Search

Abstract Background The interplay between diet and the gut microbiota in multiple sclerosis (MS) is poorly understood. We aimed to assess the interrelationship between diet, the gut microbiota, and MS. Methods We conducted a case-control study including 95 participants (44 pediatric-onset MS cases, 51 unaffected controls) enrolled from the Canadian Pediatric Demyelinating Disease Network study. All had completed a food frequency questionnaire ≤21-years of age, and 59 also provided a stool sample. Results Here we show that a 1-point increase in a Mediterranean diet score is associated with 37% reduced MS odds (95%CI: 10%–53%). Higher fiber and iron intakes are also associated with reduced MS odds. Diet, not MS, explains inter-individual gut microbiota variation. Several gut microbes abundances are associated with both the Mediterranean diet score and having MS, and these microbes are potential mediators of the protective associations of a healthier diet. Conclusions Our findings suggest that the potential interaction between diet and the gut microbiota is relevant in MS.

Background: Disease progression is observed across the spectrum of people with multiple sclerosis (MS) and identification of effective treatment strategies to halt progression remains one of the greatest unmet clinical needs. Objectives: The Canadian Prospective Cohort Study to Understand Progression in MS (CanProCo) was designed to evaluate a wide range of factors associated with the onset and rate of clinical disease progression in MS and to describe the interplay between these factors. Design: A prospective cohort study. Methods: CanProCo is a national, prospective, observational cohort study that has recruited 944 individuals from 5 large academic MS centers in Canada. Participants include people with radiologically isolated syndrome (RIS), early relapsing-remitting and primary progressive MS (RRMS, PPMS), and healthy controls (HCs). Annually, participants complete self-reported questionnaires, undergo clinical evaluation and, if clinically indicated, magnetic resonance images (MRIs) of the brain and cervical spinal cord; in a subset of participants ( n = 399), blood, and research MRIs of the brain and cervical spinal cord are collected. Linkages to health administrative databases are available at three sites. Results: Overall, 944 participants were recruited (53 HCs, 63 RIS, 751 RRMS, 77 PPMS). RIS and MS participants had a mean age of 39.0 years and 70.5% female. The mean time since diagnosis was 2.7 years. There were differences observed in the Expanded Disability Status Scale score and components of the MS performance test (walking speed test, manual dexterity test, processing speed test, and low-contrast visual acuity) between RIS and MS subtypes. Questionnaires revealed more symptoms of depression and anxiety and impaired physical and mental quality of life in people with RIS/MS versus HCs and differences across RIS/MS subtypes. Conclusion: Physical and mental neurological disability is prevalent even in the earliest stages of MS. Transdisciplinary approaches such as those used in CanProCo are needed to better characterize clinical progression in MS. Additional CanProCo results, including MRI, biological, and pharmaco-economic data will be forthcoming. Going forward, CanProCo’s data sharing and collaborative vision will facilitate numerous global collaborations, which will inform the development and implementation of effective interventions for people with MS around the world.

Objectives Individual risk factors for dementia are well known, but the influence of co-occurring chronic conditions has not been considered. We identified clusters of chronic conditions using an unsupervised machine learning approach and examined associations with incident dementia. Approach Using linked population-based administrative databases, we followed all community-dwelling adults aged 40-54 years in Ontario, Canada from April 2002 until March 2019 for incident dementia. We estimated the prevalence of 29 chronic conditions using validated algorithms and/or diagnosis codes. We reduced dataset dimensionality using multiple correspondence analysis and a fuzzy c-means clustering algorithm identified the optimal number of clusters (between 3-6 tested). Associations between clusters and incident dementia were examined using a cause-specific hazard model adjusted for sociodemographic characteristics and accounting for the competing risk of death. Results We identified 82,359 eligible individuals (random 3% sample of total eligible individuals; mean age 46.5 years; 50.4% female). Regression analyses were based on 5 comorbidity clusters (fuzzy silhouette index:0.69). Compared to the low comorbidity cluster, persons in the cerebrovascular disease/metabolic (HRadj=3.06, 95%CI[2.42,3.86]) and neuro-related/mental health clusters (HRadj=2.51, 95%CI[2.05,3.07]) had the highest rates of incident dementia, followed by the cardiovascular risk factor cluster (HRadj=1.66,95%CI[1.32,2.09]). Persons in the cancer cluster did not have an increased incidence of dementia (HRadj=0.96,95%CI[0.77,1.20]). Conclusions We found significant associations between machine learning-derived clusters of chronic conditions and dementia. Implications Unsupervised machine learning approaches to identify clusters of chronic conditions may be a useful tool for considering the impact of multimorbidity on dementia risk.

Background Multiple Sclerosis (MS) is a challenging disease to identify within large repositories of healthcare data. Diagnosis can be protracted requiring many modalities that may not form part of the repository data collection. Accurate case finding would have multiple applications for studying epidemiology. Aim Develop a case finding algorithm within the Secure Anonymised Information Linkage (SAIL) Databank that can reliably elicit Multiple Sclerosis. Method Utilising a cross sectional cohort study we used multiple datasets within SAIL; General Practice, Inpatient, Outpatient and Office of National Statistics to develop our case finding algorithm based on the coding nomenclatures and timing within these datasets. The results of this algorithm were then tested against two patient data sets: The UK MS Register (n=836), consisting of mostly self confirmed disease and a clinical cohort from South West Wales (n=713). Results From 4,757,428 records, the algorithm identified 6,194 cases of MS within Wales on 31st December 2020 (prevalence 221.65 [95%CI 216.17–227.24] per 100,000). Case finding sensitivity and specificity was 96.8% and 99.9% for the clinically validated population-based cohort and sensitivity was 96.7% from the self-declared registry population. Conclusion We successfully identified MS cases within Wales and verified this within two independent data sets.

Objective This study aims to (1) build and validate model-based case definitions for multiple sclerosis (MS) that use trends (ie, trend-based case definitions) and (2) to apply dynamic classification to identify the average number of data years needed for classification (ie, average trend needed).Design Retrospective cohort study design.Participants 608 MS cases and 59 620 MS non-cases.Setting Data from 1 April 2004 to 31 March 2022 were obtained from the Manitoba Population Research Data Repository. MS case status was ascertained from homecare records and linked to health data. Trend-based case definitions were constructed using multivariate generalised linear mixed models applied to annual numbers of general and specialist physician visits, hospitalisations and MS healthcare contacts or medication dispensations. Dynamic classification, which ascertains cases and non-cases annually, was used to estimate mean classification time. Classification accuracy performance measures, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), proportion correctly classified (PCC) and F1-scores, were compared for trend-based case definitions and a deterministic case definition of 3+MS healthcare contacts or medication dispensations.Results When applied to the full study period, classification accuracy performance measure estimates for all case definitions exceeded 0.90, except sensitivity and PPV for the trend-based dynamic case definition (0.88, 0.64, respectively). PCC was high for all case definitions (0.94–0.99); F1-scores were lower for the trend-based case definitions compared with the deterministic case definition (0.74–0.93 vs 0.96). Dynamic classification identified 5 years as the average trend needed. When applied to the average trend windows, accuracy estimates for trend-based case definitions were lower than the estimates from the full study period (sensitivity: 0.77–0.89; specificity: 0.90–0.97; PPV: 0.54–0.81; NPV: 0.97–0.99; F1-score: 0.64–0.84). Accuracy estimates for the deterministic case definition remained high, except sensitivity (0.42–0.80). F1-score was variable (0.59–0.89).Conclusions Trend-based and deterministic case definitions classifications were similar to a population-based clinician assessment reference standard for multiple measures of classification accuracy. However, accuracy estimates for both trend-based and deterministic case definitions varied as the years of data used for classification were reduced. Dynamic classification appears to be a viable option for identifying the average trend needed for trend-based case definitions.

Abstract Objective To identify gut microbiome features associated with MRI lesion burden in persons with pediatric‐onset multiple sclerosis (symptom onset 0.08). At the phylum level, high Tenericutes (relative abundance) was associated with higher T1 and T2 volumes (β coefficient = 0.25, 0.37) and high Firmicutes, Patescibacteria or Actinobacteria with lower lesion volumes (β 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.

Abstract 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

Abstract Little is known about disease-modifying drug (DMD) initiation by immigrants with multiple sclerosis (MS) in countries with universal health coverage. We assessed the association between immigration status and DMD use within 5-years after the first MS-related healthcare encounter. Using health administrative data, we identified MS cases in British Columbia (BC), Canada. The index date was the first MS-related healthcare encounter (MS/demyelinating disease-related diagnosis or DMD prescription filled), and ranged from 01/January/1996 to 31/December/2012. Those included were ≥ 18 years old, BC residents for ≥ 1-year pre- and ≥ 5-years post-index date. Persons becoming permanent residents 1985–2012 were defined as immigrants, all others were long-term residents. The association between immigration status and any DMD prescription filled within 5-years post-index date (with the latest study end date being 31/December/2017) was assessed using logistic regression, reported as adjusted odds ratios (aORs) with 95% confidence intervals (CIs). We identified 8762 MS cases (522 were immigrants). Among immigrants of lower SES, odds of filling any DMD prescription were reduced, whereas they did not differ between immigrants and long-term residents across SES quintiles (aOR 0.96; 95%CI 0.78–1.19). Overall use (odds) of a first DMD within 5 years after the first MS-related encounter was associated with immigration status.

Introduction The validity of chronic disease case definitions for administrative health data may change over time due to changes in data quality. Trend control charts to identify out-of-control (OOC; i.e., unexpected) observations in a time series may indicate where disease estimates are influenced by changes in data quality. Objective Apply and compare trend control charts methods for multiple sclerosis (MS) incidence and prevalence estimates using previously-validated case definitions for Manitoba, Canada. Methods Eight case definitions were identified from published literature and applied to Manitoba administrative health data from January 1, 1972 to December 31, 2018. Incidence and prevalence trends were modeled using negative binomial and generalized estimating equation models, respectively. Trend control charts were used to plot predicted case counts against observed case counts. Control limits to identify OOC observations were calculated using two methods: predicted case count ±0.8*standard deviation (0.8*SD) and predicted case count ±2*standard deviation (2*SD). Differences in proportion of OOC observations across case definitions was assessed using McNemar's test. Results The proportion of OOC observations ranged from 0.71 to 0.90 for incidence and 0.72 to 0.98 for prevalence when using the 0.8*SD control limits. A lower proportion of OOC observations (0.46 to 0.74 for incidence; 0.30 to 0.74 for prevalence) was observed for the 2*SD control limits. Neither method resulted in significant differences in OOC observations across case definitions. Conclusions The proportion of OOC observations in trend control charts varied with the control limit method adopted, but statistical significance did not. Trend control charts are a potentially useful tool for developing surveillance methods, but may benefit from disease-specific calibrated control limits.

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

BackgroundA 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.MethodsWe 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.ResultsOverall, 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.ConclusionPriorities 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.

Summary: 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).

Abstract Reports of cognitive impairment in inflammatory bowel disease (IBD) have been mixed. IBD and cardiovascular disease are often co-morbid, yet it remains unknown whether vascular comorbidity confers a risk for decreased cognitive functioning, as observed in other populations. Participants with IBD were recruited from a longitudinal study of immune-mediated disease. Participants were administered a standardized neuropsychological test protocol, evaluating information processing speed, verbal learning and memory, visual learning and memory, and verbal fluency/executive function. Cognitive test scores were standardized using local regression-based norms, adjusting for age, sex, and education. Vascular risk was calculated using a modified Framingham Risk Score (FRS). We tested the association between FRS and cognitive test scores using a quantile regression model, adjusting for IBD type. Of 84 IBD participants, 54 had ulcerative colitis and 30 had Crohn’s disease; mean (SD) age was 53.36 (13.95) years, and a high proportion were females (n = 58). As the risk score (FRS) increased, participants demonstrated lower performance in information processing speed (β = − 0.12; 95% CI − 0.24, − 0.006) and verbal learning (β = − 0.14; 95% CI − 0.28, − 0.01) at the 50th percentile. After adjusting for IBD type and disease activity, higher FRS remained associated with lower information processing speed (β = − 0.14; 95% CI − 0.27, − 0.065). Vascular comorbidity is associated with lower cognitive functioning in persons with IBD, particularly in the area of information processing speed. These findings suggest that prevention, identification, and treatment of vascular comorbidity in IBD may play a critical role for improving functional outcomes in IBD.

IntroductionImmune-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.MethodsParticipants 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.ResultsOf 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.DiscussionWe 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.

BackgroundFifty-one percent of individuals with multiple sclerosis (MS) develop cognitive impairment (CI) in information processing speed (IPS). Although IPS scores are associated with health and well-being, neural changes that underlie IPS impairments in MS are not understood. Resting state fMRI can provide insight into brain function changes underlying impairment in persons with MS.ObjectivesWe aimed to assess functional connectivity (FC) differences in (i) persons with MS compared to healthy controls (HC), (ii) persons with both MS and CI (MS-CI) compared to HC, (iii) persons with MS that are cognitively preserved (MS-CP) compared to HC, (iv) MS-CI compared to MS-CP, and (v) in relation to cognition within the MS group.MethodsWe included 107 participants with MS (age 49.5 ± 12.9, 82% women), and 94 controls (age 37.9 ± 15.4, 66% women). Each participant was administered the Symbol Digit Modalities Test (SDMT) and underwent a resting state fMRI scan. The MS-CI group was created by applying a z-score cut-off of ≤−1.5 to locally normalized SDMT scores. The MS-CP group was created by applying a z-score of ≥0. Control groups (HCMS-CI and HCMS-CP) were based on the nearest age-matched HC participants. A whole-brain ROI-to-ROI analysis was performed followed by specific contrasts and a regression analysis.ResultsIndividuals with MS showed FC differences compared to HC that involved the cerebellum, visual and language-associated brain regions, and the thalamus, hippocampus, and basal ganglia. The MS-CI showed FC differences compared to HCMS-CI that involved the cerebellum, visual and language-associated areas, thalamus, and caudate. SDMT scores were correlated with FC between the cerebellum and lateral occipital cortex in MS. No differences were observed between the MS-CP and HCMS-CP or MS-CI and MS-CP groups.ConclusionOur findings emphasize FC changes of cerebellar, visual, and language-associated areas in persons with MS. These differences were apparent for (i) all MS participants compared to HC, (ii) MS-CI subgroup and their matched controls, and (iii) the association between FC and SDMT scores within the MS group. Our findings strongly suggest that future work that examines the associations between FC and IPS impairments in MS should focus on the involvement of these regions.

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is characterized by inflammation of the gastrointestinal tract and is a disorder of the brain-gut axis. Neuroimaging studies of brain function and structure have helped better understand the relationships between the brain, gut, and comorbidity in IBD. Studies of brain structure have primarily employed voxel-based morphometry to measure grey matter volume and surface-based morphometry to measure cortical thickness. Far fewer studies have employed other surface-based morphometry metrics such as gyrification, cortical complexity, and sulcal depth. In this study, brain structure differences between 72 adults with IBD and 90 healthy controls were assessed using all five metrics. Significant differences were found for cortical thickness with the IBD group showing extensive left-lateralized thinning, and for cortical complexity with the IBD group showing greater complexity in the left fusiform and right posterior cingulate. No significant differences were found in grey matter volume, gyrification, or sulcal depth. Within the IBD group, a post hoc analysis identified that disease duration is associated with cortical complexity of the right supramarginal gyrus, albeit with a more lenient threshold applied.

Background and objectivesWhile randomized, controlled trials (RCTs) are the gold standard for determining treatment efficacy, they do not capture the effectiveness of treatment during real-world use. We aimed to evaluate the association between demographics and multiple sclerosis (MS) disease-modifying therapy (DMT) exposure, including treatment adherence and switches between different DMTs, on the risk of subsequent MS relapse.MethodsAll persons with relapsing-onset MS (pwRMS) living in Manitoba between 1999 and 2014 were identified from provincial healthcare databases using a validated case definition. Use of DMTs was abstracted from the provincial drug database covering all residents of Manitoba, including use of any DMT, stopping/starting any DMT, switches between different DMTs and adherence as defined by cumulative medication possession ratios (CUMMPRs) of 50, 70, 80 and 90%. Time to first-treated relapse was used as the outcome of interest in logistic regression and Cox-proportional hazards regression models adjusting for demographic covariates including age and year of diagnosis, sex, socioeconomic status and number of medical comorbidities.Results1780 pwRMS were identified, including 1,510 who were on DMT at some point in the study period. While total DMT exposure was not associated with the time to subsequent treated relapse, individuals who switched between more than 2 DMTs had higher post-switch rates of relapse. Switching to second-line DMTs was associated with a longer time to treated relapse in comparison to those who remained on a first-line DMT (HR 0.44; 95%CI: 0.32–0.62, p

Objectives Among people with immune-mediated inflammatory disease (IMID), including multiple sclerosis (MS), inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) most research has focused on mental illness rather than on mental health. We assessed dimensions of mental health among persons with IMID and compared them across IMID. We also evaluated demographic and clinical characteristics associated with flourishing mental health.Design Participants: Adults with an IMID (MS, 239; IBD, 225; RA 134; total 598) who were participating in a cohort study.Setting Tertiary care centre in Manitoba, Canada.Primary outcome measure Participants completed the Mental Health Continuum Short-Form (MHC-SF), which measures emotional, psychological and social well-being, and identifies flourishing mental health. This outcome was added midway through the study on the advice of the patient advisory group. Depression, anxiety, pain, fatigue and physical function were also assessed.Results Total MHC-SF and subscale scores were similar across IMID groups. Nearly 60% of participants were considered to have flourishing mental health, with similar proportions across disease types (MS 56.5%; IBD 58.7%; RA 59%, p=0.95). Older age was associated with a 2% increased odds of flourishing mental health per year of age (OR 1.02; 95% CI: 1.01 to 1.04). Clinically meaningful elevations in anxiety (OR 0.25; 95% CI: 0.12 to 0.51) and depressive symptoms (OR 0.074; 95% CI: 0.009 to 0.61) were associated with lower odds. Higher levels of pain, anxiety and depressive symptoms were associated with lower total Mental Health Continuum scores at the 50th quantile.Conclusions Over half of people with MS, IBD and RA reported flourishing mental health, with levels similar across the disease groups. Interventions targeting symptoms of depression and anxiety, and upper limb impairments, as well as resilience training may help a higher proportion of the IMID population achieve flourishing mental health.

Comorbid conditions commonly affect people with multiple sclerosis (MS). Population-based studies indicate that people with MS have an increased incidence of ischemic heart disease, cerebrovascular disease, peripheral vascular disease, and psychiatric disorders as compared to people without MS. People with MS from underrepresented minority and immigrant groups have higher comorbidity burdens. Comorbidities exert effects throughout the disease course, from symptom onset through diagnosis to the end of life. At the individual level, comorbidity is associated with higher relapse rates, greater physical and cognitive impairments, lower health-related quality of life, and increased mortality. At the level of the health system and society, comorbidity is associated with increased health care utilization, costs and work impairment. A nascent literature suggests that MS affects outcomes from comorbidities. Comorbidity management needs to be integrated into MS care, and this would be facilitated by determining optimal models of care.

Objective Among persons with immune-mediated inflammatory diseases (IMIDs) who received SARS-CoV-2 vaccines, we compared postvaccine antibody responses and IMID disease activity/states.Design Single-centre prospective cohort study.Setting Specialty ambulatory clinics in central Canada.Participants People with inflammatory arthritis (n=78; 77% rheumatoid arthritis), systemic autoimmune rheumatic diseases (n=84; 57% lupus), inflammatory bowel disease (n=93; 43% Crohn’s) and multiple sclerosis (n=72; 71% relapsing-remitting) (female 79.4%, white 84.7%, mean (SD) age 56.0 (14.3) years) received COVID-19 vaccinations between March 2021 and September 2022.Primary outcome Postvaccination anti-spike, anti-receptor binding domain (anti-RBD) and anti-nucleocapsid (anti-NC) IgG antibodies tested by multiplex immunoassays compared across vaccine regimens and with responses in 370 age-matched and sex-matched vaccinated controls.Secondary outcomes COVID-19 infection and self-reported IMID disease activity/state.Results Most (216/327, 66.1%) received homologous messenger RNA (mRNA) (BNT162b2 or mRNA1273) vaccines, 2.4% received homologous ChAdOx1 and 30.6% received heterologous vaccines (23.9% ChAdOx1/mRNA, 6.4% heterologous mRNA) for their first two vaccines (V1, V2). Seroconversion rates were 52.0% (91/175) for post-V1 anti-spike and 58.9% (103/175) for anti-RBD; 91.5% (214/234) for post-V2 anti-spike and 90.2% (211/234) for anti-RBD; and were lower than controls (post-V2 anti-spike 98.1% (360/370), p

ObjectiveThe literature that has examined healthcare access and needs of the multiple sclerosis (MS) population is limited. Currently, no research has engaged healthcare providers delivering services to this population to examine their perspectives on the provision of MS care in Canada. We aimed to summarize what good MS care should look like according to Canadian healthcare providers working with people with MS, and to identify the supports and resources required, within their care setting, to enable this standard of care.MethodsA qualitative descriptive approach was taken to analyze data from participants who responded to additional open-ended survey questions, within a larger “MS Models of Care Survey” targeting Canadian healthcare providers working with persons with MS.ResultsCurrently, a gap exists between what healthcare providers working with persons with MS believe MS care should encompass and what they are able to offer. Participants emphasized that their MS clinics are currently understaffed and patient-to-provider ratios are high, leaving very little time to address the array of healthcare concerns their patients present with. The healthcare providers overwhelmingly described that moving toward multidisciplinary team-based MS care that includes appropriate numbers of MS-trained neurologists, nurses, physiotherapists, occupational therapists, and mental health providers working within one location would be their prioritized approach to comprehensively managing MS care. This model of care enables all professionals to effectively coordinate care and use their time efficiently by only focusing on their area of expertise, all while meeting the needs of their patient in one setting, reducing wait-times and improving overall care.ConclusionTo meet the care needs of Canadians with MS, the healthcare system must consider standardizing and funding multidisciplinary team-based MS clinics, comparable to Stroke units, which continue to show favorable health outcomes after years of implementation.

Abstract Background Algorithms used to identify disease cases in administrative health data may be sensitive to changes in the data over time. Control charts can be used to assess how variations in administrative health data impact the stability of estimated trends in incidence and prevalence for administrative data algorithms. We compared the stability of incidence and prevalence trends for multiple juvenile diabetes algorithms using observed-expected control charts. Methods Eighteen validated algorithms for juvenile diabetes were applied to administrative health data from Manitoba, Canada between 1975 and 2018. Trends in disease incidence and prevalence for each algorithm were modelled using negative binomial regression and generalized estimating equations; model-predicted case counts were plotted against observed counts. Control limits were set as predicted case count ±0.8*standard deviation. Differences in the frequency of out-of-control observations for each algorithm were assessed using McNemar’s test with Holm-Bonferroni adjustment. Results The proportion of out-of-control observations for incidence and prevalence ranged from 0.57 to 0.76 and 0.45 to 0.83, respectively. McNemar’s test revealed no difference in the frequency of out-of-control observations across algorithms. A sensitivity analysis with relaxed control limits (2*standard deviation) detected fewer out-of-control years (incidence 0.19 to 0.33; prevalence 0.07 to 0.52), but differences in stability across some algorithms for prevalence. Conclusions Our study using control charts to compare stability of trends in incidence and prevalence for juvenile diabetes algorithms found no differences for disease incidence. Differences were observed between select algorithms for disease prevalence when using wider control limits.

ObjectiveResearch directly examining brain tissue has played an important role in understanding the pathology and pathogenesis of multiple sclerosis (MS) and other diseases of the central nervous system. Such research relies heavily on donations of post-mortem brain tissue yet little is known about the attitudes of people with multiple sclerosis (MS) about brain donation. We aimed to assess the attitudes of people with MS toward brain donation, their preferences related to discussions of brain donation, and factors associated with attitudes toward brain donation including sociodemographic and clinical characteristics, health literacy and religiosity.MethodsIn a cross-sectional study, we surveyed participants in the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry regarding their attitudes toward brain donation, reasons for participating or not participating in brain donation, and related communication preferences. We used multivariable logistic regression analyses to test factors associated with attitudes regarding brain donation.ResultsMost of the 4,520 participants were women (80.8%), self-identified as white (88.1%), with a post-secondary education, functional health literacy and moderate-severe disability. Sixty-two percent of participants would consider brain donation. Factors associated with considering brain donation included female gender, having a post-secondary education, being physically active, having moderate-severe disability and more comorbidities, and alcohol intake. Seventy-five percent of participants indicated that they preferred to receive information regarding brain donations from physicians.ConclusionTwo-thirds of people with MS would consider brain donation. People with MS desire to hear about brain donation from their health care providers rather than other sources.

Abstract Objective To examine the gut microbiota in individuals with and without pediatric‐onset multiple sclerosis (MS). Methods We compared stool‐derived microbiota of Canadian Pediatric Demyelinating Disease Network study participants ≤21 years old, with MS (disease‐modifying drug [DMD] exposed and naïve) or monophasic acquired demyelinating syndrome [monoADS] (symptom onset 0.1), taxa‐level and gut community networks did. MS (vs. monoADS) exhibited > fourfold higher relative abundance of the superphylum Patescibacteria (aRR = 4.2;95%CI:1.6–11.2, p = 0.004, Q = 0.01), and lower abundances of short‐chain fatty acid (SCFA)‐producing Lachnospiraceae (Anaerosporobacter) and Ruminococcaceae (p, Q eightfold higher abundance for Candidatus Stoquefichus and Tyzzerella (aRR = 8.8–12.8, p

Objective In this study, we aimed to determine the lifetime prevalence of substance use disorder (SUD) in a Canadian rheumatoid arthritis (RA) cohort and factors associated with SUD in RA. Methods Participants with RA (N = 154) were recruited via rheumatology clinics as part of a larger cohort study of psychiatric comorbidity in immune‐mediated inflammatory diseases. SUD is defined as the uncontrolled use of a substance despite the harmful consequences of its use. To identify lifetime SUD, the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition was administered to participants. Participants’ sociodemographic and RA clinical characteristics were also assessed. We examined factors associated with lifetime SUD using unadjusted and adjusted logistic regression modeling. Results Twenty‐three (14.9%) of 154 participants with RA met the criteria for a lifetime diagnosis of SUD. The majority of the participants were women, were White, had postsecondary education, and were on a disease‐modifying antirheumatic drug. Factors associated with increased odds of SUD were male sex (adjusted odds ratio [aOR]: 3.63, 95% confidence interval [CI]: 1.03‐12.73), younger age (aOR: 0.94, 95% CI: 0.90‐0.98), and ever smoking (aOR: 6.44, 95% CI: 1.53‐27.07). Conclusion We found that approximately 1 in 7 individuals with RA had a lifetime diagnosis of SUD, highlighting the importance of identifying and treating SUD in those with RA. In particular, the following factors were associated with higher odds of SUD: male sex, younger age, and smoking behaviors.

Abstract Background Neurological disability progression occurs across the spectrum of people living with multiple sclerosis (MS). Although there are a handful of disease-modifying treatments approved for use in progressive phenotypes of MS, there are no treatments that substantially modify the course of clinical progression in MS. Characterizing the determinants of clinical progression can inform the development of novel therapeutic agents and treatment approaches that target progression in MS, which is one of the greatest unmet needs in clinical practice. Canada, having one of the world’s highest rates of MS and a publicly-funded health care system, represents an optimal country to achieve in-depth analysis of progression. Accordingly, the overarching aim of the Canadian Prospective Cohort Study to Understand Progression in MS (CanProCo) is to evaluate a wide spectrum of factors associated with the clinical onset and rate of disease progression in MS, and to describe how these factors relate to one another to influence progression. Methods CanProCo is a prospective, observational cohort study with investigators specializing in epidemiology, neuroimaging, neuroimmunology, health services research and health economics. CanProCo’s study design was approved by an international review panel, comprised of content experts and key stakeholders. One thousand individuals with radiologically-isolated syndrome, relapsing-remitting MS, and primary-progressive MS within 10–15 years of disease onset will be recruited from 5 academic MS centres in Canada. Participants will undergo detailed clinical evaluation annually over 5 years (including advanced, app-based clinical data collection). In a subset of participants within 5–10 years of disease onset (n = 500), blood, cerebrospinal fluid, and research MRIs will be collected allowing an integrated, in-depth evaluation of factors contributing to progression in MS from multiple perspectives. Factors of interest range from biological measures (e.g. single-cell RNA-sequencing), MRI-based microstructural assessment, participant characteristics (self-reported, performance-based, clinician-assessed, health-system based), and micro and macro-environmental factors. Discussion Halting the progression of MS remains a fundamental need to improve the lives of people living with MS. Achieving this requires leveraging transdisciplinary approaches to better characterize why clinical progression occurs. CanProCo is a pioneering multi-dimensional cohort study aiming to characterize these determinants to inform the development and implementation of efficacious and effective interventions.

Background and objectivesLittle is known of the potential sex and age differences in the MS prodrome. We investigated sex and age differences in healthcare utilization during the MS prodrome.MethodsThis was a population-based matched cohort study linking administrative and clinical data from British Columbia, Canada (population = 5 million). MS cases in the 5 years preceding a first demyelinating event (“administrative cohort;” n = 6,863) or MS symptom onset (“clinical cohort;” n = 966) were compared to age-, sex- and geographically-matched controls (n = 31,865/4,534). Negative binomial and modified Poisson models were used to compare the rates of physician visits and hospitalizations per international classification of diseases chapter, and prescriptions filled per drug class, between MS cases and controls across sex and age-groups (< 30, 30–49, ≥50 years).ResultsIn the administrative cohort, males with MS had a higher relative rate for genitourinary-related visits (males: adjusted Rate Ratio (aRR) = 1.65, females: aRR = 1.19, likelihood ratio test P = 0.02) and antivertigo prescriptions (males: aRR = 4.72, females: aRR = 3.01 P < 0.01). Injury and infection-related hospitalizations were relatively more frequent for ≥50-year-olds (injuries < 30/30–49/≥50: aRR = 1.16/1.39/2.12, P < 0.01; infections 30–49/≥50: aRR = 1.43/2.72, P = 0.03), while sensory-related visits and cardiovascular prescriptions were relatively more common in younger persons (sensory 30–49/≥50: aRR = 1.67/1.45, P = 0.03; cardiovascular < 30/30–49/≥50: aRR = 1.56/1.39/1.18, P < 0.01). General practitioner visits were relatively more frequent in males (males: aRR = 1.63, females: aRR = 1.40, P < 0.01) and ≥50-year-olds (< 30/≥50: aRR = 1.32/1.55, P = 0.02), while differences in ophthalmologist visits were disproportionally larger among younger persons, < 50-years-old (< 30/30–49/≥50: aRR = 2.25/2.20/1.55, P < 0.01). None of the sex and age-related differences in the smaller clinical cohort reached significance (P ≥ 0.05).DiscussionSex and age-specific differences in healthcare use were observed in the 5 years before MS onset. Findings demonstrate fundamental heterogeneity in the MS prodromal presentation.

ObjectiveLittle work has evaluated integrated models of care in multiple sclerosis (MS) and the composition of MS care teams across Canada is largely unknown. We aimed to gather information regarding existing models of MS care across Canada, and to assess the perceptions of health care providers (HCPs) regarding the models of care required to fully meet the needs of the person with MS.MethodsWe conducted an anonymous online survey targeting Canadian HCPs working in MS Clinics, and neurologists delivering MS care whether or not they were based in an MS Clinic. We queried the types of HCPs delivering care within formal MS Clinics, wait times for HCPs, the perceived importance of different types of HCPs for good quality care, assessments conducted, and whether clinic databases were used. We summarized survey responses using descriptive statistics.ResultsOf the 716 HCPs to whom the survey was distributed, 100 (13.9%) people responded. Of the 100 respondents, 85 (85%) indicated that their clinical practice included people with MS and responded to specific questions about clinical care. The most common types of providers within MS Clinics with integrated models of care were neurologists and MS nurses. Of 23 responding MS Clinics, 10 (43.5%) indicated that there were not enough neurologists, and 16 (69.6%) indicated that there were not enough non-neurologist HCPs to provide adequate care. More than 50% of clinics reported wait times exceeding 3 months for physiatrists, physiotherapists, psychiatrists, psychologists, neuropsychologists and urologists; in some clinics wait times for these providers exceeded 1 year. Multiple disciplines were identified as important or very important for delivering good quality MS care. Over 90% of respondents thought it was important for neurologists, nurse practitioners, MS nurses and psychiatrists to be co-located within MS Clinics.ConclusionCanadian HCPs viewed the ideal MS service as being multidisciplinary in nature and ideally integrated. Efforts are needed to improve timely access to specialized MS care in Canada, and to evaluate how outcomes are influenced by access to care.

ObjectiveVascular comorbidities are associated with reduced cognitive performance and with changes in brain structure in people with multiple sclerosis (MS). Understanding causal pathways is necessary to support the design of interventions to mitigate the impacts of comorbidities, and to monitor their effectiveness. We assessed the inter-relationships among vascular comorbidity, cognition and brain structure in people with MS.MethodsAdults with neurologist-confirmed MS reported comorbidities, and underwent assessment of their blood pressure, HbA1c, and cognitive functioning (i.e., Symbol Digit Modalities Test, California Verbal Learning Test, Brief Visuospatial Memory Test-Revised, and verbal fluency). Test scores were converted to age-, sex-, and education-adjusted z-scores. Whole brain magnetic resonance imaging (MRI) was completed, from which measures of thalamic and hippocampal volumes, and mean diffusivity of gray matter and normal-appearing white matter were converted to age and sex-adjusted z-scores. Canonical correlation analysis was used to identify linear combinations of cognitive measures (cognitive variate) and MRI measures (MRI variate) that accounted for the most correlation between the cognitive and MRI measures. Regression analyses were used to test whether MRI measures mediated the relationships between the number of vascular comorbidities and cognition measures.ResultsOf 105 participants, most were women (84.8%) with a mean (SD) age of 51.8 (12.8) years and age of symptom onset of 29.4 (10.5) years. Vascular comorbidity was common, with 35.2% of participants reporting one, 15.2% reporting two, and 8.6% reporting three or more. Canonical correlation analysis of the cognitive and MRI variables identified one pair of variates (Pillai's trace = 0.45, p = 0.0035). The biggest contributors to the cognitive variate were the SDMT and CVLT-II, and to the MRI variate were gray matter MD and thalamic volume. The correlation between cognitive and MRI variates was 0.50; these variates were used in regression analyses. On regression analysis, vascular comorbidity was associated with the MRI variate, and with the cognitive variate. After adjusting for the MRI variate, vascular comorbidity was not associated with the cognitive variate.ConclusionVascular comorbidity is associated with lower cognitive function in people with MS and this association is partially mediated via changes in brain macrostructure and microstructure.

ObjectiveUse of benzodiazepines and Z-drugs (non-benzodiazepine sedative hypnotics) is controversial due to adverse health outcomes in the general population. However, little is known about their use in people with multiple sclerosis (MS). We estimated the incidence and prevalence of benzodiazepine and Z-drug use (jointly BZD) in the MS population as compared to an age-, sex- and geographically-matched population without MS, and examined the association of mood/anxiety disorders with the use of BZD over a twenty-year period.MethodsUsing administrative data from Manitoba, Canada, we identified 2,985 persons with incident MS and 14,891 persons without MS matched 5:1 on sex, birth year and region. We applied validated case definitions to identify persons with any mood/anxiety disorder. Dispensations of BZD were identified. To assess the association between MS, mood/anxiety disorders and BZD use we constructed generalized linear models adjusting for age, sex, index year, socioeconomic status, urban/rural residence, physical comorbidities, and health care use. We also examined patterns of BZD use.ResultsIn 2016, the crude incidence of benzodiazepine use in the MS cohort was 2.10% (95%CI: 1.43–2.98%), 1.49-fold higher than in the non-MS cohort (1.41%; 95%CI: 1.18–1.67%). The crude incidence of Z-drug use in the MS cohort was 1.77% (95%CI: 1.20–2.51%), 1.78-fold higher than in the non-MS cohort (0.99%; 95%CI: 0.81–1.21%). After adjusting for covariates, among individuals without an active mood/anxiety disorder, the MS cohort had a 39% increased incidence rate of benzodiazepine use and a 72% increased incidence rate of Z-drug use as compared to the non-MS cohort. Among individuals with an active mood/anxiety disorder, the incidence of BZD use did not differ between the MS and non-MS cohorts. A higher proportion of people with MS used BZD for ≥6 months than people without MS.ConclusionUse of BZD is more common in people with MS than in general population controls, and use of these agents is in persons with MS is often chronic.

BackgroundEvidence regarding the efficacy or effectiveness of the disease-modifying drugs (DMDs) in the older multiple sclerosis (MS) population is scarce. This has contributed to a lack of evidence-based treatment recommendations for the ageing MS population in practice guidelines. We examined the relationship between age (

BackgroundWomen with multiple sclerosis (MS) may face challenges related to managing reproduction, pregnancy, and menopause while simultaneously managing their disease. The purpose of this scoping review was to map the literature broadly related to topics relevant to women's health in MS to inform the clinical and research communities about the existing types and sources of evidence and knowledge gaps. Apart from coverage of topics within the field of women's health, we were interested in potential gaps related to geographic and racial and ethnic diversity. We also aimed to understand the degree of inclusion of women with progressive MS in this research.MethodsWe searched the EMBASE and Ovid Medline databases from 1980 until November 23, 2020. We included case-control and cohort studies, clinical trials and case series published in any language, conducted in women with MS, clinically isolated syndrome, or radiologically isolated syndrome, that addressed women's health. Two reviewers independently screened abstracts and full-text reports for study inclusion, and completed data extraction.ResultsOf 112,106 citations screened, 1,041 underwent full-text review and 353 met the inclusion criteria. The number of studies regarding women's health has increased exponentially over time. Almost half of the studies were conducted (at least in part) in Europe, while 21.7% were conducted in North America; only one study was conducted in Africa. Most studies did not report the race or ethnicity of their participants (n = 308, 87.2%). Among the 353 studies, 509 topics were reported as some studies addressed more than one topic. Over one-third of these focused on pregnancy (n = 201, 37.2%), followed by fetal/neonatal outcomes (14.4%) and sexual dysfunction (10%). Among the 201 studies that focused on pregnancy, only 51 (25.4%) included participants with progressive MS.ConclusionsThis review identifies important knowledge gaps related to women's health in MS and particularly the need for future studies to include participants with a broader range of races and ethnicities, with progressive MS, and living in Asia-Pacific and African regions.

Objective: Since the properties of health-related quality of life measures vary across samples, studies directly comparing the properties of different measures can be useful in understanding their relative strengths and limitations. We aimed to compare the psychometric properties of the Health Utilities Index Mark III (HUI3) and the Multiple Sclerosis Impact Scale-29 (MSIS-29).Methods: In Spring 2020, North American Research Committee on Multiple Sclerosis (NARCOMS) Registry participants completed the HUI3, MSIS-29, Patient Determined Disease Steps (PDDS) and SymptoMScreen. For the HUI3 and MSIS-29 we assessed floor and ceiling effects, construct validity, and internal consistency reliability. We used relative efficiency to compare the discriminating ability of the two measures with respect to disability.Results: We included 5,664 participants in the analysis, with mean (SD) age 63 (10.1) years; 4,579 (80.8%) were women. For the HUI3 the mean (SD) score was 0.44 (0.32), for the MSIS-29 physical it was 34.0 (24.2) and for the MSIS-29 psychological it was 25.9 (20.4). Neither of the measures had floor or ceiling effects, and internal consistency reliability was > 0.70 for both. The HUI3 and MSIS-29 physical were strongly correlated (r = −0.78; 95%CI:−0.79,−0.77). The correlation between the HUI3 and MSIS-29 psychological was weaker but remained moderately strong (r = −0.64; 95%CI:−0.66,−0.63). After adjusting for sociodemographic and clinical factors, relative efficiency to discriminate between disability (PDDS) groups was highest for the MSIS-29 physical scale, followed by the HUI3.Conclusion: Both measures had adequate validity and reliability. The MSIS-29 physical discriminated between disability groups better than the HUI3.

Objective: We developed and internally validated an algorithm for disability status in multiple sclerosis (MS) using administrative data.Methods: We linked administrative data from Manitoba, Canada to a clinical dataset with Expanded Disability Status Scale (EDSS) scores for people with MS. Clinical EDSS scores constituted the reference standard. We created candidate indicators using the administrative data. These included indicators based on use of particular health care services (home care, long-term care, rehabilitation admission), use of specific diagnostic codes (such as spasticity, quadriplegia), and codes based on use of Employment and Income Insurance. We developed algorithms to predict severe disability (EDSS ≥6.0), and to predict disability as a continuous measure. We manually developed algorithms, and also employed regression approaches. After we selected our preferred algorithms for disability, we tested their association with health care use due to any cause and infection after potential confounders.Results: We linked clinical and administrative data for 1,767 persons with MS, most of whom were women living in urban areas. All individual indicators tested had specificities >90% for severe disability, and all but a diagnosis of visual disturbance had positive predictive values (PPV) >70%. The combination of home care or long-term care use or rehabilitation admission had a sensitivity of 61.9%, specificity of 90.76%, PPV of 70.06% and negative predictive of 87.21%. Based on regression modeling, the best-performing algorithm for predicting the EDSS as a continuous variable included age, home care use, long-term care admission, admission for rehabilitation, visual disturbance, other paralytic syndromes and spasticity. The mean difference between observed and predicted values of the EDSS was −0.0644 (95%CI −0.1632, 0.0304). Greater disability, whether measured using the clinical EDSS or either of the administrative data algorithms was similarly associated with increased hospitalization rates due to any cause and infection.Conclusion: We developed and internally validated an algorithm for disability in MS using administrative data that may support population-based studies that wish to account for disability status but do not have access to clinical data sources with this information. We also found that more severe disability is associated with increased health care use, including due to infection.

Background: Although the aggregate of data among patients with multiple sclerosis (MS) have shown similar efficacy between dimethyl fumarate (DMF) and fingolimod (FTY), most studies have not assessed long-term worsening of disability. We compared long-term disability worsening over 5 years, as assessed by the Patient-Determined Disease Steps (PDDS), among participants with MS treated with DMF or FTY. Methods: We identified individuals in the North American Research Committee on Multiple Sclerosis (NARCOMS) registry who had relapsing-remitting MS (RRMS), residing in the United States (Spring 2011 to Spring 2018), who initiated treatment with DMF ( n = 689) or FTY ( n = 565) and had ⩾1 year follow-up on index treatment. Participants receiving DMF who were previously treated with FTY and those on FTY previously treated with DMF were excluded. Propensity score matching at baseline was used to match FTY-treated to DMF-treated participants. Time to 6-month confirmed disability worsening (⩾1-point increase on PDDS, sustained for ⩾6 months) was estimated using Cox regression. A sensitivity analysis was conducted to account for differences in the duration of index exposure between DMF and FTY groups. Results: After propensity score matching, 468 DMF-treated participants were matched with 468 FTY-treated participants. Median treatment duration was 3.0 years for DMF and 4.0 years for FTY. At 5 years, 68.3% [95% confidence interval (CI): 62.4–73.5] of DMF-treated participants and 63.3% (95% CI: 59.6–70.1) treated with FTY were free from 6-month confirmed PDDS worsening [hazard ratio (HR) 1.01 (95% CI: 0.79–1.28); p = 0.95]. Results were similar in the sensitivity analysis: 70.5% (95% CI: 61.8–77.6) of DMF-treated participants and 72.7% (95% CI: 65.4–78.6) of FTY-treated participants were free from 6-month confirmed PDDS worsening [HR: 1.04 (95% CI: 0.71–1.51); p = 0.84]. Conclusions: In participants with MS from the NARCOMS registry, there was no significant difference in confirmed disability (PDDS) worsening over 5 years between those treated with DMF versus FTY.

Background: Anxiety is common in patients with rheumatoid arthritis (RA) and associated with worse RA outcomes. This study assessed the feasibility and preliminary health impacts (mental and physical) of a non-therapist assisted, online mental health intervention targeting anxiety in this population. Methods: Participants with confirmed RA and elevated anxiety symptoms were enrolled into the Worry and Sadness program, an Internet-based cognitive-behavioral therapy (iCBT) intervention for anxiety and depression shown to be effective in the general population. Validated self-report measures of anxiety, depression, pain interference, fatigue, physical health-related quality of life, functional status, and patient-reported disease severity were collected at baseline, post-intervention, and at three-month follow-up. Emotional distress scores were tracked between lessons. Participants provided qualitative feedback in writing post-intervention. Results: We analyzed the responses of 34 participants; the majority was female (86%) and the mean age was 57 (SD = 13). Of these, 80% (n = 28) completed the study in its entirety. Among these completers, 94.1% described the program as worthwhile. We found statistically significant improvements in anxiety, depression and fatigue from baseline to three-month follow-up, with small to large effect sizes (d = 0.39–0.81). Post-hoc analyses revealed that statistically significant change occurred between baseline and post-intervention for anxiety and depression and was maintained at three-month follow-up, whereas statistically significant change occurred between baseline and three-month follow-up for fatigue. Statistically significant reductions in emotional distress occurred across the program, with a large effect size (d = 1.16) between the first and last lesson. Conclusion: The Worry and Sadness program shows promise as a feasible resource for improving mental health in RA.

Objective To determine whether better medication adherence in multiple sclerosis (MS) might be due to specialised disease-modifying drug (DMD) support programmes by: (1) establishing higher adherence in MS than in other chronic diseases and (2) determining if higher adherence is associated with patient-specific or treatment-specific factors.Design Retrospective cohort study with data from 1 January 1996 to 31 December 2015.Setting Population-based health administrative data from three Canadian provinces.Participants Individual cohorts were created using validated case definitions for MS, epilepsy, Parkinson’s disease (PD) and rheumatoid arthritis (RA). Subjects were included if they received ≥1 dispensation for a disease-related drug between 1 January 1997 and 31 December 2014.Main outcome measure(s) Proportion of subjects with optimal adherence (≥80%) measured by the medication possession ratio 1 year after the index date (first dispensation of disease-related drug).Results 126 478 subjects were included in the primary analysis (MS, n=6271; epilepsy, n=55 739; PD, n=21 304; RA, n=43 164). Subjects with epilepsy (adjusted OR, aOR 0.29; 95% CI 0.19 to 0.45), PD (aOR 0.42; 95% CI 0.29 to 0.63) or RA (aOR 0.26; 95% CI 0.19 to 0.35) were less likely to have optimal 1-year adherence compared with subjects with MS. Within the MS cohort, adherence was higher for DMD than for chronic-use non-MS medications, and no consistent patient-related predictors of adherence were observed across all four non-MS medication classes, including having optimal adherence to DMD.Conclusions Subjects with MS were significantly more likely to have optimal 1-year adherence than subjects with epilepsy, RA and PD, and optimal adherence appears related to treatment-specific factors rather than patient-related factors. This supports the hypothesis that higher adherence to the MS DMDs could be due to the specialised support programmes; these programmes may serve as a model for use in other chronic conditions.

Background: 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.Objectives: 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.Methods: 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.Results: 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.Conclusion: 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.

We aimed to examine rates of breast and cervical cancer screening in women with immune-mediated inflammatory diseases (IMID), including inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA) versus a matched cohort with IMID; and examine the association of psychiatric comorbidity with screening in these populations. We conducted a retrospective cohort study in Manitoba, Canada using administrative data. We identified women with IBD, MS and RA, and controls without these IMID matched on age and region. Annually, we identified individuals with any active mood/anxiety disorder. Using physician claims, we determined the proportion of each cohort who had cervical cancer screening within three-year intervals, and mammography screening within two-year intervals. We modeled the difference in the proportion of the IMID and matched cohorts who underwent mammography; and pap tests using log-binomial regression with generalized estimating equations, adjusting for sociodemographics, comorbidity and immune therapy use. We tested for additive interactions between cohort and mood/anxiety disorder status. During 2006–2016, we identified 17,230 women with IMID (4,623 with IBD, 3,399 with MS, and 9,458 with RA) and 85,349 matched controls. Having an IMID was associated with lower (-1%) use of mammography; however, this reflected a mixture of more mammography in the IBD cohort (+2.9%) and less mammography in the MS (-4.8 to -5.2%) and RA (-1.5%) cohorts. Within the IBD, MS and RA cohorts, having an active mood/anxiety disorder was associated with more mammography use than having an inactive mood/anxiety disorder. The MS and RA cohorts were less likely to undergo Pap testing than their matched cohorts. In the absence of an active mood/anxiety disorder, the IBD cohort was more likely to undergo Pap testing than its matched cohort; the opposite was true when an active mood/anxiety disorder was present. Among women with an IMID, mood/anxiety disorder influence participation in cancer screening.

BackgroundAccess to neurology specialty care can influence outcomes in individuals with multiple sclerosis (MS), but may vary based on patient sociodemographic characteristics, including immigration status.ObjectiveTo compare health services utilization in the year of MS diagnosis, one year before diagnosis and two years after diagnosis in immigrants versus long-term residents in Ontario, Canada.MethodsWe identified incident cases of MS among adults aged 20-65 years by applying a validated algorithm to health administrative data in Ontario, Canada, a region with universal health insurance and comprehensive coverage. We separately assessed hospitalizations, emergency department (ED) visits, outpatient neurology visits, other outpatient specialty visits, and primary care visits. We compared rates of health service use in immigrants versus long-term residents using negative binomial regression models with generalized estimating equations adjusted for age, sex, socioeconomic status, urban/rural residence, MS diagnosis calendar year, and comorbidity burden.ResultsFrom 2003 to 2014, there were 13,028 incident MS cases in Ontario, of whom 1,070 (8.2%) were immigrants. As compared to long-term residents, rates of hospitalization were similar (Adjusted rate ratio (ARR) 0.86; 95% CI: 0.73-1.01) in immigrants the year before MS diagnosis, but outpatient neurology visits (ARR 0.93; 95% CI: 0.87-0.99) were slightly less frequent. However, immigrants had higher rates of hospitalization during the diagnosis year (ARR 1.20, 95% CI: 1.04-1.39), and had greater use of outpatient neurology (ARR 1.17, 95% CI: 1.12-1.23) but fewer ED visits (ARR 0.86; 95% CI: 0.78-0.96). In the first post-diagnosis year, immigrants continued to have greater numbers of outpatient neurology visits (ARR 1.16; 95% CI: 1.10-1.23), but had fewer hospitalizations (ARR 0.79; 95% CI: 0.67-0.94).ConclusionsOverall, our findings were reassuring concerning health services access for immigrants with MS in Ontario, a publicly funded health care system. However, immigrants were more likely to be hospitalized despite greater use of outpatient neurology care in the year of MS diagnosis. Reasons for this may include more severe disease presentation or lack of social support among immigrants and warrant further investigation.

To investigate a potential risk for multiple sclerosis (MS) after vaccination with Arepanrix, the GlaxoSmithKline AS03-adjuvanted influenza A(H1N1)pdm09 vaccine, we used the provincewide immunization registry for Manitoba, Canada, to match 341,347 persons vaccinated during the 2009 pandemic to 485,941 unvaccinated persons on age, sex, address, and a propensity score measuring the probability of vaccination. We used a previously validated algorithm to identify MS cases from provincial hospital, physician, and prescription drug claims databases. After 12 months of follow-up, the age-adjusted incidence rate of MS was 17.7 cases per 100,000 person-years in the Arepanrix cohort and 24.2 per 100,000 in the unvaccinated cohort. The corresponding adjusted hazard ratio was 0.9. We observed similar patterns when we measured incidence over the entire follow-up period. The AS03 adjuvant, a candidate for inclusion in future pandemic vaccines, does not appear to increase the short-term risk for MS when included in influenza vaccines.

Abstract Background Though many people with multiple sclerosis (MS) have comorbidities, the use of generic and disease-specific health related quality of life (HRQOL) scales to discriminate the effects of comorbidity has not been established. The utility of these scales to discriminate differences between persons with varying levels of disability is also unknown. Methods Using online questionnaires, a convenience sample of Albertans with MS was recruited between July 2011 and March 2013. Participants completed demographic questions, a validated comorbidity questionnaire, a self-reported disability scale, and the following HRQOL scales: the Short Form (SF)-36, SF-6D, Health Utilities Index-Mark III (HUI-III), and Multiple Sclerosis Quality of Life-54 (MSQOL-54). The ability of each HRQOL scale to distinguish between comorbidity groups was assessed using a one-way analysis of covariance, adjusting for age, sex, disease course, and disability level. Results Five hundred sixty three participants completed all relevant questionnaires. All HRQOL measures distinguished between persons with or without depression, while none were able to distinguish between participants with or without hypertension, thyroid disease, irritable bowel syndrome, or osteoporosis. The SF-36 physical scale, SF-6D, HUI-III, and MSQOL-54 physical scales were able to distinguish between all disability groups, though the HUI-III was better able to distinguish between individuals with moderate versus severe disability. Conclusions Disease-specific measures would discriminate better between those with and without comorbidities than generic-specific measures and the HUI-III would discriminate best between persons with differing severities of disability. Generic or disease-specific measures may be useful in future studies examining the effects of comorbidity in MS and the effects of treatment of comorbidities in MS.

Abstract Objective Researchers have developed case definitions to estimate incidence and lifetime prevalence of depression and anxiety disorders in multiple sclerosis (MS) using administrative data. For policymakers however, the prevalence of a disease requiring ongoing treatment during a given period such as annual period prevalence may be more relevant for decision-making. We tested a case definition for annual period prevalence of depression and anxiety disorders in MS using administrative data. Results Using population-based administrative (health claims) data from Manitoba, Canada we identified 1922 persons with incident MS from 1989 to 2012, and 11,392 age, sex and geographically-matched controls from the general population. As compared to controls, MS patients had an elevated annual prevalence ratio of depression (1.77; 95% confidence interval [CI] 1.64, 1.91), and anxiety disorders (1.46; 95% CI 1.35, 1.58). The annual prevalence of depression in our matched cohort was similar to that observed in the 2012 Canadian Community Health Survey, although the annual prevalence of anxiety was slightly higher. Administrative data can be used to estimate the annual period prevalence of psychiatric disorders in MS.

Abstract Background In recent years, shared decision making (SDM) has been promoted as a model to guide interactions between persons with MS and their neurologists to reach mutually satisfying decisions about disease management – generally about deciding treatment courses of prevailing disease modifying therapies. In 2009, Dr. Paolo Zamboni introduced the world to his hypothesis of Chronic Cerebrospinal Venous Insufficiency (CCSVI) as a cause of MS and proposed venous angioplasty (‘liberation therapy’) as a potential therapy. This study explores the discussions that took place between persons with MS (PwMS) and their neurologists about CCSVI against the backdrop of the recent calls for the use of SDM to guide clinical conversations. Methods In 2012, study researchers conducted focus groups with PwMS (n = 69) in Winnipeg, Canada. Interviews with key informants were also carried out with 15 participants across Canada who were stakeholders in the MS community: advocacy organizations, MS clinicians (i.e. neurologists, nurses), clinical researchers, and government health policy makers. Results PwMS reported a variety of experiences when attempting to discuss CCSVI with their neurologist. Some found that there was little effort to engage in desired discussions or were dissatisfied with critical or cautious stances of their neurologist. This led to communication breakdowns, broken relationships, and decisions to autonomously access alternative opinions or liberation therapy. Other participants were appreciative when clinicians engaged them in discussions and were more receptive to more critical appraisals of the evidence. Key informants reported that they too had heard of neurologists who refused to discuss CCSVI with patients and that neurology as a whole had been particularly vilified for their response to the hypothesis. Clinicians indicated that they had shared information as best they could but recommended against seeking liberation therapy. They noted that being respectful of patient emotions, values, and hope were also key to maintaining good relationships. Conclusions While CCSVI proved a challenging context to carry out patient-physician discussions and brought numerous tensions to the surface, following the approach of SDM can minimize the potential for unfortunate outcomes as much as possible because it is based on principles of respect and more two-way communication.

Introduction: The objective of our study was to present model-based estimates and projections on current and future health and economic impacts of multiple sclerosis (MS) in Canada over a 20-year time horizon (2011–2031). Methods: Using Statistics Canada’s Population Health Microsimulation Model (POHEM) framework, specifically the population-based longitudinal, microsimulation model named, we identified people with MS from health administrative data sources and derived incidence and mortality rate parameters from a British Columbia population-based cohort for future MS incidence and mortality projections. We also included a utility-based measure (Health Utilities Index Mark 3) reflecting states of functional health to allow projections of health-related quality of life. Finally, we estimated caregiving parameters and health care costs from Canadian national surveys and health administrative data and included them as model parameters to assess the health and economic impact of the neurological conditions. Results: The number of incident MS cases is expected to rise slightly from 4 051 cases in 2011 to 4 794 cases per 100,000 population in 2031, and the number of Canadians affected by MS will increase from 98 385 in 2011 to 133 635 in 2031. The total per capita health care cost (excluding out-of-pocket expenses) for adults aged 20 and older in 2011 was about $16 800 for individuals with MS, and approximately $2 500 for individuals without a neurological condition. Thus, after accounting for additional expenditures due to MS (excluding out-of-pocket expenses), total annual health sector costs for MS are expected to reach $2.0 billion by 2031. As well, the average out-of-pocket expenditure for people with MS was around $1 300 annually throughout the projection period. Conclusion: MS is associated with a significant economic burden on society, since it usually affects young adults during prime career- and family-building years. Canada has a particularly high prevalence of MS, so research such as the present study is essential to provide a better understanding of the current and future negative impacts of MS on the Canadian population, so that health care system policymakers can best plan how to meet the needs of patients who are affected by MS. These findings also suggest that identifying strategies to prevent MS and more effectively treat the disease are needed to mitigate these future impacts.

Introduction : L’objectif de notre étude est de présenter des estimations et des projections des répercussions épidémiologiques et économiques de la sclérose en plaques (SP) au Canada sur 20 ans (2011-2031). Méthodologie : Nous avons utilisé un modèle de microsimulation de la santé de la population (POHEM) de Statistique Canada, plus précisément le modèle longitudinal de microsimulation démographique appelé POHEM - Maladies neurologiques. Nous avons sélectionné les personnes atteintes de SP à partir de sources de données administratives sur la santé et dérivé les paramètres liés à l’incidence de la maladie et au taux de décès d’une étude de cohorte de la Colombie-Britannique afin de prévoir quels seront l’incidence de la SP et son taux de décès. Nous avons également inclus une mesure reposant sur l’utilité (Health Utilities Index Mark 3) qui rend compte des états de santé fonctionnelle afin de réaliser des projections sur la qualité de vie liée à la santé. Enfin, nous avons estimé les paramètres de prestation de soins et de coûts des soins de santé à partir de sondages nationaux du Canada et de données administratives sur la santé et nous les avons inclus comme paramètres dans le modèle visant à évaluer les répercussions économiques et sur la santé des maladies neurologiques. Résultats : On anticipe une légère augmentation du nombre de cas incidents de SP, passant de 4 051 cas pour 100 000 personnes en 2011 à 4 974 en 2031. Le nombre de Canadiens touchés par la SP passera ainsi de 98 385 en 2001 à 133 635 en 2031. Le coût total des soins de santé par personne (à l’exception des dépenses directes) pour les adultes de 20 ans et plus atteints de SP en 2011 était d’environ 16 800 $, contre un peu moins de 2500 $ pour ceux ne souffrant d’aucune affection neurologique. Si on comptabilise les dépenses supplémentaires liées à la SP (à l’exception des dépenses directes), les coûts totaux annuels de la SP pour le secteur de la santé devraient donc atteindre deux milliards de dollars d’ici 2031. Par ailleurs, les dépenses directes moyennes des personnes atteintes de SP seront d’environ 1300 $ par année tout au long de la période de projection. Conclusion : La SP est associée à un important fardeau économique pour la société car elle touche surtout de jeunes adultes à un moment fondateur pour leur vie professionnelle et leur vie familiale. Sa prévalence étant particulièrement élevée au Canada, des recherches comme la nôtre sont essentielles afin de mieux comprendre les répercussions actuelles et futures de la SP sur la population canadienne, afin que les décideurs du réseau de la santé puissent mieux planifier les besoins en soins de santé pour les malades qui en sont atteints. Selon ces résultats, des stratégies pour prévenir la SP et la traiter plus efficacement sont essentielles pour en atténuer les futures répercussions.

We aimed to compare health care utilization of children with pediatric-onset multiple sclerosis to that of age, sex and geographically-matched children without multiple sclerosis. Using population-based administrative data from Ontario, Canada for the period 2003-2014, we applied a validated case definition to identify persons aged ≤18 years with multiple sclerosis. We identified up to 5 children without multiple sclerosis matched on sex, age, and region of residence. In each cohort, we determined annual rates of any hospitalization and physician services use. Using general linear models we compared utilization rates adjusting for age, sex, region, socioeconomic status and year. Subsequently, we limited the analysis to incident cases of multiple sclerosis and their matches, and compared rates of utilization in the year of multiple sclerosis diagnosis, and the three years thereafter. We identified 659 youth with multiple sclerosis (428 incident cases), and 3,294 matched controls. Two-thirds of both cohorts were female. After adjustment for sociodemographic factors and year, the multiple sclerosis cohort was more likely to be hospitalized than the matched cohort (odds ratio 15.2; 95%CI: 12.0, 19.1), and had higher rates of ambulatory physician visits (rate ratio 4.58; 95%CI: 4.26, 4.92). The odds of hospitalization (odds ratio 40.1; 95%CI: 27.1, 59.5) and physician visits (rate ratio 5.14; 95%CI: 4.63, 5.71) were markedly elevated in the year of MS diagnosis, declining thereafter but remaining elevated versus the matched cohort. Children with multiple sclerosis have substantially elevated rates of health care utilization as compared to matched children without multiple sclerosis, over calendar time and throughout the early disease course.

Impairment in work function is a frequent outcome in patients with chronic conditions such as immune-mediated inflammatory diseases (IMID), depression and anxiety disorders. The personal and economic costs of work impairment in these disorders are immense. Symptoms of pain, fatigue, depression and anxiety are potentially remediable forms of distress that may contribute to work impairment in chronic health conditions such as IMID. The present study evaluated the association between pain [Medical Outcomes Study Pain Effects Scale], fatigue [Daily Fatigue Impact Scale], depression and anxiety [Hospital Anxiety and Depression Scale] and work impairment [Work Productivity and Activity Impairment Scale] in four patient populations: multiple sclerosis (n = 255), inflammatory bowel disease (n = 248, rheumatoid arthritis (n = 154) and a depression and anxiety group (n = 307), using quantile regression, controlling for the effects of sociodemographic factors, physical disability, and cognitive deficits. Each of pain, depression symptoms, anxiety symptoms, and fatigue individually showed significant associations with work absenteeism, presenteeism, and general activity impairment (quantile regression standardized estimates ranging from 0.3 to 1.0). When the distress variables were entered concurrently into the regression models, fatigue was a significant predictor of work and activity impairment in all models (quantile regression standardized estimates ranging from 0.2 to 0.5). These findings have important clinical implications for understanding the determinants of work impairment and for improving work-related outcomes in chronic disease.

ABSTRACT Objectives Much clinical knowledge about multiple sclerosis (MS) has been gained from patients who attend MS specialty clinics. However, there is limited information about whether these patients are representative of the wider MS population. The objective of this study was to compare incident MS cases who were MS clinic users to non-users of the specialty MS clinics in British Columbia, Canada. Approach This was a retrospective record linkage cohort study using prospectively collected data from the BCMS database and province-wide health administrative databases. Incident MS cases were identified in the general population using a validated algorithm of hospital and physician diagnostic codes. Results There were 2,841 incident MS cases between 1996 and 2004 including 1,648 (58%) that had registered at an MS clinic (‘clinic cases’) and 1,193 (42%) that had not (‘non-clinic cases’). Sex and socioeconomic status distributions were similar; however, non-clinic cases were older, accessed health services more frequently, and had a higher burden of comorbidity than clinic cases. Only 1% of the non-clinic cases had filled a prescription for an MS-specific disease-modifying therapy, compared to 51% of the clinic cases. Conclusion Our findings have several important implications: even within a publicly funded healthcare system, a high proportion of individuals with MS may not access a specialty MS clinic; the needs of MS patients managed in the community may differ from those referred to an MS clinic; findings from studies involving clinic-based MS cohorts may not always be generalizable to the wider MS population; and access to population-based health administrative data offers the opportunity to gain a broader understanding of MS.

OBJECTIVE: To evaluate the epidemiological evidence for an etiological role of Epstein-Barr virus in multiple sclerosis (MS).