Low sun exposure is associated with both progressive-onset and relapse-onset multiple sclerosis risk: a case-control study.

BACKGROUND: Sun exposure has consistently been associated with Multiple Sclerosis (MS) onset, but case samples are predominantly relapse-onset MS (ROMS), and risk estimates have rarely been reported separately for ROMS and progressive-onset MS (POMS). We aimed to determine whether sun exposure prior to disease onset was associated with POMS, and whether the effect differed between POMS and ROMS. METHODS: This nationwide case-control study included 153 POMS cases, 204 incident ROMS cases, and 558 community controls with data from two separate datasets: the PPMS Study (2015-2019) and the Ausimmune Study (2003-2006). Information on time spent in the sun before first MS symptom, skin phenotype, sun protection behavior was collected. Satellite data on ambient ultraviolet radiation (UVR) was used to calculate cumulative UVR dose. Unconditional logistic regression was used with adjustment for covariates. RESULTS: There were consistent dose-response associations, with higher levels of UVR exposure associated with a reduced risk of POMS, both for leisure-time and occupational UVR from age 6 to symptom onset. Associations were overall stronger for POMS than ROMS. For example, cumulative leisure-time UVR dose (per 100 kJ/m2 increment) was associated with POMS (aOR 0.93, 95% CI 0.91-0.95) and the association was slightly weaker for ROMS (aOR 0.96, 95% CI 0.94-0.99) for age 6 to symptom onset (test for interaction p<0.001). CONCLUSIONS: Low levels of sun exposure, throughout the whole life span, are associated with increased risk of POMS and ROMS onset. The sun effects are usually stronger for POMS than ROMS.

Long-term disability trajectories in multiple sclerosis: a group-based trajectory analysis of the AusLong cohort.

BACKGROUND: Previous natural history studies highlighted a consistent heterogeneity of disability trajectories among individuals with primary or secondary progressive multiple sclerosis (MS). However, evidence on disability progression in relapsing onset MS is scarce.The aim of this study was to investigate heterogeneity in disability accumulation over 10 years following a first clinical diagnosis of central nervous system demyelination (FCD) and identify genetic, demographic, environmental and clinical factors associated with these trajectories. METHODS: We used group-based trajectory models to measure heterogeneity in disability trajectories based on the Expanded Disability Status Scale (EDSS) in a prospectively assessed cohort of 263 participants. To capture sustained neurological impairments and avoid issues related to significant changes in EDSS associated with relapse, we did not consider EDSS points recorded within 3 months of a relapse. RESULTS: We identified three distinct and clinically meaningful disability trajectories: No/minimal, moderate and severe. Those in the no/minimal disability trajectory showed no appreciable progression of disability (median EDSS∼1 at 10-year review) while those in the moderate and severe disability trajectories experienced disability worsening (median time to reach EDSS 4 was 9 and 7 years, respectively). Compared with the no/minimal disability trajectory, those with older age, a higher number of relapses within the first 5 years post-FCD, and a higher number of comorbidities at baseline were more likely to be in the worse disability trajectory. Surprisingly, baseline MRI and anatomical site of initial symptoms did not influence long-term outcomes. CONCLUSIONS: Those at higher risk of faster MS disability progression can be identified based on their early clinical characteristics with potential therapeutic implications for early intervention and treatment escalation.

Significantly increasing multiple sclerosis prevalence in Australia from 2010 to 2021.

BACKGROUND: Multiple sclerosis (MS) prevalence is increasing globally. OBJECTIVES: To determine whether increased prevalence is continuing within Australia using our validated prescription-based ascertainment method. METHODS: We used methods employed in our 2010 and 2017 prevalence estimates. Disease-modifying therapy (DMT) prescriptions were extracted from Australia's Pharmaceutical Benefits Scheme data for January-December 2021. DMT penetrance was calculated using data from the Australian MS Longitudinal Study. We divided the total number of monthly prescriptions by 12 or 2 (except alemtuzumab), adjusted for DMT penetrance and Australian population estimates. Prevalences in Australian states/territories were age-standardised. 2021 prevalence estimates were compared with 2010 and 2017 prevalence estimates using Poisson regression. RESULTS: Number of people with MS in Australia in 2021 was 33,335; an increase of 7728 from 2017 (30.2%) and 12,092 from 2010 (56.6%) and increasing at a faster rate than population change (+10.1%, +14.1%). Age-standardised prevalence was 136.1/100,000 (increased from 103.7/100,000 in 2017). The previously demonstrated positive latitudinal gradient in 2010 and 2017 persisted in 2021, with Tasmania (southernmost state) having the highest prevalence (age-standardised: 203.5/100,000) while northernmost states had the lowest. CONCLUSIONS: In line with global trends, MS prevalence is escalating in Australia, particularly in higher-latitude states. MS prevention is crucial to halt this disturbing trend.

Sociodemographic, Health, and Lifestyle-Related Characteristics Associated With the Commencement and Completion of a Web-Based Lifestyle Educational Program for People With Multiple Sclerosis: Randomized Controlled Trial.

BACKGROUND: Digital health interventions increase access to multiple sclerosis (MS)-related knowledge for people living with MS; however, our understanding of factors associated with engagement in web-based learning is limited. OBJECTIVE: This study aims to examine associations between participant sociodemographic, health, and lifestyle-related characteristics and the commencement and completion of the Multiple Sclerosis Online Course (MSOC) in a randomized controlled trial (RCT). METHODS: An intervention course was developed based on the Overcoming MS Program-an evidence-based lifestyle modification program for MS, and a standard care course was developed based on international MS website information. An RCT was conducted to compare the effectiveness of the intervention course versus the standard care course in improving health outcomes in people living with MS. Participant data were collected from a baseline survey. Associations between baseline participant characteristics and MSOC commencement and completion, respectively, were assessed using multivariate log-binomial regression. RESULTS: Overall, 1893 participants enrolled in the RCT, and 45.27% (n=857) completed the baseline survey: 23.5% (n=444) in the intervention course and 21.8% (n=413) in the standard care course. Of these 857 participants, 631 (73.6%) commenced the standard care course or intervention course, and 49.1% (218/444) and 54.2% (224/413) completed the intervention course and standard care course, respectively. University education, partnered relationship status, and higher mental and physical quality of life were associated with 19%, 12%, 20%, and 22% higher rates of course commencement, respectively. Clinically significant fatigue was associated with a 10% reduction in the likelihood of commencement. Strongest associations with intervention course completion included middle and older adulthood, male sex, fatigue, and preexisting adherence to a diet program, with 96%, 27%, 24%, and 19% higher rates of completion observed, respectively, whereas higher self-efficacy was associated with up to 35% lower intervention course completion. Associations with standard care course completion included practicing meditation (20% higher completion), whereas employment was associated with 22% lower completion. CONCLUSIONS: Sociodemographic and clinical factors, as well as lifestyle-related factors, were important factors in MSOC commencement and completion. These data may help guide the design and enhancement of digital health interventions tailored for people living with MS. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12621001605886; https://tinyurl.com/2vyve9p9. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12883-023-03298-0.

Baseline engagement with healthy lifestyles and their associations with health outcomes in people with multiple sclerosis enrolled in an online multimodal lifestyle course.

BACKGROUND AND PURPOSE: Healthy lifestyle behaviour modification may improve health outcomes in people with multiple sclerosis (pwMS), but empirical evidence is needed to confirm prior study findings. We developed an online multimodal lifestyle intervention (Multiple Sclerosis Online Course) to examine the impact of lifestyle modification on health outcomes in pwMS via a randomized control trial (RCT). However, the present study specifically analyses baseline data to assess engagement with healthy lifestyles by RCT participants and cross-sectional associations with health outcomes. METHODS: Baseline engagement with six "healthy lifestyle behaviours" of the intervention course (high-quality, plant-based diet; ≥5000 IU/day vitamin D; omega-3 supplementation; ≥30 min physical activity 5 times/week; ≥30 min/week meditation; and nonsmoking) was examined. Associations between individual versus collective behaviours (individual behaviours summated) and health outcomes (quality of life [QoL]/fatigue/disability) were evaluated using multivariate modelling (linear/log-binomial/multinomial). RESULTS: At baseline, 33.7% and 30.0% of participants (n = 857) engaged in one or two healthy behaviours, respectively. In total, engagement with healthy lifestyles by participants was as follows: nonsmoking, 90.7%; omega-3 supplementation, 34.5%; vitamin D supplementation, 29.8%; physical activity, 29.4%; diet, 10.7%; and meditation, 10.5%. Individual behaviours (nonsmoking/physical activity/diet) were independently associated with better health outcomes. Engagement with multiple behaviours, especially diet and physical activity, was associated with better outcomes; engaging with ≥4 behaviours was associated with a 9.0-point higher mental QoL and a 9.5-point higher physical QoL, as well as 23% and 56% lower prevalence of fatigue and moderate disability, respectively. CONCLUSIONS: Baseline engagement with ≥4 healthy behaviours, including diet and physical activity, was associated with better health outcomes.

Longitudinal epidemiology of multiple sclerosis over 60 years in Newcastle, Australia: 1961 to 2021.

INTRODUCTION: Newcastle, Australia, has been serially studied for MS epidemiology since 1961, showing consistently increasing prevalence estimates and incidence rates, including to our 2011 study. OBJECTIVES: To assess the 2011-2021 epidemiology of MS in Newcastle and to compare with previous measures. METHODS: Demographic and clinical data were extracted from medical records of MS cases residing in Newcastle, as identified by public and private clinicians. Prevalence (2011 and 2021) and incidence rates (2011-2021, from onset and from diagnosis) and mortality rate (2011-2021) were estimated and age-standardised to the 2021 Australian population. RESULTS: The 2021 prevalence was 173.1/100,000 (age-standardised = 178.7/100,000, F/M-sex-ratio = 3.3), a 42.2 % increase from 2011 (F/M-sex-ratio = 3.1), 175.0 % from 1996 (F/M-sex-ratio = 2.6), and 831.0 % from 1961 (F/M-sex-ratio = 1.2). The 2011-21 age-standardised onset incidence rate was 3.5/100,000 person-years (F/M-sex-ratio = 2.8), a 68.7 % increase from 1971 to 81 (F/M-sex-ratio = 1.1) and 44.5 % from 1986 to 96 (F/M-sex-ratio = 2.3). The age-standardised diagnosis incidence rate was 6.1/100,000 (F/M-sex-ratio = 2.2), statistically unchanged from that in 2001-2011 (6.8/100,000, F/M-sex-ratio = 3.2). The 2011-21 mortality rate was 2.1/100,000 person-years (2.2 age-standardised, F/M-sex-ratio = 1.4), with a standardised mortality ratio of 1.6. CONCLUSION: The Newcastle region continues to be a high frequency zone for MS. The incidence rate from onset is significantly increased from previous estimates, but incidence rate from diagnosis is stable. Prevalence and incidence sex ratios have stabilised at roughly 3.0, similar to other Australian sites.

Web scraping of user-simulated online nutrition information for people with multiple sclerosis.

BACKGROUND: People diagnosed with multiple sclerosis (MS) often seek to modify their diet guided by online advice, however this advice may not align with national dietary guidelines. The aim of this study was to simulate an online search for dietary advice conducted by a person with MS and evaluate the content. It was hypothesised that a variety of eating patterns are promoted for MS online and these dietary approaches can be contradictory. METHODS: An online search was simulated using Google Trends-informed search terms and Google and Bing search engines. URLs were extracted using R. Nutrition data were extracted including recommendations for diets, foods, supplements, and health professional consultation. Statistical analyses were conducted using R. RESULTS: 73 URLs from 49 websites were extracted, with only 14 results common to both search engines. Dietary recommendations included overall eating patterns (58 webpages, 79%), individual foods (55 webpages, 75%), and supplements (33 webpages, 45%). The most promoted eating pattern for MS was a balanced diet (33 recommendations, 48%), more likely by nonprofit organisations and health information websites (14 and 17 recommendations, 100% and 89%); lifestyle program websites were more likely to recommend restrictive diets (19 recommendations, 100%) (p<0.001). 52% pages advised consulting a health professional, most often a doctor or dietitian. CONCLUSION: A balanced diet is the most recommended eating pattern for MS online, though advice promoting restrictive diets persists.

A systematic review and meta-analysis of Dietary Inflammatory Index and the likelihood of multiple sclerosis/ demyelinating autoimmune disease.

Diet and inflammation may contribute to the development of multiple sclerosis (MS). The aim of this systematic review and meta-analysis was to assess the association between proinflammatory diet, as estimated by the Dietary Inflammatory Index (DII®), and the likelihood of developing MS or other demyelinating autoimmune diseases. A systematic search was performed of search engines and databases (PubMed, ISI Web of Sciences, Scopus, and Embase) to identify relevant studies before 10th June 2023. The search identified 182 potential studies, from which 39 full-text articles were screened for relevance. Five articles with case-control design (n = 4,322, intervention group: 1714; control group: 2608) met the study inclusion criteria. The exposure variable was DII, with studies using two distinct models: quartile-based comparisons of DII and assessment of continuous DII. The meta-analysis of high versus low quartiles of DII with four effect sizes showed a significant association with MS/demyelinating autoimmune disease likelihood, with an odds ratio (OR) of 3.26 (95% confidence interval (CI) 1.16, 9.10). The meta-analysis of four studies with DII fit as a continuous variable showed a 31% increased likelihood of MS per unit increment; which was not statistically significant at the nominal alpha equals 0.05 (OR 1.31; 95% CI 0.95, 1.81). In conclusion, this systematic review and meta-analysis provides evidence of a positive association between higher DII scores with the likelihood of developing MS, highlighting that diet-induced inflammation could play a role in MS or other demyelinating autoimmune diseases risk.

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.

Associations between diet and disease progression and symptomatology in multiple sclerosis: A systematic review of observational studies.

BACKGROUND: Although many people with MS (pwMS) modify their diet after diagnosis, there is still no consensus on dietary recommendations for pwMS. A number of observational studies have explored associations of diet and MS progression, but no studies have systematically reviewed the evidence. This systematic review aimed to provide an objective synthesis of the evidence for associations between diet and MS progression, including symptoms and clinical outcomes from observational studies. METHODS: We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Electronic database searches were performed for studies completed up to 26 July 2023 using PubMed (Medline), Web of Science, CINAHL, Embase (Ovid), and Scopus, followed by citation and reference list checking. We included studies using diet quality scores or dietary indices. Studies assessing individual foods, nutrients, or dietary supplements were excluded. We used the Newcastle-Ottawa Scale to assess the risk of bias of included studies. RESULTS: Thirty-two studies met the inclusion criteria. Of these, 20 were cross-sectional and 12 prospective. The most frequent outcomes assessed were disability (n = 19), quality of life (n = 12), fatigue (n = 12), depression (n = 9), relapse (n = 8), anxiety (n = 3), and magnetic resonance imaging (MRI) outcomes (n = 4). Based on prospective studies, this review suggests that diet might be associated with quality of life and disability. There were also potential effects of higher diet quality scores on improved fatigue, disability, depression, anxiety, and MRI outcomes but more evidence is needed from prospective studies. CONCLUSIONS: Observational studies show some evidence for an association between diet and MS symptoms, particularly quality of life and disability. However, the impact of diet on other MS outcomes remains inconclusive. Ultimately, our findings suggest more evidence is needed from prospective studies and well-designed tailored intervention studies to confirm associations.

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.

Examining the environmental risk factors of progressive-onset and relapsing-onset multiple sclerosis: recruitment challenges, potential bias, and statistical strategies.

It is unknown whether the currently known risk factors of multiple sclerosis reflect the etiology of progressive-onset multiple sclerosis (POMS) as observational studies rarely included analysis by type of onset. We designed a case-control study to examine associations between environmental factors and POMS and compared effect sizes to relapse-onset MS (ROMS), which will offer insights into the etiology of POMS and potentially contribute to prevention and intervention practice. This study utilizes data from the Primary Progressive Multiple Sclerosis (PPMS) Study and the Australian Multi-center Study of Environment and Immune Function (the AusImmune Study). This report outlines the conduct of the PPMS Study, whether the POMS sample is representative, and the planned analysis methods. The study includes 155 POMS, 204 ROMS, and 558 controls. The distributions of the POMS were largely similar to Australian POMS patients in the MSBase Study, with 54.8% female, 85.8% POMS born before 1970, mean age of onset of 41.44 ± 8.38 years old, and 67.1% living between 28.9 and 39.4° S. The POMS were representative of the Australian POMS population. There are some differences between POMS and ROMS/controls (mean age at interview: POMS 55 years vs. controls 40 years; sex: POMS 53% female vs. controls 78% female; location of residence: 14.3% of POMS at a latitude ≤ 28.9°S vs. 32.8% in controls), which will be taken into account in the analysis. We discuss the methodological issues considered in the study design, including prevalence-incidence bias, cohort effects, interview bias and recall bias, and present strategies to account for it. Associations between exposures of interest and POMS/ROMS will be presented in subsequent publications.

Plasma neurofilament light in behavioural variant frontotemporal dementia compared to mood and psychotic disorders.

OBJECTIVE: Blood biomarkers of neuronal injury such as neurofilament light (NfL) show promise to improve diagnosis of neurodegenerative disorders and distinguish neurodegenerative from primary psychiatric disorders (PPD). This study investigated the diagnostic utility of plasma NfL to differentiate behavioural variant frontotemporal dementia (bvFTD, a neurodegenerative disorder commonly misdiagnosed initially as PPD), from PPD, and performance of large normative/reference data sets and models. METHODS: Plasma NfL was analysed in major depressive disorder (MDD, n = 42), bipolar affective disorder (BPAD, n = 121), treatment-resistant schizophrenia (TRS, n = 82), bvFTD (n = 22), and compared to the reference cohort (Control Group 2, n = 1926, using GAMLSS modelling), and age-matched controls (Control Group 1, n = 96, using general linear models). RESULTS: Large differences were seen between bvFTD (mean NfL 34.9 pg/mL) and all PPDs and controls (all < 11 pg/mL). NfL distinguished bvFTD from PPD with high accuracy, sensitivity (86%), and specificity (88%). GAMLSS models using reference Control Group 2 facilitated precision interpretation of individual levels, while performing equally to or outperforming models using local controls. Slightly higher NfL levels were found in BPAD, compared to controls and TRS. CONCLUSIONS: This study adds further evidence on the diagnostic utility of NfL to distinguish bvFTD from PPD of high clinical relevance to a bvFTD differential diagnosis, and includes the largest cohort of BPAD to date. Using large reference cohorts, GAMLSS modelling and the interactive Internet-based application we developed, may have important implications for future research and clinical translation. Studies are underway investigating utility of plasma NfL in diverse neurodegenerative and primary psychiatric conditions in real-world clinical settings.

Changes in employment status over time in multiple sclerosis following a first episode of central nervous system demyelination, a Markov multistate model study.

BACKGROUND AND PURPOSE: Understanding predictors of changes in employment status among people living with multiple sclerosis (MS) can assist health care providers to develop appropriate work retention/rehabilitation programs. We aimed to model longitudinal transitions of employment status in MS and estimate the probabilities of retaining employment status or losing or gaining employment over time in individuals with a first clinical diagnosis of central nervous system demyelination (FCD). METHODS: This prospective cohort study comprised adults (aged 18-59 years) diagnosed with FCD (n = 237) who were followed for more than 11 years. At each review, participants were assigned to one of three states: unemployed, part-time, or full-time employed. A Markov multistate model was used to examine the rate of state-to-state transitions. RESULTS: At the time of FCD, participants with full-time employment had an 89% chance of being in the same state over a 1-year period, but this decreased to 42% over the 10-year follow-up period. For unemployed participants, there was a 92% likelihood of remaining unemployed after 1 year, but this probability decreased to 53% over 10 years. Females, those who progressed to clinically definite MS, those with a higher relapse count, and those with a greater level of disability were at increased risk of transitioning to a deteriorated employment state. In addition, those who experienced clinically significant fatigue over the follow-up period were less likely to gain employment after being unemployed. CONCLUSIONS: In our FCD cohort, we found a considerable rate of employment transition during the early years post-diagnosis. Over more than a decade of follow-up post-FCD, we found that females and individuals with a greater disability and a higher relapse count are at higher risk of losing employment.

Impact of multiple sclerosis on male sexual and reproductive health.

Multiple sclerosis (MS) is a chronic inflammatory and autoimmune neurodegenerative disease characterized by the destruction of myelin in the central nervous system, leading to significant health and quality of life burdens for patients. MS is most prevalent in younger individuals aged 20-40, a critical period when many patients hope to establish relationships and start families. While neurological disability, such as fatigue, sensory dysfunction, spasticity, and cognitive dysfunction, have been greatly improved with the advances in managing MS, physicians are frequently confronted with sexual and reproductive problems among younger male people with MS (PwMS). These issues mainly include erectile dysfunction, ejaculatory disorders, reduced libido, decreased sperm quality, and impaired male fertility. Despite recent studies indicating that MS negatively impacts the sexuality and fertility of male PwMS, these issues have not received sufficient attention. Genetic factors, autoimmunity, chronic inflammation, psychological factors, and the use of drugs may contribute to sexual/reproductive dysfunction in PwMS. However, like the overall understanding of MS pathophysiology, the complete mechanisms of its development remain unclear. In this study, we review the existing literature to summarize the range of sexual and reproductive issues unique to males with MS, explore potential underlying mechanisms, and aim to improve these issues in male PwMS. By shedding light on this overlooked aspect of MS, we hope to enhance the care and well-being of male PwMS facing these challenges.

Using qualitative free-text data to investigate the lived experience of the COVID-19 pandemic for a large cohort of Australians with different multiple sclerosis related disability levels.

BACKGROUND: No large-scale qualitative studies have investigated the lived experience of people living with multiple sclerosis (PwMS) during the pandemic according to their disability level. We used qualitative research methods to investigate the lived experience of a large cohort of Australians living with differing multiple sclerosis (MS)-related disability levels during the COVID-19 pandemic. We also provided useful contextualisation to existing quantitative work. METHODS: This was a retrospective survey-based mixed-methods cohort study. A quality-of-life study was conducted within the Australian MS Longitudinal Study during the pandemic. Disability severity was calculated using the Patient Determined Disease Steps. Qualitative free-text data regarding COVID-19 impacts was collected/analysed for word frequency and also thematically (inductively/deductively using sophisticated grounded theory) using NVivo software. We also triangulated word frequency with emerging themes. RESULTS: N=509 PwMS participated providing n=22 530 words of COVID-19-specific data. Disability severity could be calculated for n=501 PwMS. The word 'working' was important for PwMS with no disability, and 'support' and 'isolation' for higher disability levels. For PwMS with milder disability, thematic analysis established that multitasking increased stress levels, particularly if working from home (WFH) and home-schooling children. If not multitasking, WFH was beneficial for managing fatigue. PwMS with severe disability raised increased social isolation as a concern including prepandemic isolation. CONCLUSIONS: We found negative impacts of multitasking and social isolation for PwMS during the pandemic. WFH was identified as beneficial for some. We recommend targeted resourcing decisions for PwMS in future pandemics including child-care relief and interventions to reduce social isolation and suggest that these could be incorporated into some form of advanced care planning. As the nature of work changes postpandemic, we also recommend a detailed investigation of WFH for PwMS including providing tailored employment assistance.

The association between disability progression, relapses, and treatment in early relapse onset MS: an observational, multi-centre, longitudinal cohort study.

The indirect contribution of multiple sclerosis (MS) relapses to disability worsening outcomes, and vice-versa, remains unclear. Disease modifying therapies (DMTs) are potential modulators of this association. Understanding how these endo-phenotypes interact may provide insights into disease pathogenesis and treatment practice in relapse-onset MS (ROMS). Utilising a unique, prospectively collected clinical data from a longitudinal cohort of 279 first demyelinating event cases followed for up to 15 years post-onset, we examined indirect associations between relapses and treatment and the risk of disability worsening, and vice-versa. Indirect association parameters were estimated using joint models for longitudinal and survival data. Early relapses within 2.5 years of MS onset predicted early disability worsening outcomes (HR = 3.45, C.I 2.29-3.61) per relapse, but did not contribute to long-term disability worsening thereinafter (HR = 0.21, C.I 0.15-0.28). Conversely, disability worsening outcomes significantly contributed to relapse risk each year (HR = 2.96, C.I 2.91-3.02), and persisted over time (HR = 3.34, C.I 2.90-3.86), regardless of DMT treatments. The duration of DMTs significantly reduced the hazards of relapses (1st-line DMTs: HR = 0.68, C.I 0.58-0.79; 3rd-line DMTs: HR = 0.37, C.I 0.32-0.44) and disability worsening events (1st-line DMTs: HR = 0.74, C.I 0.69-0.79; 3rd-line DMTs: HR = 0.90, C.I 0.85-0.95), respectively. Results from time-dynamic survival probabilities further revealed individuals having higher risk of future relapses and disability worsening outcomes, respectively. The study provided evidence that in ROMS, relapses accrued within 2.5 years of MS onset are strong indicators of disability worsening outcomes, but late relapses accrued 2.5 years post onset are not overt risk factors for further disability worsening. In contrast, disability worsening outcomes are strong positive predictors of current and subsequent relapse risk. Long-term DMT use and older age strongly influence the individual outcomes and their associations.

Longitudinal epidemiology of multiple sclerosis in Townsville, Queensland, Australia, 2012-2022.

BACKGROUND: Townsville (population=195,564, latitude=19.3°S) is the largest city in the Northern Queensland region of Australia, an area previously defined as a low/medium-prevalence zone for multiple sclerosis (MS). However, the epidemiology of MS in this region since 1981 is unknown. AIMS: To assess the 2012 to 2022 epidemiology of MS in Townsville. METHODS: Demographic/clinical data extracted from medical records of MS cases identified by public and private clinicians. Prevalence, and incidence and mortality rates estimated for 2012 and 2022 and age-standardised to the 2022 Australian population. Differences in estimates assessed by Poisson regression. RESULTS: Females and relapsing-remitting MS comprised most cases. The 2012 prevalence was 45.0/100,000 (50.4/100,000 age-standardised, F/M sex ratio=2.0). Prevalence increased by 188% in 2022, with a crude prevalence of 86.9/100,000 (91.7/100,000 age-standardised, F/M sex ratio=2.7). 2012-22 MS onset incidence rate was 3.8/100,000 person-years (age-standardised 3.5/100,000, F/M sex ratio=2.7). Mean age increased from 49.4 to 57.3 years. Age-standardised mortality rate was 0.9/100,000 person-years, with standardised mortality ratio=1.0. DISCUSSION: These results show that Townsville is a high-frequency region for MS, with prevalence and incidence on par with that seen at higher latitudes in Australia. These results have implications for clinical practice in the region and for organisational resource allocation.

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.

The risk of secondary progressive multiple sclerosis is geographically determined but modifiable.

Geographical variations in the incidence and prevalence of multiple sclerosis have been reported globally. Latitude as a surrogate for exposure to ultraviolet radiation but also other lifestyle and environmental factors are regarded as drivers of this variation. No previous studies evaluated geographical variation in the risk of secondary progressive multiple sclerosis, an advanced form of multiple sclerosis that is characterized by steady accrual of irreversible disability. We evaluated differences in the risk of secondary progressive multiple sclerosis in relation to latitude and country of residence, modified by high-to-moderate efficacy immunotherapy in a geographically diverse cohort of patients with relapsing-remitting multiple sclerosis. The study included relapsing-remitting multiple sclerosis patients from the global MSBase registry with at least one recorded assessment of disability. Secondary progressive multiple sclerosis was identified as per clinician diagnosis. Sensitivity analyses used the operationalized definition of secondary progressive multiple sclerosis and the Swedish decision tree algorithm. A proportional hazards model was used to estimate the cumulative risk of secondary progressive multiple sclerosis by country of residence (latitude), adjusted for sex, age at disease onset, time from onset to relapsing-remitting phase, disability (Multiple Sclerosis Severity Score) and relapse activity at study inclusion, national multiple sclerosis prevalence, government health expenditure, and proportion of time treated with high-to-moderate efficacy disease-modifying therapy. Geographical variation in time from relapsing-remitting phase to secondary progressive phase of multiple sclerosis was modelled through a proportional hazards model with spatially correlated frailties. We included 51 126 patients (72% female) from 27 countries. The median survival time from relapsing-remitting phase to secondary progressive multiple sclerosis among all patients was 39 (95% confidence interval: 37 to 43) years. Higher latitude [median hazard ratio = 1.21, 95% credible interval (1.16, 1.26)], higher national multiple sclerosis prevalence [1.07 (1.03, 1.11)], male sex [1.30 (1.22, 1.39)], older age at onset [1.35 (1.30, 1.39)], higher disability [2.40 (2.34, 2.47)] and frequent relapses [1.18 (1.15, 1.21)] at inclusion were associated with increased hazard of secondary progressive multiple sclerosis. Higher proportion of time on high-to-moderate efficacy therapy substantially reduced the hazard of secondary progressive multiple sclerosis [0.76 (0.73, 0.79)] and reduced the effect of latitude [interaction: 0.95 (0.92, 0.99)]. At the country-level, patients in Oman, Tunisia, Iran and Canada had higher risks of secondary progressive multiple sclerosis relative to the other studied regions. Higher latitude of residence is associated with a higher probability of developing secondary progressive multiple sclerosis. High-to-moderate efficacy immunotherapy can mitigate some of this geographically co-determined risk.