Objective
A protective association between higher vitamin D levels and the onset of multiple sclerosis (MS) has been demonstrated; however, its role in modulating MS clinical course has been little ...studied. We investigated whether higher levels of serum 25‐hydroxyvitamin D (25‐OH‐D) were associated with a lower risk of relapses in people with MS.
Methods
We conducted a prospective cohort study of 145 participants with relapsing‐remitting MS from 2002 to 2005. Serum 25‐OH‐D levels were measured biannually, and the hazard of relapse was assessed using survival analysis.
Results
There was an inverse linear relationship between 25‐OH‐D levels and the hazard of relapse over the subsequent 6 months, with hazard ratio (HR) 0.91 (95% confidence interval CI: 0.85–0.97) per 10nmol/l increase in 25‐OH‐D level (p = 0.006). When variation due to timing of blood collection was removed by estimating 25‐OH‐D at the start of each season, this association persisted, with HR 0.90 (95% CI, 0.83–0.98) per 10nmol/l increase (p = 0.016). Taking into account the biological half‐life of 25‐OH‐D, we estimated 25‐OH‐D at monthly intervals, resulting in a slightly enhanced association, with HR 0.88 (95% CI, 0.82–0.95) per 10nmol/l increase (p = 0.001). Adjusting for potential confounders did not alter these findings.
Interpretation
In this prospective population‐based cohort study, in a cohort largely on immunomodulatory therapy, higher 25‐OH‐D levels were associated with a reduced hazard of relapse. This occurred in a dose‐dependent linear fashion, with each 10nmol/l increase in 25‐OH‐D resulting in up to a 12% reduction in risk of relapse. Clinically, raising 25‐OH‐D levels by 50nmol/l could halve the hazard of a relapse. ANN NEUROL 2010;68:193–203
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Objectives To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect.Design Systematic review and ...meta-analysis of individual participant data (IPD) from randomised controlled trials.Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015.Eligibility criteria for study selection Randomised, double blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome.Results 25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity <0.001). In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted odds ratio 0.81, 0.72 to 0.91) but not in those receiving one or more bolus doses (adjusted odds ratio 0.97, 0.86 to 1.10; P for interaction=0.05). Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L (adjusted odds ratio 0.30, 0.17 to 0.53) than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (adjusted odds ratio 0.75, 0.60 to 0.95; P for interaction=0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted odds ratio 0.98, 0.80 to 1.20, P=0.83). The body of evidence contributing to these analyses was assessed as being of high quality.Conclusions Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit.Systematic review registration PROSPERO CRD42014013953.
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BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
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.
In this cohort of 1,346 people with multiple sclerosis, followed over 2.5 years, we found that better diet quality and not consuming meat or dairy were associated with significantly less disability progression. Those with better diet quality or not consuming meat or dairy actually decreased their disability, while those with worse diet practices had static or worse disability. However, no prospective associations of diet quality with fatigue or depression were seen.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Objective:
Determine the prevalence of multiple sclerosis (MS) in Australia in 2017 using MS-specific disease-modifying therapy (DMT) prescription data and estimate the change in prevalence from ...2010.
Methods:
DMT prescriptions were extracted from Australia’s Pharmaceutical Benefits Scheme (PBS) data for January–December 2017. Percentages of people with MS using DMTs (DMT penetrance) were calculated using data from the Australian MS Longitudinal Study. Prevalence was estimated by dividing the total number of monthly prescriptions by 12 (except alemtuzumab), adjusted for DMT penetrance and Australian population estimates. Prevalences in Australian states/territories were age-standardised to the Australian population. Comparisons with 2010 prevalence data were performed using Poisson regression.
Results:
Overall DMT penetrance was 64%, and the number of people with MS in Australia in 2017 was 25,607 (95% confidence interval (CI): 24,874–26,478), a significant increase of 4324 people since 2010 (p < 0.001). The prevalence increased significantly from 95.6/100,000 (2010) to 103.7/100,000 (2017), with estimates highest in Tasmania in 2017 (138.7/100,000; 95% CI: 137.2–140.1) and lowest in Queensland (74.6/100,000; 95% CI: 73.5–75.6). From 2010 to 2017 using the median latitudes for each state/territory, the overall latitudinal variation in MS prevalence was an increase of 3.0% per degree-latitude.
Conclusion:
Consistent with global trends, Australia’s MS prevalence has increased; this probably reflecting decreased mortality, increased longevity and increased incidence.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Background:
Little is known about the work productivity loss in multiple sclerosis (MS).
Objectives:
To quantify the MS-related work productivity loss and to compare factors associated with labour ...force participation and work productivity loss.
Methods:
Participants were from the Australian MS Longitudinal Study. MS-related work productivity loss included absenteeism (time missed from work) and presenteeism (reduced productivity while working). Data were analysed using log-binomial and Cragg hurdle regression.
Results:
Among 740 MS employees, 56% experienced any work productivity loss due to MS in the past 4 weeks. The mean total work productivity loss was 2.5 days (14.2% lost productive time), absenteeism 0.6 days (3.4%) and presenteeism 1.9 days (10.8%)), leading to AU$6767 (US$4985, EURO€4578) loss per person annually. Multivariable analyses showed that work productivity was determined most strongly by symptoms, particularly ‘fatigue and cognitive symptoms’ and ‘pain and sensory symptoms’, while older age, and lower education level were also predictive of not being in the labour force.
Conclusion:
MS-related presenteeism was three times higher than absenteeism, highlighting the importance of presenteeism being included in employment outcomes. The dominance of symptom severity as predictors of both work participation and productivity loss emphasises the need for improved management of symptoms.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Background:
More work is needed to understand the burden of comorbidities in people with multiple sclerosis (MS).
Objective:
To assess prevalence of 30 comorbidities and impacts of comorbidities on ...employment outcomes in a working-aged MS cohort.
Methods:
Participants were from the Australian MS Longitudinal Study (n = 929). Information on specific comorbidity was obtained (whether or not each was present, doctor-diagnosed, limited their activities and being treated).
Results:
Comorbidities most frequently reported to limit activities were osteoarthritis (51%), migraines (40%), anxiety (33%), depression (29%) and allergies (18%). Mean MS-related work productivity loss in past 4 weeks was 1.3 days for those without comorbidities and 2.5 days for those with any comorbidity. The annual population costs of work productivity loss were highest for people with depression, allergies, anxiety, migraines and osteoarthritis. Higher number of comorbidities was associated with more work productivity loss and a higher likelihood of not working. These associations were substantially reduced after adjustment for MS symptom severity.
Conclusions:
Comorbidities substantially impact employment outcomes and these effects were mainly mediated through MS symptom severity. This suggests that optimal and simultaneous management of comorbidities may be a viable strategy to reduce MS symptom severity, which in turn could improve employment outcomes.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Multiple sclerosis (MS) patients may be at an increased risk of comorbidities due to the debilitating and chronic nature of the disease. An increased understanding of comorbidities and disease course ...in MS may provide new insights and enhance MS management. We aimed at investigating the frequency of comorbidities and their associations with clinical disability and relapse in MS.
A prospective cohort of 198 MS patients was followed during 2002-2005 and queried about specific doctor-diagnosed comorbidities. In Australia, the MS cohort was compared to the 2007 general population with regard to the prevalence of comorbidities. Multilevel mixed-effects linear regression was used to assess the difference in subsequent disability between those who reported comorbidities and those who did not. The association of comorbidities with the hazard of relapse was assessed using survival analysis.
The age-standardised prevalence of hypertension, dyslipidaemia, asthma, psoriasis, eczema and anaemia was significantly higher in the MS cohort compared to that in the general Australian population. The level of disability (Multiple Sclerosis Severity Score) in those who reported overweight/obesity (β: 0.76 (95% CI 0.04-1.48), p = 0.037), or dyslipidaemia (β: 1.05 (95% CI 0.07-2.02), p = 0.036) was significantly higher compared to those who did not report these comorbidities, even after adjustment for potential confounders. There were no significant associations between comorbidities and change in disability. For relapse analyses, rheumatoid arthritis and anaemia were associated with more than threefold (hazard ratio, HR 3.70 (95% CI 1.80-7.58), p < 0.001) and twofold (HR 2.04 (95% CI 1.11-3.74), p = 0.022) increased risk of subsequent relapse respectively.
The prevalence of some comorbidities was higher in MS patients and associated with greater disability and relapse risk. Treatment of these comorbidities in patients with MS has the potential to improve disease course and help in the understanding of the prognosis and outcomes of MS.
Objectives:
To quantify life expectancy (LE), quality-adjusted life years (QALYs) and total lifetime societal costs for a hypothetical cohort of Australians with multiple sclerosis (MS).
Methods:
A ...4-state Markov model simulated progression from no/mild to moderate and severe disability and death for a cohort of 35-year-old women over a lifetime horizon. Death risks were calculated from Australian life tables, adjusted by disability severity. State-dependent relapse probabilities and associated disutilities were considered. Probabilities of MS progression and relapse were estimated from AusLong and TasMSL MS epidemiological databases. Annual societal (direct and indirect) costs (2017 Australian dollars) and health-state utilities for each state were derived from the Australian MS Longitudinal Study. Costs were discounted at 5% annually.
Results:
Mean (95% confidence interval (CI)) LE from age 35 years was 42.7 (41.6–43.8) years. This was 7.5 years less than the general Australian population. Undiscounted QALYs were 28.2 (26.3–30.0), a loss of 13.1 QALYs versus the Australian population. Discounted lifetime costs were $942,754 ($347,856–$2,820,219).
Conclusion:
We have developed a health economics model of the progression of MS, calculating the impact of MS on LE, QALYs and lifetime costs in Australia. It will form the basis for future cost-effectiveness analyses of interventions for MS.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
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