduction of deep learning architectures. The experiments herein prove that the proposed system is competitive if compared to other commercial systems.

A 5-day in vivo rat model was evaluated as an approach to estimate chemical exposures that may pose minimal risk by comparing benchmark dose (BMD) values for transcriptional changes in the liver and kidney to BMD values for toxicological endpoints from traditional toxicity studies. Eighteen chemicals, most having been tested by the National Toxicology Program in 2-year bioassays, were evaluated. Some of these chemicals are potent hepatotoxicants (eg, DE71, PFOA, and furan) in rodents, some exhibit toxicity but have minimal hepatic effects (eg, acrylamide and α,β-thujone), and some exhibit little overt toxicity (eg, ginseng and milk thistle extract) based on traditional toxicological evaluations. Male Sprague Dawley rats were exposed once daily for 5 consecutive days by oral gavage to 8-10 dose levels for each chemical. Liver and kidney were collected 24 h after the final exposure and total RNA was assayed using high-throughput transcriptomics (HTT) with the rat S1500+ platform. HTT data were analyzed using BMD Express 2 to determine transcriptional gene set BMD values. BMDS was used to determine BMD values for histopathological effects from chronic or subchronic toxicity studies. For many of the chemicals, the lowest transcriptional BMDs from the 5-day assays were within a factor of 5 of the lowest histopathological BMDs from the toxicity studies. These data suggest that using HTT in a 5-day in vivo rat model provides reasonable estimates of BMD values for traditional apical endpoints. This approach may be useful to prioritize chemicals for further testing while providing actionable data in a timely and cost-effective manner., (Published by Oxford University Press on behalf of the Society of Toxicology 2020. This work is written by US Government employees and is in the public domain in the US.)