The impact of source and consumption of news on mental distress among inflammatory bowel disease patients during the COVID-19 pandemic.

Background: We sought to understand the trends in media use, and how consumption and source affected mental health of persons with inflammatory bowel disease during the early parts of the pandemic. Dissemination of news during the coronavirus disease 2019 (COVID-19) pandemic was integral to educating the public but also could be harmful if constantly consumed, leading to worsening anxiety. Methods: We performed a survey study in autumn 2020 during the second wave of COVID-19 in Manitoba. The survey included questions on consumption of COVID-19 news, along with validated measures of perceived stress, generalized anxiety, health anxiety, and depression. We used multivariable logistic regression analysis to assess trusted sources of news as a predictor of clinically significant mental health symptoms. Results: Of the 2940 participants in the registry, 1384 (47.1%) persons responded. The most trusted sources of news were television (64.2%), internet (46.1%), newspaper (27.6%), friends/family (21.7%), social media (16.9%), and radio (16.6%). Those who trusted social media had higher odds of depression (aOR 1.52, 95%CI 1.04-2.22), and perceived stress (aOR 2.56, 95%CI 1.09-2.21). Persons who reported extreme difficulty limiting their time-consuming news about COVID-19 and who spent more than 1 h daily consuming information on COVID-19 both had increased odds of any clinically significant mental health symptoms. Conclusions: It is unknown if consumption of COVID-19 news led to heightened mental health symptoms or if increasing anxieties and concerns led to consuming more news. Further research is needed to assess whether these elevated mental health symptoms led to worse disease outcomes.

When Should I Get My Next COVID Vaccine? Data from the SUrveillance of responses to COVID-19 vaCcines in systEmic immunE mediated inflammatory Diseases (SUCCEED)study.

OBJECTIVE: To determine how serologic responses to COVID vaccination/infection in immunemediated inflammatory disease (IMID) are affected by time since last vaccination and other factors. METHODS: Post-COVID-19 vaccination, data and dried blood spots/sera were collected from adults with rheumatoid arthritis, inflammatory bowel disease, systemic lupus, ankylosing spondylitis/spondylarthritis and psoriasis/psoriatic arthritis. First sample was at enrolment and then 2-4 weeks and 3, 6, and 12 months after latest vaccine dose. Multivariate generalized estimating equation regressions (including medications, demographics, and vaccination history) evaluated serologic response, based on log-transformed anti-RBD IgG titres; we also measured anti-nucleocapsid IgG. RESULTS: Positive associations for log-transformed anti-RBD titres were seen with female sex, number of doses, and self-reported COVID infections in 2021-2023. Negative associations were seen with prednisone, anti-TNF agents, and rituximab.Over 2021-2023, most (94%) of anti-nucleocapsid positivity was associated with a self-reported infection in the 3 months prior. From March 2021 to Feb 2022, anti-nucleocapsid positivity was present in 5-15% of samples and was highest in the post-Omicron era, with anti-nucleocapsid positivity trending to 30-35% or higher as of March 2023. Anti-nucleocapsid positivity in IMID remained lower than Canada's general population seroprevalence (>50% in 2022 and >75% in 2023).Time since last vaccination was negatively associated with log-transformed anti-RBD titres, particularly after 210 days. CONCLUSION: Ours is the first pan-Canadian IMID assessment of how vaccine history and other factors affect serologic COVID-19 vaccine responses. These findings may help individuals personalize vaccination decisions, including consideration of additional vaccination when >6 months has elapsed since last COVID vaccination/infection.

Assessment of dietary intake and its inflammatory potential in persons with pediatric-onset multiple sclerosis.

OBJECTIVE: To compare diet and the modified dietary inflammatory index (mDII) between individuals with pediatric-onset multiple sclerosis (PoMS), monophasic acquired demyelinating syndromes (monoADS), and controls. METHODS: The association between diet, mDII, and disease status was examined in 131 individuals with PoMS/monoADS/controls (38/45/48) using logistic regression. RESULTS: The associations between diet and PoMS were modest, reaching significance for whole grain intake (adjusted odds ratio, aOR=0.964, 95 % confidence intervals, CI:0.934-0.995) but not mDII (aOR=1.20, 95 %CI:0.995-1.46) versus controls. No findings for monoADS reached significance versus controls. CONCLUSIONS: Individuals with PoMS, but not monoADS, had lower dietary whole grain intake than controls.

Crohn's Disease Phenotypes and Associations With Comorbidities, Surgery Risk, Medications and Nonmedication Approaches: The MAGIC in IMAGINE Study.

BACKGROUND: We aimed to establish a cohort of persons with Crohn's disease (CD) enrolled from 14 Canadian centers to describe the contemporary presentation of CD in Canada. METHODS: All enrollees were at least 18 years old and underwent chart review for phenotype documentation by Montreal Classification at time of enrollment, comorbidities, inflammatory bowel disease (IBD) and other surgeries, and use IBD and other therapies. RESULTS: Of 2112 adults, 59% were female, and the mean age was 44.1 (+/-14.9SD) years. The phenotype distribution was B1 = 50.4%, B2 = 22.4%, B3 = 17.3%, and missing information = 9.9%. Perineal disease was present in 14.2%. Pertaining to disease location, 35.2% of patients had disease in L1, 16.8% in L2, 48% in L3, and 0.4% in L4. There was no difference in phenotype by gender, anxiety score, depression score. Disease duration was significantly different depending on disease behavior type (B1 = 12.2 ±â€…10.1; B2 = 19.4 ±â€…12.9; B3 = 18.9 ±â€…11.8, P < .0001). Isolated colonic disease was much less likely to be fibrostenotic or penetrating than inflammatory disease. Penetrating disease was more likely to be associated with ileocolonic location than other locations. Perineal disease was most commonly seen in persons with B3 disease behavior (24%) than other behaviors (11% B1; 20% B2 disease, P < .0001) and more likely to be seen in ileocolonic disease (L3;19%) vs L2 (17%) and L1 (11%; P < .0001). Surgery related to IBD occurred across each behavior types at the following rates: B1 = 23%, B2 = 64%, and B3 = 74%. Inflammatory bowel disease-related surgery rates by location of disease were L1 = 48%, L2 = 21%, and L3 = 51%. CONCLUSIONS: In exploring this large contemporary CD cohort we have determined that inflammatory disease is the main CD phenotype in Canada and that CD-related surgery remains very common.

Dynamic Prediction of Advanced Colorectal Neoplasia in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Colonoscopic surveillance is recommended in patients with colonic inflammatory bowel disease (IBD) given their increased risk of colorectal cancer (CRC). We aimed to develop and validate a dynamic prediction model for the occurrence of advanced colorectal neoplasia (aCRN, including high-grade dysplasia and CRC) in IBD. METHODS: We pooled data from 6 existing cohort studies from Canada, The Netherlands, the United Kingdom, and the United States. Patients with IBD and an indication for CRC surveillance were included if they underwent at least 1 follow-up procedure. Exclusion criteria included prior aCRN, prior colectomy, or an unclear indication for surveillance. Predictor variables were selected based on the literature. A dynamic prediction model was developed using a landmarking approach based on Cox proportional hazard modeling. Model performance was assessed with Harrell's concordance-statistic (discrimination) and by calibration curves. Generalizability across surveillance cohorts was evaluated by internal-external cross-validation. RESULTS: The surveillance cohorts comprised 3731 patients, enrolled and followed-up in the time period from 1973 to 2021, with a median follow-up period of 5.7 years (26,336 patient-years of follow-up evaluation); 146 individuals were diagnosed with aCRN. The model contained 8 predictors, with a cross-validation median concordance statistic of 0.74 and 0.75 for a 5- and 10-year prediction window, respectively. Calibration plots showed good calibration. Internal-external cross-validation results showed medium discrimination and reasonable to good calibration. CONCLUSIONS: The new prediction model showed good discrimination and calibration, however, generalizability results varied. Future research should focus on formal external validation and relate predicted aCRN risks to surveillance intervals before clinical application.

Patient preferences for active ulcerative colitis treatments and fecal microbiota transplantation.

Background: Fecal microbiota transplantation (FMT) is a promising treatment for active ulcerative colitis (UC). Understanding patient preferences can identify treatment features that may impact treatment decisions, improve shared decision-making, and contribute to patient-centered care, which is especially important in the context of novel treatments like FMT. Objectives: We aimed to quantify preferences for active UC treatments, specifically FMT and biologics, and identify patient characteristics associated with different preference patterns. Design: This is a cross-sectional survey study. Methods: We administered a discrete choice experiment (DCE) survey to elicit preferences in a sample of Canadian adults with UC. DCE data were analyzed using a main-effects mixed logit model and used to predict uptake of hypothetical scenarios reflecting alternative combinations of treatment features. Latent class modeling identified heterogeneity in patient preference patterns. Results: Participants' (n = 201) mean age was 47.1 years (SD: 14.5 years), 58% were female, and most (84%) had at least some post-secondary education. Almost half were willing to undergo FMT. When considering treatments for active UC, the most important attributes were chance of remission and severity of rare unknown side effects. All else equal, participants were most likely to uptake treatment that involves oral capsules/pills. Participants in the class with the highest utility for chance of remission were younger, had more severe disease, and 58% indicated that they would be willing to undergo FMT. Conclusion: We identified characteristics of UC patients who are more likely to be interested in FMT using preference elicitation methods. Patient-centered care can be enhanced by knowing which patients are more likely to be interested in FMT, potentially improving satisfaction with and adherence to treatments for active UC to maximize the effectiveness of treatment while considering heterogeneity in patient preferences.

Background and aims: Fecal microbiota transplantation (FMT) is a promising new treatment for active ulcerative colitis. Questions remain around the benefits and risks of FMT treatment for patients with ulcerative colitis. Understanding how patients weigh the treatment features and how treatment features influence their decisions may improve shared decision-making and contribute to patient-centered care, which is especially important for novel treatments like FMT.Using an experimentally designed survey, we aimed to:1. Elicit patient preferences for features of active ulcerative colitis treatments, specifically FMT and biologics; and,2. Identify patient characteristics associated with different preference patterns. Results: We found that younger patients with more severe disease are more likely to try FMT for the treatment of active ulcerative colitis. Oral capsules/pills are the preferred mode of treatment administration. Conclusions: These findings can enhance patient-centered care by characterizing patients who are more likely to be interested in FMT. Aligning treatment with the features that are important to patients can potentially improve satisfaction with and adherence to treatments for active ulcerative colitis to maximize their effectiveness for individual patients.

Patient preferences for active ulcerative colitis treatments and fecal microbiota transplantation.

Hormonal Contraceptives Reduce Active Symptomatic Disease but May Increase Intestinal Inflammation in IBD.

BACKGROUND: Among women of reproductive age with inflammatory bowel disease (IBD), we aimed to assess the relationship of hormonal contraceptives (HCs) with IBD-related symptoms, and intestinal inflammation. METHODS: A nested cohort of women in the longitudinal Manitoba Living with IBD Study, ages 18 to 49, were followed for 1 year, with bi-weekly online surveys. This included a validated measure of disease activity; IBD Symptom Inventory (IBDSI), and stool samples obtained at 3 time-points for assessment of fecal calprotectin (FCAL). Use of HC included oral and vaginal intrauterine devices. Logistic regression analysis was used to assess the association between HC and IBD-related symptoms (IBDSI>14 for Crohn disease, >13 for ulcerative colitis), or inflammation (FCAL>250 ug/g) at any measurement point in the study. RESULTS: Of 71 women, 17 (24%) reported taking HC in the 1 year period. Adjusting for age, disease type, disease duration, and smoking status, the odds of having increased IBD-related symptoms (IBDSI) during the year were lower for women using HC compared with women not using HC [adjusted odds ratio 0.16, 95% CI, 0.02-0.90]. Conversely, women using HC were more likely to have inflammation during the year [adjusted odds ratio 5.7, 95% CI, 1.23-43.6]. CONCLUSIONS: HC use among women with IBD was associated with a lower likelihood of IBD-related symptoms but a higher likelihood of experiencing intestinal inflammation (FCAL>250 ug/g) over 1 year. Further work is needed to examine this dichotomous result, potentially examining aspects such as duration of HC use, and the types of HC.

Health Services Utilization and Specialist Care in Pediatric Inflammatory Bowel Disease: A Multiprovince Population-Based Cohort Study.

BACKGROUND: Patterns of health services utilization among children with inflammatory bowel disease (IBD) are important to understand as the number of children with IBD continues to increase. We compared health services utilization and surgery among children diagnosed <10 years of age (Paris classification: A1a) and between 10 and <16 years of age (A1b). METHODS: Incident cases of IBD diagnosed <16 years of age were identified using validated algorithms from deterministically linked health administrative data in 5 Canadian provinces (Alberta, Manitoba, Nova Scotia, Ontario, Quebec) to conduct a retrospective cohort study. We compared the frequency of IBD-specific outpatient visits, emergency department visits, and hospitalizations across age groups (A1a vs A1b [reference]) using negative binomial regression. The risk of surgery was compared across age groups using Cox proportional hazards models. Models were adjusted for sex, rural/urban residence location, and mean neighborhood income quintile. Province-specific estimates were pooled using random-effects meta-analysis. RESULTS: Among the 1165 (65.7% Crohn's) children with IBD included in our study, there were no age differences in the frequency of hospitalizations (rate ratio [RR], 0.88; 95% confidence interval [CI], 0.74-1.06) or outpatient visits (RR, 0.95; 95% CI, 0.78-1.16). A1a children had fewer emergency department visits (RR, 0.70; 95% CI, 0.50-0.97) and were less likely to require a Crohn's-related surgery (hazard ratio, 0.49; 95% CI, 0.26-0.92). The risk of colectomy was similar among children with ulcerative colitis in both age groups (hazard ratio, 0.71; 95% CI, 0.49-1.01). CONCLUSIONS: Patterns of health services utilization are generally similar when comparing children diagnosed across age groups.

Among 1165 children with inflammatory bowel disease, health services utilization was similar for children diagnosed <10 years of age and those diagnosed ≥10 years of age, except younger children had fewer emergency department visits and Crohn's disease­related surgeries.

Ultra-Processed Food, Disease Activity, and Inflammation in Ulcerative Colitis: The Manitoba Living With IBD Study.

INTRODUCTION: The purpose of this study was to investigate the relationship between ultra-processed food (UPF) consumption and (i) symptomatic disease and (ii) intestinal inflammation among adults with inflammatory bowel disease (IBD). METHODS: We identified participants (Crohn's disease [CD] and ulcerative colitis [UC]) from the Manitoba Living with IBD study. Active disease was defined using the IBD Symptom Inventory (score >14 for CD; >13 for UC); fecal calprotectin was measured for intestinal inflammation (>250 µg/g). Diet data were collected using the Harvard Food Frequency Questionnaire. UPF consumption was determined by the NOVA classification system. Percentage of energy consumption from UPFs was calculated and divided into 3 tertiles (T1 = low; T3 = high). Multiple linear regression analysis was used for active disease and inflammation predicted by UPF consumption. RESULTS: Among 135 participants (65% with CD), mean number of episodes of active disease (14.2 vs 6.21) and active inflammation (1.6 vs 0.6) was significantly higher among participants with UC in T3 compared with T1 of UPF consumption ( P < 0.05). When adjusting for age, sex, disease type, and duration, number of episodes of active disease was lower in T1 compared with T3 (ß = -7.11, P = 0.02); similarly, number of episodes of intestinal inflammation was lower in T1 (ß = -0.95, P = 0.03). No significant differences were observed among participants with CD. DISCUSSION: UPF consumption may be a predictor of active symptomatic disease and inflammation among participants with UC. Reducing UPF consumption is a dietary strategy that can be suggested for minimizing symptoms and inflammation among people living with IBD.

Variation in the Care of Children with Inflammatory Bowel Disease Within and Across Canadian Provinces: A Multi-Province Population-Based Cohort Study.

Purpose: The incidence of childhood-onset inflammatory bowel disease (IBD) is rising. We described variation in health services utilization and need for surgery among children with IBD between six and 60 months following IBD diagnosis across Canadian pediatric centers and evaluated the associations between care provided at diagnosis at each center and the variation in these outcomes. Patients and Methods: Using population-based deterministically-linked health administrative data from four Canadian provinces (Alberta, Manitoba, Nova Scotia, Ontario) we identified children diagnosed with IBD <16 years of age using validated algorithms. Children were assigned to a pediatric center of care using a hierarchical approach based on where they received their initial care. Outcomes included IBD-related hospitalizations, emergency department (ED) visits, and IBD-related abdominal surgery occurring between 6 and sixty months after diagnosis. Mixed-effects meta-analysis was used to pool results and examine the association between center-level care provision and outcomes. Results: We identified 3784 incident cases of pediatric IBD, of whom 2937 (77.6%) were treated at pediatric centers. Almost a third (31.4%) of children had ≥1 IBD-related hospitalization and there were 0.66 hospitalizations per person during follow-up. More than half (55.8%) of children had ≥1 ED visit and there were 1.64 ED visits per person. Between-center heterogeneity was high for both outcomes; centers where more children visited the ED at diagnosis had more IBD-related hospitalizations and more ED visits during follow-up. Between-center heterogeneity was high for intestinal resection in Crohn's disease but not colectomy in ulcerative colitis. Conclusion: There is variation in health services utilization among children with IBD and risk of undergoing intestinal resection in those with Crohn's disease, but not colectomy among children with ulcerative colitis, across Canadian pediatric tertiary-care centers. Improvements in clinical care pathways are needed to ensure all children have equitable and timely access to high quality care.

Forecasting the Incidence and Prevalence of Inflammatory Bowel Disease: A Canadian Nationwide Analysis.

INTRODUCTION: Canada has a high burden of inflammatory bowel disease (IBD). Historical trends of IBD incidence and prevalence were analyzed to forecast the Canadian burden over the next decade. METHODS: Population-based surveillance cohorts in 8 provinces derived from health administrative data assessed the national incidence (2007-2014) and prevalence (2002-2014) of IBD. Autoregressive integrated moving average models were used to forecast incidence and prevalence, stratified by age, with 95% prediction intervals (PI), to 2035. The average annual percentage change (AAPC) with 95% confidence interval (CI) was calculated for the forecasted incidence and prevalence. RESULTS: The national incidence of IBD is estimated to be 29.9 per 100,000 (95% PI 28.3-31.5) in 2023. With a stable AAPC of 0.36% (95% CI -0.05 to 0.72), the incidence of IBD is forecasted to be 31.2 per 100,000 (95% PI 28.1-34.3) in 2035. The incidence in pediatric patients (younger than 18 years) is increasing (AAPC 1.27%; 95% CI 0.82-1.67), but it is stable in adults (AAPC 0.26%; 95% CI -0.42 to 0.82). The prevalence of IBD in Canada was 843 per 100,000 (95% PI 716-735) in 2023 and is expected to steadily climb (AAPC 2.43%; 95% CI 2.32-2.54) to 1,098 per 100,000 (95% PI 1,068-1,127) by 2035. The highest prevalence is in seniors with IBD (1,174 per 100,000 in 2023; AAPC 2.78%; 95% CI 2.75-2.81). DISCUSSION: Over the next decade, the Canadian health care systems will contend with the juxtaposition of rising incidence of pediatric IBD and a rising prevalence of overall IBD driven by the aging population.

A randomized trial evaluating the utility of non-targeted biopsies for colorectal neoplasia detection in adults with inflammatory bowel disease: a pilot study protocol.

BACKGROUND: Persons with inflammatory bowel diseases are at increased risk of developing colorectal cancer and require frequent colonoscopy surveillance. Guidelines recommend taking 30 to 40 non-targeted biopsies throughout the colorectum to detect "invisible" neoplasia in this setting, despite a lack of evidence supporting this practice. We sought to assess the utility of this practice through a randomized controlled trial. We first propose an internal pilot study to assess recruitment potential, protocol adherence and data capture to guide the full trial. METHODS: We have designed a multi-centre, parallel-group, non-inferiority randomized controlled trial to test the utility of non-targeted biopsies as an adjunct to colonoscopy surveillance for neoplasia detection in persons with inflammatory bowel disease involving the colorectum in routine clinical practice. Participants are randomized 1:1, stratified by study site, to either standard of care high-definition white-light colonoscopy with 32 to 40 non-targeted biopsies of non-neoplastic-appearing mucosa along with a sampling of abnormal-appearing mucosa (control group) or modified colonoscopy with targeted sampling alone (intervention group). The primary outcome for the full trial will be the proportion of persons with ≥ 1 neoplastic focus detected during colonoscopy. For the pilot phase, we will assess the feasibility of recruiting a minimum of 15% of the estimated sample size within 1 year, under identical conditions as the full trial, while maintaining ≥ 90-95% rate of protocol adherence and data capture. These participants will contribute data to the full trial. The trial is being conducted at 12 centres across Canada, with a total sample size of 1952 persons. DISCUSSIONS: The trial protocol has been approved by the ethics committees of all participating sites, and the pilot study has received funding through the Canadian Institutes of Health Research (PJT 159607). If feasibility metrics are met during the pilot phase, we will complete the full trial. The trial outcomes will contribute to update the practice guidelines in this area. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04067778.

Psychometric Performance of Fatigue Scales in Inflammatory Bowel Disease.

BACKGROUND: Fatigue is highly prevalent in people with inflammatory bowel disease (IBD). Fatigue scales are important for studies testing fatigue interventions, but information about psychometric properties of many scales is insufficient in IBD. We compared the psychometric properties of multiple generic fatigue scales in participants with IBD. METHODS: Individuals with IBD (N = 216) completed the Daily Fatigue Impact Scale (DFIS), the vitality subscale of the RAND-36, and the Patient Health Questionnaire-9 (PHQ-9) fatigue item twice. A subgroup (n = 84) also completed the Fatigue Impact Scale (FIS) once, from which we also scored the 21 items from the Modified Fatigue Impact Scale (MFIS-IBD). We assessed floor/ceiling effects, construct validity, and internal consistency reliability. Using relative efficiency (RE), we compared discriminating ability and comparative responsiveness of the measures regarding disease activity and employment status and changes. RESULTS: The FIS, MFIS, and RAND-36-vitality scales did not exhibit floor or ceiling effects. The DFIS showed mild floor effects (19.4%), and the PHQ-9 fatigue item showed floor (18.1%) and ceiling (20.8%) effects. Internal consistency reliability exceeded 0.93 for FIS, MFIS-IBD, and DFIS and was 0.81 for the RAND-36-vitality scale. In the subgroup analysis, the FIS, MFIS-IBD, and DFIS were strongly correlated with each other (r ≥ 0.90). The ability to discriminate between disease activity groups was highest for the FIS and MFIS-IBD, followed by the DFIS. The FIS, MFIS-IBD, and DFIS were responsive to changes in work impairment. CONCLUSIONS: The FIS, MFIS-IBDs and DFIS had adequate validity and reliability for assessing fatigue in IBD.

Fatigue is very common in people with inflammatory bowel disease (IBD). Fatigue scales are important for studies testing treatments for fatigue. However, information about how well these fatigue scales measure fatigue is inadequate in IBD. In this study, we compared the how well multiple fatigue scales worked in people with IBD. We focused on scales that can be used in many different clinical populations including the Fatigue Impact Scale (FIS), the Modified Fatigue Impact Scale-IBD (MFIS), the Daily Fatigue Impact Scale (DFIS), RAND-36-vitality scales and Patient Health Questionnaire fatigue item. Scores on the three FIS, MFIS and DFIS were strongly related to each other, and these three scales generally performed well; the others did not. The FIS and MFIS-IBD were best able to discrminate between people with IBD who did and did not have ongoing disease activity.

Short-chain fatty acid producers in the gut are associated with pediatric multiple sclerosis onset.

OBJECTIVE: The relationship between multiple sclerosis and the gut microbiome has been supported by animal models in which commensal microbes are required for the development of experimental autoimmune encephalomyelitis. However, observational study findings in humans have only occasionally converged when comparing multiple sclerosis cases and controls which may in part reflect confounding by comorbidities and disease duration. The study of microbiome in pediatric-onset multiple sclerosis offers unique opportunities as it is closer to biological disease onset and minimizes confounding by comorbidities and environmental exposures. METHODS: A multicenter case-control study in which 35 pediatric-onset multiple sclerosis cases were 1:1 matched to healthy controls on age, sex, self-reported race, ethnicity, and recruiting site. Linear mixed effects models, weighted correlation network analyses, and PICRUSt2 were used to identify microbial co-occurrence networks and for predicting functional abundances based on marker gene sequences. RESULTS: Two microbial co-occurrence networks (one reaching significance after adjustment for multiple comparisons; q < 0.2) were identified, suggesting interdependent bacterial taxa that exhibited association with disease status. Both networks indicated a potentially protective effect of higher relative abundance of bacteria observed in these clusters. Functional predictions from the significant network suggested a contribution of short-chain fatty acid producers through anaerobic fermentation pathways in healthy controls. Consistent family-level findings from an independent Canadian-US study (19 case/control pairs) included Ruminococaccaeae and Lachnospiraceae (p < 0.05). Macronutrient intake was not significantly different between cases and controls, minimizing the potential for dietary confounding. INTERPRETATION: Our results suggest that short-chain fatty acid producers may be important contributors to multiple sclerosis onset.

Brain-Gut Axis: Invasive and Noninvasive Vagus Nerve Stimulation, Limitations, and Potential Therapeutic Approaches.

Inflammatory bowel disease (IBD) is a chronic relapsing condition with no known etiology and is characterized by disrupted gut homeostasis, chronic inflammation, and ulcerative lesions. Although current treatments can reduce disease activity, IBD frequently recurs once treatments are discontinued, indicating that treatments are ineffective in providing long-term remission. The lack of responsiveness and reluctance of some affected persons to take medications because of potential adverse effects has enhanced the need for novel therapeutic approaches. The vagus nerve (VN) is likely important in the pathogenesis of IBD, considering the decreased activity of the parasympathetic nervous system, especially the VN, and the impaired interaction between the enteric nervous system and central nervous system in patients with IBD. Vagus nerve stimulation (VNS) has demonstrated anti-inflammatory effects in various inflammatory disorders, including IBD, by inhibiting the production of inflammatory cytokines by immune cells. It has been suggested that stimulating the vagus nerve to induce its anti-inflammatory effects may be a potential therapeutic approach for IBD. Noninvasive techniques for VNS have been developed. Considering the importance of VN function in the brain-gut axis, VNS is a promising treatment option for IBD. This review discusses the potential therapeutic advantages and drawbacks of VNS, particularly the use of noninvasive transcutaneous auricular vagus nerve stimulation.

As some patients do not respond well to current treatments, novel therapeutic approaches are needed for inflammatory bowel disease (IBD). With diminished parasympathetic anti-inflammatory activity in IBD patients, especially in the vagus nerve, stimulation of the vagus nerve may be a potential therapeutic approach.

Understanding Predictors of Fatigue Over Time in Persons With Inflammatory Bowel Disease: The Importance of Depressive and Anxiety Symptoms.

INTRODUCTION: Fatigue is a complex and frequent symptom in persons with inflammatory bowel disease (IBD), with detrimental impact. We aimed to determine predictors of fatigue over time. METHODS: Two hundred forty-seven adults with IBD participated in a prospective study conducted in Manitoba, Canada, providing data at baseline and annually for 3 years. Participants reported fatigue impact (Daily Fatigue Impact Scale [DFIS]), depression and anxiety symptoms (Hospital Anxiety and Depression Scale [HADS]), and pain (Pain Effects Scale [PES]). Physician-diagnosed comorbidities, IBD characteristics, and physical and cognitive functioning were also assessed. We tested factors associated with fatigue using multivariable generalized linear models that estimated within-person and between-person effects. RESULTS: Most participants were women (63.2%), White (85.4%), and had Crohn's disease (62%). At baseline, 27.9% reported moderate-severe fatigue impact, 16.7% had clinically elevated anxiety (HADS-A ≥11), and 6.5% had clinically elevated depression (HADS-D ≥11). Overall fatigue burden was stable over time, although approximately half the participants showed improved or worsening fatigue impact between annual visits during the study. On multivariable analysis, participants with a one-point higher HADS-D score had, on average, a 0.63-point higher DFIS score, whereas participants with a one-point higher PES score had a 0.78-point higher DFIS score. Within individuals, a one-point increase in HADS-D scores was associated with 0.61-point higher DFIS scores, in HADS-A scores with 0.23-point higher DFIS scores, and in PES scores with 0.38-point higher DFIS scores. No other variables predicted fatigue. DISCUSSION: Anxiety, depression, and pain predicted fatigue impact over time in IBD, suggesting that targeting psychological factors and pain for intervention may lessen fatigue burden.

A cross-sectional study of MRI features and the gut microbiome in pediatric-onset multiple sclerosis.

OBJECTIVE: To identify gut microbiome features associated with MRI lesion burden in persons with pediatric-onset multiple sclerosis (symptom onset <18 years). METHODS: A cross-sectional study involving the Canadian Paediatric Demyelinating Disease Network study participants. Gut microbiome features (alpha diversity, phylum- and genus-level taxa) were derived using 16S rRNA sequencing from stool samples. T1- and T2-weighted lesion volumes were measured on brain MRI obtained within 6 months of stool sample procurement. Associations between the gut microbiota and MRI metrics (cube-root-transformed) were assessed using standard and Lasso regression models. RESULTS: Thirty-four participants were included; mean ages at symptom onset and MRI were 15.1 and 19.0 years, respectively, and 79% were female. The T1- and T2-weighted lesion volumes were not significantly associated with alpha diversity (age and sex-adjusted p > 0.08). At the phylum level, high Tenericutes (relative abundance) was associated with higher T1 and T2 volumes (ß coefficient = 0.25, 0.37) and high Firmicutes, Patescibacteria or Actinobacteria with lower lesion volumes (ß coefficient = -0.30 to -0.07). At the genus level, high Ruminiclostridium, whereas low Coprococcus 3 and low Erysipelatoclostridium were associated with higher lesion volumes. INTERPRETATION: Our study characterized the gut microbiota features associated with MRI lesion burden in pediatric-onset MS, shedding light onto possible pathophysiological mechanisms.

Sex differences evident in elevated anxiety symptoms in multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis.

Introduction: Immune-mediated inflammatory diseases (IMID), such as multiple sclerosis (MS), inflammatory bowel disease (IBD) or rheumatoid arthritis (RA) have high rates of elevated anxiety symptoms. This can may worsen functioning and increase IMID disease burden. The rate of and factors associated with elevated anxiety symptoms may differ between males and females, which, in turn can affect diagnosis and disease management. We evaluated whether the frequency and factors associated with comorbid elevated anxiety symptoms in those with an IMID differed by sex. Methods: Participants with an IMID (MS, IBD or RA) completed two anxiety measures (HADS, GAD-7). We used logistic regression to investigate whether sex differences exist in the presence of comorbid elevated anxiety symptoms or in the endorsement of individual anxiety items in those with an IMID. Results: Of 656 participants, females with an IMID were more likely to have elevated anxiety symptoms compared to males (adjusted odds ratio [aOR] 2.05; 95%CI: 1.2, 3.6). Younger age, higher depressive symptoms and income were also associated with elevated anxiety symptoms in IMID. Lower income in males with an IMID, but not females, was associated with elevated anxiety symptoms (aOR: 4.8; 95%CI: 1.5, 15.6). No other factors demonstrated a sex difference. Males had nearly twice the odds of endorsing restlessness on the GAD-7 (OR = 1.8, 95%CI: 1.07, 3.15) compared to females. Discussion: We found evidence for sex differences in the factors associated with experiencing elevated anxiety symptoms in those with an IMID. These findings could be helpful to sensitize clinicians to monitor for comorbid anxiety symptoms in males with an IMID.

The Impact of COVID-19 on Health Anxiety and Perceived Stress Among Persons with IBD: A Population-representative Study.

Background: The Corona Virus Immune Disease-2019 (COVID-19) pandemic has broadly impacted the mental health of individuals worldwide, especially with restrictions including social distancing and quarantining. Persons with IBD are at increased risk of mental health disorders. The aim was to understand how the COVID-19 pandemic affected adults with a chronic health issue, inflammatory bowel disease (IBD), using a population-based sample. Methods: A survey study in Manitoba was conducted during the second COVID-19 wave in autumn 2020. We assessed proportions of health anxiety and perceived stress using validated measures, as well as stressors during the COVID-19 pandemic. We used univariable and multivariable logistic regression analysis to assess predictors of perceived stress and health anxiety. Results: A total of 1,384 (47.1%) persons responded, with a mean age of 58.0, and 46.9% had Crohn's disease. Almost three quarters (73.7%) had increased stress, with 37.7% having increased stress about their IBD, and 33.6% worried about their IBD worsening. 46.0% felt increased stress about accessing their doctor or nurse, and 56.5% felt they had good access to their gastroenterologist. Elevated stress and health anxiety were seen in 63.5% and 17.2% of respondents, respectively. Younger age and being on immune-modifying therapy (IMT) was predictive of increased health anxiety and stress. Longer IBD duration was associated with decreased stress, including those on IMT. Conclusion: Persons with IBD reported high rates of stress and health anxiety early in the COVID-19 pandemic, especially among those on IMT. It will be important to determine how this evolved over time and to what extent this impacted on disease course.