Diet and omega-3 and vitamin D supplement use predict five-year fatigue and disability trajectories in people with multiple sclerosis.

BACKGROUND: Fatigue and disability are indicators of disease progression experienced by many people with multiple sclerosis (pwMS). Understanding trajectories of these outcomes, and their predictors, may provide insight to potential interventions for MS management. METHODS: Survey data from 839 pwMS from the Health Outcomes and Lifestyle in pwMS study were analysed. Fatigue was defined as mean Fatigue Severity Scale >5, and severe disability as Patient Determined Disease Steps >5. Group-based trajectory modelling was used to identify fatigue and disability trajectories over five-years. Dietary predictors associated with outcome trajectory group membership were assessed using log-binomial regression. Demographic and clinical characteristics were considered in multivariable models. RESULTS: Distinct trajectories for fatigue and disability were identified. For fatigue, 58 % of pwMS were assigned to low-, and 42 % to high-, fatigue trajectory groups. For disability, 85 % of pwMS were assigned to low-, and 15 % to high-, disability groups. Baseline high-quality diet, and omega-3 and vitamin D supplement use, were associated with reduced risk of being in high-fatigue and high-disability trajectories, while meat and dairy consumption were associated with increased risk. CONCLUSIONS: A high-quality diet, avoiding meat and dairy, and omega-3 and vitamin D supplement use, individually predict better fatigue and disability trajectories. Dietary modifications should be considered in MS management.

Stressful life events and depression and fatigue in people with multiple sclerosis: a cross-sectional analysis of an international cohort.

BACKGROUND: Relationships between stressful life events (SLEs) and health outcomes in people living with multiple sclerosis (plwMS), beyond relapse, are not well-established. We examined associations between SLEs and fatigue and symptoms of depression in plwMS. METHODS: 948 participants were queried whether they had experienced any of the 16 SLEs (Holmes-Rahe Social Readjustment Rating Scale) in the preceding 12 months. SLEs were summated to estimate SLE number and SLE load (weighted for the degree of associated stress). Cross-sectional associations between SLE (number, load and individual) and fatigue, and depressive symptoms were examined using log-binomial or log-multinomial regression adjusted for age, sex, relapse symptoms, education, MS type at baseline, disability, fatigue, comorbidity, depression, and antidepressant/antifatigue medications, as appropriate. Sub-analyses restricted to SLEs with a negative emotional impact were performed. RESULTS: Median SLE number and load were 2 (IQR 1-2) and 57 (IQR 28-97), respectively. SLE number and load were not associated with a higher prevalence of fatigue, or depressive symptoms, even when restricting analyses to SLEs with a perceived negative emotional impact. A new relationship or family member with a negative impact was associated with a threefold and 2.5-fold higher prevalence of depressive symptoms, respectively. Serious illness was associated with a 28% higher prevalence of depressive symptoms. CONCLUSION: Psychological support for SLEs, and/or intervention targeted to SLE appraisal, may be beneficial in mitigating the adverse effects of SLEs with a perceived negative emotional impact on depressive symptoms in plwMS. Potential associations between serious illness and increased prevalence of depressive symptoms may warrant further investigation.

Longitudinal associations between quality of diet and disability over 7.5 years in an international sample of people with multiple sclerosis.

BACKGROUND AND PURPOSE: Modifiable lifestyle factors, including diet, have been implicated in multiple sclerosis (MS) progression, but prospective evidence is limited. The aim of this study was to examine prospective relationships between quality of diet and subsequent disability over 7.5 years in an international cohort of people living with MS (pwMS). METHODS: Data from 602 participants in the HOLISM (Health Outcomes and Lifestyle In a Sample of people with Multiple sclerosis) study were analysed. Quality of diet was assessed using the modified Diet Habits Questionnaire (DHQ). Disability was assessed using the Patient-determined MS Severity Score (P-MSSS). Characteristics of disability were assessed by log-binomial, log-multinomial and linear regression, adjusted for demographic and clinical covariates, as appropriate. RESULTS: Higher baseline total DHQ scores (>80-89, >89%) were associated with lower risks of increased P-MSSS at 7.5 years (adjusted risk ratio [aRR] 0.46, 95% confidence interval [CI] 0.23, 0.91 and aRR 0.48, 95% CI 0.26, 0.89, respectively), and with less P-MSSS accrual (aß = -0.38, 95% CI -0.78, 0.01 and aß = -0.44, 95% CI -0.81, -0.06). Of the DHQ domains, fat subscore was most strongly associated with subsequent disability. Participants with reducing baseline-to-2.5- years total DHQ scores had greater risk of increased P-MSSS at 7.5 years (aRR 2.77, 95% CI 1.18, 6.53) and higher P-MSSS accrual (aß = 0.30, 95% CI 0.01, 0.60). Participants reporting baseline meat and dairy consumption had greater risk of increased P-MSSS at 7.5 years (aRR 2.06, 95% CI 1.23, 3.45 and aRR 2.02, 95% CI 1.25, 3.25) and higher P-MSSS accrual (aß = 0.28, 95% CI 0.02, 0.54 and aß = 0.43, 95% CI 0.16, 0.69, respectively). However, reported meat consumption was confounded by quality of diet. Changes in meat or dairy consumption from baseline were inconsistently associated with subsequent disability. CONCLUSIONS: We show for the first time robust long-term associations between quality of diet and subsequent disability progression in pwMS. Subject to replication, dietary modification may represent a point of intervention for reducing disability in pwMS.

Study protocol for an online lifestyle modification education course for people living with multiple sclerosis: the multiple sclerosis online course (MSOC).

BACKGROUND: People living with multiple sclerosis (plwMS) seek access to information on evidence-based lifestyle-related risk factors associated with multiple sclerosis (MS). As the internet has made delivery of lifestyle information increasingly accessible and cost-effective, we designed the Multiple Sclerosis Online Course (MSOC) to deliver a multimodal lifestyle modification program for plwMS. Two MS online courses were developed: the intervention course based on lifestyle recommendations of the Overcoming Multiple Sclerosis (OMS) program and the standard-care course representing standard lifestyle recommendations from other MS websites. We examined for feasibility in a pilot randomised controlled trial (RCT), where satisfactory completion and accessibility were achieved across both study arms. From this success, a protocol for a larger RCT was developed to examine the effectiveness of MSOC in improving health-related quality of life (HRQoL) and other health outcomes in plwMS. METHODS/DESIGN: This single-blinded RCT will recruit n = 1,054 plwMS. Participants in the intervention arm will receive access to a MSOC with seven modules providing evidence-based information on the OMS program. Participants in the control group will receive access to a MSOC of identical format, with seven modules providing general MS-related information and lifestyle recommendations sourced from popular MS websites, e.g. MS societies. Participants will complete questionnaires at baseline and at 6, 12, and 30 months after course completion. The primary endpoint is HRQoL, as measured by MSQOL-54 (both physical and mental health domains) at 12 months following course completion. Secondary outcomes are changes to depression, anxiety, fatigue, disability, and self-efficacy as measured by Hospital Anxiety and Depression Scale, Patient-Determined Disease Steps and University of Washington Self-Efficacy Scale, respectively, assessed at each timepoint. Further assessments will include quantitative post-course evaluation, adoption and maintenance of behaviour change from follow-up survey data, and qualitative analysis of participants' outcomes and reasons for course completion or non-completion. DISCUSSION: This RCT aims to determine whether an online intervention course delivering evidence-based lifestyle modification recommendations based on the Overcoming Multiple Sclerosis program to plwMS is more effective at improving HRQoL, and other health outcomes post-intervention, compared with an online standard-care course. TRIAL REGISTRATION: This trial was registered prospectively with the Australian New Zealand Clinical Trials Registry, www.anzctr.org.au , identifier ACTRN12621001605886. DATE OF REGISTRATION: 25 November 2021.

Engagement with three or more healthy lifestyle behaviours is associated with improved quality of life over 7.5 years in people with multiple sclerosis.

BACKGROUND AND PURPOSE: People with multiple sclerosis (pwMS) report reduced quality of life (QoL). Engagement with healthy lifestyle behaviours, including consuming a healthy diet, regular physical activity, and adequate vitamin D exposure, is associated with higher QoL. We aim to assess whether individual lifestyle behaviours are more beneficial to QoL than others, and whether there are additive benefits to QoL by engaging in multiple healthy behaviours concurrently. METHODS: Data from pwMS who completed an online survey at baseline, and at 2.5-, 5- and 7.5-year follow-up, were analysed. Behaviours assessed were consumption of a no-meat/dairy-plus-omega-3 supplementation diet, meditation practice, physical activity, non-smoking, and vitamin D exposure. Mental QoL (mQoL) and physical QoL (pQoL) were assessed by the Multiple Sclerosis Quality of Life (MSQOL-54) questionaire. Linear regression analyses were performed to assess associations of individual behaviours at baseline and follow-up time points with QoL, as well as between number of behaviours and QoL. RESULTS: At baseline, healthy diet and regular physical activity were associated with higher mQoL (5.3/100 and 4.0/100) and higher pQoL (7.8/100 and 6.7/100). Prospectively, diet was positively associated with mQoL, and physical activity with both mQoL and pQoL. At baseline, engagement with ≥3 behaviours was positively associated with mQoL and pQoL, with additive positive associations for each additional behaviour. Prospectively, engagement with ≥3 behaviours was positively associated with mQoL and pQoL, with strongest associations observed with engagement with five behaviours. CONCLUSION: Consumption of a healthy diet, and regular physical activity, are both potential interventions to improve QoL. Engagement with multiple lifestyle behaviours may provide additional benefits and should be encouraged and supported for multiple sclerosis management.

Self-reported ongoing adherence to diet is associated with lower depression, fatigue, and disability, in people with multiple sclerosis.

Introduction: Increasingly, dietary improvements have been shown to have positive associations with health outcomes in people with multiple sclerosis (pwMS). However, adhering to a MS-specific or high-quality diet may be a challenge. We therefore assessed the level of diet-adherence necessary to improve health outcomes of depression, fatigue, and disability. Methods: Data from an international population of pwMS followed over 7.5 years (n = 671) were analyzed. Self-reported diet quality via diet habits questionnaire (DHQ), and adherence to six MS-diets [Ashton Embry Best Bet, McDougall, Overcoming MS (OMS), Paleolithic (Paleo), Swank, and Wahls] were queried at two timepoints. Four levels of diet adherence were assessed: non-adherence at either timepoint; ceased at second timepoint; commenced at second timepoint; and ongoing at both timepoints. Associations between adherence to OMS and high-quality diet (DHQ score > median) with depression, fatigue, and disability, were assessed by log-binomial regression models adjusted for confounders. Results: Forty-two percent of pwMS reported ongoing-adherence to a MS-diet at both timepoints, OMS (33%), Swank (4%), Wahls (1.5%), other (<1%). Of these, only OMS-diet adherence was analyzed for associations due to data availability. Ongoing-adherence to the OMS-diet or a high-quality diet, was associated with lower depression compared to non-adherence [OMS: Risk ratios (RR) = 0.80, p = 0.021; DHQ: RR = 0.78, p = 0.009] and ceased-adherence (OMS: RR = 0.70, p = 0.008; DHQ: RR = 0.70, p = 0.010), respectively. Ongoing-adherence to OMS-diet was associated with lower fatigue (RR = 0.71, p = 0.031) and lower severe disability (RR = 0.43, p = 0.033) compared to ceased-adherence. Conclusion: Results suggest potential benefits of adherence to the OMS- or a high-quality diet on MS health outcomes, with ongoing-adherence likely best. Diet modification and maintenance may serve as a point of intervention to manage MS symptoms, especially depression, in pwMS.

Higher diet quality is associated with short and long-term benefits on SF-6D health state utilities: a 5-year cohort study in an international sample of people with multiple sclerosis.

BACKGROUND/PURPOSE: Health state utilities (HSU) are a subjective measure of an individual's health-related quality of life (HRQoL), adjusted by societal or patient relative preference weights for living in different states of health-related quality of life (HRQoL), derived from patient-reported responses to multi-attribute utility instrument (MAUI), and can be used as inputs for cost-utility analyses and in clinical assessment. This research assessed associations of diet with subsequent HSU in a large international cohort of people living with multiple sclerosis (MS), a progressive autoimmune condition of the central nervous system. METHODS: HSUs were generated from responses to Short-Form Six-Dimension (SF-6D) MAUI, and quality-of-the-diet by Diet Habits Questionnaire (DHQ). Cross-sectional, and short- and long-term prospective associations of DHQ with HSU evaluated by linear regression at 2.5- and 5-years. Pooled prospective associations between DHQ and HSU evaluated using linear and quantile regression. Analyses adjusted for relevant demographic and clinical covariates. RESULTS: Among 839 participants, baseline DHQ scores showed short- and long-term associations with subsequent HSU, each 10-unit increase in total DHQ score associated with 0.008-0.012 higher HSU (out of 1.00). These associations were dose-dependent, those in the top two quartiles of baseline DHQ scores having 0.01-0.03 higher HSU at follow-up, 0.03 being the threshold for a minimally clinically important difference. Fat, fiber, and fruit/vegetable DHQ subscores were most strongly and consistently associated with better HSU outcomes. However, baseline meat and dairy consumption were associated with 0.01-0.02 lower HSU at subsequent follow-up. CONCLUSIONS: A higher quality-of-the-diet showed robust prospective relationships with higher HSUs 2.5- and 5-years later, substantiating previous cross-sectional relationships in this cohort. Subject to replication, these results suggest interventions to improve the quality-of-the-diet may be effective to improve HRQoL in people living with MS.

A multiple sclerosis lifestyle behavior online course: Qualitative analysis of participants' motivations, expectations and experiences.

Background: Modification of lifestyle-related risk factors for multiple sclerosis (MS) has been associated with improved health outcomes when compared with standard medical management alone. Based on an existing lifestyle modification program offered as a residential workshop, the MS Online Course (MSOC) was developed to translate the workshop into an online intervention. We performed a pilot randomized controlled trial (RCT), to assess the feasibility concepts of accessibility, learnability and desirability through quantitative and qualitative analyzes. In the present study, we performed additional qualitative analyzes to explore participants' motivations, expectations, and experiences of the MSOC. This study aims to complement prior feasibility analyzes and inform recruitment strategies and course content redevelopment so that its effectiveness may be assessed by examining behavior change and health outcomes in a future larger RCT. Methods: Participants were recruited via online advertisements and randomized to either: the standard care course, containing material sourced from public facing MS websites; or the intervention course, based on an evidence-based lifestyle modification program for people with MS. Course completers were invited to participate in semi-structured interviews. Within a qualitative paradigm, reflexive thematic analysis of interviews was undertaken. Results: Of 31 eligible participants, 17 completed the MSOC and 14 agreed to be interviewed. Four themes were identified in this analysis: (1) "Wanting to help others" (helping through volunteering, contributing to knowledge base, spreading the word; (2) "Seeking knowledge" (confirmation of existing knowledge; obtaining new knowledge, relevant, credible information); (3) "Doing what I can to help myself" (understanding lifestyle modification, changing my lifestyle, remaining well); and (4) "Changing attitudes" (finding positivity, feeling more confident and in control). Conclusions: Participants were motivated to help others through research, help themselves by improving knowledge and to find ways to better manage their MS. Expectations included obtaining credible, reliable information, to substantiate existing knowledge, and to further understand lifestyle modification. Participants' experiences included confirmation of and obtaining new knowledge, and early implementation of modified lifestyle behaviors. These insights surrounding participants' motivations, expectations and experiences will assist in recruitment strategies, course redevelopment and outcome measures for the future RCT to examine the effectiveness of the MSOC.

Using Online 24-h Dietary Methodology to Validate the Psychometric Properties of a Dietary Scoring Tool with an International Sample of Adults Living with Multiple Sclerosis.

Understanding the dietary characteristics of people living with multiple sclerosis (plwMS) may assist in the planning of nutrition interventions for multiple sclerosis; yet dietary assessment methods in existing studies are not well established. The aim of this study was to validate the psychometric properties (construct validity and internal consistency) of the Dietary Habits Questionnaire (DHQ) against repeated online 24-h recall dietary assessments. The DHQ is a 24-item tool that is scored using ten dietary sub-scores. Total DHQ scores can range from 20−100 and are considered indicative of the quality of dietary intake with higher scores reflecting increased quality. People living with a relapsing-remitting MS phenotype who had completed a modified DHQ were recruited from the international Health Outcomes and Lifestyle In a Sample of people with Multiple sclerosis (HOLISM) cohort. Repeated 24-h recall via the online Automated Self-administered Assessment-24 (ASA-24) tool were modelled to reflect usual dietary intakes using the Multiple Source Method. DHQ scores of eight sub-scores: three key nutrients, three food groups and two food preparation practices, were calculated and statistically compared with ASA-24 usual intake data. Principal component analysis of the ASA-24 data was undertaken to understand dietary patterns of the sample. Of the 105 participants, valid 24-h recall data were available for 96 plwMS (n = 66 1 day, n = 30 ≥ 2 day). The median total DHQ score was 84.50 (IQR: 77.04, 91.83) points. The highest absolute correlations were between the DHQ scores and ASA-24 data for cereal (r = 0.395, p < 0.001), fruit and vegetables (r = 0.436, p < 0.001), and total dietary fiber (r = 0.482, p < 0.001). Five dietary patterns emerged from the data explaining 42.12% variance and reflecting exposure of plwMS to the influence of 'MS diets'. The DHQ appears to be appropriate for screening participants with relapsing-remitting MS. Evidence-based dietary models focusing on food are required to monitor the quality of an overall dietary pattern and set priorities for the planning nutrition interventions for plwMS.

Mining the Gems of a Web-Based Mindfulness Intervention: Qualitative Analysis of Factors Aiding Completion and Implementation.

BACKGROUND: Digital health interventions provide a cost effective and accessible means for positive behavior change. However, high participant attrition is common and facilitators for implementation of behaviors are not well understood. OBJECTIVE: The goal of the research was to identify elements of a digital mindfulness course that aided in course completion and implementation of teachings. METHODS: Inductive thematic analysis was used to assess participant comments regarding positive aspects of the online mindfulness course Mindfulness for Well-being and Peak Performance. Participants were aged 18 years and older who had self-selected to register and voluntarily completed at least 90% the course. The course comprised educator-guided lessons and discussion forums for participant reflection and feedback. Participant comments from the final discussion forum were analyzed to identify common themes pertaining to elements of the course that aided in course completion and implementation of teachings. RESULTS: Of 3355 course completers, 283 participants provided comments related to the research question. Key themes were (1) benefits from the virtual community, (2) appeal of content, (3) enablers to participation and implementation, and (4) benefits noted in oneself. Of subthemes identified, some, such as community support, variety of easily implementable content, and free content access, align with that reported previously in the literature, while other subthemes, including growing together, repeating the course, evidence-based teaching, and immediate benefits on physical and mental well-being, were novel findings. CONCLUSIONS: Themes identified as key elements for aiding participant completion of a mindfulness digital health intervention and the implementation of teachings may inform the effective design of future digital health interventions to drive positive health behaviors. Future research should focus on understanding motivations for participation, identification of effective methods for participant retention, and behavior change techniques to motivate long-term adherence to healthy behaviors.

A qualitative analysis of free text comments of participants from a massive open online mindfulness course.

Introduction: Mindfulness-based interventions are associated with improved health and wellbeing. Online mindfulness interventions offer potential scalability and cost advantages over face-to-face interventions. However, little is known about the experiences of learners, what they identify as being helpful to developing a practice of mindfulness and what outcomes they experience from undertaking an online mindfulness program. Methods: The Mindfulness for Wellbeing and Peak Performance Massive Open Online Course is a 4-week mindfulness program which includes psychoeducation, mindfulness meditation, applications and moderated discussion forums. Of the 3,335 participants who completed the March 2020 course, 527 (16%) responded to the final forum which invited participants to describe the highlights of the course. In order to enhance understanding of participant experiences and perceived outcomes of undertaking the course, a qualitative analysis of these free text comments was conducted using reflexive thematic analysis. Results: Two overarching themes were identified: (1) internal mechanisms of developing mindfulness (subthemes: paying attention to the present moment, learning to let go and find acceptance, cultivating an attitude of gentleness, and learning through a sense of belonging) and (2) the translation of mindfulness into daily living (subthemes: mindfulness being a support to mental wellbeing, learning to deal with uncertainty and adversity, living a more conscious life, a greater connection with self and others and channeling attention into productivity). Discussion: The themes and subthemes provided insights into the mechanisms learners used to develop mindfulness and how they translated mindfulness into their lives in a variety of beneficial ways. This understanding of learners' experiences could inform delivery of future online mindfulness interventions.

Severity of COVID19 infection among patients with multiple sclerosis treated with interferon-ß.

BACKGROUND: Interferon-ß, a disease-modifying therapy (DMT) for MS, may be associated with less severe COVID-19 in people with MS. RESULTS: Among 5,568 patients (83.4% confirmed COVID-19), interferon-treated patients had lower risk of severe COVID-19 compared to untreated, but not to glatiramer-acetate, dimethyl-fumarate, or pooled other DMTs. CONCLUSIONS: In comparison to other DMTs, we did not find evidence of protective effects of interferon-ß on the severity of COVID-19, though compared to the untreated, the course of COVID19 was milder among those on interferon-ß. This study does not support the use of interferon-ß as a treatment to reduce COVID-19 severity in MS.

Updated Results of the COVID-19 in MS Global Data Sharing Initiative: Anti-CD20 and Other Risk Factors Associated With COVID-19 Severity.

BACKGROUND AND OBJECTIVES: Certain demographic and clinical characteristics, including the use of some disease-modifying therapies (DMTs), are associated with severe acute respiratory syndrome coronavirus 2 infection severity in people with multiple sclerosis (MS). Comprehensive exploration of these relationships in large international samples is needed. METHODS: Clinician-reported demographic/clinical data from 27 countries were aggregated into a data set of 5,648 patients with suspected/confirmed coronavirus disease 2019 (COVID-19). COVID-19 severity outcomes (hospitalization, admission to intensive care unit [ICU], requiring artificial ventilation, and death) were assessed using multilevel mixed-effects ordered probit and logistic regression, adjusted for age, sex, disability, and MS phenotype. DMTs were individually compared with glatiramer acetate, and anti-CD20 DMTs with pooled other DMTs and with natalizumab. RESULTS: Of 5,648 patients, 922 (16.6%) with suspected and 4,646 (83.4%) with confirmed COVID-19 were included. Male sex, older age, progressive MS, and higher disability were associated with more severe COVID-19. Compared with glatiramer acetate, ocrelizumab and rituximab were associated with higher probabilities of hospitalization (4% [95% CI 1-7] and 7% [95% CI 4-11]), ICU/artificial ventilation (2% [95% CI 0-4] and 4% [95% CI 2-6]), and death (1% [95% CI 0-2] and 2% [95% CI 1-4]) (predicted marginal effects). Untreated patients had 5% (95% CI 2-8), 3% (95% CI 1-5), and 1% (95% CI 0-3) higher probabilities of the 3 respective levels of COVID-19 severity than glatiramer acetate. Compared with pooled other DMTs and with natalizumab, the associations of ocrelizumab and rituximab with COVID-19 severity were also more pronounced. All associations persisted/enhanced on restriction to confirmed COVID-19. DISCUSSION: Analyzing the largest international real-world data set of people with MS with suspected/confirmed COVID-19 confirms that the use of anti-CD20 medication (both ocrelizumab and rituximab), as well as male sex, older age, progressive MS, and higher disability are associated with more severe course of COVID-19.

The Feasibility of a Web-Based Educational Lifestyle Program for People With Multiple Sclerosis: A Randomized Controlled Trial.

Background: Modifiable lifestyle factors are important to aid people with multiple sclerosis in the self-management of their disease. Current self-management programs are limited by their face-to-face mode of delivery but there is immense potential with the internet to deliver these programs effectively. Objective: The aims of this study are to assess the feasibility of a digitalized educational lifestyle self-management program for people with MS. Methods: In this randomized controlled trial, people with MS were randomly allocated to participate in a 6-week tailored web-based educational lifestyle program or 6-week generic standard-care educational course, and were blinded to their allocation. Participants were recruited through multiple sclerosis (MS) Societies in four countries: Australia, New Zealand, Canada, and the United States. The primary outcome was to assess acceptability of the program defined as percentage completion of all modules at 6-weeks post-course commencement. Secondary outcomes included evaluating participant responses to the follow-up survey across three domains: accessibility, learnability, and desirability. Results: Thirty-five participants from Australia, Canada, New Zealand, and the US completed the baseline survey and were randomized. Four participants were deemed ineligible due to incomplete baseline data; therefore, nine out of 15 and eight out of 16 participants completed 100% of the course in the intervention and standard-care arm courses, respectively. Conclusions: This study found that this web-based educational lifestyle program is a feasible means of delivering educational content to people with MS via the internet according to our a priori targets of >40% of participants in the intervention arm, and >25% in the control arm to completing 100% of the course. It is therefore appropriate to evaluate this intervention further in a large, randomized controlled trial. Trial registration: This study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ID: ACTRN12621000245897).

Undertaking specific stress-reducing activities are associated with reduced fatigue and depression, and increased mastery, in people with multiple sclerosis.

BACKGROUND: Multiple sclerosis is a demyelinating autoimmune disease, presenting with heterogenous symptoms that impact daily living. Undertaking stress-reducing activities may reduce symptoms including depression and fatigue, and enhance mastery, the sense of control of one's life. We assessed cross-sectional associations of undertaking stress-reducing activities or meditation on depression, fatigue, and mastery, and 5-year prospective relationships between meditation and these outcomes. METHODS: Data were extracted from the longitudinal Health Outcomes and Lifestyle In a Sample of people with Multiple sclerosis (HOLISM) study. Stress-reducing activities were categorised to relaxation, physical, mind-body, and spiritual. Meditation was analysed as a dichotomous term, and for duration and frequency of practice. Depression, fatigue, and mastery were assessed by Patient's Health Questionnaire-9, Fatigue Severity Scale, and Pearlin Mastery Scale, respectively. Associations with depression, fatigue and mastery were assessed by log-binomial regression. Models were adjusted for age, sex, symptoms due to relapse, socioeconomic status, employment status, and antidepressant and anti-fatigue medication use, as appropriate. RESULTS: Cross-sectionally, physical and relaxation activities were associated with 40% and 33% lower frequencies of depression, respectively. Physical activities were additionally associated with 19% lower frequency of fatigue. Meditation was associated with 30% lower frequency of depression and 17% higher mastery. Prospectively, meditation was associated with 28% decreased depression, and 48% reduction of developing depression at 5-year follow-up. CONCLUSION: Potential benefits of undertaking stress-reducing activities, or meditation, on depression, fatigue, and mastery are promising and should be further assessed prospectively. Meditation practice should be encouraged as a safe and inexpensive intervention for prevention of depression.

Prospective associations of better quality of the diet with improved quality of life over 7.5 years in people with multiple sclerosis.

BACKGROUND: There is increasing interest in the role of diet in multiple sclerosis (MS) progression and whether a healthier diet may lead to improved health and wellbeing in people living with MS (plwMS). OBJECTIVE: To assess the prospective relationship of the quality of dietary intakes with quality of life (QoL) in an international cohort of plwMS followed over 7.5 years. METHODS: Data from the Health Outcomes and Lifestyle In a Sample of people with Multiple sclerosis (HOLISM) cohort from baseline to 7.5-year review were analysed. Quality of the diet was assessed using the Diet Habits Questionnaire (DHQ). QoL was measured by the MSQOL-54, including physical and mental health composite scores and multiple subdomains. Linear regression was used to determine cross-sectional and prospective relationships with QoL, adjusted for clinical and demographic covariates. RESULTS: Amongst 948 participants, median physical- and mental-health QoL scores at 7.5-year review were 66.9 and 78.2, respectively. Baseline total DHQ was positively associated with subsequent change in physical-QoL to 7.5-year review, such that participants in the top two quartiles of baseline DHQ had 0.65 and 0.64 higher physical-QoL per year, though a similar association with mental-QoL did not persist on adjustment. Baseline meat consumption was associated with 0.38 lower physical-QoL per year, while baseline dairy consumption was associated with 0.50 and 0.41 lower physical- and mental-QoL per year, respectively. CONCLUSIONS: These results suggest efforts to improve the quality of dietary intake could be beneficial to the wellbeing of plwMS. Subject to replication, this aspect of lifestyle could be a useful intervention in better managing MS.

Higher-quality diet and non-consumption of meat are associated with less self-determined disability progression in people with multiple sclerosis: A longitudinal cohort study.

BACKGROUND AND PURPOSE: Modifiable lifestyle factors, including diet, may affect clinical outcomes in multiple sclerosis (MS). This study assessed the relationships between diet, and disability, fatigue, and depression risk in people with MS. METHODS: Participants from the Health Outcomes and Lifestyle In a Sample of people with Multiple sclerosis (HOLISM) international cohort were assessed over 2.5 years. Dietary data were obtained using a modified Diet Habits Questionnaire (DHQ), disability using the calculated Patient-determined MS Severity Score (P-MSSS), fatigue using the Fatigue Severity Scale, and depression risk using the Patient Health Questionnaire-2. Participants reported whether they were experiencing symptoms due to a recent relapse. Cross-sectional and prospective relationships of diet and disease outcomes were explored, adjusted for relevant confounders. RESULTS: Among 1,346 participants, higher DHQ scores showed significant dose-dependent associations with lower frequencies of severe disability, fatigue, and depression risk, cross-sectionally. Prospectively, higher baseline DHQ scores were associated with a lower risk of increasing disability, those above the median having 41% and 36% lower risk of increasing disability, and 0.30 P-MSSS points less disability progression, but were not associated with fatigue or depression risk. Meat consumption was associated with 0.22 P-MSSS points higher disability cross-sectionally, while prospectively, baseline meat consumption was associated with 76% higher risk of increasing disability and 0.18 P-MSSS points higher disability progression. Dairy consumption showed mixed associations cross-sectionally and prospectively. CONCLUSIONS: These results show that better quality of diet, as well as not consuming meat, were associated with reduced disability progression in people with MS. Substantiation of these findings in other settings may inform opportunities to manage disability progression in people with MS using dietary modifications.

Greater mastery is associated with lower depression risk in a large international cohort of people with multiple sclerosis over 2.5 years.

BACKGROUND: Mastery is the extent to which an individual perceives their life circumstances as being under their control and not predominantly influenced by external factors. The relationship of mastery with clinical outcomes in people with multiple sclerosis (pwMS) has not been well-researched. We assessed the relationships of mastery with fatigue, disability, relapse number, and depression risk among pwMS over 2.5 years' follow-up. METHODS: Data from the Health Outcomes and Lifestyle in a Sample of people with Multiple sclerosis study, among 839 participants who completed the 2.5 and 5-year reviews, were analysed. Mastery was measured by the Pearlin Mastery Scale, fatigue by Fatigue Severity Scale, depression risk by Patient Health Questionnaire-9, and disability by Patient-Determined Disease Steps, and diagnosed relapse number in the previous 12 months was queried. Cross-sectional and prospective analyses were undertaken by log-binomial, log-multinomial, and Poisson regression, as appropriate, adjusted for relevant confounders. RESULTS: Cross-sectionally, pwMS with the highest quartile mastery (> 25/28) had 90% lower frequency of depression risk, 60% lower frequency of clinically significant fatigue, and 77% fewer had severe disability, all largely robust to adjustment. Prospectively, those in the top two quartiles of mastery (> 21-25, > 25/28) had 66% and 74% lower subsequent depression risk, robust to adjustment. No significant associations were seen prospectively for change in fatigue, disability, or relapse number, however, and no robust associations of mastery with relapse number were evident. CONCLUSIONS: Prospectively, a protective relationship of mastery with subsequent risk of depression was observed, suggesting this may be a point of intervention to improve wellbeing in pwMS.

Experiences of and attitudes to lifestyle modification for the management of multiple sclerosis: A qualitative analysis of free-text survey data.

BACKGROUND: Growing evidence suggests a role of lifestyle modification in improved health outcomes for people with multiple sclerosis (pwMS); however, perspectives of pwMS who engage in lifestyle modification are lacking. OBJECTIVE: We explored perspectives of pwMS regarding the modification of lifestyle-related risk factors in multiple sclerosis (MS) for disease management to understand attitudes to and experiences of lifestyle modification as part of self-management from a patient perspective. DESIGN: Participants were ≥18 years and English speaking who responded to a free-text open-ended question in the Health Outcomes and Lifestyle In a Sample of pwMS (HOLISM), an international online survey. Responses were analysed utilizing inductive thematic analysis. RESULTS: Under the exploration of lifestyle modification, themes describing the experiences and attitudes of participants included practical challenges and physical and psychological barriers, enablers of change and experienced outcomes. Although participants reported some practical and psychological challenges to adoption and maintenance of lifestyle behaviours, many expressed an ability to gain control of MS through engagement with lifestyle behaviours and the development of hope and optimism that accompanied this sense of control, at times leading to a sense of personal transformation. CONCLUSION: Findings highlight the challenges experienced by pwMS in adopting lifestyle modifications for disease management as well as the positive benefits from following healthy lifestyle behaviours. Our findings may form the basis of more focussed qualitative explorations of the experiences and outcomes of lifestyle modification in MS in the future. PATIENT CONTRIBUTION: Consenting pwMS completed a survey capturing data on demographics, clinical course, lifestyle behaviours and health outcomes.

Associations between Lifestyle Behaviors and Quality of Life Differ Based on Multiple Sclerosis Phenotype.

Multiple sclerosis (MS), a neuroinflammatory disorder, occurs as non-progressive or progressive phenotypes; both forms present with diverse symptoms that may reduce quality of life (QoL). Adherence to healthy lifestyle behaviors has been associated with higher QoL in people with MS; whether these associations differ based on MS phenotype is unknown. Cross-sectional self-reported observational data from 1108 iConquerMS participants were analysed. Associations between lifestyle behaviors and QoL were assessed by linear regression, and phenotype differences via moderation analyses. Diet, wellness, and physical activity, but not vitamin D or omega-3 supplement use, were associated with QoL. Specifically, certain diet types were negatively associated with QoL in relapsing-remitting MS (RRMS), and positively associated in progressive MS (ProgMS). Participation in wellness activities had mixed associations with QoL in RRMS but was not associated in ProgMS. Physical activity was positively associated with QoL in RRMS and ProgMS. Phenotype differences were observed in diet and wellness with physical QoL, and physical activity with most QoL subdomains. Our findings show lifestyle behaviors are associated with QoL and appear to differ based on MS phenotype. Future studies assessing timing, duration, and adherence of adopting lifestyle behaviors may better inform their role in MS management.