Publications by authors named "Charles N Bernstein"

453 Publications

Patient Perspectives on the Long-term Management of Celiac Disease.

J Clin Gastroenterol 2021 Jul 30. Epub 2021 Jul 30.

Department of Internal Medicine, Section of Gastroenterology Department of Clinical Health Psychology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba St. Boniface Hospital Research Centre, Winnipeg, MB, Canada Harvard Celiac Research Program, Boston Children's Hospital, Harvard Medical School, Boston, MA.

Goal: The aim of this study was to survey adults with celiac disease (CD) on the utility of specific aspects of follow-up and on information needs.

Background: Currently, the treatment for CD is strict gluten avoidance. Although this places the onus on the patient for disease management, patient perspectives on CD care have not been formally assessed.

Study: The Manitoba Celiac Disease Cohort prospectively enrolled adults newly diagnosed with CD using serology and histology. At the 24-month study visits, participants rated the utility of aspects of CD care on a 5-point scale anchored by "not at all useful" and "very useful" and the helpfulness of information on CD-related topics on a 6-point scale anchored by "not at all helpful" and "very helpful."

Results: The online survey was completed by 149 of 211 cohort members [median age 40 (interquartile range 30 to 56) y; 68% female]. Adherence to a gluten-free diet was good. Most participants (87%) responded that they should be seen regularly for medical follow-up of CD, preferably every 6 (26%) or 12 months (48%). Blood tests were the most highly rated care component (rated scored ≥4/5 by 78% of respondents), followed by the opportunity to ask about vitamins and supplements (50%), symptom review (47%), and information on CD research (44%). Diet review was not considered helpful.

Conclusions: Two years after diagnosis, most individuals with CD find regular specialist follow-up helpful, particularly for biochemical assessment of disease activity and its complications. Furthermore, information on research and long-term complications of CD is also valued.
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http://dx.doi.org/10.1097/MCG.0000000000001584DOI Listing
July 2021

Continued 5ASA use after initiation of anti-TNF or immunomodulator confers no benefit in IBD: a population-based study.

Aliment Pharmacol Ther 2021 Jul 11. Epub 2021 Jul 11.

Division of Gastroenterology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.

Background: With the advent of biological therapy in IBD, it is uncertain to what extent 5aminosalicylates (5ASA) are used.

Aims: To explore whether or not 5ASA is continued once biological or immunomodulator therapy is initiated, and the outcomes in those who continued the 5ASAs.

Methods: We conducted a retrospective cohort study using the population-based University of Manitoba IBD Epidemiologic Database which includes prescription drug dispensation from 1996 through 2018. We assessed outcomes among 5ASA users who continued versus discontinued 5ASA after initiation of anti-TNF therapy or immunomodulators.

Results: In all, 8379 (77%) of persons with IBD received at least one 5ASA dispensation (85% of ulcerative colitis, UC and 68% of Crohn's disease, CD). There was a reduction in later years, particularly for CD. The most common pattern of 5ASA use was intermittent at 65.1% (stopping and restarting use) versus one-time (4.1%), previous continuous (13.8%) and persistent (17%). Among the total IBD population use was 59% oral, 3% rectal and 14% combination. Of all 5ASA starts, only 25% were continued longer than 20 months. After immunomodulator or anti-TNF initiation, there was no difference in either UC or CD for negative outcomes (hospitalisation, surgery, corticosteroid starts, colorectal cancers or drug-related adverse events) between those who continued 5ASA versus those who discontinued.

Conclusions: 5ASA remains commonly prescribed in UC and CD. Rates of persistent use in UC are low. Once an anti-TNF or immunomodulator is initiated, continuation of 5ASA seems to add no benefit.
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http://dx.doi.org/10.1111/apt.16518DOI Listing
July 2021

The impact of the coronavirus (COVID-19) pandemic on individuals with gastrointestinal disorders: A protocol of an international collaborative study.

J Psychosom Res 2021 Jun 29;148:110561. Epub 2021 Jun 29.

Swinburne University of Technology, Melbourne, Victoria, Australia.

Objective: The COVID-19 pandemic has had a significant impact on mental health across the globe. People living with a chronic gastrointestinal (GI) disorder might be particularly at risk of mental health complications given higher rates of comorbid anxiety and depression compared to the healthy population. As GI disorders affect up to 40% of the population worldwide, this international collaborative study seeks to evaluate the extent of the impact of the COVID-19 pandemic on GI symptoms specifically and more generally on the well-being of those living with chronic GI conditions.

Methods: A longitudinal survey with three time points (baseline, 6-month, and 12-month) will be conducted online. Adult participants with GI disorders from multiple countries will be recruited via patient associations, social media advertising, utilizing snowball sampling. Participants will be invited to complete a battery of questionnaires including demographic and health parameters, and measures of gastrointestinal symptoms, fear of COVID-19, perceived impact of COVID-19, illness perceptions, coping, depression, anxiety, stress, catastrophizing, and quality of life, using validated measures where available. Statistical analyses will include univariate descriptive models, multivariate models utilizing regression, mediation, and moderation, and latent growth models.

Conclusions: This project may present novel information to the field of psychogastroenterology and may provide crucial information regarding the areas of impact for individuals with GI disorders during and following the pandemic. Further, this information can guide healthcare providers and patient associations on how to target support related to the pandemic mental health sequelae for these patients.
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http://dx.doi.org/10.1016/j.jpsychores.2021.110561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240440PMC
June 2021

Higher Framingham Risk Scores are associated with greater loss of brain volume over time in multiple sclerosis.

Mult Scler Relat Disord 2021 Jun 17;54:103088. Epub 2021 Jun 17.

Departments of Psychiatry, Psychology & Neuroscience, and Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.

Background: Few studies have evaluated the association between comorbidities associated with increased vascular risk and brain volume changes in multiple sclerosis (MS). To date, findings have not been consistent with respect to which comorbidities are associated with lower brain volumes or whether comorbidities associated with increased vascular risk are associated with greater brain volume loss over time.

Objectives: We aimed to evaluate the association between the Framingham Risk Score (FRS) which evaluates vascular risk and normalized whole brain volume in MS.

Methods: We included 98 participants with MS who underwent two brain MRIs two years apart, from which whole brain volumes were calculated. Each participant reported their comorbidities and medications taken. Blood pressure, height and weight were recorded and we calculated the FRS. We tested the association between the FRS at baseline and brain volume at the second time point using quantile regression adjusting for baseline normalized brain volume, age, gender and use of disease-modifying therapy.

Results: As the FRS increased, brain volume was lower, both at enrollment (β= -0.24; 95%CI: -0.42, -0.04) and at follow-up (-0.27; 95%CI: -0.45, -0.08). After further adjustment for age, gender, and use of disease modifying therapy, higher FRS remained associated with lower brain volume at follow-up at the 90th percentile of brain volume (β= -2.22; 95%CI: -3.40, -1.04) but not at the 10th or 50th percentiles.

Conclusion: Higher FRS were associated with lower brain volumes in persons with MS at baseline, and with brain volume loss over time. This effect was most pronounced for persons with higher brain volumes at baseline, which suggests that prevention, detection and effective management of comorbidities associated with vascular risk in people with MS is particularly important early in the disease course.
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http://dx.doi.org/10.1016/j.msard.2021.103088DOI Listing
June 2021

Inflammatory bowel disease increases the risk of venous thromboembolism in children: a population-based matched cohort study.

J Crohns Colitis 2021 Jun 27. Epub 2021 Jun 27.

SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada.

Background And Aims: Although venous thromboembolism (VTE) is a well-known complication of inflammatory bowel disease (IBD) in adults, limited data exist on the risk in children. We report the incidence of VTE among children with and without IBD.

Methods: We conducted a matched cohort study within a distributed network of population-based Canadian provincial health administrative databases. Children diagnosed with IBD <16 years were identified using validated algorithms from administrative data in Alberta, Manitoba, Nova Scotia, Ontario, and Québec and compared to age- and sex-matched children without IBD. Hospitalizations for VTE within five years of IBD diagnosis were identified. Generalized linear mixed-effects models were used to pool province-specific incidence rates and incidence rate ratios (IRR) with 95% confidence intervals (CI). Hazard ratios (HR) from Cox proportional hazards models were pooled with fixed-effects meta-analysis.

Results: The five-year incidence of VTE among 3593 children with IBD was 31.2 (95%CI 23.7-41.0) per 10,000 person-years (PY) compared to 0.8 (95%CI 0.4-1.7) per 10,000 PY among 16,289 children without IBD (unadjusted IRR 38.84, 95%CI 16.59-90.83; adjusted HR 22.91, 95%CI 11.50-45.63). VTE was less common in Crohn's disease than ulcerative colitis (unadjusted IRR 0.47, 95%CI 0.27-0.83; adjusted HR 0.52, 95%CI 0.29-0.94). Findings were similar for deep vein thrombosis (DVT) and pulmonary embolism (PE) when comparing children with and without IBD.

Conclusions: The risk of VTE is much higher in children with IBD than controls without IBD. While the absolute risk is low, we found a higher incidence rate than previously described in the pediatric literature.
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http://dx.doi.org/10.1093/ecco-jcc/jjab113DOI Listing
June 2021

Comorbidity before and after a diagnosis of inflammatory bowel disease.

Aliment Pharmacol Ther 2021 Jun 22. Epub 2021 Jun 22.

Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada.

Background: Comorbidity is an important predictor of how disease course in inflammatory bowel (IBD) evolves.

Aims: To determine pre-diagnosis relative rates (RR) and post-diagnosis hazard ratios (HR) of component diseases of the Charlson Comorbidity Index (CCI) in a cohort study of persons with IBD.

Methods: The University of Manitoba IBD Epidemiology Database includes all Manitobans with IBD from 1 April 1984 through 31 March 2018 and matched controls. All outpatient physician claims and hospital discharge abstracts were searched for diagnostic codes for CCI component diseases. Some diseases were collapsed into one group such that we assessed 12 conditions. We report the RR of these conditions prior to IBD and the incidence of these diagnoses after IBD. Using Cox proportional hazards regression we report post-diagnosis HR. Confidence intervals were adjusted for Bonferroni correction.

Results: The RR of cardiovascular diseases, peripheral vascular diseases, chronic pulmonary diseases, connective tissue disease/rheumatic diseases, renal disease, liver diseases, peptic ulcer disease, and cancer were all increased prior to diagnoses of IBD compared to controls. All comorbidities were increased post IBD diagnosis. The increased HR for dementia in persons with Crohn's disease was a concerning novel finding. The increased association with paraplegia/hemiplegia was unexpected. For all comorbidities, except diabetes, the age at diagnosis was younger in IBD than controls.

Conclusions: Persons with IBD have a higher comorbidity burden than persons without IBD. Optimal care plans for persons with IBD should include an assessment for other comorbidities that include just about every other organ system.
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http://dx.doi.org/10.1111/apt.16444DOI Listing
June 2021

COVID-19-related personal product shortages are associated with psychological distress in people living with gastrointestinal disorders: A cross-sectional survey.

Neurogastroenterol Motil 2021 Jun 18:e14198. Epub 2021 Jun 18.

Department of Psychological Sciences, Swinburne University of Technology, Victoria, Australia.

Background: The mental health response to the coronavirus (COVID-19) pandemic-related product shortages in those living with chronic gastrointestinal (GI) disorders has received little attention. We aimed to explore the association between the pandemic-related product shortages and psychological distress in people with GI disorders.

Methods: This online cross-sectional survey was nested within an ongoing, international, prospective study of well-being in people with GI disorders. The study was advertised in multiple countries in May-September 2020 via patient organizations and social media. The primary outcome measure was distress, evaluated by the Depression Anxiety Stress Scale. We utilized linear regressions, adjusting for covariates and testing individual moderation effects.

Key Results: Overall, 831 people completed the survey from 27 countries, of whom 82% were female (mean age = 49 years). The most common disorders included inflammatory bowel disease (n = 322), celiac disease (n = 273), and irritable bowel syndrome (n = 260). Significant problems accessing food were reported by 19.8%, non-medical therapies by 16%, toilet paper by 10.8%, and essential medication by 8.9% of the sample (>5% pain medication). There was a positive association between toilet paper and pain medication shortages and distress, and a negative association between food shortages and distress. Significant moderation effects were identified for COVID-19 prevalence and toilet paper and food shortages, and between COVID-19 fear and pain medication shortages.

Conclusions And Inferences: The study documented a significant relationship between product shortages and psychological distress, which were associated with COVID-19 prevalence and fear. Strategies addressing COVID-19 fear could potentially modify the relationship between shortages and distress.
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http://dx.doi.org/10.1111/nmo.14198DOI Listing
June 2021

What Are the Most Challenging Aspects of Inflammatory Bowel Disease? An International Survey of Gastroenterologists Comparing Developed and Developing Countries.

Inflamm Intest Dis 2021 May 5;6(2):78-86. Epub 2021 Feb 5.

Section of Gastroenterology, Max Rady School of Medicine and University of Manitoba IBD Clinical and Research Centre, Winnipeg, Manitoba, Canada.

Background And Aims: As inflammatory bowel disease (IBD) becomes more prevalent, the challenges that gastroenterologists face in managing these patients evolve. We aimed to describe the most important challenges facing gastroenterologists from around the world and compare these between those working in developed and developing countries.

Methods: An online questionnaire was developed, and a link distributed to gastroenterologists. Data were analyzed descriptively using Friedman and Wilcoxon matched-pair signed rank tests to compare rankings for responses. Mann-Whitney tests were used to compare rankings between responses from gastroenterologists from developed and developing countries. Lower scores reflected greater challenges.

Results: Of 872 who started, 397 gastroenterologists (45.5%) completed the survey. Respondents represented 65 countries (226 [56.9%] from developed countries). Overall, the challenge ranked most important (smallest number) was increasing IBD prevalence (13.6%). There were significant differences in mean ranking scores for many simple aspects of care for those from developing countries compared to providers from developed countries, such as access to simple IBD treatments (5.52 vs. 6.02, = 0.01), access to anti-TNF drugs including dose escalation (3.33 vs. 3.93, < 0.01), access to good stoma care (2.57 vs. 3.03, < 0.001), access to therapeutic drug monitoring (1.47 vs. 1.84, < 0.001), and access to care for people from low socioeconomic status (2.77 vs. 3.37, < 0.001).

Conclusions: Increasing IBD prevalence is seen by gastroenterologists as the greatest challenge facing them. There are significant differences between the IBD challenges facing gastroenterologists from developed and developing countries that reflect inequities in access to health care.
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http://dx.doi.org/10.1159/000512310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160566PMC
May 2021

Psychiatric comorbidity in immune-mediated inflammatory diseases.

World Psychiatry 2021 Jun;20(2):298-299

Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.

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http://dx.doi.org/10.1002/wps.20873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129838PMC
June 2021

Uptake of influenza vaccination among persons with inflammatory bowel disease, multiple sclerosis or rheumatoid arthritis: a population-based matched cohort study.

CMAJ Open 2021 Apr-Jun;9(2):E510-E521. Epub 2021 May 14.

Department of Internal Medicine (Marrie, Hitchon, Marriott, Bernstein), Department of Community Health Sciences (Marrie, Lix, Katz), Manitoba Centre for Health Policy (Walld, Katz), Department of Psychiatry (Bolton, Sareen), Department of Family Medicine (Singer, Katz), Department of Clinical Health Psychology (El-Gabalawy) and Department of Anesthesiology and Perioperative and Pain Medicine (El-Gabalawy), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Man.; Department of Community Health Sciences (Patten), Cumming School of Medicine, University of Calgary, Calgary, Alta.; Departments of Psychiatry (Fisk), of Psychology and Neuroscience (Fisk) and of Medicine (Fisk), Dalhousie University, Halifax, NS.

Background: Individuals with immune-mediated inflammatory diseases, such as inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis, are at increased risk for influenza and related complications. We examined and compared the uptake of influenza vaccination among people with and without these diseases, as well as the influence of psychiatric comorbidity on vaccine uptake.

Methods: Using administrative data from Apr. 1, 1984, to Mar. 31, 2016, we conducted a retrospective matched cohort study in Manitoba, Canada. We matched persons 18 years of age or older who had a diagnosis of inflammatory bowel disease, multiple sclerosis or rheumatoid arthritis (the immune-mediated inflammatory disease cohorts) with persons who did not have these diagnoses (the control cohorts) on age, sex and region. We then identified cohort members with any mood or anxiety disorder (depression, anxiety disorders, bipolar disorder). We identified influenza vaccinations through billing codes. Using binomial regression, we modelled the difference in the proportion of the immune-mediated inflammatory disease and matched cohorts vaccinated annually, with adjustment for sociodemographic characteristics, comorbidity and immune therapy. We tested additive interaction effects between a person's cohort and presence of a mood or anxiety disorder.

Results: We identified 32 880 individuals with 1 or more immune-mediated inflammatory diseases (10 148 with inflammatory bowel disease, 6158 with multiple sclerosis and 16 975 with rheumatoid arthritis) and a total of 164 152 controls. In fiscal year 2015, 8668 (41.3%, 95% confidence interval [CI] 40.6% to 42.0%) of the 20 982 persons with an immune-mediated inflammatory disease received an influenza vaccination, a rate higher than among controls (35 238 of 104 634; 33.7%, 95% CI 33.4% to 34.0%). After adjustment, participants with an immune-mediated inflammatory disease but no mood or anxiety disorder had 6.44% (95% CI 5.79% to 7.10%) greater uptake of vaccination than participants without such a disease. Among participants without an immune-mediated inflammatory disease, having a mood or anxiety disorder was associated with 4.54% (95% CI 4.20% to 4.89%) greater uptake of vaccination. However, we observed a subadditive interaction between immune-mediated inflammatory disease and psychiatric status (-1.38%, 95% CI -2.26% to -0.50%).

Interpretation: Uptake of influenza vaccination was consistently low in populations with immune-mediated inflammatory disease, and although psychiatric morbidity is associated with greater vaccine uptake by Manitobans, it negatively interacts with these diseases to reduce uptake. Changes in care delivery are needed to mitigate this gap in care.
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http://dx.doi.org/10.9778/cmajo.20200105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157981PMC
May 2021

Editorial: trends in paediatric inflammatory bowel disease attributable direct costs-authors' reply.

Aliment Pharmacol Ther 2021 06;53(11):1234-1235

IBD Clinical and Research Center, University of Manitoba, Winnipeg, MB, Canada.

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http://dx.doi.org/10.1111/apt.16376DOI Listing
June 2021

Endoscopic evaluation of surgically altered bowel in inflammatory bowel disease: a consensus guideline from the Global Interventional Inflammatory Bowel Disease Group.

Lancet Gastroenterol Hepatol 2021 06 17;6(6):482-497. Epub 2021 Apr 17.

Clinical and Research Centre for Inflammatory Bowel Disease, Clinical Centre ISCARE, Prague, Czech Republic.

The majority of patients with Crohn's disease and a proportion of patients with ulcerative colitis will ultimately require surgical treatment despite advances in diagnosis, therapy, and endoscopic interventions. The surgical procedures that are most commonly done include bowel resection with anastomosis, strictureplasty, faecal diversion, and ileal pouch. These surgical treatment modalities result in substantial alterations in bowel anatomy. In patients with inflammatory bowel disease, endoscopy plays a key role in the assessment of disease activity, disease recurrence, treatment response, dysplasia surveillance, and delivery of endoscopic therapy. Endoscopic evaluation and management of surgically altered bowel can be challenging. This consensus guideline delineates anatomical landmarks and endoscopic assessment of these landmarks in diseased and surgically altered bowel.
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http://dx.doi.org/10.1016/S2468-1253(20)30394-0DOI Listing
June 2021

Use of thiopurines in inflammatory bowel disease: an update.

Intest Res 2021 Apr 15. Epub 2021 Apr 15.

Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India.

Inflammatory bowel disease (IBD), once considered a disease of the Western hemisphere, has emerged as a global disease. As the disease prevalence is on a steady rise, management of IBD has come under the spotlight. 5-Aminosalicylates, corticosteroids, immunosuppressive agents and biologics are the backbone of treatment of IBD. With the advent of biologics and small molecules, the need for surgery and hospitalization has decreased. However, economic viability and acceptability is an important determinant of local prescription patterns. Nearly one-third of the patients in West receive biologics as the first/initial therapy. The scenario is different in developing countries where biologics are used only in a small proportion of patients with IBD. Increased risk of reactivation of tuberculosis and high cost of the therapy are limitations to their use. Thiopurines hence become critical for optimal management of patients with IBD in these regions. However, approximately one-third of patients are intolerant or develop adverse effects with their use. This has led to suboptimal use of thiopurines in clinical practice. This review article discusses the clinical aspects of thiopurine use in patients with IBD with the aim of optimizing their use to full therapeutic potential.
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http://dx.doi.org/10.5217/ir.2020.00155DOI Listing
April 2021

Trends in paediatric inflammatory bowel disease-attributable direct costs: a population-based analysis.

Aliment Pharmacol Ther 2021 06 9;53(11):1201-1208. Epub 2021 Apr 9.

IBD Clinical and Research Center, University of Manitoba, Winnipeg, MB, Canada.

Background: In addition to its morbidities, inflammatory bowel disease (IBD) has a major financial burden on patients and healthcare systems. However, there is a paucity of evidence on IBD-attributable costs in children.

Aims: To determine the trends of IBD-attributable direct costs over time using a population-based analysis.

Methods: Data were extracted from Manitoba Health Provider Claims and other population registry datasets from 1995 to 2017. Children with IBD were matched by age, sex and location with children without IBD. IBD-attributable direct costs were calculated using utilization counts from the administrative data and cost estimates from different sources. Inpatient hospitalisation and outpatient procedure costs were estimated using the resource intensity weight (RIW) that is attached to each record in the data. Costs were expressed in Canadian dollars.

Results: We included 733 (428 with Crohn's disease) prevalent cases who were diagnosed with IBD before the age of 18 years and were followed for 2450 person-years. A matched control group of 6763 persons who were followed for 21 558 person-years was included. The median annual costs of physician services billed per patient increased from $381 (IQR 215-1064) in 1995 to $936 (IQR 579-1932) in 2017 (P < 0.001). The annual medication costs per patient increased from a median of $270 in 1995 to $7944 in 2017 (P < 0.0001). The median annual direct cost per patient was $1810 in 2004 as compared to $14 791 (P < 0.0001) in 2017.

Conclusions: Over two decades, there was a significant increase in the paediatric IBD-attributable direct costs mainly driven by medication costs.
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http://dx.doi.org/10.1111/apt.16358DOI Listing
June 2021

Altered brain structural connectivity in patients with longstanding gut inflammation is correlated with psychological symptoms and disease duration.

Neuroimage Clin 2021 9;30:102613. Epub 2021 Mar 9.

G. Oppenheimer Center for Neurobiology of Stress and Resilience at UCLA, United States; Vatche and Tamar Manoukian Division of Digestive Diseases at UCLA, United States; UCLA Microbiome Center, United States. Electronic address:

Objective: We aimed to identify differences in network properties of white matter microstructure between asymptomatic ulcerative colitis (UC) participants who had a history of chronic gut inflammation, healthy controls (HCs) and a disease control group without gut inflammation (irritable bowel syndrome; IBS).

Design: Diffusion weighted imaging was conducted in age and sex-matched participants with UC, IBS, and HCs (N = 74 each), together with measures of gastrointestinal and psychological symptom severity. Using streamline connectivity matrices and graph theory, we aimed to quantify group differences in brain network connectivity. Regions showing group connectivity differences were correlated with measures showing group behavioral and clinical differences.

Results: UC participants exhibited greater centrality in regions of the somatosensory network and default mode network, but lower centrality in the posterior insula and globus pallidus compared to HCs (q < 0.05). Hub analyses revealed compromised hubness of the pallidus in UC and IBS compared to HCs which was replaced by increased hubness of the postcentral sulcus. Surprisingly, few differences in network matrices between UC and IBS were identified. In UC, centrality measures in the secondary somatosensory cortex were associated with depression (q < 0.03), symptom related anxiety (q < 0.04), trait anxiety (q < 0.03), and symptom duration (q < 0.05).

Conclusion: A history of UC is associated with neuroplastic changes in several brain networks, which are associated with symptoms of depression, trait and symptom-related anxiety, as well as symptom duration. When viewed together with the results from IBS subjects, these findings suggest that chronic gut inflammation as well as abdominal pain have a lasting impact on brain network organization, which may play a role in symptoms reported by UC patients, even when gut inflammation has subsided.
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http://dx.doi.org/10.1016/j.nicl.2021.102613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050027PMC
July 2021

The association between childhood maltreatment and pain catastrophizing in individuals with immune-mediated inflammatory diseases.

J Psychosom Res 2021 Jun 30;145:110479. Epub 2021 Mar 30.

Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Department of Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada. Electronic address:

Objective: Childhood maltreatment is associated with pain catastrophizing. Both childhood maltreatment and pain catastrophizing are prevalent in certain immune-mediated inflammatory disease (IMID) populations. However, it is unknown whether childhood maltreatment contributes to the high rates of pain catastrophizing in IMID cohorts. We assessed the relationship between childhood maltreatment and pain catastrophizing in individuals with IMID, and whether this differed across IMID.

Methods: Between November 2014 and July 2016 we recruited individuals with multiple sclerosis (MS), inflammatory bowel disease (IBD), and rheumatoid arthritis (RA). Participants completed the Childhood Trauma Questionnaire-Short Form, the Pain Catastrophizing Scale, and Hospital Anxiety and Depression Scale. We tested the association between childhood maltreatment and pain catastrophizing using multivariable logistic regression.

Results: We included 577 individuals with IMID (MS: 232, IBD: 215, RA: 130). Overall, 265 (46%) participants with IMID reported any childhood maltreatment, with the most common type of maltreatment being emotional neglect. Childhood maltreatment was associated with pain catastrophizing (OR 3.32; 95% CI 1.89-5.85) independent of other risk factors, including sociodemographics and symptoms of anxiety and depression.

Conclusion: Pain catastrophizing is highly prevalent in our IMID population, and strongly associated with childhood maltreatment in this population. Interventions that consider childhood maltreatment and pain catastrophizing should be incorporated into the clinical management of IMID patients.
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http://dx.doi.org/10.1016/j.jpsychores.2021.110479DOI Listing
June 2021

Dietary gluten avoidance in Canada: a cross-sectional study using survey data.

CMAJ Open 2021 Apr-Jun;9(2):E317-E323. Epub 2021 Apr 1.

Department of Food and Human Nutritional Sciences (Mudryj, Waugh, Slater, Riediger), Faculty of Agricultural and Food Sciences, University of Manitoba; Department of Internal Medicine (Duerksen, Bernstein), Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba; Department of Community Health Sciences (Slater, Riediger), Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Man.

Background: A gluten-free diet (GFD) is required for the management of some conditions, whereas some Canadians may follow a GFD for discretionary reasons. We sought to estimate the prevalence of Canadians who adhere to a GFD, identify factors associated with adherence to a GFD, and describe and compare the location of food preparation and consumption for those who follow a GFD, those who report no dietary avoidances and those reporting other dietary avoidances.

Methods: We used cross-sectional data from the 2015 Canadian Community Health Survey - Nutrition ( = 20 487). Demographic variables included sex, age group, ethnicity, highest level of household education and income adequacy. The relations between respondent characteristics and report of a GFD were estimated using logistic regression. Respondents were further categorized as avoiding dietary gluten, other dietary avoidances and no dietary avoidances.

Results: An estimated 1.9% of Canadians follow a GFD. Women had 2 times higher odds (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.32 to 3.27) of reporting a GFD than men. After adjustment for income adequacy, household education, sex, age group and ethnicity, residents of Ontario and Quebec had about half the odds (OR 0.52, 95% CI 0.31 to 0.87, and OR 0.55, 95% CI 0.32 to 0.94, respectively) of reporting a GFD compared with residents of Atlantic Canada. Canadians who followed a GFD consumed significantly fewer calories from foods prepared at restaurants than both Canadians who reported no dietary avoidances and those who reported dietary avoidances other than gluten. Canadians following a GFD reported that 2.0% (95% CI 1.1% to 2.9%) of their daily kilocalories were from foods prepared at restaurants, compared with 6.7% (95% CI 5.4% to 7.9%) for Canadians reporting 1 or more dietary avoidances other than gluten, and 6.4% (95% CI 6.0% to 6.9%) for those reporting no avoidances.

Interpretation: The estimated 1.9% prevalence of dietary gluten avoidance likely includes individuals with celiac disease, wheat allergies and nonceliac gluten sensitivity, as well as individuals excluding gluten in the management of irritable bowel syndrome or for reasons related to dietary trends. Canadians eating GFDs consume fewer daily calories from restaurant-prepared foods than other Canadians, which may have social implications.
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http://dx.doi.org/10.9778/cmajo.20200082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034255PMC
April 2021

Persistently High Rate of Venous Thromboembolic Disease in Inflammatory Bowel Disease: A Population-Based Study.

Am J Gastroenterol 2021 Jul;116(7):1476-1484

Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.

Introduction: Venous thromboembolism (VTE) is known to be increased in inflammatory bowel disease (IBD). We aimed to determine whether rates of VTE in IBD have reduced over the past 30 years.

Methods: We used the population-based University of Manitoba IBD Epidemiology Database (1984-2018) to determine the incidence of VTE in IBD and the incidence rate ratio vs matched controls. In persons with IBD with and without VTE, we assessed for variables that were associated with an increased risk of VTE on multivariate logistic regression.

Results: The incidence of VTE in the IBD cohort was 7.6% which was significantly greater than in controls (3.3%, P < 0.0001). The overall age-standardized incidence rate of VTE was 433 per 100,000 in IBD and 184 per 100,000 in controls. The incidence of VTE was higher in Crohn's disease (8.4%) than in ulcerative colitis (6.9%, P = 0.0028). The incidence rate ratio in IBD vs controls was 2.36 (95% confidence interval 2.16-2.58). The increased risk was similar in males and females and in Crohn's disease compared with ulcerative colitis. The incidence rate among persons with IBD from 1985 to 2018 decreased very slowly, with annual percent change of -0.7% (P = 0.0003). Hospital admission, high comorbidity, use of antibodies to tumor necrosis factor for less than 3 years up until the time of the VTE, and the combination of steroid and antibodies to tumor necrosis factor increased the risk of VTE.

Discussion: Despite advancements in IBD management in the past 30 years, the rates of VTE have only been slowly decreasing and remain significantly increased compared with controls.
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http://dx.doi.org/10.14309/ajg.0000000000001237DOI Listing
July 2021

Trends in Corticosteroid Use During the Era of Biologic Therapy: A Population-Based Analysis.

Am J Gastroenterol 2021 06;116(6):1284-1293

The Ottawa Hospital IBD Center, University of Ottawa and Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

Introduction: Corticosteroids are effective for inducing clinical remission in inflammatory bowel disease (IBD), but not for maintaining remission. Reducing corticosteroid use and dependence is an important treatment goal since their use is associated with adverse events. The extent to which the improvements in IBD therapy have led to less corticosteroid use in the modern era remains unclear.

Methods: We used the University of Manitoba Inflammatory Bowel Disease Epidemiologic Database to assess the cumulative annual dosing of corticosteroids on a per-patient basis for all persons with IBD in the province of Manitoba between 1997 and 2017. Joinpoint analysis was used to assess for trends in corticosteroid use and to look at variation in the trends over time.

Results: The mean annual exposure to corticosteroids decreased from 419 mg/yr (1997) to 169 mg/yr (2017) for Crohn's disease (CD) (annual decline: 3.8% per year, 95% confidence interval 3.1-4.6) and from 380 to 240 mg/yr in ulcerative colitis (UC) (annual decline: 2.5% per year, 95% confidence interval 2.1-2.8). In CD, there was an acceleration in the rate of decline after 2007 (pre-2007, 1.9% decline per year; after 2007, 5.7% per year); there was no corresponding acceleration in the rate of decline in UC.

Discussion: Corticosteroid use has decreased in both CD and UC over the past 2 decades, becoming more pronounced after 2007 in CD. Potential explanations include introduction and increasing penetrance of biologic therapy in CD and greater awareness of corticosteroid-related adverse events in IBD. Further work is required understand the drivers of persistent corticosteroid use in IBD and how this can be further reduced.
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http://dx.doi.org/10.14309/ajg.0000000000001220DOI Listing
June 2021

Lifetime Prevalence and Comorbidity of Mental Disorders in the Two-wave 2002-2018 Canadian Armed Forces Members and Veterans Mental Health Follow-up Survey (CAFVMHS): Prévalence et Comorbidité de Durée de vie Des Troubles Mentaux Dans l'Enquête de Suivi Sur la Santé Mentale Auprès des Membres des Forces Armées Canadiennes et Des ex-Militaires (ESSMFACM) en Deux Cycles de 2002 à 2018.

Can J Psychiatry 2021 Mar 15:7067437211000636. Epub 2021 Mar 15.

Department of Psychiatry, University of Manitoba, Winnipeg, Manitoba, Canada.

Objective: The current study used the Canadian Armed Forces Members and Veterans Mental Health Follow-up Survey (CAFVMHS) to (1) examine the incidence and prevalence of mental disorders and (2) estimate the comorbidity of mental disorders over the follow-up period.

Method: The CAFVMHS (2018) is a longitudinal study with two time points of assessment. The sample is comprised of 2,941 Canadian Forces members and veterans who participated in the 2002 Canadian Community Health Survey: Canadian Forces Supplement. The World Health Organization Composite International Diagnostic Interview (WHO-CIDI) was utilized to diagnose -IV post-traumatic stress disorder (PTSD), major depressive episode (MDE), generalized anxiety disorder, social anxiety disorder (SAD), and alcohol abuse and dependence. Self-report health professional diagnoses were assessed for attention deficit hyperactivity disorder (ADHD), mania, obsessive compulsive disorder (OCD), and personality disorder. We established weighted prevalence of mental disorders and examined the association between mental disorders using logistic regression.

Results: In 2018, lifetime prevalence of any WHO-CIDI-based or self-reported mental disorder was 58.1%. Lifetime prevalence of any mood or anxiety disorder or PTSD was 54.0% in 2018. MDE (39.9%), SAD (25.7%), and PTSD (21.4%) were the most common mental disorders. There was a substantial increase in new onset or recurrence/persistence of mental disorders between the two measurement points (16-year assessment gap); 2002-2018 period prevalences were 43.5% for mood and anxiety disorder and 16.8% for alcohol abuse or dependence. The prevalence of self-reported ADHD, OCD, any personality disorder, and mania were 3.3%, 3.0%, 0.8%, and 0.8%, respectively. Comorbidity between mental disorders increased over the follow-up.

Conclusions: This study demonstrates a high burden of mental disorders among a large Canadian military and veteran cohort. These findings underscore the importance of prevention and intervention strategies to reduce the burden of mental disorders and alcohol use disorders in these populations.
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http://dx.doi.org/10.1177/07067437211000636DOI Listing
March 2021

Lifetime Prevalence and Comorbidity of Mental Disorders in the Two-wave 2002-2018 Canadian Armed Forces Members and Veterans Mental Health Follow-up Survey (CAFVMHS): Prévalence et Comorbidité de Durée de vie Des Troubles Mentaux Dans l'Enquête de Suivi Sur la Santé Mentale Auprès des Membres des Forces Armées Canadiennes et Des ex-Militaires (ESSMFACM) en Deux Cycles de 2002 à 2018.

Can J Psychiatry 2021 Mar 15:7067437211000636. Epub 2021 Mar 15.

Department of Psychiatry, University of Manitoba, Winnipeg, Manitoba, Canada.

Objective: The current study used the Canadian Armed Forces Members and Veterans Mental Health Follow-up Survey (CAFVMHS) to (1) examine the incidence and prevalence of mental disorders and (2) estimate the comorbidity of mental disorders over the follow-up period.

Method: The CAFVMHS (2018) is a longitudinal study with two time points of assessment. The sample is comprised of 2,941 Canadian Forces members and veterans who participated in the 2002 Canadian Community Health Survey: Canadian Forces Supplement. The World Health Organization Composite International Diagnostic Interview (WHO-CIDI) was utilized to diagnose -IV post-traumatic stress disorder (PTSD), major depressive episode (MDE), generalized anxiety disorder, social anxiety disorder (SAD), and alcohol abuse and dependence. Self-report health professional diagnoses were assessed for attention deficit hyperactivity disorder (ADHD), mania, obsessive compulsive disorder (OCD), and personality disorder. We established weighted prevalence of mental disorders and examined the association between mental disorders using logistic regression.

Results: In 2018, lifetime prevalence of any WHO-CIDI-based or self-reported mental disorder was 58.1%. Lifetime prevalence of any mood or anxiety disorder or PTSD was 54.0% in 2018. MDE (39.9%), SAD (25.7%), and PTSD (21.4%) were the most common mental disorders. There was a substantial increase in new onset or recurrence/persistence of mental disorders between the two measurement points (16-year assessment gap); 2002-2018 period prevalences were 43.5% for mood and anxiety disorder and 16.8% for alcohol abuse or dependence. The prevalence of self-reported ADHD, OCD, any personality disorder, and mania were 3.3%, 3.0%, 0.8%, and 0.8%, respectively. Comorbidity between mental disorders increased over the follow-up.

Conclusions: This study demonstrates a high burden of mental disorders among a large Canadian military and veteran cohort. These findings underscore the importance of prevention and intervention strategies to reduce the burden of mental disorders and alcohol use disorders in these populations.
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March 2021

A Unique Case of Esophagitis in an Immunocompromised Patient.

Gastroenterology 2021 Feb 18. Epub 2021 Feb 18.

Department of Medicine, Max Rady Faculty of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. Electronic address:

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http://dx.doi.org/10.1053/j.gastro.2021.02.037DOI Listing
February 2021

Genetic predictors of gene expression associated with psychiatric comorbidity in patients with inflammatory bowel disease - A pilot study.

Genomics 2021 May 12;113(3):919-932. Epub 2021 Feb 12.

Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, MB, Canada; Department of Electrical and Computer Engineering, University of Manitoba, Winnipeg, MB, Canada; Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. Electronic address:

Background: Inflammatory bowel disease (IBD) affects millions of people in North America, and patients with IBD have a high incidence of psychiatric comorbidities (PC). The genetic mechanisms underlying the link are, in general, poorly understood.

Materials And Methods: A transcriptome-wide association study (TWAS) was performed using genetically regulated gene expression profiles imputed from the genetic profiles of 240 IBD patients in the Manitoba IBD Cohort Study. The imputation was performed using the 44 non-diseased human tissue-specific reference models from the GTEx database. Linear modeling and gene set enrichment analysis were performed to identify genes and pathways that are significantly associated with IBD patients with PC compared to IBD alone in each of the 44 non-diseased human tissues. Finally, an enrichment map was generated to investigate networks of the enriched gene sets associated with IBD patients with PC.

Results: The genes RBPMS in skeletal muscle (adjusted p = 0.05), KCNA5 in the cerebellar hemisphere of the brain (adjusted p = 0.09), GSR, SMIM34A, and LIPT2 in the frontal cortex of the brain (adjusted p = 0.09 for each) were the top genetically regulated genes with a suggestive association with IBD patients with PC. We identified three gene set networks, which include gene sets and pathways with a suggestive association with IBD patients with PC: one with 7 gene sets overlapping in apolipoprotein B mRNA editing subunit genes, one with 3 gene sets including pigmentation gene sets, and the other one with 3 gene sets including peptidyl tyrosine phosphorylation regulation related gene sets.

Conclusions: Our TWAS analysis has identified genes and pathways with a suggestive association with IBD patients with PC. These findings can be potentially used for illustrating the mechanism of developing PC in the patients with IBD and developing diagnosis tool or drug targets for IBD patients with PC.
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http://dx.doi.org/10.1016/j.ygeno.2021.02.001DOI Listing
May 2021

Increased Incidence of Inflammatory Bowel Disease After Hirschsprung Disease: A Population-based Cohort Study.

J Pediatr 2021 Jun 2;233:98-104.e2. Epub 2021 Feb 2.

Children's Hospital of Eastern Ontario (CHEO) Inflammatory Bowel Disease Center, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Eastern Ontario, Ontario, Canada; CHEO Research Institute, Ottawa, Ontario, Canada; ICES uOttawa, Ottawa, Ontario, Canada; Department of Pediatrics and School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada.

Objective: To determine the frequency with which inflammatory bowel disease (IBD) is diagnosed in persons with Hirschsprung disease in population-based datasets from 3 Canadian provinces.

Study Design: In study I, Ontario data were used to assess the incidence of IBD in a birth cohort of children with Hirschsprung disease relative to children without Hirschsprung disease. In study II, a case-control design was used in Alberta and Manitoba to determine the frequency of previously diagnosed Hirschsprung disease in persons with IBD, compared with the frequency of Hirschsprung disease in matched controls. Validated algorithms for Hirschsprung disease and IBD were applied to each provincial health registry.

Results: In study I, of the 716 children diagnosed with Hirschsprung disease in Ontario since 1991, 18 (2.5%) ultimately developed IBD (168.8 per 100 000 person-years), compared with 7109 of 3 377 394 children without Hirschsprung disease (0.2%, 14.2 per 100 000 person-years). The percentage of males with post-Hirschsprung disease IBD was 77.8%. The incidence rate ratio was 11.9 (95% CI, 7.5-18.8). In study II, the OR of having had Hirschsprung disease before a diagnosis of IBD compared with controls was 74.9 (95% CI, 17.1-328.7) in Alberta and 23.8 (95% CI, 4.6-123) in Manitoba. Crohn's disease was more common after Hirschsprung disease than ulcerative colitis.

Conclusions: IBD can emerge in more than 2% of patients with Hirschsprung disease and, like Hirschsprung disease itself, is more common in males. IBD is much more common after a diagnosis of Hirschsprung disease than in the general population.
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http://dx.doi.org/10.1016/j.jpeds.2021.01.060DOI Listing
June 2021

Pancreastatin Reduces Alternatively Activated Macrophages, Disrupts the Epithelial Homeostasis and Aggravates Colonic Inflammation. A Descriptive Analysis.

Biomedicines 2021 Feb 1;9(2). Epub 2021 Feb 1.

Department of Immunology, University of Manitoba, Winnipeg, MB R3E 0T5, Canada.

Ulcerative colitis (UC) is characterized by modifying alternatively activated macrophages (AAM) and epithelial homeostasis. Chromogranin-A (CHGA), released by enterochromaffin cells, is elevated in UC and is implicated in inflammation progression. CHGA can be cleaved into several derived peptides, including pancreastatin (PST), which is involved in proinflammatory mechanisms. Previously, we showed that the deletion of decreased the onset and severity of colitis correlated with an increase in AAM and epithelial cells' functions. Here, we investigated PST activity in colonic biopsies of participants with active UC and investigated PST treatment in dextran sulfate sodium (DSS)-induced colitis using mice, macrophages, and a human colonic epithelial cells line. We found that the colonic protein expression of PST correlated negatively with mRNA expression of AAM markers and tight junction (TJ) proteins and positively with mRNA expression of interleukin (IL)-8, IL18, and collagen in human. In a preclinical setting, intra-rectal administration of PST aggravated DSS-induced colitis by decreasing AAM's functions, enhancing colonic collagen deposition and disrupting epithelial homeostasis in and mice. This effect was associated with a significant reduction in AAM markers, increased colonic IL-18 release, and decreased TJ proteins' gene expression. In vitro, PST reduced and AAM polarization and decreased anti-inflammatory mediators' production. Conditioned medium harvested from PST-treated and AAM reduced Caco-2 cell migration, viability, proliferation, and mRNA levels of TJ proteins and increased oxidative stress-induced apoptosis and proinflammatory cytokines release. In conclusion, PST is a CHGA proinflammatory peptide that enhances the severity of colitis and the inflammatory process via decreasing AAM functions and disrupting epithelial homeostasis.
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http://dx.doi.org/10.3390/biomedicines9020134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912769PMC
February 2021

Performance of Regression-Based Norms for Cognitive Functioning of Persons With Multiple Sclerosis in an Independent Sample.

Front Neurol 2020 14;11:621010. Epub 2021 Jan 14.

Department of Psychology & Neuroscience, Dalhousie University, Halifax, NS, Canada.

Cognitive impairment is common in multiple sclerosis (MS). Interpretation of neuropsychological tests requires the use of normative data. Traditionally, normative data have been reported for discrete categories such as age. More recently continuous norms have been developed using multivariable regression equations that account for multiple demographic factors. Regression-based norms have been developed for use in the Canadian population for tests included in the MACFIMS and BICAMS test batteries. Establishing the generalizability of these norms is essential for application in clinical and research settings. We aimed to (i) test the performance of previously published Canadian regression-based norms in an independently collected sample of Canadian healthy controls; (ii) compare the ability of Canadian and non-Canadian regression-based norms to discriminate between healthy controls and persons with MS; and (iii) develop regression-based norms for several cognitive tests drawn from batteries commonly used in MS that incorporated race/ethnicity in addition to age, education, and sex. We included 93 adults with MS and 96 healthy adults in this study, with a replication sample of 104 (MS) and 39 (healthy adults). Participants reported their sociodemographic characteristics, and each was administered the oral Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test (CVLT-II), and the Brief Visuospatial Memory Test-Revised (BVMT-R). From the healthy control data, we developed regression-based norms incorporating race, age, education and sex. We then applied existing discrete norms and regression-based norms for the cognitive tests to the healthy controls, and generated z-scores which were compared using Spearman rank and concordance coefficients. We also used receiver operating characteristic (ROC) curves to compare the ability of each set of norms to discriminate between participants with and without MS. Within the MS samples we compared the ability of each set of norms to discriminate between differing levels of disability and employment status using relative efficiency. When we applied the published regression norms to our healthy sample, impairment classification rates often differed substantially from expectations (7%), even when the norms were derived from a Canadian (Ontario) population. Most, but not all of the Spearman correlations between z-scores based on different existing published norms for the same cognitive test exceeded 0.90. However, concordance coefficients were often lower. All of the norms for the SDMT reliably discriminated between the MS and healthy control groups. In contrast, none of the norms for the CVLT-II or BVMT-R discriminated between the MS and healthy control groups. Within the MS population, the norms varied in their ability to discriminate between disability levels or employment status; locally developed norms for the SDMT and CVLT-II had the highest relative efficiency. Our findings emphasize the value of local norms when interpreting the results of cognitive tests and demonstrate the need to consider and assess the performance of regression-based norms developed in other populations when applying them to local populations, even when they are from the same country. Our findings also strongly suggest that the development of regression-based norms should involve larger, more diverse samples to ensure broad generalizability.
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http://dx.doi.org/10.3389/fneur.2020.621010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840703PMC
January 2021

The Relationship Between Symptoms of Depression and Anxiety and Disease Activity in IBD Over Time.

Inflamm Bowel Dis 2021 Jul;27(8):1285-1293

Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, CANADA.

Brackground: We aimed to examine associations between elevated symptoms of depression and anxiety and disease activity in inflammatory bowel disease (IBD). Previous findings have been inconsistent and have not accounted for variability in the courses of these conditions over time.

Methods: We followed 247 participants with IBD (153 Crohn's disease [CD], 94 ulcerative colitis [UC]) for 3 years. Annually, participants underwent an abdominal examination, reported therapies used for IBD, and completed the Hospital Anxiety and Depression Scale (HADS) questionnaire. We evaluated associations of elevated symptoms (scores ≥11) of anxiety (HADS-A) and depression (HADS-D) with the presence of active IBD as measured using the Powell Tuck Index for UC and the Harvey-Bradshaw Disease Activity Index for CD. We employed logistic regression with generalized estimating equations, simultaneously estimating between-person and within-person effects.

Results: Of 247 participants, 15 (6.1%) had elevated symptoms of depression (HADS-D ≥11) at enrollment, 41 (16.6%) had elevated symptoms of anxiety (HADS-A ≥11), and 101 (40.9%) had active IBD. On average, individuals with elevated symptoms of depression (odds ratio [OR], 6.27; 95% CI, 1.39-28.2) and anxiety (OR, 2.17; 95% CI, 1.01-4.66) had increased odds of active IBD. Within individuals, elevations in symptoms of depression over time were associated with increased odds of active IBD (OR, 2.70; 95% CI, 1.15-6.34), but elevated symptoms of anxiety were not. After adjustment for covariates (including disease activity), elevated symptoms of depression were also associated with increased odds of biologic therapy use (OR, 2.02; 95% CI, 1.02-4.00).

Conclusion: Symptoms of depression and anxiety are associated with disease activity in IBD over time. Reducing these symptoms should be incorporated into the management of IBD.
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http://dx.doi.org/10.1093/ibd/izaa349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8314114PMC
July 2021

A Rare Complication of Pancreatitis.

Gastroenterology 2021 Apr 17;160(5):1479-1480. Epub 2020 Dec 17.

Department of Medicine, Max Rady Faculty of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. Electronic address:

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http://dx.doi.org/10.1053/j.gastro.2020.12.022DOI Listing
April 2021

Neuregulin-1 beta 1 is implicated in pathogenesis of multiple sclerosis.

Brain 2021 02;144(1):162-185

Department of Physiology and Pathophysiology, Regenerative Medicine Program, Spinal Cord Research Centre, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.

Multiple sclerosis is characterized by immune mediated neurodegeneration that results in progressive, life-long neurological and cognitive impairments. Yet, the endogenous mechanisms underlying multiple sclerosis pathophysiology are not fully understood. Here, we provide compelling evidence that associates dysregulation of neuregulin-1 beta 1 (Nrg-1β1) with multiple sclerosis pathogenesis and progression. In the experimental autoimmune encephalomyelitis model of multiple sclerosis, we demonstrate that Nrg-1β1 levels are abated within spinal cord lesions and peripherally in the plasma and spleen during presymptomatic, onset and progressive course of the disease. We demonstrate that plasma levels of Nrg-1β1 are also significantly reduced in individuals with early multiple sclerosis and is positively associated with progression to relapsing-remitting multiple sclerosis. The functional impact of Nrg-1β1 downregulation preceded disease onset and progression, and its systemic restoration was sufficient to delay experimental autoimmune encephalomyelitis symptoms and alleviate disease burden. Intriguingly, Nrg-1β1 therapy exhibited a desirable and extended therapeutic time window of efficacy when administered prophylactically, symptomatically, acutely or chronically. Using in vivo and in vitro assessments, we identified that Nrg-1β1 treatment mediates its beneficial effects in EAE by providing a more balanced immune response. Mechanistically, Nrg-1β1 moderated monocyte infiltration at the blood-CNS interface by attenuating chondroitin sulphate proteoglycans and MMP9. Moreover, Nrg-1β1 fostered a regulatory and reparative phenotype in macrophages, T helper type 1 (Th1) cells and microglia in the spinal cord lesions of EAE mice. Taken together, our new findings in multiple sclerosis and experimental autoimmune encephalomyelitis have uncovered a novel regulatory role for Nrg-1β1 early in the disease course and suggest its potential as a specific therapeutic target to ameliorate disease progression and severity.
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http://dx.doi.org/10.1093/brain/awaa385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880664PMC
February 2021

The Impact of Psychiatric Comorbidity on Health Care Utilization in Inflammatory Bowel Disease: A Population-based Study.

Inflamm Bowel Dis 2020 Dec 4. Epub 2020 Dec 4.

Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.

Background: Inflammatory bowel disease (IBD) is associated with an increase in psychiatric comorbidity (PC) compared with the general population. We aimed to determine the impact of PC on health care utilization in persons with IBD.

Methods: We applied a validated administrative definition of IBD to identify all Manitobans with IBD from April 1, 2006, to March 31, 2016, and a matched cohort without IBD. A validated definition for PC in IBD population was applied to both cohorts; active PC status meant ≥2 visits for psychiatric diagnoses within a given year. We examined the association of active PC with physician visits, inpatient hospital days, proportion with inpatient hospitalization, and use of prescription IBD medications in the following year. We tested for the presence of a 2-way interaction between cohort and PC status.

Results: Our study matched 8459 persons with IBD to 40,375 controls. On crude analysis, IBD subjects had ≥3.7 additional physician visits, had >1.5 extra hospital days, and used 2.1 more drug types annually than controls. Subjects with active PC had >10 more physician visits, had 3.1 more hospital days, and used >6.3 more drugs. There was a synergistic effect of IBD (vs no IBD) and PC (vs no PC) across psychiatric disorders of around 4%. This synergistic effect was greatest for anxiety (6% [2%, 9%]). After excluding psychiatry-related visits and psychiatry-related hospital stays, there remained an excess health care utilization in persons with IBD and PC.

Conclusion: Inflammatory bowel disease with PC increases health care utilization compared with matched controls and compared with persons with IBD without PC. Active PC further increases health care utilization.
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http://dx.doi.org/10.1093/ibd/izaa310DOI Listing
December 2020
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