Fotini Pittas

Higher 25-hydroxyvitamin D Is Associated with Lower Relapse Risk in Multiple Sclerosis

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.

Prevalence and concurrence of anxiety, depression and fatigue over time in multiple sclerosis

Background: Anxiety, depression and fatigue are commonly reported by persons with multiple sclerosis (PwMS). Objectives: We estimated the prevalence of each factor in a representative sample of PwMS, and in subgroups defined by age, sex and disease duration, at cohort entry and over time. We further examined whether and how these factors clustered together. Methods: A population-based longitudinal cohort of 198 PwMS was followed 6-monthly for 2.5 years. The Hospital Anxiety and Depression Scale (HADS) was used to measure anxiety (cut-point >7) and depression (>7) and the Fatigue Severity Scale (FSS) to measure fatigue (≥5). Results: At cohort entry, prevalence of anxiety was 44.5% (95%CI 37–51%), depression 18.5% (95%CI 12.6–23.4%), and fatigue 53.7% (95%CI 47–61%). Fatigue was more common in males than females (RR 1.29, p=0.01), with attenuation of the effect after adjustment for Expanded Disability Status Scale (adjusted RR 1.18, p=0.13). Prevalence of anxiety (but not depression or fatigue) decreased by 8.1% per year of cohort observation (RR 0.92, 95%CI 0.86–0.98, p=0.009), with the effect more pronounced in women (14.6%, RR 0.85, 95%CI 0.79–0.93, –<0.001) than men (2.6%, RR 1.03, 95%CI 0.90–1.17, p=0.77). There was no apparent seasonal variation in the prevalence of any of the three factors (p>0.05). All three factors occurred contemporaneously at cohort entry in a higher proportion of the cohort than expected by chance (p<0.001). Conclusions: Anxiety, depression and fatigue are common in PwMS and tend to cluster together. The findings are important for clinical management of PwMS and to the exploration of possible shared causal biological pathways.

Monthly Ambient Sunlight, Infections and Relapse Rates in Multiple Sclerosis

Background: Monthly variation in multiple sclerosis (MS) relapses has been found. The relationship between seasonal environmental factors, infections, serum vitamin D [25(OH)D] and MS relapses is undetermined. Methods: We prospectively followed a population-based cohort of relapsing-remitting (RR) MS patients in Southern Tasmania for a mean 2.3 years (January 2002–April 2005). Associations between monthly ambient environmental factors, estimated serum 25(OH)D, upper respiratory tract (URT) infections and relapse rates were examined using weighted Pearson’s correlation and linear regression. Results: Of 199 definite MS patients, 142 had RRMS. The lowest relapse rate of 0.5 per 1,000 days (95% CI: 0.2–1.3) occurred in February (mid-late summer) versus the March–January RR of 1.1 per 1,000 days (95% CI: 0.9–1.3; p = 0.018, weighted regression). Monthly relapse rates correlated with: (1) prior erythemal ultraviolet radiation (EUV): lagged 1.5 months, r = –0.32, p = 0.046; (2) URT infection rate: no lag, r = 0.39, p = 0.014; (3) 25(OH)D: no lag, r = –0.31, p = 0.057. The association between URT infections and relapses was reduced after adjustment for monthly EUV. Conclusions: Relapse rates were inversely associated with EUV and serum 25(OH)D levels and positively associated with URT infections. The demonstrated lag between EUV but not 25(OH)D and relapse rates is consistent with a role for EUV-generated 25(OH)D in the alteration of relapse rates. Future work on the association between URT infections and relapses should be considered in the context of ultraviolet radiation and vitamin D.

Smoking is associated with progressive disease course and increased progression in clinical disability in a prospective cohort of people with multiple sclerosis

BackgroundMultiple sclerosis has a variable disease course. The contribution of modifiable lifestyle factors to disease course has not been well studied, although one cohort has reported that smoking is associated with conversion to secondary progressive MS course and another that smoking is not.MethodsWe conducted a prospective cohort study of people with MS in Southern Tasmania from 2002 to 2004 with 78 % (203/259) of eligible participating and 198 with one or more reviews and confirmed MS. The cohort had a high retention rate (90 % (183/203)). The median follow- up time was 909 days. Smoking data were collected at baseline and six-monthly reviews. Clinical disability assessments were conducted annually in conjunction with a real time clinical notification system for relapses. A repeated measures analysis and other statistical methods were used.ResultsCumulative pack-years (p-y) smoked after cohort entry was associated with an increase in longitudinal MSSS (p < 0.001). Relative to the 0 pack years (p-y) category (in the year prior to the MSSS measure) those in the 0 to 1 p-y category had an adjusted mean difference in MSSS of 0.34 (95 % CI 0.28, 0.66); those in the 1 to 2 p-y category had a 0.41 (95 % CI −0.03, 0.85) increase; and those in the 2 or more p-y category had a 0.99 (95 % CI 0.41, 1.58) increase in MSSS. Similar results were found using a variety of statistical approaches or EDSS as a clinical outcome. Smoking during the cohort period was not associated with relapse (cumulative pack years smoked after cohort entry, HR 0.94 (0.69, 1.26) per pack year).ConclusionA better understanding of the mechanisms underlying smoking and multiple sclerosis, particularly progressive forms of the disease, may provide new insights for the eventual goal of better treatment and prevention of multiple sclerosis.

Interferon-β and serum 25-hydroxyvitamin D interact to modulate relapse risk in MS

Objective: To determine whether interferon-β (IFN-β) medication use is associated with vitamin D levels and whether the two interact in exerting effects on relapse risk. Methods: In a prospective cohort of 178 persons with clinically definite multiple sclerosis (MS) living in southern Tasmania in 2002–2005, serum 25-hydroxyvitamin D [25(OH)D] was measured biannually, with assessment by questionnaire for relevant factors, including IFN-β treatment. Results: Subjects reporting IFN-β use had significantly higher mean 25(OH)D than persons who did not (p < 0.001). This was mediated by an interaction between personal sun exposure and IFN-β, with treated persons realizing nearly three times 25(OH)D per hour of sun exposure of persons not on therapy. The association between 25(OH)D and 1,25-dihydroxyvitamin D did not differ by IFN-β therapy (p = 0.82). 25(OH)D was associated with a reduced relapse risk only among persons on IFN-β (p < 0.001). Importantly, IFN-β was only protective against relapse among persons with higher 25(OH)D (hazard ratio [HR] 0.58 [95% confidence interval (CI) 0.35–0.98]), while among 25(OH)D-insufficient persons, IFN-β increased relapse risk (HR 2.01 [95% CI 1.22–3.32]). Conclusion: In this study, we found that IFN-β therapy is associated with greater production of vitamin D from sun exposure, suggesting part of the therapeutic effects of IFN-β on relapse in MS may be through modulation of vitamin D metabolism. These findings suggest persons being treated with IFN-β should have vitamin D status monitored and maintained in the sufficiency range. Classification of evidence: This study provided Class III evidence that IFN-β is associated with reduced risk of relapse, and this effect may be modified by a positive effect of IFN-β on serum 25(OH)D levels.

Adherence to the immunomodulatory drugs for multiple sclerosis: contrasting factors affect stopping drug and missing doses

Long‐term immunomodulatory drug (IMD) treatment is now common in multiple sclerosis (MS). However, predictors of adherence are not well understood; past studies lacked lifestyle factors such as alcohol use and predictors of missed doses have not been evaluated. We examined both levels of non‐adherence—stopping IMD and missing doses.

Trends in the epidemiology of multiple sclerosis in Greater Hobart, Tasmania: 1951 to 2009

Background Hobart, Tasmania has been the site of two major studies of multiple sclerosis (MS) frequency, in 1951–1961 and 1971–1981. Since then, there have been no studies of MS frequency in Hobart. Methods Using a prevalent cohort of 226 cases in 2001 and 265 in 2009, the authors undertook a two-stage survey of MS frequency in Hobart. Combined with the published data from the two preceding studies, the authors conducted a time-trend analysis of MS epidemiology over 1951–2009. Results The age-standardised prevalence in 2001 was 96.6/100 000, and 99.6/100 000 in 2009, a significant increase from the 1961 prevalence of 32.5/100 000 (p<0.001). Female prevalence increased over each time point; male prevalence increased between 1961 and 2001 but was unchanged thereafter. Incidence over 2001–2009 was 3.7/100 000, significantly increased from the 1951–1961 incidence of 2.2/100 000 (p=0.004), though the majority of this was between 1951–1961 and 1971–1981. Mortality fell by half from 2.4/100 000 in 1951–1959 to 1.0/100 000 in 2001–2009—this decreased mortality and an older cohort contribute to the increase in prevalence. Neither prevalence (p=0.48) nor incidence (p=0.18) sex ratios changed significantly between 1951 and 2009. Conclusions Between 1951 and 2009, the age-standardised prevalence of MS in Hobart increased threefold, and the incidence nearly doubled. Part of the increase in prevalence was due to an increased longevity, decreased mortality and increased incidence. Differences in patterns by birthplace may be explained by the Australian assisted-migration programme of 1945–1981. These data do not demonstrate the strong and significant changes in sex ratio observed elsewhere.

Anti-HHV-6 IgG titer significantly predicts subsequent relapse risk in multiple sclerosis

Background: Some of the strongest associations with MS onset are for human herpesviruses, particularly Epstein–Barr virus (EBV) and human herpesvirus 6 (HHV-6). Their role in MS clinical course is less clear, however. Methods: Prospective cohort of 198 persons with clinically definite MS, followed 2002–5, and serum samples obtained from all subjects at study entry to measure anti-HHV-6 and anti-EBV (Epstein–Barr nuclear antigen [EBNA] and viral capsid antigen [VCA]) IgG titers. Association with relapse evaluated using survival analysis; association with disability/progression evaluated using linear regression or multilevel mixed-effects linear regression. Results: For the 145 persons with relapsing–remitting MS followed beyond one review, anti-HHV-6 IgG titer was positively associated with the hazard of relapse with a dose-dependent trend (p = 0.003), not affected by adjustment for anti-EBV IgG titers, neither of which were independently associated with relapse. There was no significant association between anti-human herpesvirus IgG titers and baseline-measured disability scores, or change in disability scores; however, anti-HHV-6 IgG titers were 2.8 times higher among progressive-course females than progressive-course males. Discussion: These findings suggest that, in addition to a potential etiological role in MS, HHV-6 infection or the immune response to HHV-6 antigens may have an effect on the risk of MS relapses and possibly on progressive courses of MS. The observed effect was directly related to anti-HHV-6 IgG titers and may indicate that either HHV-6 infection or factors associated with an altered humoral immune response to HHV-6 may have an effect on MS clinical course. Anti-HHV-6 IgG titer may be a useful prognostic factor in relapsing–remitting MS clinical course.

The cost of multiple sclerosis in Australia

Multiple sclerosis (MS) represents a significant economic burden both to the patient and to society. This study aims to provide information about direct and indirect costs of MS in Australia. Detailed questionnaires were completed for 100 patients over a 6-month period (12 months for hospitalization costs). Overall, the average annual direct and indirect costs per patient were AU

Novel modulating effects of PKC family genes on the relationship between serum vitamin D and relapse in multiple sclerosis

20 396 and AU