Carotid intima media thickness in multiple sclerosis: A CLSA study.

BACKGROUND: People with multiple sclerosis (MS) have an increased incidence of atherosclerotic disease, including ischemic heart disease and stroke, compared to people without MS even after accounting for risk factors such as hypertension, dyslipidemia, diabetes and smoking. We compared carotid intima media thickness (CIMT), a surrogate of atherosclerosis, in people with MS and in two groups of people without MS (rheumatoid arthritis [RA]; all other participants). METHODS: We used data from participants in the Canadian Longitudinal Study on Aging (CLSA) who did not have known vascular disease (ischemic heart disease, stroke, transient ischemic attack, peripheral vascular disease) and who underwent carotid ultrasound for assessment of CIMT. We selected participants with MS, RA and controls who did not have MS or RA. Using age and gender-stratified norms for average CIMT in the CLSA, we identified participants in each cohort with a CIMT ≥75th percentile (subclinical atherosclerosis). We also calculated ten-year level of cardiovascular risk using the Framingham Risk Score (FRS). We tested the association between cohort membership (MS, RA, controls) and atherosclerosis using logistic regression, adjusted for FRS, abdominal obesity, excess alcohol intake, education and elevated symptoms of depression. We adjusted all analyses for the stratified sampling design. RESULTS: We included 78 participants with MS, 364 participants with RA and 13,891 controls. Overall, the average (SE) CIMT was 0.699 (0.002), and this did not differ between cohorts. Logistic regression analyses revealed that cohort membership was not associated with atherosclerosis based on the average CIMT in unadjusted or adjusted models. However, a 1-point higher FRS was associated with 1.032 (95 %CI: 1.021, 1.043) increased odds of atherosclerosis. CONCLUSION: Average CIMT does not differ between people with MS, people with RA and people without these diseases. Subclinical atherosclerosis as defined by a CIMT ≥75 % is not observed in people with MS at an increased rate beyond what FRS would predict. Further evaluation is needed to determine what mechanisms underlie the increased rates of cardiovascular disease and stroke in MS.

Association of patient-reported cognitive impairment with quality of life and employment in multiple sclerosis.

BACKGROUND: Cognition is frequently affected in persons with multiple sclerosis (MS). Cognitive impairment (CI) is associated with decreased quality of life (QOL) and employment status. Yet, CI assessed using patient-reported outcome measures is not as well studied and is thought to be influenced by other symptoms. Health Utilities Index 3 (HUI3) is a multi-attribute health-status classification system that assesses 8 different single attributes, including cognition. METHODS: The North American Consortium of Multiple Sclerosis (NARCOMS) Registry, a voluntary, self-report registry for persons with MS, Spring 2019 survey collected the HUI3 and self-reported assessment of health-related QOL (RAND-12), cognitive status, depression, fatigue, disability, employment, disease-modifying therapy use, and sociodemographic data. We assessed the relationship between patient-reported cognitive CI from the HUI3 (HUI-C), QOL, and employment while adjusting for factors previously associated with the outcomes. For employment outcomes, the cohort was limited to participants 65 years of age or younger. RESULTS: Of the 6,227 respondents, 56.4 % reported cognitive difficulty with the HUI-C. After adjusting for multiple covariates, cognitive difficulty was associated with 1.2 point lower physical QOL for each 0.1 decrease in HUI-C (p < 0.0001). Mental QOL decreased by 2 points for each 0.1 decrease in HUI-C (p < 0.0001). Cognitive difficulty was associated with a 10 % decreased odds of employment in the multivariable model (p < 0.0001). DISCUSSION: Patient-reported CI was associated with lower health-related and vocational outcomes for MS patients, even after accounting for age, income, depression, fatigue, and disability associated with cognition. The HUI-C is a single attribute score derived from the HUI3 that may facilitate the evaluation of CI in MS.

Algorithmic approach to finding people with multiple sclerosis using routine healthcare data in Wales.

BACKGROUND: Identification of multiple sclerosis (MS) cases in routine healthcare data repositories remains challenging. MS can have a protracted diagnostic process and is rarely identified as a primary reason for admission to the hospital. Difficulties in identification are compounded in systems that do not include insurance or payer information concerning drug treatments or non-notifiable disease. AIM: To develop an algorithm to reliably identify MS cases within a national health data bank. METHOD: Retrospective analysis of the Secure Anonymised Information Linkage (SAIL) databank was used to identify MS cases using a novel algorithm. Sensitivity and specificity were tested using two existing independent MS datasets, one clinically validated and population-based and a second from a self-registered MS national registry. RESULTS: From 4 757 428 records, the algorithm identified 6194 living cases of MS within Wales on 31 December 2020 (prevalence 221.65 (95% CI 216.17 to 227.24) per 100 000). Case-finding sensitivity and specificity were 96.8% and 99.9% for the clinically validated population-based cohort and sensitivity was 96.7% for the self-declared registry population. DISCUSSION: The algorithm successfully identified MS cases within the SAIL databank with high sensitivity and specificity, verified by two independent populations and has important utility in large-scale epidemiological studies of MS.

Subclinical atherosclerosis in multiple sclerosis.

Background: People with multiple sclerosis (MS) have an increased risk of ischemic heart disease as compared to people without MS after accounting for traditional vascular risk factors. Objective: We assessed whether subclinical atherosclerosis, an inflammatory disease of arteries, occurs in persons with MS who do not have traditional vascular risk factors, and whether the Framingham Score (FRS) predicted carotid intima media thickness (CIMT) similarly in people with and without MS. Methods: We recruited participants with and without MS who did not have vascular disease. Participants completed questionnaires, physical assessments, underwent an ultrasound (CIMT), and provided samples for HbA1c and lipid measurements. We defined subclinical atherosclerosis as an average CIMT ≥75th percentile, and tested the association between MS/not-MS, FRS, and atherosclerosis using logistic regression. Results: We recruited 106 participants with MS 101 without MS. The average (SD) CIMT did not differ between the MS (0.60 [0.11]) and non-MS (0.61 [0.12]) cohorts (p = 0.69), nor did the proportion with atherosclerosis (MS: 11.3% vs. non-MS 13.4%, p = 0.58). On regression analysis a 1-point increase in the FRS was associated with 11% increased odds of having atherosclerosis (95%CI: 1.04, 1.19) but MS was not. Conclusion: MS was not associated with subclinical atherosclerosis.

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.

Disease-modifying therapy initiation patterns in multiple sclerosis in three large MS populations.

Background: Treatment guidelines recommend early disease-modifying therapy (DMT) initiation after diagnosis of multiple sclerosis (MS). Multinational comparative studies that assess time to DMT initiation in MS may allow detection of barriers inherent to healthcare systems to explain potential adverse systematic delays in commencing DMTs. Objectives: To investigate and compare the time to first DMT and its association with sociodemographic and clinical variables after MS diagnosis in three large MS registries. Design: This observational study was conducted using data from the German MS Registry (GMSR), the North American Research Committee on MS Registry (NARCOMS, US data only), and the United Kingdom MS Registry (UKMSR, both self- and clinician-reported). Methods: Data from relapsing people with MS (PwMS), with a diagnosis of MS between 2014 and 2019, and available DMT and disability status were pooled using a meta-analytic approach. Results: A total of 5395 PwMS were included in the analysis (GMSR: n = 2658; NARCOMS: n = 447; UKMSR: n = 2290). Kaplan-Meier estimates for the time to first DMT [median months (95% CI)] were 2.0 (1.9-2.0), 3.0 (2-4), and 9.0 (7.7-10.6) for GMSR, NARCOMS, and UKMSR, respectively. Pooled multivariable Cox regression demonstrated shorter time to first DMT for PwMS diagnosed after 2017 [1.65 (1.42-1.92), p < 0.01], and longer time to DMT when a higher-efficacy DMT was selected (0.69 (0.54-0.90), p < 0.0001]. Conclusion: Time to DMT initiation differs across the populations studied, indicating that barriers may exist in early access to DMT, particularly in the United Kingdom. However, a consistent decrease in time to DMT initiation was noted since 2017 across all registries. Further studies are warranted comparing the effects of time to DMT and time to higher-efficacy DMT on long-term outcome.

Priority setting: women's health topics in multiple sclerosis.

Background: A scoping review found that most studies on women's health in multiple sclerosis (MS) focused on pregnancy, fetal/neonatal outcomes and sexual dysfunction. Few studies addressed menopause, contraception, gynecologic cancers/cancer screening. However, the perceived relative importance of these knowledge gaps to people living with MS and other partners is unknown. We engaged a range of partners, including people living with MS, health care providers, researchers, and patient advocacy groups, to set priorities for future research in women's health in MS. Methods: We employed a three-step global engagement process. First, we identified which broad research topics relevant to women's health in MS were of highest priority using two surveys. Second, we developed specific research questions within these topics using focus groups. Finally, we prioritized the research questions with a third survey. Results: Overall, 5,266 individuals responded to the initial surveys [n = 1,430 global survey, mean (SD) age 50.0 (12.6), all continents; n = 3,836 North American Research Committee on Multiple Sclerosis survey, mean (SD) age 64.8 (9.6), United States]. Menopause, sexual dysfunction, pregnancy, gynecologic cancer/cancer screening, hormones and parenthood were identified as the most important topics. Focus groups generated 80 potential research questions related to these topics. In the final survey 712 individuals prioritized these questions. The highest priority questions in each research topic were: (i) How do perimenopause and menopause affect disease activity, course, response to disease-modifying treatment and quality of life in MS; (ii) What are the most effective strategies for managing issues around sexual intimacy, including related to low sexual desire, changes in physical function, and MS symptoms; (iii) Are there long-term effects of disease-modifying therapies on the children of persons with MS; (iv) What are the short and long-term effects of disease-modifying drugs on gynecologic cancer risk, particularly for high efficacy disease-modifying drugs and hematopoietic stem cell transplantation; (v) Are there hormone related treatments that can stabilize fluctuations in MS symptoms; and (vi) How does MS fatigue impact parenting strategies. Conclusion: Priorities for research relating to women's health issues for persons with MS have been delineated using a collaborative process with key partners. Alignment of future research with these priorities should be monitored.

Incidence rate and prevalence of pediatric-onset multiple sclerosis in Sweden: A population-based register study.

BACKGROUND AND PURPOSE: Pediatric-onset multiple sclerosis (PoMS) is associated with high health care use. To plan resource allocation for this patient group, knowledge of the incidence rate and prevalence is important. However, such studies are scarce, few are population-based, and the methodology varies widely. We aimed to address this knowledge gap by performing a nationwide study of the incidence rate and prevalence of PoMS in Sweden, an area of high multiple sclerosis (MS) incidence and prevalence. METHODS: MS cases were identified by linking two nationwide registers, the National Patient Register and the Swedish MS Registry. MS cases having their first central nervous system demyelinating event or MS clinical onset before age 18 years were classified as pediatric onset. Incidence rate and prevalence were estimated annually over the study period (2006-2016) for the total population and stratified by sex and age group (<12, 12-15, and 16-17 years). Temporal trends and ratios between sexes and age groups were estimated. RESULTS: We identified 238 incident cases from 2006 to 2016, corresponding to an overall crude incidence rate of 1.12 per 100,000 person-years and an overall crude prevalence of 2.82 per 100,000 population. There was a higher incidence rate among females and the highest age category. The overall incidence rate and prevalence estimates remained stable during the study period. CONCLUSIONS: Sweden exhibits a consistently high incidence rate and prevalence of PoMS that has remained stable over time. This knowledge serves as a tool to aid in planning resource allocation and health services for this patient population.

Investigating the Prevalence of Comorbidity in Multiple Sclerosis Clinical Trial Populations.

BACKGROUND AND OBJECTIVES: Comorbidity is common in multiple sclerosis (MS) with the most prevalent conditions being depression, anxiety, hypertension, and hyperlipidemia. Limited information regarding the representation of comorbidity status is available from phase III clinical trials in MS leading to concern about the potential underrepresentation of individuals with comorbidity in clinical trials. The objective was to estimate the prevalence of comorbidities in MS clinical trial populations. METHODS: Individual-level data from multiple sponsors were requested for a 2-stage meta-analysis of phase III clinical trials of MS disease-modifying therapies. To ensure consistency of our approach across trials, we followed the Maelstrom retrospective harmonization guidelines. Chronic comorbidities at clinical trial enrollment recommended by the International Advisory Committee on Clinical Trials in MS were considered (depression, anxiety, hypertension, hyperlipidemia, migraine, diabetes, chronic lung disease). Additional comorbidities were also classified. Classification was based on medical history data. Individual comorbidities were summed and categorized as 0, 1, 2, or ≥3. We report the pooled prevalence (95% confidence interval [95% CI]) of comorbidity. The pooled prevalence and prevalence ratios across age, sex, race, disability level, and treatment were also reported. Heterogeneity was assessed using the I2 statistic. RESULTS: Seventeen trials involving 17,926 participants were included. Fourteen trials enrolled participants with relapsing MS (RMS) while 3 enrolled participants with progressive MS (PMS). The distributions of sex, age, and disability level were generally consistent within RMS and PMS trials. When pooled, almost half of trial participants (46.5%) had ≥1 comorbidity (1: 25.0%, 95% CI 23.0-27.0, I2 = 89.9; 2: 11.4% [9.3-14.0], I2 = 96.3; ≥3: 6.0% [4.2-8.4], I2 = 97.7). Depression (16.45% [12.96-20.88], I2 = 98.3) was the most prevalent comorbidity reported, followed by hypertension (10.16% [8.61-11.98], I2 = 93.2). Heterogeneity was high across trials. Older age and female participants were associated with increased number of comorbidities. Older individuals and male participants had a higher prevalence of hyperlipidemia, while older individuals and female participants had a higher prevalence of depression and anxiety. DISCUSSION: Individuals with comorbidities are included in clinical trials, although they may still be underrepresented compared with the general MS population. Given the comorbidity prevalence in the trial populations and studies suggesting an association of comorbidities with disease activity, comorbidity may influence outcomes in clinical trials.

Epstein-Barr Virus Strongly Associates With Pediatric Multiple Sclerosis, But Not Myelin Oligodendrocyte Glycoprotein-Antibody-Associated Disease.

Reported rates of Epstein-Barr virus (EBV) seropositivity in children meeting multiple sclerosis (MS) diagnostic criteria are considerably lower than those reported in adult-onset MS, putting in question a requisite role for EBV in MS development. As prior work preceded recognition of myelin oligodendrocyte glycoprotein-associated disease (MOGAD), we assessed viral serologies in 251 children with incident demyelination and prospectively ascertained diagnoses. When MOGAD was serologically accounted for, the prevalence of EBV infection among MS children exceeded 90%, whereas remote EBV infection was not associated with MOGAD risk. Together, these findings substantiate EBV's role across the MS spectrum, and support distinct pathobiological mechanisms in MS versus MOGAD. ANN NEUROL 2024;95:700-705.

Clinical trials for progressive multiple sclerosis: progress, new lessons learned, and remaining challenges.

Despite the success of disease-modifying treatments in relapsing multiple sclerosis, for many individuals living with multiple sclerosis, progressive disability continues to accrue. How to interrupt the complex pathological processes underlying progression remains a daunting and ongoing challenge. Since 2014, several immunomodulatory approaches that have modest but clinically meaningful effects have been approved for the management of progressive multiple sclerosis, primarily for people who have active inflammatory disease. The approval of these drugs required large phase 3 trials that were sufficiently powered to detect meaningful effects on disability. New classes of drug, such as Bruton tyrosine-kinase inhibitors, are coming to the end of their trial stages, several candidate neuroprotective compounds have been successful in phase 2 trials, and innovative approaches to remyelination are now also being explored in clinical trials. Work continues to define intermediate outcomes that can provide results in phase 2 trials more quickly than disability measures, and more efficient trial designs, such as multi-arm multi-stage and futility approaches, are increasingly being used. Collaborations between patient organisations, pharmaceutical companies, and academic researchers will be crucial to ensure that future trials maintain this momentum and generate results that are relevant for people living with progressive multiple sclerosis.

Adverse Events Associated With Disease-Modifying Drugs for Multiple Sclerosis: A Multiregional Population-Based Study

BACKGROUND AND OBJECTIVES: It is not possible to fully establish the safety of a disease-modifying drug (DMD) for multiple sclerosis (MS) from randomized controlled trials as only very common adverse events occurring over the short-term can be captured, and the quality of reporting has been variable. We examined the relationship between the DMDs for MS and potential adverse events in a multiregion population-based study. METHODS: We identified people with MS using linked administrative health data from 4 Canadian provinces. MS cases were followed from the most recent of first MS or related demyelinating disease event on January 1, 1996, until the earliest of emigration, death, or December 31, 2017. DMD exposure primarily comprised ß-interferon, glatiramer acetate, natalizumab, fingolimod, dimethyl fumarate, teriflunomide, and alemtuzumab. We examined associations between DMD exposure and infection-related hospitalizations and physician visits using recurrent events proportional means models and between DMD exposure and 15 broad categories of incident adverse events using stratified multivariate Cox proportional hazard models. RESULTS: We identified 35,894 people with MS. While virtually all DMDs were associated with a 42%-61% lower risk of infection-related hospitalizations, there was a modest increase in infection-related physician visits by 10%-33% for select DMDs. For incident adverse events, most elevated risks involved a second-generation DMD, with alemtuzumab's hazard of thyroid disorders being 19.42 (95% CI 9.29-36.51), hypertension 4.96 (95% CI 1.78-13.84), and cardiovascular disease 3.72 (95% CI 2.12-6.53). Natalizumab's highest risk was for cardiovascular disease (adjusted hazard ratio [aHR] 1.61; 95% CI 1.24-2.10). For the oral DMDs, fingolimod was associated with higher hazards of cerebrovascular (aHR 2.04; 95% CI 1.27-3.30) and ischemic heart diseases (aHR 1.64; 95% CI 1.10-2.44) and hypertension (aHR 1.73; 95% CI 1.30-2.31); teriflunomide with higher hazards of thyroid disorders (aHR 2.30; 95% CI 1.11-4.74), chronic liver disease (aHR 1.94; 95% CI 1.19-3.18), hypertension (aHR 1.76; 95% CI 1.32-2.37), and hyperlipidemia (aHR 1.61; 95% CI 1.07-2.44); and from complementary analyses (in 1 province), dimethyl fumarate with acute liver injury (aHR 6.55; 95% CI 1.96-21.87). DISCUSSION: Our study provides an extensive safety profile of several different DMDs used to treat MS in the real-world setting. Our findings not only complement those observed in short-term clinical trials but also provide new insights that help inform the risk-benefit profile of the DMDs used to treat MS in clinical practice. The results of this study highlight the continued need for long-term, independent safety studies of the DMDs used to treat MS. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with MS, while DMD exposure reduces the risk of infection-related hospitalizations, there are increased risks of infection-related physician visits and incident adverse events for select DMDs.

Predicting time to serologic diagnosis of AQP4+ NMOSD based on clinical factors and social determinants of health.

BACKGROUND: Early serologic diagnosis and initiation of targeted therapy are associated with better outcomes in aquaporin-4 IgG positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD). OBJECTIVE: To determine predictors of time to serologic diagnosis of AQP4+ NMOSD. METHODS: In CANOPTICS, a multi-centre, Canadian cohort study of NMOSD, we retrospectively evaluated time from the first clinical attack to first positive AQP4-IgG serology. We used a multivariable negative binomial regression model to evaluate possible predictors of time to diagnosis. RESULTS: We identified 129 participants with AQP4+ NMOSD from 7 centres. Diagnostic delay of >1 month was observed in 82 (63.6 %). Asian compared to European (White) ethnicity (IRR:0.40, 95 % CI:0.21-0.78), female sex (IRR:0.56, 95 % CI:0.32-0.99), later calendar year (IRR:0.84, 95 % CI:0.81-0.86), and hospitalization for the first attack (IRR:0.35, 95 % CI:0.20-0.62) were associated with shorter times to serologic diagnosis. We did not observe any overall effect of Afro-Caribbean ethnicity, but in exploratory analyses, Afro-Caribbean individuals with low income had longer times to diagnosis. CONCLUSION: More than 60 % of patients with NMOSD experienced delays to AQP4-IgG serologic diagnosis in this cohort. Given evidence of more adverse long-term outcomes in Afro-Caribbean individuals with NMOSD, intersectional effects of ethnicity and social determinants of health merit further study.

Disease-modifying drugs, multiple sclerosis and infection-related healthcare use in British Columbia, Canada: a population-based study.

Background: Much remains unknown surrounding the disease-modifying drugs (DMDs) used to treat multiple sclerosis and infection-related healthcare use in the 'real-world' setting. We examined if DMD exposure was associated with altered infection-related healthcare use. Methods: We assessed if DMD (versus no) exposure was associated with altered infection-related hospitalizations, physician claims, and prescriptions filled in British Columbia, Canada (1996-2017). Healthcare use was assessed using negative binomial and proportional means regression models, reported as sex-/age-/comorbidity-/calendar year-/socioeconomic-adjusted rate and hazard ratios [aRR, aHR], with 95% confidence intervals [CIs]). Findings: We identified 19,360 multiple sclerosis cases (13,940/19,360; 72.0% women; mean age at study start = 44.5 standard deviation, SD = 13.3; mean follow-up = 11.7 [SD = 7.3] years). Relative to unexposed periods, exposure to any DMD was associated with a lower infection-related rate of physician claims (aRR = 0.88; 95% CI:0.85-0.92) and hazard of hospitalization (aHR = 0.64; 95% CI:0.56-0.73), and a higher rate of infection-related prescriptions (aRR = 1.14; 95% CI:1.08-1.20). Exposure to any injectable or oral DMD was associated with a lower infection-related rate of physician claims (injectable aRR = 0.88; 95% CI:0.84-0.92, oral aRR = 0.83; 95% CI:0.77-0.90) and hazard of hospitalization (injectable aHR = 0.65; 95% CI:0.56-0.75, oral aHR = 0.54; 95% CI:0.38-0.77), whereas intravenous DMD exposure was not (aRR = 0.99; 95% CI:0.86-1.14, aHR = 0.73; 95% CI:0.49-1.09). Exposure to any injectable or intravenous DMD was associated with a higher rate of infection-related prescriptions (injectable aRR = 1.15; 95% CI:1.08-1.22, intravenous = 1.34; 95% CI:1.15-1.56), whereas oral DMDs were not (aRR = 0.98; 95% CI:0.91-1.05). Interpretation: DMD exposure for the treatment of MS was associated with differences in infection-related healthcare use. While infection-related hospitalizations and physician visits were lower, prescription fills were higher. How these differences in infection-related healthcare use affect outcomes in persons with multiple sclerosis warrants consideration. Funding: Canadian Institutes of Health Research (CIHR); German Research Foundation (DFG).

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.

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.

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.

Incidence and prevalence of paediatric-onset multiple sclerosis in two Canadian provinces: a population-based study representing over half of Canada's population.

BACKGROUND: Population-based studies estimating the epidemiology of paediatric-onset multiple sclerosis (PoMS) are scarce. METHODS: We accessed population-based health administrative data from two provinces in Canada, Ontario and British Columbia (BC). Individuals with PoMS were identified via a validated case definition. The index date ('MS onset') was the first demyelinating or MS specific claim recorded ≤18 years of age. We estimated the age-standardised annual incidence and prevalence of PoMS, and 95% CIs between 2003 and 2019. We used negative binomial regression models to assess the temporal changes in the annual crude incidence and prevalence of PoMS, and the ratios comparing sex groups. RESULTS: From 2003 to 2019, a total of 148 incident PoMS cases were identified in BC, and 672 in Ontario. The age-standardised annual incidence of PoMS was stable in both provinces, averaging 0.95 (95% CI 0.79 to 1.13) in BC and 0.98 (95%CI 0.84 to 1.12) in Ontario per 100 000 person-years. The incidence ratio by sex (female vs male) was also stable over the study period, averaging 1.5:1 (95% CI 1.06 to 2.08, BC) and 2.0:1 (95% CI 1.61 to 2.59, Ontario). The age-standardised prevalence per 100 000 people rose from 4.75 (2003) to 5.52 (2019) in BC and from 2.93 (2003) to 4.07 (2019) in Ontario, and the increase was statistically significant in Ontario (p=0.002). There were more female prevalent PoMS cases than males in both provinces. CONCLUSIONS: Canada has one of the highest rates of PoMS globally, and the prevalence, but not incidence, has increased over time. Allocation of resources to support the growing youth population with MS should be a priority.

Perceived Need for Mental Health Care in a Cohort of Persons With Inflammatory Bowel Disease.

BACKGROUND: Psychiatric comorbidity is common in inflammatory bowel disease (IBD) and can negatively affect disease outcomes. We explored the perceived need for mental health care among persons with IBD. STUDY: Persons with IBD completed self-report questionnaires, including the Hospital Anxiety and Depression Scale (HADS), and reported whether they wanted help with their mood. Each was also assessed using the Structured Clinical Interview for DSM-IV-TR Axis-I Disorders (SCIDs). We used logistic regression analyses to determine factors associated with the perceived need for mental health care. RESULTS: Of 245 participants, 28% met the criteria for a past diagnosis of depression or anxiety disorder by SCID, and nearly 23% met the criteria for a current diagnosis of depression or anxiety disorder. One-third (n = 74) reported a perceived need for mental health care. Among those meeting criteria for a current SCID diagnosis of depression or anxiety, only 58% reported needing mental health care. Need for mental health care was reported by 79% of persons currently treated for either depression or 71% treated for anxiety. Persons with a perceived need for mental health care had higher mean HADS for depression and HADS for anxiety scores and also higher IBD symptom activity scores. Of those reporting no perceived need for mental health care, 13% had a current diagnosis of depression or anxiety disorder by SCID; even fewer had symptoms of depression or anxiety. CONCLUSIONS: Symptoms of depression or anxiety are more important than a formal diagnosis of depression or anxiety in predicting which persons with IBD will perceive a need for mental health care.