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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.)

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.)

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.)

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.)

Background & Aims: Sexual transmission of hepatitis C virus (HCV) is well documented among human immunodeficiency virus (HIV)-uninfected individuals. The use of HIV pre-exposure prophylaxis (PrEP) may be associated with engagement in activities that facilitate the transmission of sexually transmitted infections (STIs) and possibly HCV among PrEP users., Methods: Between 2012 and 2019, the incidence of HCV and bacterial STIs were calculated among HIV-negative indviduals receiving PrEP at the University Health Network HIV Prevention Clinic. Mucosal, anal, and blood samples were taken to test for HIV, syphilis, and anti-HCV antibodies., Results: Among 344 HIV-uninfected patients receiving PrEP, 86% were men having sex with men (MSM). Five individuals were HCV-antibody positive at the time of PrEP initiation. Serologic and virologic follow-up data were available for 109 HCV-negative individuals over 282 patient-years (PY). Two new infections were recorded, yielding an incidence of primary HCV infection of 0.7 per 100 PY. In contrast with HCV, the incidence rates of chlamydia, gonorrhea, and syphilis were 49.2 per 100 PY, 36.3 per 100 PY, and 5.2 per 100 PY, respectively. Both individuals with new HCV diagnoses reported being MSM with a history of unprotected intercourse and 1 individual also reported recreational drug use. Both individuals were asymptomatic at the time of diagnosis and the infections were detected by routine laboratory monitoring., Conclusions: The low incidence of HCV infections despite significantly higher rates of other STIs suggests that sexual transmission of HCV is uncommon in HIV-negative MSM PrEP users in this community. Performing routine risk-based HCV surveillance among PrEP users should be evaluated. The high incidence of STIs in this population indicates a vital role for periodic STI monitoring in those receiving PrEP., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: To systematically evaluate the prevalence of disclosed and undisclosed financial conflicts of interest (FCOI) among clinical practice guidelines (CPGs)., Methods: In this systematic review, we ascertained the prevalence and types of FCOI for CPGs from January 1, 1980, to March 3, 2019. The primary outcome was the prevalence of FCOI among authors of CPGs. FCOI disclosures were compared between medical subspecialties and societies producing CPGs., Results: Among the 37 studies including 14,764 total guideline authors, 45% had at least one FCOI. The prevalence of FCOI per study ranged from 6% to 100%. More authors had FCOI involving general payments (39%) compared with research payments (29%). Oncology, neurology, and gastroenterology had the highest prevalence of FCOI compared with other medical specialties. Among the 8 studies that included the monetary values in US dollars of FCOI, average payments per author ranged from $578 to $242,300. Among the 10 studies that included data on undisclosed FCOI, 32% of authors had undisclosed industry payments., Conclusion: There are numerous FCOI among authors of CPGs, many of which are undisclosed . Our study found a significant difference in FCOI prevalence based on types of FCOI and CPG sponsor society. Additional research is required to quantify the implications of FCOI on clinical judgment and patient care., (© 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc.)

Competing Interests: Conflicts of interest: All authors declare no conflict of interest due to financial or personal relationships that could potentially bias this work.

Introduction: De-escalation of biologic therapy is a commonly encountered clinical scenario. Although biologic discontinuation has been associated with high rates of relapse, the effectiveness of dose de-escalation is unclear. This review was performed to determine the effectiveness of dose de-escalation of biologic therapy in inflammatory bowel disease., Methods: We searched EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials from inception to October 2019. Randomized controlled trials and observational studies involving dose de-escalation of biologic therapy in adults with inflammatory bowel disease in remission were included. Studies involving biologic discontinuation only and those lacking outcomes after dose de-escalation were excluded. Risk of bias was assessed using the Newcastle-Ottawa Scale., Results: We identified 1,537 unique citations with 20 eligible studies after full-text review. A total of 995 patients were included from 18 observational studies (4 prospective and 14 retrospective), 1 nonrandomized controlled trial, and 1 subgroup analysis of a randomized controlled trial. Seven studies included patients with Crohn's disease, 1 included patients with ulcerative colitis, and 12 included both. Overall, clinical relapse occurred in 0%-54% of patients who dose de-escalated biologic therapy (17 studies). The 1-year rate of clinical relapse ranged from 7% to 50% (6 studies). Eighteen studies were considered at high risk of bias, mostly because of the lack of a control group., Discussion: Dose de-escalation seems to be associated with high rates of clinical relapse; however, the quality of the evidence was very low. Additional controlled prospective studies are needed to clarify the effectiveness of biologic de-escalation and identify predictors of success.

[This corrects the article DOI: 10.1159/000454979.]., (Copyright © 2017 by S. Karger AG, Basel.)

Key Points: A high-fat diet (60% kcal from fat) is associated with motility disorders inducing constipation and loss of nitrergic myenteric neurons in the proximal colon. Gut microbiota dysbiosis, which occurs in response to HFD, contributes to endotoxaemia. High levels of lipopolysaccharide lead to apoptosis in cultured myenteric neurons that express Toll-like receptor 4 (TLR4). Consumption of a Western diet (WD) (35% kcal from fat) for 6 weeks leads to gut microbiota dysbiosis associated with altered bacterial metabolites and increased levels of plasma free fatty acids. These disorders precede the nitrergic myenteric cell loss observed in the proximal colon. Mice lacking TLR4 did not exhibit WD-induced myenteric cell loss and dysmotility. Lipopolysaccharide-induced in vitro enteric neurodegeneration requires the presence of palmitate and may be a result of enhanced NO production. The present study highlights the critical role of plasma saturated free fatty acids that are abundant in the WD with respect to driving enteric neuropathy and colonic dysmotility., Abstract: The consumption of a high-fat diet (HFD) is associated with myenteric neurodegeneration, which in turn is associated with delayed colonic transit and constipation. We examined the hypothesis that an inherent increase in plasma free fatty acids (FFA) in the HFD together with an HFD-induced alteration in gut microbiota contributes to the pathophysiology of these disorders. C57BL/6 mice were fed a Western diet (WD) (35% kcal from fat enriched in palmitate) or a purified regular diet (16.9% kcal from fat) for 3, 6, 9 and 12 weeks. Gut microbiota dysbiosis was investigated by fecal lipopolysaccharide (LPS) measurement and metabolomics (linear trap quadrupole-Fourier transform mass spectrometer) analysis. Plasma FFA and LPS levels were assessed, in addition to colonic and ileal nitrergic myenteric neuron quantifications and motility. Compared to regular diet-fed control mice, WD-fed mice gained significantly more weight without blood glucose alteration. Dysbiosis was exhibited after 6 weeks of feeding, as reflected by increased fecal LPS and bacterial metabolites and concomitant higher plasma FFA. The numbers of nitrergic myenteric neurons were reduced in the proximal colon after 9 and 12 weeks of WD and this was also associated with delayed colonic transit. WD-fed Toll-like receptor 4 (TLR4) -/- mice did not exhibit myenteric cell loss or dysmotility. Finally, LPS (0.5-2 ng·ml -1 ) and palmitate (20 and 30 μm) acted synergistically to induce neuronal cell death in vitro, which was prevented by the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester. In conclusion, WD-feeding results in increased levels of FFA and microbiota that, even in absence of hyperglycaemia or overt endotoxaemia, synergistically induce TLR4-mediated neurodegeneration and dysmotility., (© 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.)

Background & Aims: High-fat diet (HFD) feeding is associated with gastrointestinal motility disorders. We recently reported delayed colonic motility in mice fed a HFD mice for 11 weeks. In this study, we investigated the contributing role of gut microbiota in HFD-induced gut dysmotility., Methods: Male C57BL/6 mice were fed a HFD (60% kcal fat) or a regular/control diet (RD) (18% kcal fat) for 13 weeks. Serum and fecal endotoxin levels were measured, and relative amounts of specific gut bacteria in the feces assessed by real time PCR. Intestinal transit was measured by fluorescent-labeled marker and bead expulsion test. Enteric neurons were assessed by immunostaining. Oligofructose (OFS) supplementation with RD or HFD for 5 weeks was also studied. In vitro studies were performed using primary enteric neurons and an enteric neuronal cell line., Results: HFD-fed mice had reduced numbers of enteric nitrergic neurons and exhibited delayed gastrointestinal transit compared to RD-fed mice. HFD-fed mice had higher fecal Firmicutes and Escherichia coli and lower Bacteroidetes compared to RD-fed mice. OFS supplementation protected against enteric nitrergic neurons loss in HFD-fed mice, and improved intestinal transit time. OFS supplementation resulted in a reductions in fecal Firmicutes and Escherichia coli and serum endotoxin levels. In vitro , palmitate activation of TLR4 induced enteric neuronal apoptosis in a p-JNK1 dependent pathway. This apoptosis was prevented by a JNK inhibitor and in neurons from TLR4 -/- mice., Conclusions: Together our data suggest that intestinal dysbiosis in HFD fed mice contribute to the delayed intestinal motility by inducing a TLR4-dependant neuronal loss. Manipulation of gut microbiota with OFS improved intestinal motility in HFD mice.