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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.
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Esclerose Múltipla , Humanos , Prevalência , Austrália/epidemiologia , Esclerose Múltipla/epidemiologia , Adulto , Pessoa de Meia-Idade , Masculino , Feminino , Estudos Longitudinais , Adulto Jovem , Fatores Imunológicos/uso terapêutico , Idoso , AdolescenteRESUMO
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.
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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.
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Esclerose Múltipla , Adulto , Feminino , Humanos , Esclerose Múltipla/epidemiologia , Estudos Prospectivos , Emprego , Recidiva , Sistema Nervoso CentralRESUMO
Understanding how variations in the plasma and brain proteome contribute to multiple sclerosis susceptibility can provide important insights to guide drug repurposing and therapeutic development for the disease. However, the role of genetically predicted protein abundance in multiple sclerosis remains largely unknown. Integrating plasma proteomics (n = 3301) and brain proteomics (n = 376 discovery; n = 152 replication) into multiple sclerosis genome-wide association studies (n = 14 802 cases and 26 703 controls), we employed summary-based methods to identify candidate proteins involved in multiple sclerosis susceptibility. Next, we evaluated associations of the corresponding genes with multiple sclerosis at tissue-level using large gene expression quantitative trait data from whole-blood (n = 31 684) and brain (n = 1194) tissue. Further, to assess transcriptional profiles for candidate proteins at cell-level, we examined gene expression patterns in immune cell types (Dataset 1: n = 73 cases and 97 controls; Dataset 2: n = 31 cases and 31 controls) for identified plasma proteins, and in brain cell types (Dataset 1: n = 4 cases and 5 controls; Dataset 2: n = 5 cases and 3 controls) for identified brain proteins. In a longitudinal multiple sclerosis cohort (n = 203 cases followed up to 15 years), we also assessed the corresponding gene-level associations with the outcome of disability worsening. We identified 39 novel proteins associated with multiple sclerosis risk. Based on five identified plasma proteins, four available corresponding gene candidates showed consistent associations with multiple sclerosis risk in whole-blood, and we found TAPBPL upregulation in multiple sclerosis B cells, CD8+ T cells and natural killer cells compared with controls. Among the 34 candidate brain proteins, 18 were replicated in a smaller cohort and 14 of 21 available corresponding gene candidates also showed consistent associations with multiple sclerosis risk in brain tissue. In cell-specific analysis, six identified brain candidates showed consistent differential gene expression in neuron and oligodendrocyte cell clusters. Based on the 39 protein-coding genes, we found 23 genes that were associated with disability worsening in multiple sclerosis cases. The findings present a set of candidate protein biomarkers for multiple sclerosis, reinforced by high concordance in downstream transcriptomics findings at tissue-level. This study also highlights the heterogeneity of cell-specific transcriptional profiles for the identified proteins and that numerous candidates were also implicated in disease progression. Together, these findings can serve as an important anchor for future studies of disease mechanisms and therapeutic development.
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Esclerose Múltipla , Humanos , Esclerose Múltipla/genética , Estudo de Associação Genômica Ampla , Biomarcadores , Proteínas Sanguíneas/genética , Encéfalo , Imunoglobulinas/genética , Proteínas de Membrana/genéticaRESUMO
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.
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Esclerose Múltipla Crônica Progressiva , Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Esclerose Múltipla Crônica Progressiva/epidemiologia , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/diagnóstico , Esclerose Múltipla Recidivante-Remitente/epidemiologia , Raios Ultravioleta , Progressão da Doença , Recidiva Local de NeoplasiaRESUMO
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.
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Doença de Alzheimer , Transtorno Bipolar , Transtorno Depressivo Maior , Demência Frontotemporal , Transtornos Psicóticos , Humanos , Doença de Alzheimer/diagnóstico , Biomarcadores , Transtorno Bipolar/diagnóstico , Transtorno Depressivo Maior/diagnóstico , Demência Frontotemporal/diagnóstico , Filamentos IntermediáriosRESUMO
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.
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Internet , Estilo de Vida , Esclerose Múltipla , Humanos , Esclerose Múltipla/psicologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Educação de Pacientes como Assunto/métodosRESUMO
BACKGROUND: There are currently no specific biomarkers for multiple sclerosis (MS). Identifying robust biomarkers for MS is crucial to improve disease diagnosis and management. METHODS: This study first used six Mendelian randomisation methods to assess causal relationship of 174 metabolites with MS, incorporating data from European-ancestry metabolomics (n=8569-86 507) and MS (n=14 802 MS cases, 26 703 controls) genomewide association studies. Genetic scores for identified causal metabolite(s) were then computed to predict MS disability progression in an independent longitudinal cohort (AusLong study) of 203 MS cases with up to 15-year follow-up. RESULTS: We found a novel genetic causal effect of serine on MS onset (OR=1.67, 95% CI 1.51 to 1.84, p=1.73×10-20), such that individuals whose serine level is 1 SD above the population mean will have 1.67 times the risk of developing MS. This is robust across all sensitivity methods (OR ranges from 1.49 to 1.67). In an independent longitudinal MS cohort, we then constructed time-dynamic and time-fixed genetic scores based on serine genetic instrument single-nucleotide polymorphisms, where higher scores for raised serum serine level were associated with increased risk of disability worsening, especially in the time-dynamic model (RR=1.25, 95% CI 1.10 to 1.42, p=7.52×10-4). CONCLUSIONS: These findings support investigating serine as an important candidate biomarker for MS onset and disability progression.
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Pessoas com Deficiência , Esclerose Múltipla , Humanos , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/genética , Causalidade , Metabolômica , Biomarcadores , Progressão da DoençaRESUMO
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.
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População Australasiana , COVID-19 , Esclerose Múltipla , Humanos , Austrália/epidemiologia , Estudos de Coortes , Estudos Longitudinais , Esclerose Múltipla/epidemiologia , Pandemias , Estudos RetrospectivosRESUMO
BACKGROUND: We previously reported an association between household chemical exposures and an increased risk of paediatric-onset multiple sclerosis. METHODS: Using a case-control paediatric multiple sclerosis study, gene-environment interaction between exposure to household chemicals and genotypes for risk of paediatric-onset multiple sclerosis was estimated.Genetic risk factors of interest included the two major HLA multiple sclerosis risk factors, the presence of DRB1*15 and the absence of A*02, and multiple sclerosis risk variants within the metabolic pathways of common household toxic chemicals, including IL-6 (rs2069852), BCL-2 (rs2187163) and NFKB1 (rs7665090). RESULTS: 490 paediatric-onset multiple sclerosis cases and 716 controls were included in the analyses. Exposures to insect repellent for ticks or mosquitos (OR 1.47, 95% CI 1.06 to 2.04, p=0.019), weed control products (OR 2.15, 95% CI 1.51 to 3.07, p<0.001) and plant/tree insect or disease control products (OR 3.25, 95% CI 1.92 to 5.49, p<0.001) were associated with increased odds of paediatric-onset multiple sclerosis. There was significant additive interaction between exposure to weed control products and NFKB1 SNP GG (attributable proportions (AP) 0.48, 95% CI 0.10 to 0.87), and exposure to plant or disease control products and absence of HLA-A*02 (AP 0.56; 95% CI 0.03 to 1.08). There was a multiplicative interaction between exposure to weed control products and NFKB1 SNP GG genotype (OR 2.30, 95% CI 1.00 to 5.30) but not for other exposures and risk variants. No interactions were found with IL-6 and BCL-2 SNP GG genotypes. CONCLUSIONS: The presence of gene-environment interactions with household toxins supports their possible causal role in paediatric-onset multiple sclerosis.
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Interação Gene-Ambiente , Esclerose Múltipla , Criança , Humanos , Esclerose Múltipla/induzido quimicamente , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/genética , Predisposição Genética para Doença/genética , Interleucina-6 , Cadeias HLA-DRB1/genética , Fatores de Risco , Genótipo , Antígenos HLA , Estudos de Casos e Controles , Proteínas Proto-Oncogênicas c-bcl-2/genéticaRESUMO
BACKGROUND: A pro-inflammatory diet has been posited to induce chronic inflammation within the central nervous system (CNS), and multiple sclerosis (MS) is an inflammatory disease of the CNS. OBJECTIVE: We examined whether Dietary Inflammatory Index (DII®)) scores are associated with measures of MS progression and inflammatory activity. METHODS: A cohort with a first clinical diagnosis of CNS demyelination was followed annually (10 years, n = 223). At baseline, 5- and 10-year reviews, DII and energy-adjusted DII (E-DIITM) scores were calculated (food frequency questionnaire) and assessed as predictors of relapses, annualised change in disability (Expanded Disability Status Scale) and two magnetic resonance imaging measures; fluid-attenuated inversion recovery (FLAIR) lesion volume and black hole lesion volume. RESULTS: A more pro-inflammatory diet was associated with a higher relapse risk (highest vs. lowest E-DII quartile: hazard ratio = 2.24, 95% confidence interval (CI) = -1.16, 4.33, p = 0.02). When we limited analyses to those assessed on the same manufacturer of scanner and those with a first demyelinating event at study entry (to reduce error and disease heterogeneity), an association between E-DII score and FLAIR lesion volume was evident (ß = 0.38, 95% CI = 0.04, 0.72, p = 0.03). CONCLUSION: There is a longitudinal association between a higher DII and a worsening in relapse rate and periventricular FLAIR lesion volume in people with MS.
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Esclerose Múltipla , Humanos , Esclerose Múltipla/diagnóstico por imagem , Estudos Prospectivos , Dieta , Doença Crônica , Inflamação/diagnóstico por imagem , Imageamento por Ressonância Magnética , RecidivaRESUMO
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.
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Esclerose Múltipla , Qualidade de Vida , Humanos , Esclerose Múltipla/terapia , Estilo de Vida Saudável , Estilo de Vida , Vitamina D , VitaminasRESUMO
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.
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Esclerose Múltipla , Humanos , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/complicações , Estudos Prospectivos , Dieta , Estilo de Vida , Inquéritos e QuestionáriosRESUMO
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.
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Estilo de Vida , Esclerose Múltipla , Humanos , Austrália , Qualidade de Vida , Ansiedade , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
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.
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Esclerose Múltipla , Qualidade de Vida , Humanos , Qualidade de Vida/psicologia , Estudos de Coortes , Dieta , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Multiple sclerosis (MS) is an inflammatory, neurodegenerative disease of the central nervous system which results in disability over time and reduced quality of life. To increase the sensitivity of the EQ-5D-5L for psychosocial health, four bolt-on items from the AQoL-8D were used to create the nine-item EQ-5D-5L-Psychosocial. We aimed to externally validate the EQ-5D-5L-Psychosocial in a large cohort of people with MS (pwMS) and explore the discriminatory power of the new instrument with EQ-5D-5L/AQoL-8D. METHODS: A large representative sample from the Australian MS Longitudinal Study completed the AQoL-8D and EQ-5D-5L (including EQ VAS) and both instruments health state utilities (HSUs) were scored using Australian tariffs. Sociodemographic/clinical data were also collected. External validity of EQ-5D-5L-Psychosocial scoring algorithm was assessed with mean absolute errors (MAE) and Spearman's correlation coefficient. Discriminatory sensitivity was assessed with an examination of ceiling/floor effects, and disability severity classifications. RESULTS: Among 1683 participants (mean age: 58.6 years; 80% female), over half (55%) had moderate or severe disability. MAE (0.063) and the distribution of the prediction error were similar to the original development study. Mean (± standard deviation) HSUs were EQ-5D-5L: 0.58 ± 0.32, EQ-5D-5L-Psychosocial 0.62 ± 0.29, and AQoL-8D: 0.63 ± 0.20. N = 157 (10%) scored perfect health (i.e. HSU = 1.0) on the EQ-5D-5L, but reported a mean HSU of 0.90 on the alternative instruments. The Sleep bolt-on dimension was particularly important for pwMS. CONCLUSIONS: The EQ-5D-5L-Psychosocial is more sensitive than the EQ-5D-5L in pwMS whose HSUs approach those reflecting full health. When respondent burden is taken into account, the EQ-5D-5L-Psychosocial is preferential to the AQoL-8D. We suggest a larger confirmatory study comparing all prevalent multi-attribute utility instruments for pwMS.
Assuntos
Esclerose Múltipla , Doenças Neurodegenerativas , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Qualidade de Vida/psicologia , Inquéritos e Questionários , Estudos Longitudinais , Austrália , Psicometria/métodosRESUMO
BACKGROUND: The Greater Hobart region (42.5°S) of Tasmania has consistently had the highest recorded prevalence and incidence rates of multiple sclerosis (MS) in Australia. We reassessed MS epidemiology in 2009-2019 and assessed longitudinal changes over 68 years. METHODS: Cases recruited from clinic-based datasets and multiple other data sources. 2019 prevalence and 2009-2019 annual incidence and mortality rates estimated, and differences assessed using Poisson regression. RESULTS: 436 MS cases resident on prevalence day were identified, and 130 had symptom onset within 2009-2019. Prevalence 197.1/100 000 (95% CI 179.4 to 216.5; 147.2/100 000 age standardised, 95% CI 126.5 to 171.3), a 36% increase since 2001 and 3.1-fold increase since 1961. 2009-2019 incidence rate=5.9/100 000 person-years, 95% CI 5.0 to 7.0 (6.1/1000 000 age standardised, 95% CI 4.7 to 7.9), a 2.8-fold increase since 1951-1961 and 65% since 2001-2009. 2009-2019 mortality rate=1.5/100 000 person-years, 95% CI 1.1 to 2.2 (0.9/100 000 age standardised, 95% CI 0.4 to 1.7), comparable to 2001-2009 (1.0/100 000) but reduced by 61% from 1951 to 1959 (2.1/100 000). 2001-2009 standardised mortality ratio=1.0 in 2009-2019, decreased from 2.0 in 1971-1979. Female:male prevalence sex ratio was 2.8, comparable to the 2009 value (2.6); incidence sex ratio (2.9) increased from 2001 to 9 (2.1). Comparisons with Newcastle, Australia (latitude=32.5°S) demonstrate a near complete abrogation of the latitudinal gradients for prevalence (ratio=1.0) and incidence (ratio=1.1), largely attributable to changing Hobart demography. CONCLUSIONS: Prevalence and incidence of MS continue to increase significantly in Hobart, alongside marked reductions in mortality and increased case longevity. The marked increase in incidence is of particular note and may reflect longstanding changes in MS risk behaviours including changing sun exposure, obesity rates, and smoking behaviours, particularly in females. Falling mortality contributes to increase longevity and prevalence, likely reflecting improved overall MS healthcare and implementation of disease-modifying therapy.
RESUMO
BACKGROUND: People with multiple sclerosis face significant employment-related challenges, with little known of the drivers of these outcomes. OBJECTIVE: We examined prospective trajectories of employment-related outcomes up to 11 years following a first episode of central nervous system (CNS) demyelination (FCD). METHODS: Participants were aged 18-59 years, at FCD, with at least two observations and were employed at study entry or anytime during follow-up (n = 207). Outcomes were employment status (full-time, part-time and unemployed), average workhours per week and disability support pension (DSP; receiving/not receiving). We used group-based trajectory modelling to identify groups with common trajectories. Factors associated with trajectory membership were explored using log-multinomial regression. RESULTS: Distinct trajectories were identified for employment (4), workhours (4) and DSP (2). Compared with stable full-time, female sex was strongly associated with being in the stable part-time trajectory (risk ratio (RR): 5.35; 95% confidence interval (CI) = 2.56-11.20; p < 0.001). A greater level of disability at 5-year review (RR: 1.35; 95% CI = 1.19-1.53) and having more than two comorbidities at baseline (RR: 2.77; 95% CI = 1.37-5.64) were associated with being in early and late deteriorated employment trajectories, respectively. Compared with the increased part-time trajectory, every additional relapse during the 5 years post-FCD was associated with a 10% increased risk of being in the reduced part-time trajectory (RR = 1.10; 95%CI = 1.00-1.22). For every additional EDSS point at 5-year review, the risk of being in the DSP trajectory increased (RR = 1.21; 95% CI = 1.05-1.41). CONCLUSION: These trajectories indicate substantial heterogeneity and the complex impact of MS on employment from its earliest timepoints. Understanding these trends could enable better targeting of interventions to facilitate workforce retention, particularly for females, those with a higher number of comorbidities, more frequent relapses and greater rate of disability accrual.
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Pessoas com Deficiência , Esclerose Múltipla , Emprego , Feminino , Humanos , Pensões , Estudos Prospectivos , RecidivaRESUMO
BACKGROUND: Disease-modifying therapies (DMTs) are used to treat people with relapsing-onset multiple sclerosis (ROMS), but our knowledge is largely limited to their short-term effects. OBJECTIVE: To determine (1) the impact of national-level DMT subsidy policy on DMT use and health outcomes in people with MS (PwMS) and (2) the long-term effects of DMT on disability and quality of life (QoL; 5-level EQ-5D version (EQ-5D-5L) utility value). METHODS: This observational cohort study compared Australian and New Zealand populations with different levels of DMT availability 10-20 years post-ROMS diagnosis. Between-country differences were assessed using standardised differences. Associations were assessed with multivariable linear regression models. RESULTS: We recruited 328 Australians and 256 New Zealanders. The Australian cohort had longer DMT treatment duration, greater proportion of disease course treated and shorter duration between diagnosis and starting DMT. The Australian cohort had lower median Expanded Disability Status Scale (EDSS) (3.5 vs 4.0) and Multiple Sclerosis Severity Score (MSSS) (3.05 vs 3.71) and higher QoL (0.71 vs 0.65). In multivariable models, between-country differences in disability and QoL were largely attributed to differential use of DMT. CONCLUSIONS: This study provides evidence for the impact of national-level DMT policy on disability outcomes in PwMS. Where DMTs are more accessible, PwMS experienced less disability progression and improved QoL 10-20 years post-diagnosis.
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Pessoas com Deficiência , Esclerose Múltipla , Austrália , Humanos , Esclerose Múltipla/tratamento farmacológico , Políticas , Qualidade de VidaRESUMO
Over the recent years, the treatment of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) has evolved very rapidly and a large number of disease-modifying treatments (DMTs) are now available. However, most DMTs are associated with adverse events, the most frequent of which being infections. Consideration of all DMT-associated risks facilitates development of risk mitigation strategies. An international focused workshop with expert-led discussions was sponsored by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and was held in April 2021 to review our current knowledge about the risk of infections associated with the use of DMTs for people with MS and NMOSD and corresponding risk mitigation strategies. The workshop addressed DMT-associated infections in specific populations, such as children and pregnant women with MS, or people with MS who have other comorbidities or live in regions with an exceptionally high infection burden. Finally, we reviewed the topic of DMT-associated infectious risks in the context of the current SARS-CoV-2 pandemic. Herein, we summarize available evidence and identify gaps in knowledge which justify further research.