A pro-inflammatory diet is associated with long-term depression and anxiety levels but not fatigue in people with multiple sclerosis.

BACKGROUND: Multiple sclerosis is characterised by acute and chronic inflammation in the CNS. Diet may influence inflammation, and therefore MS outcomes. OBJECTIVE: To determine whether the Dietary Inflammatory Index (DII®)) is associated with depression, anxiety, and fatigue in a prospective cohort of people with MS. METHODS: People with a first clinical diagnosis of demyelination were followed over 10 years (n=223). DII and energy-adjusted DII (E-DIITM) scores were calculated from the dietary intake in the preceding 12 months measured by food frequency questionnaire. Depression and anxiety were assessed by the Hospital Anxiety and Depression Scale (HADS-A and HADS-D, respectively), and fatigue by the Fatigue Severity Scale. RESULTS: A higher E-DII score was associated with higher levels of depression and anxiety five years later (e.g., highest vs lowest E-DII quartile, HADS-D score: ß=2.23, 95%CI=0.98,3.48, p<0.001; HADS-A score: ß=1.90, 95%CI=0.59,3.21, p<0.001). A cumulative E-DII score was associated with depression (p<0.01) and anxiety (p=0.05) at the 10-year review. No associations were seen for fatigue. CONCLUSION: Our findings suggest that, in people with MS, a more pro-inflammatory diet may long-term adverse impact on depression and anxiety, but not fatigue.

Improving telehealth for persons with multiple sclerosis - a cross-sectional study from the Australian MS longitudinal study.

PURPOSE: The COVID-19 pandemic impacted healthcare delivery, especially for people with chronic disease. We investigated telehealth use by persons with multiple sclerosis (MS) during the COVID-19 pandemic and their suggestions to improve their telehealth experience. METHODS: From persons with MS, we collected data on demographic, disease-related and social determinants of health, telehealth use during the COVID-19 pandemic, satisfaction with telehealth, and suggestions to improve telehealth. We conducted univariate log-binomial regression to establish factors associated with telehealth use versus no use, summarised experiences and suggestions for improvement with frequency tables, and conducted thematic analysis on free-text suggestions for improvement. RESULTS: Of 1,485 participants, 69.8% used telehealth during the first phase of the COVID-19 pandemic. Only small differences were observed for demographic, disease and social health determinants between telehealth users and non-users. Most participants who used telehealth had good or very good experiences (new providers:74.3%; existing providers:78.6%). The most common suggestion for improving telehealth experience was "guidance on preparing for telehealth sessions." Participants also wanted expansion in telehealth availability and utility. CONCLUSION: Persons with MS in Australia commonly used telehealth during the COVID-19 pandemic and were generally satisfied with their experiences. Implementing the suggested improvements will help optimise telehealth for persons with MS. REGISTRATION: N/A.

Australians with multiple sclerosis (MS) had good or very good experiences of telehealth during the first year of the pandemic.Telehealth is a useful consultation tool for many rehabilitation professions and may be appropriate for use across the whole MS population.To improve the delivery of rehabilitation through telehealth, provision of better guidance on preparing for telehealth consultations and provision of digital equipment to monitor their health is wanted by persons with MS.Rehabilitation professionals and researchers should take opportunities to identify if proficiency in the English language and cultural background may influence experiences with telehealth in persons with MS.

Higher dietary quality is prospectively associated with lower MRI FLAIR lesion volume, but not with hazard of relapse, change in disability or black hole volume in people with Multiple Sclerosis.

BACKGROUND: The influence of diet quality on multiple sclerosis (MS) progression or inflammatory activity is not well understood. METHODS: Study participants with MS from the AusLong cohort, were followed annually (10 years, n = 223 post-onset). At baseline, 5 and 10-year reviews, indices of dietary quality - the Australian Recommended Food Score (ARFS) and Diet Quality Tracker (DQT) - were calculated from self-reported dietary intake data of the preceding 12 months (Food Frequency Questionnaire, Dietary Questionnaire for Epidemiological Studies v2). Associations were examined between measures of dietary quality with measures of MS progression and inflammatory activity hazard of relapse, annualised disability progression (Expanded Disability Status Scale, EDSS) and Magnetic Resonance Imaging (MRI) outcomes. MRI outcomes included fluid-attenuated inversion recovery (FLAIR, T2 MRI) lesion volume and black hole volume (T1 MRI) in the juxtacortical, periventricular, and infratentorial regions of the brain, as well as total calculated from the sum of the three regions. RESULTS: A higher diet quality (at least with the ARFS) was associated with lower FLAIR lesion volume in the periventricular region only (highest vs lowest quartile: ß=-1.89,95%CI=-3.64, -0.13, p = 0.04, periventricular FLAIR region median (IQR) for 5-year review: 4.41 (6.06) and 10-year review: 4.68 (7.27)). Associations with black hole lesion volume, hazard of relapse, and annualised EDSS progression, lacked in significance and/or dose-dependency. CONCLUSION: We found evidence that diet quality may have a role in modulating one aspect of MS inflammatory activity (periventricular MRI FLAIR lesion volume), but not other MRI and clinical outcome measures.

Long-term dietary acid load is associated with depression in multiple sclerosis, but less evidence was found with fatigue and anxiety.

BACKGROUND: Diet-dependent acid-base load has been associated with worsening in mental health, but to date no study has examined this in people with multiple sclerosis (PwMS). We examined the association between potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores and depression, anxiety, and fatigue in PwMS. METHODS: Participants with a first clinical diagnosis of CNS demyelination were followed prospectively as part of the AusLong Study (aged 18-59 years at cohort entry). At baseline, 5- and 10-year reviews, PRAL and NEAP scores were calculated using dietary intake in the preceding 12 months calculated from a food frequency questionnaire. At 5- and 10-year reviews, the Hospital Anxiety and Depression Scale was used to assess depression and anxiety, and the Fatigue Severity Scale assessed fatigue. RESULTS: Higher PRAL and NEAP scores were associated with increased subsequent absolute value and change in HADS depression scores over five years' follow-up (e.g., highest vs lowest PRAL quartile, 5-year change in HADS-D score: ß=+3.01, 95%CI= 1.54, 4.48, p<0.001). The level of depression at the 10-year review was determined by both the baseline dietary acid scores and baseline-5-year changes in dietary acid scores (e.g., PRAL change from baseline to 5-year review, 10-year review HADS-D score: ß=+0.09, 95%CI= 0.03, 0.15, p<0.001, NEAP change from baseline to 5-year review, 10-year review HADS-D score: ß=+0.07, 95%CI= 0.01, 0.14, p=0.03). Some associations were observed with anxiety and fatigue but were much weaker and less consistent. CONCLUSION: Our findings indicate that a higher dietary acid load potentially has a long-term influence on the level of depression in PwMS. The evidence is less convincing for anxiety and fatigue.

Associations between diet quality and depression, anxiety, and fatigue in multiple sclerosis.

BACKGROUND: Many people with multiple sclerosis (MS) modify their dietary intake post diagnosis, but there is little evidence that dietary modifications influence MS outcomes. METHODS: People with a first clinical diagnosis of central nervous system demyelination were followed annually for 10 years. Depression, anxiety, and fatigue were assessed at the 5-and 10-year reviews using the Hospital Anxiety and Depression Scale and Fatigue Severity Scale, respectively. Dietary intake in the preceding 12 months was assessed at baseline, and 5-and 10-year reviews using a food frequency questionnaire. We used the Australian Recommended Food Score (ARFS) and the Diet Quality Tracker (DQT) to assess diet quality. RESULTS: A higher diet quality in the previous 12 months using the ARFS score, but not the DQT, was associated with lower levels of depression (e.g., highest vs lowest quartile: ß=-1.35,95%CI=-2.44,-0.26,p=0.01), but neither score was associated with anxiety or fatigue. After assessing diet quality prospectively with outcomes five years later, we found that higher ARFS score, but not DQT score, was associated with lower levels of subsequent anxiety and depression (highest vs lowest quartile; Anxiety: ß=-1.61,95%CI=-2.76,-0.46,p=0.01, Depression: ß=-1.25,95%CI=-2.44,-0.07,p=0.04), but not fatigue. No associations were observed between diet quality and subsequent change in depression and anxiety over five years, although an association was observed between diet quality and change in fatigue (e.g., highest vs lowest DQT quartile: ß=-1.06,95%CI=-1.92,-0.21,p=0.02). When examining the cumulative effect of diet quality across the study period with our 10-year outcomes, only the cumulative DQT score was associated with depression but not anxiety or fatigue. CONCLUSION: We found significant inverse associations between diet quality and depression and anxiety, but the effect sizes were modest and there was a lack of consistency between the two diet quality measures (ARFS and DQT). A diet measure that correlates with diet quality might underlie our observed associations.

Changes in multiple sclerosis symptoms are associated with changes in work productivity of people living with multiple sclerosis.

BACKGROUND: While employment rates have increased in people with multiple sclerosis (PwMS), little is known about the longitudinal trends of work productivity. OBJECTIVE: To describe the longitudinal patterns of work productivity and examine the factors associated with annual change of work productivity of PwMS. METHODS: Study participants were employed participants of the Australian MS Longitudinal Study (AMSLS) followed from 2015 to 2019 with at least two repeated measures (n = 2121). We used linear mixed models to examine if the within-individual variations in MS symptoms are associated with changes in work productivity. RESULTS: The mean annual change in work productivity between 2015 and 2019 was -0.23% (SD = 18.68%). Not the actual severity of symptoms but rather the changes in severity of symptoms that are associated with change in work productivity in the same year. In a multivariable model, every unit increase in mean annual change in 'pain and sensory symptoms', 'feelings of anxiety and depression', and 'fatigue and cognitive symptoms' were independently associated with 2.43%, 1.55% and 1.01% annual reductions in work productivity, respectively. CONCLUSION: Individual changes in work productivity are largely driven by the changes in symptom severity rather than the absolute severity. Stabilising/improving MS symptoms might improve work productivity.

Childhood infections, vaccinations, and tonsillectomy and risk of first clinical diagnosis of CNS demyelination in the Ausimmune Study.

BACKGROUND: The association between childhood vaccinations and infections and risk of multiple sclerosis is unclear; few studies have considered age at vaccination/infection. OBJECTIVE: To explore age-related associations between childhood vaccinations, infection and tonsillectomy and risk of a first clinical diagnosis of CNS demyelination. METHODS: Data on case (n = 275, 76.6% female; mean age 38.6 years) and age- and sex-matched control (n = 529) participants in an incident population-based case-control study included self-reported age at time of childhood vaccinations, infections, and tonsillectomy. Conditional logistic regression models were used to calculate adjusted odds ratios (AOR) and 95% confidence intervals (CI). RESULTS: Poliomyelitis vaccination prior to school-age was associated with increased risk of a first clinical diagnosis of CNS demyelination (AOR = 2.60, 95%CI 1.02-6.68), based on a very small unvaccinated reference group. Late (11-15 years) rubella vaccination (compared to none) was associated with lower odds of being a case (AOR = 0.47, 95%CI 0.27-0.83). Past infectious mononucleosis at 11-15 years (AOR = 2.84, 95%CI 1.0-7.57) and 16-20 years (AOR = 1.92, 95%CI 1.12-3.27) or tonsillectomy in adolescence (11-15 years: AOR = 2.45, 95%CI 1.12-5.35), including after adjustment for IM, were associated with increased risk of a first clinical diagnosis of CNS demyelination. CONCLUSIONS: Age at vaccination, infection or tonsillectomy may alter the risk of subsequent CNS demyelination. Failing to account for age effects may explain inconsistencies in past findings.

Patient-reported outcomes are worse for progressive-onset multiple sclerosis than relapse-onset multiple sclerosis, particularly early in the disease process.

BACKGROUND AND PURPOSE: Treatments for progressive-onset multiple sclerosis (MS) are lacking. To improve the disease management for progressive-onset MS, the differences between relapse-onset MS and progressive-onset MS in patient-reported disability, progression and symptoms were examined. METHODS: A total of 1985 participants of the Australian Multiple Sclerosis Longitudinal Study were included. Associations between onset type and outcomes were assessed with negative binomial regression. RESULTS: The severity of 17 of the 19 outcomes was significantly higher for progressive-onset MS patients than relapse-onset MS patients, including perspectives from disability, progression over the last year, fatigue, sensory, walking difficulties, pain, balance, spasticity, sexual dysfunction, bladder, bowel, anxiety, depression and the European quality of life (EQ-5D) (P < 0.05; adjusted mean ratio ranged from 1.11 to 1.52). The differences between the two onset types were most pronounced early in the disease process and reduced with increasing MS duration, and the interaction was significant for disability, progression over the last year, walking difficulties, bladder problems, bowel problems and spasticity. CONCLUSION: Participants with progressive-onset MS were significantly worse off on nearly all patient-reported outcomes than relapse-onset MS participants, and the differences were most pronounced early in the disease course, highlighting the importance of early intervention for those with progressive-onset MS.

Predictors of Beagley-Gibson skin cast grade in older adults.

BACKGROUND AND PURPOSE: The Beagley-Gibson (BG) grading system utilizes microtopographical skin changes to generate an individualized, objective estimate of cumulative, lifetime ultraviolet radiation (UVR) exposure. However, predictors of BG grade are ill-defined, particularly in older populations. The aim of this cross-sectional study was to describe the factors associated with skin damage as measured by the BG method in 835 community-dwelling older adults. METHODS: Study participants aged 53-83 years had silicone casts taken from the dorsum of both hands and graded by the BG method. Lifetime sun exposure, skin phenotypic traits and smoking status were assessed by questionnaire. 25-hydroxyvitamin D and melanin density were measured using radioimmunoassay and spectrophotometry, respectively. Ordered logistic regression was used to compute a single odds ratio (OR) by taking BG grade as the outcome variable. RESULTS: Higher 25-hydroxyvitamin D was associated with increasing BG grade (OR = 1.39, P = 0.02) in adjusted analysis. Age (OR = 1.14, P < 0.001), occupational sun exposure (OR = 1.62, P < 0.001), ability to tan (OR = 1.40, P < 0.001), melanin density (OR=0.79, P = 0.001), lifetime leisure time sun exposure (OR = 1.21, P = 0.004), current smoking (OR = 1.82, P = 0.007), propensity to sunburn (OR = 1.18, P = 0.016), and waist-hip ratio (OR = 1.10, P = 0.02) were independent predictors of BG grade. Hair colour, number of sunburns, body mass index and gender were not independent predictors of BG grade. CONCLUSIONS: Beagley-Gibson skin cast grade is a biologically relevant marker of UVR exposure in older adults influenced by both intrinsic and extrinsic factors.

Anxiety, depression and fatigue at 5-year review following CNS demyelination.

BACKGROUND: Anxiety and depression are common in multiple sclerosis (MS). We evaluated the prevalence and factors associated with anxiety, depression and fatigue at the 5-year review of a longitudinal cohort study following a first clinical diagnosis of CNS demyelination (FCD). METHODS: Cases with a FCD were recruited soon after diagnosis and followed annually thereafter. A variety of environmental, behavioural and clinical covariates were measured at five-year review. Anxiety and depression were measured using the Hospital Anxiety & Depression Scale (HADS), and fatigue by the Fatigue Severity Scale (FSS). RESULTS: Of the 236 cases, 40.2% had clinical anxiety (median HADS-A: 6.0), 16.0% had clinical depression (median HADS-D: 3.0), and 41.3% had clinical fatigue (median FSS: 4.56). The co-occurrence of all three symptoms was 3.76 times greater than expectation. Younger age, higher disability, concussion or other disease diagnosis were independently associated with a higher anxiety score; male sex, higher disability, being unemployed, less physical activity, and antidepressant and/or anxiolytic-sedative medication use were independently associated with a higher depression score. Higher disability, immunomodulatory medication use, other disease diagnosis and anxiolytic-sedative medication use were independently associated with having fatigue, while female sex, higher BMI, having had a concussion, being unemployed and higher disability were associated with a higher fatigue score. CONCLUSION: These results support previous findings of the commonality of anxiety, depression and fatigue in established MS and extend this to post-FCD and early MS cases. The clustering of the three symptoms indicates that they may share common antecedents.

Modulating effects of WT1 on interferon-ß-vitamin D association in MS.

OBJECTIVE: To investigate whether those genes involved in the vitamin D pathway modulate the relationship between 25-hydroxyvitamin D (25(OH)D) and IFN-ß, the relationship between IFN-ß and sun in predicting 25(OH)D, and the interaction between IFN-ß and 25(OH)D in modulating relapse risk in patients with MS. METHODS: Prospective cohort study of 169 participants with MS and genotype data followed 2002-2005. Gene-IFN-ß and gene-IFN-ß-sun interactions predicting 25(OH)D evaluated by multilevel mixed-effects linear regression. Gene-IFN-ß interactions with 25(OH)D in modulating in relapse risk assessed using survival analysis. RESULTS: The cohort was 71.6% female and of mean age 47.8. Two-independent intronic genotyped SNPs (rs10767935 and rs5030244) in WT1 significantly modified the IFN-ß-25(OH)D association after adjustment (P(interaction) = 0.001, 0.0002; P(adj) = 0.003, 0.006, respectively). There was a marked difference in the interaction between self-reported sun exposure and IFN-ß in predicting 25(OH)D by level of rs10767935, although this did not reach statistical significance. No SNPs modified the interaction between IFN-ß and 25(OH)D in predicting relapse. CONCLUSIONS: We have demonstrated that two-independent SNPs (rs10767935 and rs5030244) in WT1 modified the IFN-ß-25(OH)D association in patients with MS. Some evidence was shown for a difference in the sun-IFN-ß-25(OH)D association by level of rs10767935. These findings indicate that WT1 variants may play a role in altering the effects of IFN-ß on vitamin D in MS.

The relationship between ambient ultraviolet radiation (UVR) and objectively measured personal UVR exposure dose is modified by season and latitude.

Despite the widespread use of ambient ultraviolet radiation (UVR) as a proxy measure of personal exposure to UVR, the relationship between the two is not well-defined. This paper examines the effects of season and latitude on the relationship between ambient UVR and personal UVR exposure. We used data from the AusD Study, a multi-centre cross-sectional study among Australian adults (18-75 years), where personal UVR exposure was objectively measured using polysulphone dosimeters. Data were analysed for 991 participants from 4 Australian cities of different latitude: Townsville (19.3°S), Brisbane (27.5°S), Canberra (35.3°S) and Hobart (42.8°S). Daily personal UVR exposure varied from 0.01 to 21 Standard Erythemal Doses (median = 1.1, IQR: 0.5-2.1), on average accounting for 5% of the total available ambient dose. There was an overall positive correlation between ambient UVR and personal UVR exposure (r = 0.23, p < 0.001). However, the correlations varied according to season and study location: from strong correlations in winter (r = 0.50) and at high latitudes (Hobart, r = 0.50; Canberra, r = 0.39), to null or even slightly negative correlations, in summer (r = 0.01) and at low latitudes (Townsville, r = -0.06; Brisbane, r = -0.16). Multiple regression models showed significant effect modification by season and location. Personal exposure fraction of total available ambient dose was highest in winter (7%) and amongst Hobart participants (7%) and lowest in summer (1%) and in Townsville (4%). These results suggest season and latitude modify the relationship between ambient UVR and personal UVR exposure. Ambient UVR may not be a good indicator for personal exposure dose under some circumstances.

EBV & HHV6 reactivation is infrequent and not associated with MS clinical course.

BACKGROUND: Among the environmental factors associated with multiple sclerosis (MS) causation, some of the strongest associations are with Epstein-Barr virus (EBV), and to a lesser extent human herpesvirus 6 (HHV6). Associations with clinical course are less conclusive, however. METHODS: We evaluated serum anti-EBV-EA-R IgG and anti-HHV6 IgM, and EBV and HHV6 viral load (VL) for their associations with relapse, disability, and progression in disability in a prospective cohort of 198 participants with clinically definite MS. RESULTS: Anti-EBV-EA-R IgG was detected in 81.8% of cases at study entry, and titers remained essentially unchanged during the study. Anti-HHV6 IgM was detected in only one participant, and EBV-VL (29%) and HHV6-VL (1.8%) were detected in a minority of samples, and where detected levels were low. Our previously demonstrated association between anti-HHV6 IgG and relapse hazard was not affected by adjustment for parameters of reactivation. We found no evidence that any of the viral markers were associated with disability or progression in disability. In relation to relapse, only EBV-VL was positively associated, although this was strongly influenced by a single individual. CONCLUSION: Using a prospective cohort design, we found no convincing evidence that reactivation parameters of EBV or HHV6 were associated with subsequent MS relapse hazard or progression in disability, confirming previous findings, and indicating that herpesvirus reactivation is not an important driver of relapse or disability in this established MS population.

Higher levels of reported sun exposure, and not vitamin D status, are associated with less depressive symptoms and fatigue in multiple sclerosis.

OBJECTIVE: Insufficient sun exposure and vitamin D deficiency have both been associated with increased risk of multiple sclerosis (MS). Depressi on, anxiety, fatigue and cognitive impairment are prevalent and disabling symptoms in MS. Our objective was to examine the associations between personal sun exposure and serum 25-hydroxyvitamin D (25(OH)D), and depression, anxiety, fatigue and cognition. METHODS: A total of 198 participants with multiple sclerosis were followed prospectively for an average of 2.3 years. Assessments of serum 25(OH)D, sun exposure, depression, anxiety and fatigue were carried out biannually; cognition was assessed annually. RESULTS: Personal reported sun exposure was inversely associated with depression scores (ß -0.26 (95%CI -0.40, -0.12);P ≤ 0.001) and fatigue scores (ß -0.65 (95%CI -1.23, -0.07); P = 0.028). Only high levels of 25(OH)D (>80 nm) were inversely associated depression scores (ß -0.64 (95%CI -1.15, -0.13); P = 0.015), but this was not significant after adjustment for reported sun exposure. No associations were seen between reported sun exposure or serum 25(OH)D levels and anxiety or cognition scores. CONCLUSION: We found that higher levels reported sun exposure, rather than 25(OH)D levels, were associated with less depressive symptoms and levels of fatigue. The role of UV or light therapy will need to be evaluated in randomized controlled trials to confirm an effect on these symptoms in MS.

Meta-analyses to investigate gene-environment interactions in neuroepidemiology.

BACKGROUND: Most chronic neurological diseases are caused by a combination of multiple genetic and environmental factors. Increasingly, gene-environment interactions (GxE) are being examined, providing opportunities to combine studies systematically using meta-analysis. METHODS: Systematic review of the literature on how to examine GxE using observational study designs, and how to conduct a meta-analysis of studies on GxE. RESULTS: Most methods and challenges related to a standard meta-analysis apply to a GxE meta-analysis. There are, however, some substantive differences. With GxE, there is the capability of using a case-only design. Research on GxE interactions may be more prone to publication bias, since interactions are usually not the primary hypothesis and only 'exciting' significant GxE findings are reported out of a range of secondary analyses. In disease aetiology research, there has been debate whether to measure interaction on a multiplicative or additive scale. There are some significant challenges associated with measuring interaction on an additive scale, and thus the uptake of the measures of additive interaction has been limited. As a result, the methods of analysing interaction have been less consistent and reporting has been highly variable. We suggest using the STROBE/STREGA reporting guidelines to allow evaluation of interaction on both scales. CONCLUSIONS: We identified a number of differences of a GxE meta-analysis over a standard meta-analysis. Awareness of these issues is important. Using established reporting guidelines for GxE studies is recommended. The development of consortia for neurological disorders that include both genetic and environmental data might offer benefits for GxE meta-analyses in the future.

Early-life hygiene-related factors affect risk of central nervous system demyelination and asthma differentially.

The increasing prevalence of immune-related diseases, including multiple sclerosis, may be partly explained by reduced microbial burden during childhood. Within a multi-centre case-control study population, we examined: (i) the co-morbid immune diseases profile of adults with a first clinical diagnosis of central nervous system demyelination (FCD) and (ii) sibship structure in relation to an autoimmune (FCD) and an allergic (asthma) disease. FCD cases (n = 282) were aged 18-59 years; controls (n = 558) were matched on age, sex and region. Measures include: history of doctor-diagnosed asthma; sibling profile (number; dates of birth); and regular childcare attendance. FCD cases did not differ from controls with regard to personal or family history of allergy, but had a greater likelihood of chronic fatigue syndrome [odds ratio (OR) = 3·11; 95% confidence interval (CI) 1·11, 8·71]. Having any younger siblings showed reduced odds of FCD (OR = 0·68; 95% CI: 0·49, 0·95) but not asthma (OR = 1·47; 95% CI: 0·91, 2·38). In contrast, an increasing number of older siblings was associated with reduced risk of asthma (P trend = 0·04) but not FCD (P trend = 0·66). Allergies were not over-represented among people presenting with FCD. Sibship characteristics influence both FCD and asthma risk but the underlying mechanisms differ, possibly due to the timing of the putative 'sibling effect'.

Occupational exposure and risk of central nervous system demyelination.

Inconsistent evidence exists regarding the association between work-related factors and risk of multiple sclerosis (MS). We examined the association between occupational exposures and risk of a first clinical diagnosis of central nervous system demyelination (FCD), which is strongly associated with progression to MS, in a matched case-control study of 276 FCD cases and 538 controls conducted in Australia (2003-2006). Using a personal residence and work calendar, information on occupational history and exposure to chemicals and animals was collected through face-to-face interviews. Few case-control differences were noted. Fewer cases had worked as professionals (≥6 years) than controls (adjusted odds ratio (AOR) = 0.60, 95% confidence interval (CI): 0.37, 0.96). After further adjustment for number of children, cases were more likely to have ever been exposed to livestock than controls (AOR = 1.54, 95% CI: 1.03, 2.29). Among women, there was an increase in FCD risk associated with 10 or more years of exposure to livestock (AOR = 2.78, 95% CI: 1.22, 6.33) or 6 or more years of farming (AOR = 2.00, 95% CI: 1.23, 3.25; also adjusted for number of children). Similar findings were not evident among men. Thus, farming and exposure to livestock may be important factors in the development of FCD among women, with this finding further revealed after the confounding effect of parity or number of children is considered.

The AusD Study: a population-based study of the determinants of serum 25-hydroxyvitamin D concentration across a broad latitude range.

Observational studies suggest that people with a high serum 25-hydroxyvitamin D (25(OH)D) concentration may have reduced risk of chronic diseases such as osteoporosis, multiple sclerosis, type 1 diabetes, cardiovascular disease, and some cancers. The AusD Study (A Quantitative Assessment of Solar UV Exposure for Vitamin D Synthesis in Australian Adults) was conducted to clarify the relationships between ultraviolet (UV) radiation exposure, dietary intake of vitamin D, and serum 25(OH)D concentration among Australian adults residing in Townsville (19.3°S), Brisbane (27.5°S), Canberra (35.3°S), and Hobart (42.8°S). Participants aged 18-75 years were recruited from the Australian Electoral Roll between 2009 and 2010. Measurements were made of height, weight, waist:hip ratio, skin, hair, and eye color, blood pressure, and grip strength. Participants completed a questionnaire on sun exposure and vitamin D intake, together with 10 days of personal UV dosimetry and an associated sun-exposure and physical-activity diary that was temporally linked to a blood test for measurement of 25(OH)D concentration. Ambient solar UV radiation was also monitored at all study sites. We collected comprehensive, high-quality data from 1,002 participants (459 males, 543 females) assessed simultaneously across a range of latitudes and through all seasons. Here we describe the scientific and methodological issues considered in designing the AusD Study.

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.