Low-Field (64mT) Portable MRI for Rapid Point-of-Care Diagnosis of DIS in Patients Presenting with Optic Neuritis.

BACKGROUND AND PURPOSE: Low-field 64mT portable brain MRI (pMRI) has recently shown diagnostic promise for MS. This study aimed to evaluate the utility of pMRI in assessing dissemination in space (DIS) in patients presenting with optic neuritis and determine whether deploying pMRI in the MS clinic can shorten the time from symptom onset to MRI. MATERIALS AND METHODS: Newly diagnosed optic neuritis patients referred to a tertiary academic MS center from July 2022 to January 2024 underwent both point-of-care pMRI and subsequent conventional 3T MRI (cMRI). Images were evaluated for periventricular (PV), juxtacortical (JC) and infratentorial (IT) lesions. DIS was determined on brain MRI per 2017 McDonald criteria. Test characteristics were computed using cMRI as the reference. Interrater and intermodality agreement between pMRI and cMRI were evaluated using Cohen's kappa. Time from symptom onset to pMRI and cMRI during the study period was compared to the preceding 1.5 years before pMRI implementation using Kruskal-Wallis with post-hoc Dunn's tests. RESULTS: Twenty patients (median age: 32.5 [IQR, 28-40]; 80% females) were included, of whom 9 (45%) and 5 (25%) had DIS on cMRI and pMRI, respectively. Median time interval between pMRI and cMRI was 7 days (IQR, 3.5-12.5). Interrater agreement was very good for PV (95%, κ=0.89), and good for JC and IT lesions (90%, κ=0.69 for both). Intermodality agreement was good for PV (90%, κ=0.80) and JC (85%, κ=0.63), and moderate for IT lesions (75%, κ=0.42) and DIS (80%, κ=0.58). pMRI had a sensitivity of 56% and specificity of 100% for DIS.The median time from symptom onset to pMRI was significantly shorter (8.5 days [IQR 7-12]) compared to the interval to cMRI before pMRI deployment (21 days [IQR 8-49], n=50) and after pMRI deployment (15 days [IQR 12-29], n=30) (both p<0.01). Time from symptom onset to cMRI in those periods was not significantly different (p=0.29). CONCLUSIONS: In optic neuritis patients, pMRI exhibited moderate concordance, moderate sensitivity and high specificity for DIS compared to cMRI. Its integration into the MS clinic reduced the time from symptom onset to MRI. Further studies are warranted to evaluate the role of pMRI in expediting early MS diagnosis and as an imaging tool in resource-limited settings. ABBREVIATIONS: pMRI = portable MRI; cMRI = conventional MRI; pwMS = patients with MS; PV = periventricular; JC= juxtacortical; IT = infratentorial; DIS = dissemination in space.

Implementation of Food is Medicine Programs in Healthcare Settings: A Narrative Review.

Food is Medicine (FIM) programs to improve the accessibility of fruits and vegetables (FVs) or other healthy foods among patients with low income and diet-related chronic diseases are promising to improve food and nutrition security in the United States (US). However, FIM programs are relatively new and implementation guidance for healthcare settings using an implementation science lens is lacking. We used a narrative review to describe the evidence base on barriers and facilitators to FIM program integration in US healthcare settings following the Exploration, Preparation, Implementation, and Sustainment (EPIS) Framework. Evidence surrounding the EPIS Inner Context was a focus, including constructs Leadership, Organizational Characteristics, Quality and Fidelity Monitoring and Support, Organizational Staffing Processes, and Individual Characteristics. Peer-reviewed and grey literature about barriers and facilitators to FIM programs were of interest, defined as programs that screen and refer eligible patients with diet-related chronic disease experiencing food insecurity to healthy, unprepared foods. Thirty-one sources were included in the narrative review, including 22 peer-reviewed articles, four reports, four toolkits, and one thesis. Twenty-eight sources (90%) described EPIS Inner Context facilitators and 26 sources (84%) described FIM program barriers. The most common barriers and facilitators to FIM programs were regarding Quality and Fidelity Monitoring and Support (e.g., use of electronic medical records for tracking and evaluation, strategies to support implementation) and Organizational Staffing Processes (e.g., clear delineation of staff roles and capacity); although, barriers and facilitators to FIM programs were identified among all EPIS Inner Context constructs. We synthesized barriers and facilitators to create an EPIS-informed implementation checklist for healthcare settings for use among healthcare organizations/providers, partner organizations, and technical assistance personnel. We discuss future directions to align FIM efforts with implementation science terminology and theories, models, and frameworks to improve the implementation evidence base and support FIM researchers and practitioners.

Differences in resting state functional connectivity relative to multiple sclerosis and impaired information processing speed.

Background: Fifty-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. Objectives: We 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. Methods: We 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. Results: Individuals 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. Conclusion: Our 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.

Vascular Disease Is Associated With Differences in Brain Structure and Lower Cognitive Functioning in Inflammatory Bowel Disease: A Cross-Sectional Study.

BACKGROUND: Vascular disease and cognitive impairment have been increasingly documented in inflammatory bowel disease (IBD), and both have been individually correlated with changes in brain structure. This study aimed to determine if both macro- and microstructural brain changes are prevalent in IBD and whether alterations in brain structure mediate the relationship between vascular disease and cognitive functioning. METHODS: Eighty-four IBD participants underwent multimodal magnetic resonance imaging. Volumetric and mean diffusivity measures of the thalamus, hippocampus, normal-appearing white matter, and white matter lesions were converted to age- and sex-adjusted z scores. Vascular comorbidity was assessed using a modified Framingham Risk Score and cognition was assessed using a battery of neuropsychological tests. Test scores were standardized using local regression-based norms. We generated summary statistics for the magnetic resonance imaging metrics and cognitive tests, and these were examined using canonical correlation analysis and linear regression modeling. RESULTS: Greater vascular comorbidity was negatively correlated with thalamic, normal-appearing white matter, and white matter lesion volumes. Higher Framingham Risk Score were also correlated with lower processing speed, learning and memory, and verbal fluency. Increased vascular comorbidity was predictive of poorer cognitive functioning, and this effect was almost entirely mediated (94.76%) by differences in brain structure. CONCLUSIONS: Vascular comorbidity is associated with deleterious effects on brain structure and lower cognitive functioning in IBD. These findings suggest that proper identification and treatment of vascular disease is essential to the overall management of IBD, and that certain brain areas may serve as critical targets for predicting the response to therapeutic interventions.

Vascular disease is associated with decreased cognitive performance in persons with inflammatory bowel disease, and this is mainly driven by changes in the brain, including both gray matter and white matter regions.

Switching to second line MS disease-modifying therapies is associated with decreased relapse rate.

Background and objectives: While 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. Methods: All 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. Results: 1780 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 < 0.0001). Discussion: Switching to high-efficacy DMTs reduces the rates of subsequent MS relapse at the population level.

Within-person fluctuations over three years in depression, anxiety, fatigue, and health-related quality of life in multiple sclerosis.

BACKGROUND: Longitudinal studies of health-related quality of life (HRQoL) in multiple sclerosis (MS) are limited. Most have examined average changes within the population, rather than dynamic changes within individuals. OBJECTIVE: To assess the between- and within-individual association between depression, anxiety, fatigue, cognition, physical functioning, and physical comorbidities and HRQoL. METHODS: Adults with MS underwent physical and cognitive assessments and reported symptoms of fatigue (Daily Fatigue Impact Scale), depression and anxiety (Hospital Anxiety and Depression Scale (HADS)), and HRQoL (RAND-36) annually (n = 4 visits). We evaluated associations of elevated symptoms of anxiety (HADS-A) and depression (HADS-D), fatigue, physical function (timed-walk and nine-hole peg test), cognitive function and comorbidity count with physical (PCS-36) and mental (MCS-36) HRQoL using multivariable linear models-estimating between-person and within-person effects. RESULTS: Of 255 participants with MS enrolled, 81.6% were women. After adjustment, within-person increases in depression and fatigue were associated with decreases in physical HRQoL. Increases in depression, anxiety, and comorbidity count were associated with decreases in mental HRQoL. CONCLUSIONS: Within-person increases in symptoms of depression, anxiety and fatigue, and comorbidity count are associated with HRQoL decreases among adults with MS, highlighting the potential magnitude of individual benefit of intervention for these symptoms.

Pain and participation in social activities in people with relapsing remitting and progressive multiple sclerosis.

Background: Differences in pain between subtypes of multiple sclerosis are understudied. Objective: To compare the prevalence of pain, and the association between pain and: (a) pain interference and (b) social participation in people with relapsing-remitting multiple sclerosis and progressive multiple sclerosis. Methods: Participants completed the McGill Pain Questionnaire Short-Form-2, Pain Effects Scale and Ability to Participate in Social Roles and Activities-V2.0 questionnaires. We tested the association between multiple sclerosis subtype, pain severity, and pain interference/social participation using quantile regression. Results: Of 231 participants (relapsing-remitting multiple sclerosis: 161, progressive multiple sclerosis: 70), 82.3% were women. The prevalence of pain was 95.2%, of more than mild pain was 38.1%, and of pain-related limitations was 87%; there were no differences between multiple sclerosis subtypes. Compared to participants with relapsing-remitting multiple sclerosis, those with progressive multiple sclerosis reported higher pain interference (mean (standard deviation) Pain Effects Scale; progressive multiple sclerosis: 15[6.0] vs relapsing-remitting multiple sclerosis: 13[5], p = 0.039) and lower social participation (Ability to Participate in Social Roles and Activities T-scores 45[9.0] vs 48.3[8.9], p = 0.011). However, on multivariable analysis accounting for age, physical disability, mood/anxiety and fatigue, multiple sclerosis subtype was not associated with differences in pain interference or social participation. Conclusions: Pain was nearly ubiquitous. Over one-third of individuals with relapsing-remitting multiple sclerosis and progressive multiple sclerosis reported pronounced pain, although this did not differ by multiple sclerosis subtype.

Assessment of differential item functioning of the PHQ-9, HADS-D and PROMIS-depression scales in persons with and without multiple sclerosis.

OBJECTIVE: We tested for the presence of differential item functioning (DIF) in commonly used measures of depressive symptoms, in people with multiple sclerosis (MS) versus people with a psychiatric disorder without MS. METHODS: Participants included individuals with MS, or with a lifetime history of a depressive or anxiety disorder (Dep/Anx) but no immune-mediated inflammatory disease. Participants completed the Patient Health Questionnaire (PHQ-9), Hospital Anxiety and Depression Scale (HADS), and the Patient Reported Outcome Measurement Information System (PROMIS)-Depression. We assessed unidimensionality of the measures using factor analysis. We evaluated DIF using logistic regression, with and without adjustment for age, gender and body mass index (BMI). RESULTS: We included 555 participants (MS: 252, Dep/Anx: 303). Factor analysis showed that each depression symptom measure had acceptable evidence of unidimensionality. In unadjusted analyses comparing the MS versus Dep/Anx groups we identified multiple items with evidence of DIF, but few items showed DIF effects that were large enough to be clinically meaningful. We observed non-uniform DIF for one PHQ-9 item, and three HADS-D items. We also observed DIF with respect to gender (one HADS-D item), and BMI (one PHQ-9 item). For the MS versus Dep/Anx groups, we no longer observed DIF post-adjustment for age, gender and BMI. On unadjusted and adjusted analyses, we did not observe DIF for any PROMIS-D item. CONCLUSION: Our findings suggest that DIF exists for the PHQ-9 and HADS-D with respect to gender and BMI in clinical samples that include people with MS whereas DIF was not observed for the PROMIS-Depression scale.

Well-being and flourishing mental health in adults with inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis in Manitoba, Canada: a cross-sectional study.

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.

Vascular comorbidity is associated with decreased cognitive functioning in inflammatory bowel disease.

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 (ß = - 0.12; 95% CI - 0.24, - 0.006) and verbal learning (ß = - 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 (ß = - 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.

Use of Benzodiazepines and Z-Drugs in Inflammatory Bowel Disease.

INTRODUCTION: We estimated the incidence and prevalence of benzodiazepine and Z-drug (separately and jointly as BZD) use in the inflammatory bowel disease (IBD) population compared with matched controls without IBD and examined the association of mood/anxiety disorders (M/ADs) with the use of BZD from 1997 to 2017. METHODS: Using administrative data from Manitoba, Canada, we identified 5,741 persons with incident IBD who were matched in a 1:5 ratio to controls on sex, birth year, and region. Validated case definitions were used to identify M/AD. Dispensations of BZD were identified. Multivariable generalized linear models were used to assess the association between IBD, M/AD, and BZD use. RESULTS: In 2016, the incident age/sex-standardized benzodiazepine use rates per 1,000 were 28.06 (95% confidence interval [CI] 26.41-29.81) in the IBD cohort and 16.83 (95% CI 16.28-17.39) in controls (adjusted rate ratio = 1.69 [95% CI 1.56-1.79]). Benzodiazepine incidence rates were higher for women with IBD than men, but the RR between cases and controls were similar for men and women. The incident age/sex-standardized Z-drug use rate per 1,000 was 21.07 (95% CI 19.69-22.41) in the IBD cohort. This was 1.87-fold higher than in controls (95% CI 1.73-2.01). In 2017, approximately 20% of persons with IBD used benzodiazepines and 20% used Z-drugs. There was a subadditive effect of both benzodiazepine and Z-drug uses between IBD and M/AD after adjusting for covariates. DISCUSSION: The use of BZD is more common in people with IBD than in population controls. Strategies to reduce the use of BZDs in persons with IBD and to offer alternative management strategies for M/ADs, sleep disorders, and other symptomatic concerns are needed.

Effects of Vascular Comorbidity on Cognition in Multiple Sclerosis Are Partially Mediated by Changes in Brain Structure.

Objective: Vascular 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. Methods: Adults 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. Results: Of 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. Conclusion: Vascular comorbidity is associated with lower cognitive function in people with MS and this association is partially mediated via changes in brain macrostructure and microstructure.

Racial/Ethnic Disparities in Food Pantry Use and Barriers in Massachusetts during the First Year of the COVID-19 Pandemic.

This study sought to describe racial disparities in food insecurity, food pantry use, and barriers to and experiences with food pantries during the first year of the COVID-19 pandemic. We surveyed 2928 adults in Massachusetts regarding food access in the year before and during the first year of the pandemic. Weighted multivariable logistic regression models assessed racial differences in barriers to and experiences with pantry use during the pandemic. Black and Latino adults experienced the highest prevalence of food insecurity and pantry use. Additionally, Black and Latino adults reported more barriers to, but less stigma around, pantry use compared to White adults. Latino adults were less likely to know about pantry hours/locations and encounter staff who spoke their language. Black and Latino adults were also more likely to find pantry hours/locations inconvenient and have difficulty with transportation. The COVID-19 pandemic resulted in increased food insecurity, and food access inequities persisted. Programmatic policies to improve pantry access in communities of color could include increasing the hours/days that pantries are open, increasing bilingual staff, providing transportation or delivery, and creating multilingual public awareness campaigns on how to locate pantries.

Use of Benzodiazepines and Z-Drugs in Multiple Sclerosis.

Objective: Use 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. Methods: Using 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. Results: In 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. Conclusion: Use 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.

Depressive symptom trajectories and polygenic risk scores in individuals with an immune-mediated inflammatory disease.

OBJECTIVE: To develop group-based trajectories of depressive symptoms in immune-mediated inflammatory disease (IMID) to understand their evolution and identify any associated factors, with the overall goal of identifying those at highest risk of higher depressive symptom burden. METHOD: 922 participants had an IMID or anxiety/depression. The PHQ-9 was administered at four visits, and polygenic risk scores (PRS) for major depressive disorder, depressive symptoms, and body mass index (BMI) were generated. Group-based trajectory modelling of PHQ-9 scores estimated distinct trajectories. Regression tested whether specific factors were associated with the trajectories. Mediation analyses assessed whether IMID mediated the association between BMI PRS and trajectories. RESULTS: Three trajectories were identified. Regression demonstrated those in Group 3 ('high symptoms') had significantly higher PRS for the three traits, compared to Group 1 ('minimal symptoms') (OR: 1.34-1.66, P < 0.01). Stratified analyses in the IMID subgroup revealed an increased effect for BMI PRS in Group 3 (OR: 2.31, P < 0.001), in contrast, BMI PRS was no longer associated in the non-IMID sample. No significant indirect effect of BMI PRS on depressive symptoms trajectories was identified via IMID. CONCLUSIONS: A significant association between polygenicity and PHQ-9 trajectories supports a role for genetic inheritance in the variability in depressive symptoms in IMID.

Mesenchymal stem cell therapy and cognition in MS: Preliminary findings from a phase II clinical trial.

BACKGROUND: Mesenchymal stem cell (MSC) therapies are being evaluated in multiple sclerosis (MS) for possible neural repair. To date, the potential benefits on cognition have received little attention. The objective of the current study was to comprehensively evaluate cognition before and after MSC therapy in those with MS as part of a double-blind, phase II clinical trial. METHODS: Twenty-eight individuals with a confirmed diagnosis of MS were randomly assigned into two study arms. Cognition was evaluated using an expanded Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) battery. The battery was administered at Week 0, Week 24, and Week 48 and results were analysed at the group and individual level. RESULTS: No detectable effect of MSC-mediated neural repair was noted in the short-term with respect to cognition, although some cognitive stability or improvement was observed. Decline was noted in some cognitive areas immediately following the procedure at Week 24; though these were temporary with performance returning to baseline levels at Week 48. CONCLUSIONS: While MSC therapy does not lead to improvement in cognition, at least in the short-term, neither does the procedure have lasting deleterious effects. The current findings lend support to the safety and feasibility of MSC therapy as a potentially viable treatment option for individuals with MS.

High or increasing serum NfL is predictive of impending multiple sclerosis relapses.

BACKGROUND: One-off serum levels of neurofilament light chain (sNfL) is an established predictor of emerging disease activity in multiple sclerosis (MS). However, the importance of longitudinal increases in sNfL is yet to be enumerated, an important consideration as this test is translated for serial monitoring. Glial Fibrillary Acidic Protein (sGFAP) is another biomarker of predictive interest. Our objective was to assess the association between longitudinal changes sNfL and prediction of future relapses, as well as a possible role for sGFAP. METHODS: Participants with active MS were prospectively monitored for one year as part of a clinical trial testing mesenchymal stem cells. Visits every three months or less included clinical assessments, MRI scans and serum draws. sNfL and sGFAP concentrations were quantified with Single Molecule Array immunoassay. We used Kaplan-Meier estimates and Anderson-Gill Cox regression models with and without adjustment for age, sex, disease subtype, disease duration and expanded disability status score (EDSS) to estimate the rate of relapse predicted by baseline and longitudinal changes in biomarker. RESULTS: 58 Canadian and Italian participants with MS were enrolled in this study. Higher baseline sNfL was future relapse (Log-rank p = 0.0068), MRI lesions (p=0.0096), composite-relapse associated worsening (p=0.01) and progression independent of relapse activity (p=0.0096). Conversely, baseline sGFAP was only weakly associated with MRI lesions (0.044). Cross-sectional analyses of baseline sNfL revealed that a two-fold difference in baseline sNfL, e.g. from 10 to 20 pg/mL, was associated with a 2.3-fold increased risk of relapse during follow-up (95% confidence interval 1.65-3.17). Longitudinally, a two-fold increase in sNfL level from the first measurement was associated with an additional 1.46 times increased risk of relapse (1.07-2.00). The impact of longitudinal increases in sNfL on the risk of relapse were most pronounced for patients with lower baseline values of sNfL (<10 pg/mL: HR = 1.54, 1.06-2.24). These associations remained significant after adjustment for potential confounders. CONCLUSION: We enumerate the risk of relapse associated with dynamic changes in sNfL. Both baseline and longitudinal change in sNfL may help identify patients who would benefit from early treatment optimisation. TRIAL REGISTRATIONS: Canada:NCT02239393, Italy:NCT01854957&EudraCT, 2011-001295-19 CLASSIFICATION OF EVIDENCE: This study provides class 1 evidence that high baseline and longitudinal increases in sNfL are predictive of impending relapses in patients with active MS.

Development of an indicator of smoking status for people with multiple sclerosis in administrative data.

BACKGROUND: Administrative data lack health behavior information. METHODS: We developed an administrative case definition for past or current ('ever smoking') in 1320 individuals with MS from Manitoba, Canada. Candidate indicators for 'ever smoked' included smoking cessation medications, and diagnosis codes for tobacco use and chronic obstructive pulmonary disease, using variable lookback periods. RESULTS: When compared to self-reported smoking status, the case definition incorporating all indicators over a lifetime lookback period had a sensitivity of 31.98%, and positive predictive value of 78.26%. CONCLUSION: This smoking status definition could only partially control for confounding due to smoking because of the low sensitivity.

The comorbidity and cognition in multiple sclerosis (CCOMS) neuroimaging protocol: Study rationale, MRI acquisition, and minimal image processing pipelines.

The Comorbidity and Cognition in Multiple Sclerosis (CCOMS) study represents a coordinated effort by a team of clinicians, neuropsychologists, and neuroimaging experts to investigate the neural basis of cognitive changes and their association with comorbidities among persons with multiple sclerosis (MS). The objectives are to determine the relationships among psychiatric (e.g., depression or anxiety) and vascular (e.g., diabetes, hypertension, etc.) comorbidities, cognitive performance, and MRI measures of brain structure and function, including changes over time. Because neuroimaging forms the basis for several investigations of specific neural correlates that will be reported in future publications, the goal of the current manuscript is to briefly review the CCOMS study design and baseline characteristics for participants enrolled in the three study cohorts (MS, psychiatric control, and healthy control), and provide a detailed description of the MRI hardware, neuroimaging acquisition parameters, and image processing pipelines for the volumetric, microstructural, functional, and perfusion MRI data.