ORCID Profile
0000-0001-9009-7472
Current Organisation
University of Tasmania
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Publisher: Wiley
Date: 27-12-2013
Publisher: SAGE Publications
Date: 17-06-2021
Abstract: Multiple sclerosis (MS)-related knowledge is an important evaluation metric for health education interventions. However, few MS knowledge assessment tools are currently available for use. This study aims to develop a reliable and valid Multiple Sclerosis Knowledge Assessment Scale (MSKAS) for use in the MS community and the general public. The MSKAS was developed using a Delphi study methodology and was administered to participants in the first open enrolment of the Understanding Multiple Sclerosis (UMS) online course. Rasch analysis was used to examine its psychometric properties and develop the final scale. Experts from across the MS community participated in the development of the MSKAS, resulting in an initial scale of 42 items. Five hundred and forty-three UMS participants completed the MSKAS 89% were female and 30% were people with MS. The final unidimensional 22-item scale has a person separation index of 2.16, a person reliability index of 0.82, an item separation index of 11.19, and a Cronbach’s alpha (kr-20) test reliability of 0.87. The MSKAS is a unidimensional scale with good construct validity and internal consistency. The MSKAS has the potential to be useful for the assessment of MS knowledge in research and clinical practice.
Publisher: Informa UK Limited
Date: 17-09-2020
DOI: 10.1080/09638288.2020.1817985
Abstract: Multiple sclerosis (MS) often leads to reduced physical activity and exercise participation. Sedentary behaviour is associated with poor health, whereas exercise is effective in managing MS symptoms. This study assessed physical activity, exercise and sedentary sitting time, and identified associations with symptoms. Participants of the Australian MS Longitudinal Study completed surveys in 2016. We measured physical activity and sitting time via the International Physical Activity Questionnaire (short-form), and assessed participation in exercise (type and duration). Multivariable regression models assessed associations between physical activity, sitting time and exercise and demographic characteristics and MS-related symptoms. Of the 1216 participants, 53.0% reported moderate-high physical activity levels (71.5% among those with no/mild disability). Median sitting time was 7 h/day. Most (78.4%) participated in aerobic exercise, while only 16.4% participated in strength training. Having a progressive MS onset, more severe symptoms (i.e., cognitive impairment, depression, fatigue, mobility impairment) and being male was indicative of lower physical activity levels and higher sitting time. Health promotion efforts should encourage physical activity and exercise, in particular strength training, among people with MS. People with more severe symptoms and progressive disease may require focused exercise promotion from healthcare professionals.Implications for RehabilitationComprehensive MS management should include strategies to increase physical activity and exercise participation, with particular focus upon people with higher MS-symptom burden (i.e., depression, fatigue and mobility and cognitive impairment), men, and those with progressive onset MS.Efforts to promote physical activity guidelines for people with MS and address barriers to physical activity must be implemented in standard MS care, with a particular focus on adhering to strength training guidelines.Exercise type and duration varies among people with MS, and it would behove healthcare professionals and researchers to consider promoting activities which align with in iduals preferences and abilities when promoting exercise.
Publisher: Elsevier BV
Date: 2011
Publisher: Elsevier BV
Date: 12-2014
DOI: 10.1016/J.JNS.2014.10.020
Abstract: Vascular comorbidities are common in the general population and are associated with adverse health outcomes. In people with multiple sclerosis (MS), an increasing amount of evidence suggests that vascular comorbidities are also common, but an association with MS risk and disability has not been conclusively established. This review aims to critically examine published data on the relationship between vascular comorbidities (including vascular risk factors) and MS. The evidence suggests an increased risk of MS in people with a high BMI during childhood or adolescence but not adulthood. People with established MS appear to have a slightly increased risk of cardiovascular disease and a greater proportion of people with MS die from cardiovascular disease, which has important implications for clinicians trying to identify risk factors for cardiovascular disease and reviewing treatment options. In relation to whether vascular comorbidities influence MS clinical disability or other aspects of the disease course, the key finding was that having type-2-diabetes, hypertension, dyslipidaemia or peripheral vascular disease at any point in the disease course may be associated with a greater progression in disability. Additionally, a negative effect of high cholesterol and triglycerides and a positive effect of higher HDL (high density lipoprotein) levels on acute inflammatory activity were observed on magnetic resonance imaging. The results of the published clinical trials of statins as an intervention in MS were however conflicting and care needs to be taken when treating people with MS with statins. Taken together, the literature seems to indicate a potential association of vascular comorbidities with MS risk and disability, but the number of prospective studies was sparse, thus precluding ascription of causality. We therefore recommend that future studies of the frequency and effects of vascular comorbidities on MS risk and disability should be prospective and objective where relevant.
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.1016/J.JNS.2014.12.022
Abstract: Alterations in peripheral blood mononuclear cell (PBMC) cytokine production have been found in multiple sclerosis (MS) compared to healthy controls. We have previously found that stimulated PBMC-produced TNF-α and IFN-γ modulated MS relapse risk, such that raised TNF-α was protective, while raised IFN-γ increased relapse risk. To assess whether SNPs within genes for relevant cytokines and their receptors modulate the associations of TNF-α and IFN-γ with relapse, thus providing additional information about these cytokine effects and the roles of these genes in MS. Prospective cohort of 91 participants with relapsing-remitting MS and cytokine and genotype data. SNPs (N=361) within a window of 10 kb around each cytokine/cytokine receptor gene (N=84) were selected for analysis. Predictors of PBMC cytokines were evaluated by multilevel mixed-effects linear regression. Predictors of relapse were evaluated by Cox proportional hazards regression. Bonferroni correction was used to adjust for multiple testing thus p<1.39 × 10(-4) was defined as significant. In iduals of GG genotype of rs3218295 (within the gene IL2RB) demonstrated a significant protective effect of TNF-α on relapse while those of GA/AA genotype showed a significant positive association (pinteraction=5.04 × 10(-5)). Carriers of CC genotype of rs522807 (3' region of TNFRSF1B) and the AA genotype of rs25879 (5' region of IL3) showed a strong association between IFN-γ and increased relapse risk (pinteraction=8.21 × 10(-5) and 1.70 × 10(-5), respectively). Our results show novel modulation of TNF-α and IFN-γ associations with relapse by SNPs in major cytokines. These findings suggest the potential for these genes and/or their products as potential therapeutic targets in MS.
Publisher: Elsevier BV
Date: 08-2007
DOI: 10.1016/J.JNEUROIM.2007.06.012
Abstract: We measured the levels of IFNgamma, TNFalpha, Il-4 and Il-10 produced by mitogen-stimulated peripheral blood mononuclear cells (PBMC) from healthy people, and those with the relapse/remitting form of multiple sclerosis. Blood was taken in summer and winter. Healthy people had a summer excess of Il-4, Il-10 and TNFalpha, and a winter excess of IFNgamma. Untreated MS cases had a summer excess of Il-10, whereas those treated with Interferon-beta had lower levels of all cytokines, and displayed no seasonal effect.
Publisher: SAGE Publications
Date: 11-07-2016
Abstract: Infection with the Epstein-Barr virus (EBV) is associated with an increased risk of multiple sclerosis (MS). We sought genetic loci influencing EBV nuclear antigen-1 (EBNA-1) IgG titers and hypothesized that they may play a role in MS risk. We performed a genome-wide association study (GWAS) of anti-EBNA-1 IgG titers in 3599 in iduals from an unselected twin family cohort, followed by a meta-analysis with data from an independent EBNA-1 GWAS. We then examined the shared polygenic risk between the EBNA-1 GWAS (effective s le size ( N eff ) = 5555) and a large MS GWAS ( N eff = 15,231). We identified one locus of strong association within the human leukocyte antigen (HLA) region, of which the most significantly associated genotyped single nucleotide polymorphism (SNP) was rs2516049 ( p = 4.11 × 10 −9 ). A meta-analysis including data from another EBNA-1 GWAS in a cohort of Mexican-American families confirmed that rs2516049 remained the most significantly associated SNP ( p = 3.32 × 10 −20 ). By examining the shared polygenic risk, we show that the genetic risk for elevated anti-EBNA-1 titers is positively correlated with the development of MS, and that elevated EBNA-1 titers are not an epiphenomena secondary to MS. In the joint meta-analysis of EBNA-1 titers and MS, loci at 1p22.1, 3p24.1, 3q13.33, and 10p15.1 reached genome-wide significance ( p 5 × 10 −8 ). Our results suggest that apart from the confirmed HLA region, the association of anti-EBNA-1 IgG titer with MS risk is also mediated through non-HLA genes, and that studies aimed at identifying genetic loci influencing EBNA immune response provides a novel opportunity to identify new and characterize existing genetic risk factors for MS.
Publisher: Frontiers Media SA
Date: 19-02-2019
Publisher: BMJ
Date: 19-02-2019
Abstract: To investigate whether lipid-related or body mass index (BMI)–related common genetic polymorphisms modulate the associations between serum lipid levels, BMI and disability progression in multiple sclerosis (MS). The association between disability progression (annualised Expanded Disability Status Scale (EDSS) change over 5 years, ΔEDSS) and lipid-related or BMI-related genetic polymorphisms was evaluated in a longitudinal cohort (n=184), diagnosed with MS. We constructed a cumulative genetic risk score (CGRS) of associated polymorphisms (p .05) and examined the interactions between the CGRS and lipid levels (measured at baseline) in predicting ΔEDSS. All analyses were conducted using linear regression. Five lipid polymorphisms (rs2013208, rs9488822, rs17173637, rs10401969 and rs2277862) and one BMI polymorphism (rs2033529) were nominally associated with ΔEDSS. The constructed lipid CGRS showed a significant, dose-dependent association with ΔEDSS (p trend =1.4×10 −6 ), such that participants having ≥6 risk alleles progressed 0.38 EDSS points per year faster compared with those having ≤3. This CGRS model explained 16% of the variance in ΔEDSS. We also found significant interactions between the CGRS and lipid levels in modulating ΔEDSS, including high-density lipoprotein (HDL p interaction =0.005) and total cholesterol:high-density lipoprotein ratio (TC:HDL p interaction =0.030). The combined model (combination of CGRS and the lipid parameter) explained 26% of the disability variance for HDL and 27% for TC:HDL. In this prospective cohort study, both lipid levels and lipid-related polymorphisms in idually and jointly were associated with significantly increased disability progression in MS. These results indicate that these polymorphisms and tagged genes might be potential points of intervention to moderate disability progression.
Publisher: BMJ
Date: 19-06-2019
Abstract: Previous studies have demonstrated a strong latitudinal gradient in multiple sclerosis (MS) prevalence. Herein, we present a meta-analysis of the latitudinal gradient of MS prevalence including studies published since our 2011 review, seeking to assess the latitudinal gradient and whether it has changed since our previous analysis. Studies published up to December 2018 were located via Embase, Web of Knowledge and PubMed, using standardised search terms data were extracted from peer-reviewed studies and these studies added to those from our previous analysis. Where age-specific data were available, prevalence estimates were age-/sex-standardised to the 2009 European population. Prevalence estimates were adjusted for study prevalence year and ascertainment methods. The latitudinal association with MS prevalence was assessed by meta-regression. A total of 94 studies met inclusion criteria, yielding 230 new prevalence points and 880 altogether with those from the prior study. There was a significant positive gradient in time-corrected MS prevalence with increasing latitude (5.27/100 000 per degree latitude), attenuating slightly to 4.34/100 000 on age-standardisation, these associations persisting on adjustment for ascertainment method. Of note, the age-standardised gradient was consistently significantly enhanced from our previous study, regardless of whether it was as-measured, time-corrected or adjusted for ascertainment methods. Certain areas, such as the Scandinavian and Atlantic Coast/Central Europe regions, showed changes in MS prevalence gradient over time, but other regional gradients were similar. This new meta-analysis confirms that MS prevalence is still strongly positively associated with increasing latitude and that the gradient is increasing, suggesting that potentially modifiable environmental factors, such as sun exposure, are still strongly associated with MS risk.
Publisher: Wiley
Date: 11-2005
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-08-2023
DOI: 10.1212/WNL.0000000000207489
Abstract: In multiple sclerosis (MS), accelerated aging of the immune system (immunosenescence) may be associated with disease onset or drive progression. DNA methylation (DNAm) is an epigenetic factor that varies among lymphocyte subtypes, and cell-specific DNAm is associated with MS. DNAm varies across the life span and can be used to accurately estimate biological age acceleration, which has been linked to a range of morbidities. The objective of this study was to test for cell-specific epigenetic age acceleration (EAA) in people with MS. This was a case-control study of EAA using existing DNAm data from several independent previously published studies. Data were included if .idat files from Illumina 450K or EPIC arrays were available for both a case with MS and an age-matched and sex-matched control, from the same study. Multifactor statistical modeling was performed to assess the primary outcome of EAA. We explored the relationship of EAA and MS, including interaction terms to identify immune cell-specific effects. Cell-sorted DNA methylation data from 3 independent datasets were used to validate findings. We used whole blood DNA methylation data from 583 cases with MS and 643 non-MS controls to calculate EAA using the GrimAge algorithm. The MS group exhibited an increased EAA compared with controls (approximately 9 mths, 95% CI 3.6–14.4), p = 0.001). Statistical deconvolution showed that EAA is associated with MS in a B cell–dependent manner ( β int = 1.7, 95% CI 0.3–2.8), p = 0.002), irrespective of B-cell proportions. Validation analysis using 3 independent datasets enriched for B cells showed an EAA increase of 5.1 years in cases with MS compared with that in controls (95% CI 2.8–7.4, p = 5.5 × 10 −5 ). By comparison, there was no EAA difference in MS in a T cell–enriched dataset. We found that EAA was attributed to the DNAm surrogates for Beta-2-microglobulin (difference = 47,546, 95% CI 10,067–85,026 p = 7.2 × 10 −5 ), and smoking pack-years (difference = 8.1, 95% CI 1.9–14.2, p = 0.002). This study provides compelling evidence that B cells exhibit marked EAA in MS and supports the hypothesis that premature B-cell immune senescence plays a role in MS. Future MS studies should focus on age-related molecular mechanisms in B cells.
Publisher: No publisher found
Date: 2017
Publisher: Elsevier BV
Date: 2013
Publisher: Society of Exploration Geophysicists
Date: 07-2015
Abstract: A key objective of stage 2 of the Cooperative Research Centre for Greenhouse Gas Technologies Otway Project is to evaluate the seismic detection limit of greenhouse gas injected into a saline aquifer. For this purpose, injection of a small amount of [Formula: see text]-rich gas into the Paaratte Formation, a saline aquifer located at a depth of approximately 1.5 km, is planned. Before the injection experiment is undertaken, we assessed the detectability of injected gas with seismic methods in a modeling study. A key objective of this study was to model changes in elastic properties caused by [Formula: see text]-saturation effects using predictions of reservoir simulations. To this end, we established an elastic property orosity relation to link the reservoir flow model and the elastic properties of the subsurface. Predicting changes in elastic properties requires suitable velocity-saturation relations. To choose an appropriate velocity-saturation relation, we analyzed the effect of fluid distribution on the time-lapse seismic response by performing 1.5D poroelastic and elastic modeling based on reservoir simulations. The modeling results emphasized the importance of taking the variability of rock properties into account and to carefully estimate dry bulk moduli to adequately represent the sensitivity of rock properties to fluid changes. Furthermore, we determined that the Gassmann-Wood relation was an appropriate velocity-saturation relation at seismic frequencies for the Paaratte Formation. However, changes in acoustic contrasts caused by [Formula: see text] saturation between layers below the seismic resolution had to be considered. In this sense, an appropriate velocity-saturation relation also depends on the scale at which we model the seismic response.
Publisher: Informa UK Limited
Date: 10-2014
DOI: 10.2217/CLP.14.41
Publisher: Elsevier BV
Date: 07-2013
DOI: 10.1016/J.JSBMB.2013.01.011
Abstract: Vitamin D deficiency is common and implicated in risk of several human diseases. Evidence on the relative quantitative contribution of environmental, genetic and phenotypic factors to vitamin D status (assessed by the serum concentration of 25-hydroxyvitamin D, 25(OH)D) in free-living populations is sparse. We conducted a cross-sectional study of 494 Caucasian adults aged 18-61years, randomly selected from the Australian Electoral Roll according to groups defined by age, sex and region (spanning 27°-43°South). Data collected included personal characteristics, sun exposure behaviour, biomarkers of skin type and past sun exposure, serum 25(OH)D concentration and candidate single nucleotide polymorphisms. Ambient ultraviolet radiation (UVR) levels in the month six weeks before blood s ling best predicted vitamin D status. Serum 25(OH)D concentration increased by 10nmol/L as reported time in the sun doubled. Overall, 54% of the variation in serum 25(OH)D concentration could be accounted for: 36% of the variation was explained by sun exposure-related factors 14% by genetic factors (including epistasis) and 3.5% by direct measures of skin phenotype. Novel findings from this study are demonstration of gene epistasis, and quantification of the relative contribution of a wide range of environmental, constitutional and genetic factors to vitamin D status. Ambient UVR levels and time in the sun were of prime importance but it is nonetheless important to include the contribution of genetic factors when considering sun exposure effects. This article is part of a Special Issue entitled 'Vitamin D Workshop'.
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.JNS.2016.11.060
Abstract: This review discusses the role of Epstein-Barr virus (EBV), human herpesvirus 6 (HHV6) and human endogenous retroviruses (HERVs) in the onset and progression of multiple sclerosis (MS). Although EBV has been established as one of the causal factors in MS onset, its role in MS progression is still uncertain. Moreover, interactions between EBV and other risk factor on MS development still need more investment. With less consistent evidence than EBV, HHV6 has also been implicated in the pathogenesis of MS moreover, it showed a closer connection with the disease activity. Recent studies found that HERVs were associated with the development and progression of MS. Some antiviral treatments have shown promise for clinical interventions in the future. Future studies are yet needed to fully clarify the role of these agents in MS onset and disease course and the modes by which they realise these effects.
Publisher: Elsevier BV
Date: 09-2020
Publisher: Elsevier BV
Date: 04-2020
DOI: 10.1016/J.MSARD.2019.101895
Abstract: Multiple sclerosis (MS) symptom measurements often use multiple-item scales per symptom, creating a high burden when multiple symptoms are assessed. We aimed to examine the validity, stability and responsiveness of single-item 0-10 numeric rating MS Symptom Scores (MSSymS). The study included 1,985 participants from the Australian Multiple Sclerosis Longitudinal Study. Thirteen MS symptoms were assessed using the MSSymS, of which we were able to validate six (walking difficulties, fatigue, pain, feelings of anxiety, feelings of depression and vision problems). Comparison measures included Patient Determined Disease Steps (PDDS), Fatigue Severity Scale (FSS), Hospital Anxiety and Depression Scale (HADS), and Assessment of Quality of Life (AQoL). We used spearman rank correlation for concurrent validity, linear regression for predictive validity, intra-class correlations for stability, and percentage change for responsiveness. We found high correlations between walking difficulties and PDDS (r = 0.82), pain and AQoL-pain (r = 0.77), fatigue and FSS (r = 0.72) moderate correlations between feelings of anxiety and HADS-Anxiety (r = 0.68), feelings of depression and HADS-Depression (r = 0.63) and low correlation between vision and AQoL-vision (r = 0.43) For predictive validity, the graphs with quality of life were largely overlapping and the R The six assessed symptoms of the MSSymS performed equally well compared to validated comparison measures in terms of concurrent and predictive validity, temporal stability and responsiveness.
Publisher: Elsevier BV
Date: 10-2021
Publisher: BMJ
Date: 20-03-2017
Abstract: To investigate the prospective associations between adiposity and lipid-related variables and conversion to multiple sclerosis (MS), time to subsequent relapse and progression in disability. A cohort of 279 participants with a first clinical diagnosis of central nervous system demyelination was prospectively followed to 5-year review. Height, weight, waist and hip circumference were measured, and serum s les taken for measurement of lipids and apolipoproteins. Survival analysis was used for conversion to MS and time to relapse, and linear regression for annualised change in disability (Expanded Disability Status Scale). Higher body mass index (BMI adjusted HR (aHR): 1.22 (1.04 to 1.44) per 5 kg/m Higher levels of adiposity, non-HDL and TC/HDL ratio were prospectively associated with a higher rate of disability progression, and higher adiposity and triglycerides were associated with relapse but not with conversion to MS. Improving the lipid profile and losing weight into the healthy range could reduce the accumulation of disability.
Publisher: SAGE Publications
Date: 21-07-2016
Abstract: We examined the combined effect of having multiple key risk factors and the interactions between the key risk factors of multiple sclerosis (MS). We performed an incident case-control study including cases with a first clinical diagnosis of central nervous system demyelination (FCD) and population-based controls. Compared to those without any risk factors, those with one, two, three, and four or five risk factors had increased odds of being an FCD case of 2.12 (95% confidence interval (CI), 1.11–4.03), 4.31 (95% CI, 2.24–8.31), 7.96 (95% CI, 3.84–16.49), and 21.24 (95% CI, 5.48–82.40), respectively. Only HLA-DR15 and history of infectious mononucleosis interacted significantly on the additive scale (Synergy index, 3.78 p = 0.03). The five key risk factors jointly accounted for 63.8% (95% CI, 43.9–91.4) of FCD onset. High anti-EBNA IgG was another important contributor. A high proportion of FCD onset can be explained by the currently known risk factors, with HLA-DR15, ever smoking and low cumulative sun exposure explaining most. We identified a significant interaction between HLA-DR15 and history of IM in predicting an FCD of CNS demyelination, which together with previous observations suggests that this is a true interaction.
Publisher: Elsevier BV
Date: 2023
DOI: 10.1016/J.MSARD.2022.104415
Abstract: 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. 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. 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: β=+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: β=+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: β=+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. 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.
Publisher: BMJ
Date: 09-08-2003
Publisher: Elsevier BV
Date: 11-2023
Publisher: SAGE Publications
Date: 12-03-2015
Abstract: Multiple sclerosis (MS) is a multifaceted condition, with a range of environmental, behavioural and genetic factors implicated in its aetiology and clinical course. Successes in advancing our appreciation of the roles of Epstein-Barr virus, vitamin D/UV and the HLA-DRB1 locus and our greater understanding of these and related factors’ modes of action in MS and other conditions, can be attributed in no small part to the work of generations of epidemiologists. Hardly content to rest on our laurels, however, there are yet a range of unsolved conundrums in MS, including some changes in epidemiological characteristics (e.g. increasing incidence and sex ratio), to say nothing of the unresolved parts regarding what underlies MS risk and its clinical course. There is evidence that epidemiology will continue to play a crucial role in unravelling the architecture of MS causation and clinical course. While classic epidemiological methods are ongoing, novel avenues for research include gene-environment interaction studies, the world of ‘-omic’ research, and the utilisation of mobile and social media tools to both access and track study populations, which means that the epidemiological discoveries of the past century may be but a glimpse of our understanding in the next few decades.
Publisher: SAGE Publications
Date: 23-07-2020
Abstract: Dietary patterns and their association with subsequent clinical course have not been well studied in early multiple sclerosis (MS). To describe dietary patterns in people in 5 years following first clinical demyelination and assess associations with MS conversion and relapse. This study included baseline food frequency questionnaire dietary intake (entry to the Ausimmune Study) and 5-year follow-up iterated principal factor analysis was applied. MS conversion and relapse risks were assessed by Cox proportional hazards models, adjusted for age, sex, study site, education, body mass index (BMI), smoking and omega-3 supplement use. In cases with a first clinical diagnosis of central nervous system (CNS) demyelination, we identified three major dietary patterns, ‘Prudent’, ‘High-Vegetable’ and ‘Mixed’, explaining 43%, 37% and 24% of diet variance in dietary intake, respectively. Fruits, vegetables, fish, wholegrains and nuts loaded highly on the Prudent pattern, starchy vegetables and legumes on the High-Vegetable pattern, and meats and alcohol on the Mixed pattern. Diet factor scores were not associated with MS conversion risk. Those with baseline Prudent scores above the median had significantly lower relapse risk (adjusted hazard ratio = 0.54, 95% confidence interval (CI) 0.37, 0.81) with some evidence of a plateau effect. Prudent diet factor score above the median was prospectively associated with lower relapse risk in the 5 years following the first clinical demyelinating event.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-06-2012
Publisher: Wiley
Date: 07-01-2019
DOI: 10.1111/CDOE.12445
Abstract: The literature describing the oral health of people with Multiple Sclerosis (MS) is scant and the findings equivocal. The aim of this study was to describe the oral health and oral self-care behaviours of people living with MS and compare it to the Australian population. Participants enrolled with the Australian MS Longitudinal Study (AMSLS) were invited to participate in the survey using an online or paper-based questionnaire. Data were collected on level of disability, oral health, oral self-care and factors influencing attendance for oral health care. Completed questionnaires were received for 1523 respondents. Over one-fifth (n = 320 22%) rated their oral health as fair or poor, and more than half (n = 840 57%) reported toothache in the last 12 months. These proportions were higher than those for the general Australian adult population (oral health prevalence ratio (PR) = 1.25 [1.12, 1.40] toothache PR = 3.63 [3.39, 3.88]), and this is despite comparable or better self-maintenance habits and dental attendance reported by respondents. People with MS reported high rates of mouth dryness (68.4%), teeth sensitivity (64.7%), change of taste (40.5%) and orofacial pain (39.0%) fewer than 10% experienced none of these. There was a lower prevalence of self-reported need for treatment (extraction or filling) than in the Australian adult population (15.8% vs 32.9%). People with MS have a greater oral health burden, demonstrated by their poorer self-reported oral health than the Australian adult population. Furthermore, they experience high rates of toothache, mouth dryness, teeth sensitivity, change of taste and orofacial pain. These findings are contrary to their self-reported good oral self-care and dental attendance habits and suggest some of the oral health impacts are due to MS rather than dental behaviours.
Publisher: Elsevier BV
Date: 05-2011
DOI: 10.1016/J.NCL.2010.12.007
Abstract: In this review, the evidence for the leading environmental and lifestyle factors thought to play a role in multiple sclerosis (MS) onset, including Epstein-Barr virus, sun exposure or vitamin D, and smoking, will be discussed. The Causal Pie Model is used as a conceptual framework to understand the causation. Given that no single factor leads to the development of MS, the joint action or interaction of these factors, along with genetic factors, most particularly the HLA-DR15*1501 genotype, is a primary focus.
Publisher: Frontiers Media SA
Date: 08-06-2018
Publisher: Springer Science and Business Media LLC
Date: 04-2009
DOI: 10.1007/S00415-009-0120-2
Abstract: Multiple 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. We 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. Cumulative 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). A 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.
Publisher: Elsevier BV
Date: 05-2014
DOI: 10.1016/J.JNS.2014.02.038
Abstract: There is increasing evidence that serum lipids and apolipoproteins may be associated with multiple sclerosis (MS) clinical course. To investigate the associations between serum lipids, apolipoproteins, body mass index and relapse in MS. A prospective cohort of 141 participants with relapsing-remitting MS was followed from 2002 to 2005. Serum lipid and apolipoprotein levels were measured biannually, and body mass index at baseline. The association with hazard of relapse was assessed using survival analysis. Neither body mass index nor any of the lipid-related measures were associated with the hazard of relapse. Serum lipid profile and body mass index are not associated with the hazard of relapse in MS.
Publisher: SAGE Publications
Date: 14-09-2021
Abstract: The symptoms that have the largest impact on health-related quality of life (HRQoL) in people with multiple sclerosis (MS) may vary by MS phenotype (relapsing-remitting MS (RRMS), secondary progressive MS (SPMS) and primary progressive MS (PPMS)). Knowing these symptoms assists in symptom management. To examine the associations between 13 common MS symptoms and HRQoL in the total s le and stratified by MS phenotype. The study included 1985 participants. HRQoL was measured with two multi-attribute utility instruments: assessment of quality of life with eight dimensions (AQoL-8D) and European quality of life with five dimensions and five levels for each dimension (EQ-5D-5L). Multivariable linear regression was used to identify the symptoms that had the largest impact on the HRQoLs. Feelings of depression, pain, fatigue, and feelings of anxiety were most strongly associated with AQoL-8D and EQ-5D-5L. Walking difficulties additionally contributed to reduced EQ-5D-5L. The strongest single predictors in the multivariable analyses were feelings of depression or pain for AQoL-8D and walking difficulties for EQ-5D-5L, irrespective of MS phenotype. The strongest single predictors for the AQoL-8D and EQ-5D-5L were feelings of depression, pain and walking difficulties, irrespective of MS phenotype. Reducing these symptoms may have the largest impact on improving HRQoL in all MS phenotypes of people with MS.
Publisher: Elsevier BV
Date: 04-2022
DOI: 10.1016/J.JSBMB.2022.106060
Abstract: Low 25-hydroxyvitamin D (25(OH)D) concentration is a recognised risk factor for multiple sclerosis (MS). Associations with vitamin D metabolites and vitamin D binding globulin (VDBG) have not been widely studied. We assessed the association between vitamin D metabolites (25(OH)D
Publisher: Wiley
Date: 30-11-2018
DOI: 10.1002/ANA.25359
Publisher: Society of Exploration Geophysicists
Date: 09-2014
Abstract: Waves in patchy-saturated rocks are attenuated through the mechanism of wave-induced pressure diffusion. Previous studies reveal that attenuation and phase-velocity dispersion depend on the fluid patch size and distribution. These patch characteristics in turn can be influenced by capillary forces. The effect of capillarity on wave attenuation in patchy-saturated rocks is not fully understood. We studied the combined effects of wave-induced pressure diffusion and capillarity on acoustic signatures. To do so we made use of the concept of patch membrane stiffness as a macroscopic expression of capillarity. We incorporated the membrane stiffness into the continuous random media model of patchy saturation. The membrane stiffness is associated with a pressure discontinuity at patch interfaces. This pressure discontinuity impedes wave-induced pressure diffusion and, therefore, reduces wave attenuation. Conversely, the phase velocity increases due to additional capillarity reinforcement. We applied this capillarity-extended random media model to interpret velocity-saturation relations (VSR) and attenuation-saturation relations (ASR) retrieved from an ultrasonically monitored core flooding experiment. Because the fluid distribution is approximately known from accompanying computerized tomographic images, all but one required model input parameters can be inferred. The elusive input parameter is a shape factor quantifying the geometric irregularity of the pore channels. We found, however, that the experimental data can be consistently modeled only if the capillarity effect is accounted for. The results suggested that wave-induced fluid-pressure diffusion at mesoscopic patches in conjunction with capillary action can have important implications for interpreting ultrasonic VSR and ASR in patchy-saturated rocks.
Publisher: Elsevier BV
Date: 03-2022
DOI: 10.1016/J.MSARD.2022.103561
Abstract: Infections with Epstein-Barr virus (EBV) and human herpesvirus-6 (HHV-6) have been implicated in multiple sclerosis (MS) onset but little work has studied their relationships in early disease. Evaluate associations between markers of EBV and HHV-6 infection/reactivation and MS conversion, relapse and EDSS/MSSS amongst 205 CIS participants with EBV/HHV-6 data followed over 5 years. Baseline serological and viral load measures of EBV and HHV-6 exposure/reactivation were measured and infectious mononucleosis (IM) history recorded. Conversion to MS and relapses were assessed annually, and EDSS/MSSS measured at 5-year review. Determinants of MS conversion and relapse assessed by Cox regression, and disability progression by linear regression. IM history showed a strong positive trend with higher relapse risk (aHR=1.45,95%CI=0.97-2.16) but was not associated with MS conversion (aHR=0.92,95%CI=0.57-1.48). Anti-HHV-6 IgG titre>40 also showed strong positive trends with higher relapse (aHR=1.61,95%CI=0.99-2.63) and MS conversion risks (aHR=1.48,95%CI=0.89-2.46). Anti-HHV-6 IgG titre≥640 was significantly associated with higher MSSS (0.15(95%CI=0.00,0.30) and also showed a strong positive trend with higher EDSS 0.10(95%CI=-0.02,0.21). HHV-6 DNA detection showed strong positive trends with 83%(95%CI=-6-357) and 77%(95%CI=-4-328) higher MS conversion and relapse risk. Anti-EBV-EA-D IgG titre was associated with a lower annualised disability progression by EDSS (p Overall, our data provides evidence that higher HHV-6 IgG was associated with increased risk of MS conversion and relapse but of borderline significance, and greater annualised disability progression, while that for EBV was more limited.
Publisher: Elsevier BV
Date: 09-2020
Publisher: Informa UK Limited
Date: 31-07-2021
Publisher: Wiley
Date: 24-03-2014
DOI: 10.1111/PHP.12265
Abstract: Personal ultraviolet dosimeters have been used in epidemiological studies to understand the risks and benefits of in iduals' exposure to solar ultraviolet radiation (UVR). We investigated the types and determinants of noncompliance associated with a protocol for use of polysulphone UVR dosimeters. In the AusD Study, 1002 Australian adults (aged 18-75 years) were asked to wear a new dosimeter on their wrist each day for 10 consecutive days to quantify their daily exposure to solar UVR. Of the 10 020 dosimeters distributed, 296 (3%) were not returned or used (Type-I noncompliance) and other usage errors were reported for 763 (8%) returned dosimeters (Type-II noncompliance). Type-I errors were more common in participants with predominantly outdoor occupations. Type-II errors were reported more frequently on the first day of measurement weekend days or rainy days and among females younger people more educated participants or those with outdoor occupations. Half (50%) the participants reported a noncompliance error on at least 1 day during the 10-day period. However, 92% of participants had at least 7 days of usable data without any apparent noncompliance issues. The factors identified should be considered when designing future UVR dosimetry studies.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2016
Publisher: Elsevier BV
Date: 03-2022
Publisher: Wiley
Date: 20-07-2017
DOI: 10.1111/PHP.12780
Abstract: Data on personal sun exposure over a period exceeding the immediate past days or weeks are typically self-reported in brief questionnaire items. The validity of such self-reporting of longer term personal sun exposure, for ex le over a year, including detail on variation across seasons, has not previously been investigated. In a volunteer s le (n = 331) of Australian adults aged 18 years and over, we assessed the 12-month reliability of sun exposure reported separately for each season, and its accuracy compared to a daily sun diary in the same season. Seasonal time outdoors displayed fair-to-good reliability between baseline and end of study (12 months), with responses showing higher agreement at lower levels of time outdoors. There was good agreement for ranking of in iduals' time outdoors with the daily sun diary data, although the actual diary time outdoors was typically considerably lower than the self-reported questionnaire data. Place of residence, education, being a smoker, day of the week (i.e. working day vs nonworking day) and working mainly outdoors were significant predictors of agreement. While participants overestimated their actual time outdoors, the self-report questionnaire provided a valid ranking of long-term sun exposure against others in the study that was reliable over time.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2021
Publisher: SAGE Publications
Date: 25-07-2014
Abstract: The modulating effects of the multiple sclerosis (MS) risk-associated single-nucleotide polymorphisms (SNPs) on MS clinical course are not well established. The objective of this paper is to investigate whether known MS risk-associated SNPs were associated with clinical course, and whether these SNPs modified the 25(OH)D-relapse association. Using a prospective cohort of 141 participants with relapsing–remitting MS and genotype data followed between 2002 and 2005, genotype-vitamin D interactions and the genetic predictors of relapse were assessed using survival analysis, and genetic predictors of 25(OH)D and disability progression were evaluated by multilevel mixed-effects linear regression. While no SNP reached statistical significance after multiple testing, five SNPs were associated with relapse, with significant cumulative genotype risk effects and two demonstrated significant allele dose-response. Two SNPs altered the 25(OH)D-relapse association with significant allele dose-response. Five SNPs modified levels of 25(OH)D, with significant cumulative genotype ‘risk’ effect, and three demonstrated significant allele dose-response. We found no consistent evidence for an association between any SNPs and disability. Our study provides evidence for an association between known MS risk-associated SNPs and relapse. Our findings indicate gene-environment interactions may be an important mechanism on MS clinical course, and provide support for the role of vitamin D in MS relapse.
Publisher: Wiley
Date: 30-09-2011
DOI: 10.1111/J.1399-3038.2010.01099.X
Abstract: Observations of increasing allergy prevalence with decreasing distance from the Equator and positive associations with ambient ultraviolet radiation have contributed to a growing interest in the possible role of vitamin D in the etiology of allergy. The aims of this study were to describe any latitudinal variation in the prevalence of childhood allergy in Australia and to evaluate, in parallel, the in idual associations between ultraviolet radiation (UVR)- and vitamin D-related measures and hayfever asthma and both conditions. Participants were population-based controls who took part in a multicenter case-control study, aged 18-61 yr and resident in one of four study regions ranging in latitude from 27°S to 43°S. Data were derived from a self-administered questionnaire, interview and examination by a research officer and biologic s ling. Latitude and longitude coordinates were geocoded from participants' residential locations and climatic data were linked to postcodes of current residence. Stored serum was analyzed for 25-hydroxyvitamin D concentrations and silicone rubber casts of the skin were used as an objective measure of cumulative actinic damage. There was an inverse latitude gradient for asthma (a 9% decrease per increasing degree of latitude) however, this pattern did not persist after adjusting for average daily temperature. There was no association between any of the UVR- or vitamin D-related measures and childhood asthma, but greater time in the sun in winter between the ages 6-15 yr was associated with an increase in the odds of having hayfever [adjusted odds ratios (OR) 1.29 95% CI 1.01-1.63]. Oral supplementation with cod liver oil in childhood increased the odds of a history of having both asthma and hayfever (2.87 1.00-8.32). Further investigation of the possible role of early vitamin D supplementation in the development of allergy is warranted. Our results also suggest that solar exposure during childhood may be important in allergic sensitization. Plausible explanations, including biologic mechanisms, exist for both observations.
Publisher: Elsevier BV
Date: 08-2002
DOI: 10.1016/S1011-1344(02)00331-7
Abstract: Recent advances have enabled quite accurate estimations of cutaneous melanin density by spectrophotometry using reflectance of light at wavelengths 400 and 420 nm. Our purpose was to assess the effect of body hair and seasonal variation at the upper inner arm and buttock on measurements of melanin density. We estimated melanin density of 104 volunteers at 3-monthly intervals over 12 months both before and after shaving. Removing body hair at the upper inner arm had no effect, but substantially reduced melanin estimates at the buttock in men. Significant seasonal variation was only observed at the upper inner arm, with highest readings in summer-autumn. In case-control studies, misclassification due to body hair at the buttock and seasonal variation at the upper inner arm could affect the observed odds ratio substantially. However, both sources of error can be reduced by careful attention to key aspects of study design.
Publisher: Elsevier BV
Date: 10-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-02-2011
Publisher: Walter de Gruyter GmbH
Date: 2017
Abstract: Vitamin D deficiency has been associated with adverse health outcomes. We examined genetic and environmental determinants of serum 25(OH)D The study s le consisted of 322 healthy Australian children (predominantly Caucasians) who provided a venous blood s le. A parental interview was conducted and skin phototype and anthropometry measures were assessed. Concentrations of 25(OH)D Deseasonalised log 25(OH)D Environmental factors and genetic factors contributed to both vitamin D metabolite concentrations. The intriguing finding that the higher ambient UVR contributed to higher 1,25(OH)
Publisher: Elsevier BV
Date: 04-2022
DOI: 10.1016/J.MSARD.2022.103717
Abstract: Little is known about the impact of online health education on multiple sclerosis (MS)-related knowledge and other health outcomes in the MS community. To estimate the impact of participating in a massive open online course (MOOC) about MS on course completer MS-related knowledge, health literacy (HL), self-efficacy, resilience, quality of life, and MS symptom severity. In this cohort study, using a single group pre-test ost-test design (n=560), we examined the effects of MOOC participation on MS-related knowledge and other outcomes using a paired t-test. We used regression and structural equation modelling to examine the association between participant characteristics, changes in other outcomes, and changes in MS-related knowledge. We found significant increases in MS-related knowledge for people living with MS (PwMS) (+2.13 points, p<0.001) and those without MS (+5.16 points, p<0.001), with larger effect sizes for those with higher educational levels. Among PwMS, there were also significant increases in seven HL subscales and self-efficacy, but no increase in resilience, MS symptoms severity or quality of life. Among people without MS, there were increases in two HL subscales and quality of life, but no increase in resilience or self-efficacy. Changes in MS-related knowledge were not associated with sex or changes in other study outcomes. There was a significant increase in MS-related knowledge, which was unrelated to the changes in the other study outcomes, both for PwMS and for those not living with MS. Outcome-specific health educational interventions may be needed to effect change in other health outcomes.
Publisher: Wiley
Date: 10-2012
DOI: 10.1111/J.1445-5994.2012.02788.X
Abstract: This study aims to describe the lifetime picture of vitamin D deficiency, as measured by serum 25(OH)D concentration, in Tasmania (latitude 43°S). Five cross-sectional studies were used: a s le of primary schoolchildren (n = 201, aged 7-8 years), two s les of adolescents (s le 1: n = 374, aged 15-18 years s le 2: n = 136, aged 16-19 years), a s le of young to middle-aged adults (n = 262, aged 19-59 years) and a s le of older adults (n = 1092, aged 50-80 years). In winter/spring, approximately two-thirds of the adolescents and adults (young, middle-aged and older) had 25(OH)D levels ≤50 nmol/L, and around 10% had 25(OH)D levels ≤25 nmol/L. The prevalence of vitamin D deficiency was much lower for primary schoolchildren (11.5% < 50 nmol/L, 0.5% ≤ 25 nmol/L). In summer/autumn, approximately one-third of the adolescents and adults had 25(OH)D levels ≤50 nmol/L, and very few had 25(OH)D levels ≤25 nmol/L. For the adolescents and adults, even among those who reported the highest category of sun exposure, approximately 45% had 25(OH)D levels ≤50 nmol/L in winter/spring. Vitamin D deficiency was uncommon among our s le of primary school children but increased substantially during the teenage years and seemed to remain high throughout the rest of life, suggesting that mild vitamin D deficiency is endemic in Tasmania apart from in the very young.
Publisher: SAGE Publications
Date: 11-09-2016
Abstract: There is contradictory evidence for a role of dietary fat in risk of multiple sclerosis (MS). To examine the association between usual fat intake (total, saturated, monounsaturated (MUFA), polyunsaturated (PUFA), omega-3 and omega-6) and risk of a first clinical diagnosis of CNS demyelination (FCD). Multi-centre incident case-control study in four regions of Australia during 2003–2006. Cases were aged 18–59 years and had a FCD controls were matched to a case on age, sex and location. Dietary data were collected using a validated food frequency questionnaire. In 267 cases and 517 controls with dietary data, higher intake (per g/day) of omega-3 PUFA (adjusted odds ratio, AOR=0.61 (95% CI 0.40–0.93)), and particularly that derived from fish (AOR=0.54 (95% CI 0.31–0.93)) rather than from plants (AOR=0.75 (95% CI 0.39–1.43)) was associated with a decreased risk of FCD. Total fat intake and intake of other types of fat were not associated with FCD risk. There was a significant decrease in FCD risk with higher intake of omega-3 PUFA, particularly that originating from fish. There was no evidence to indicate that the intake of other types of dietary fat or fat quantity in the previous 12 months was associated with an altered risk of FCD.
Publisher: SAGE Publications
Date: 03-09-2021
Abstract: No studies have assessed changes in employment survival in multiple sclerosis (MS) populations over recent decades, including the introduction of disease-modifying therapies (DMTs). To evaluate factors associated with leaving employment due to MS to assess whether the risk of leaving employment has changed over recent decades in Australia, stratified by MS phenotype. We included 1240 participants who were working before MS diagnosis. Information on employment status, reasons for leaving employment and year of leaving were collected. Data were analysed using competing risk survival analysis. Males, progressive MS, lower education level and older age at diagnosis were associated with a higher sub-distribution hazard of leaving employment. Compared to the period before 2010, the sub-distribution hazard during 2010–2016 for relapsing-remitting multiple sclerosis (RRMS) was reduced by 43% (sub-distribution hazard ratio (sHR) 0.67, 95% confidence interval (CI): 0.50 to 0.90), while no significant reduction was seen for primary-progressive multiple sclerosis (PPMS) (sHR 1.25, 95% CI: 0.72 to 2.16) or secondary-progressive multiple sclerosis (SPMS) (sHR 1.37, 95% CI: 0.84 to 2.25). Males, people with progressive MS and those of lower education level were at higher risk of leaving employment. The differential changed risk of leaving employment between people with different MS phenotype after 2010 coincides with the increased usage of high-efficacy DMTs for RRMS.
Publisher: BMJ
Date: 16-05-2022
Abstract: 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. 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. 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. 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.
Publisher: Oxford University Press (OUP)
Date: 12-04-2013
DOI: 10.1093/AJE/KWS361
Abstract: 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.
Publisher: SAGE Publications
Date: 21-04-2009
Abstract: Multiple studies have provided evidence for an association between reduced sun exposure and increased risk of multiple sclerosis (MS), an association likely to be mediated, at least in part, by the vitamin D hormonal pathway. Herein, we examine whether the vitamin D receptor ( VDR), an integral component of this pathway, influences MS risk in a population-based s le where winter sun exposure in early childhood has been found to be an important determinant of MS risk. Three polymorphisms within the VDR gene were genotyped in 136 MS cases and 235 controls, and associations with MS and past sun exposure were examined by logistic regression. No significant univariate associations between the polymorphisms, rs11574010 ( Cdx-2A G), rs10735810 ( Fok1T C), or rs731236 ( Taq1C T) and MS risk were observed. However, a significant interaction was observed between winter sun exposure during childhood, genotype at rs11574010, and MS risk ( P = 0.012), with the ‘G’ allele conferring an increased risk of MS in the low sun exposure group (≤2 h/day). No significant interactions were observed for either rs10735810 or rs731236, after stratification by sun exposure. These data provide support for the involvement of the VDR gene in determining MS risk, an interaction likely to be dependent on past sun exposure.
Publisher: Springer Science and Business Media LLC
Date: 08-08-2020
DOI: 10.1038/S41430-019-0476-Z
Abstract: The evidence for diet as a risk factor for multiple sclerosis (MS) is inconclusive. We examined the associations between fish consumption and risk of a first clinical diagnosis of central nervous system demyelination (FCD), a common precursor to MS. The 2003-2006 Ausimmune Study was a case-control study examining environmental risk factors for FCD, with participants recruited from four regions of Australia and matched on age, sex, and study region. Dietary intake data were collected using a food frequency questionnaire. We used conditional logistic regression models to test associations between fish consumption (total, tinned, grilled, and fried) and risk of FCD (249 cases and 438 controls), adjusting for history of infectious mononucleosis, smoking, serum 25-hydroxyvitamin D concentrations, socio-economic status, omega-3 supplement use, dietary under-reporting, and total energy intake. Higher total fish consumption (per 30 g/day, equivalent to two serves/week) was associated with an 18% reduced risk of FCD (AOR 0.82 95% CI 0.70, 0.97). While we found no statistically significant associations between grilled and fried fish consumption and risk of FCD, higher tinned fish consumption (per 30 g/day) was associated with a 41% reduced risk of FCD (AOR 0.59 95% CI 0.39, 0.89). Tinned fish is predominantly oily, whereas grilled and fried fish are likely to be a combination of oily and white types. Oily fish is high in vitamin D and very long chain polyunsaturated omega-3 fatty acids, both of which may be beneficial in relation to MS.
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.1016/J.JPHOTOBIOL.2014.12.029
Abstract: To examine the effects of meteorological factors on weekend sun exposure behaviours and personal received dose of ultraviolet radiation (UVR) in Australian adults. Australian adults (n=1002) living in Townsville (19°S, 146°E), Brisbane (27°S, 153°E), Canberra (35°S, 149°E) and Hobart (43°S, 147°E) were recruited between 2009 and 2010. Data on sun exposure behaviours were collected by daily sun exposure dairies personal UVR exposure was measured with a polysulphone dosimeter. Meteorological data were obtained from the Australian Bureau of Meteorology ambient UVR levels were estimated using the Ozone Monitoring Instrument data. Higher daily maximum temperatures were associated with reduced likelihood of wearing a long-sleeved shirt or wearing long trousers in Canberra and Hobart, and higher clothing-adjusted UVR dose in Canberra. Higher daily humidity was associated with less time spent outdoors in Canberra. Higher ambient UVR level was related to a greater clothing-adjusted personal UVR dose in Hobart and a greater likelihood of using sunscreen in Townsville. The current findings enhance our understanding of the impact of weather conditions on the population's sun exposure behaviours. This information will allow us to refine current predictive models for UVR-related diseases, and guide future health service and health promotion needs.
Publisher: Springer Science and Business Media LLC
Date: 02-09-2021
Publisher: BMJ
Date: 18-07-2014
Abstract: The interplay between genes and environmental factors on multiple sclerosis (MS) clinical course has been little studied. We conducted a prospective cohort study of 141 participants with relapsing-remitting MS (RRMS) and genotype data followed from 2002 to 2005 and examined genes in the vitamin D metabolism and vitamin D receptor (VDR)/retinoid X receptor (RXR) transcription factor formation pathway. Gene-vitamin D interactions and the genetic predictors of relapse were assessed using survival analysis. Genetic predictors of 25-hydroxyvitamin D (25(OH)D) were evaluated by multilevel mixed-effects linear regression. Significance threshold was adjusted by Bonferroni correction for the number of genes evaluated. The relationship between 25(OH)D and hazard of relapse was significantly different for different alleles of two intronic single nucleotide polymorphisms (SNPs) (rs908742 in PRKCZ and rs3783785 in PRKCH) in the protein kinase C (PKC) family genes (p(interaction)=0.001, p(adj)=0.021, respectively). Two other intronic SNPs (rs1993116 in CYP2R1and rs7404928 in PRKCB) were significantly associated with lower levels of 25(OH)D (p(interaction)=0.001, p(adj)=0.021, respectively). A cumulative effect of multiple 'risk' genotypes on 25(OH)D levels and hazard of relapse was observed for the significant SNPs (p(trend)=7.12×10(-6) for 25(OH)D levels, p(trend)=8.86×10(-6) for hazard of relapse). Our data support the hypothesis that gene-vitamin D interactions may influence MS clinical course and that the PKC family genes may play a role in the pathogenesis of MS relapse through modulating the association between 25(OH)D and relapse.
Publisher: BMJ
Date: 27-07-2022
Abstract: Sleep difficulties are common in people with multiple sclerosis (MS), but whether associations between poor sleep quality and quality of life are independent of MS symptoms, obesity and other MS-related factors remains unclear. Cross-sectional analyses of data from the Australian MS Longitudinal Study (n=1717). Sleep was assessed using the Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale and International Restless Legs Syndrome Study Group Rating Scale health-related quality of life using the Assessment of Quality-of-Life 8-D. Poor sleep quality was common (67%), and more common than in community s les. Sleep measures clustered independently within MS symptoms. The clusters 'fatigue and cognitive', 'feelings of anxiety and depression', 'pain and sensory', were independently associated with poor sleep quality. Quality-of-Life utility scores were a clinically meaningful 0.19 units lower in those with poor sleep. Sleep quality, daytime sleepiness and restless leg syndrome were associated with reduced quality of life, independent of MS-related symptoms and body mass index. Poor sleep quality is common in MS and was strongly associated with worse health-related quality of life, independent of other MS symptoms and did not cluster with other common MS symptoms. Improving sleep quality may substantially improve quality of life in people with MS.
Publisher: S. Karger AG
Date: 2008
DOI: 10.1159/000166602
Abstract: i Background: /i 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. i Methods: /i 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. i Results: /i 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. i Conclusions: /i 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.
Publisher: SAGE Publications
Date: 06-09-2016
Abstract: There is substantial evidence that stress increases multiple sclerosis disease activity, but limited evidence on its association with the onset of multiple sclerosis. To examine the association between stressful life events and risk of first demyelinating event (FDE). This was a multicentre incident case–control study. Cases ( n = 282 with first diagnosis of central nervous system (CNS) demyelination, including n = 216 with ‘classic FDE’) were aged 18–59 years. Controls without CNS demyelination ( n = 558) were matched to cases on age, sex and study region. Stressful life events were assessed using a questionnaire based on the Social Readjustment Rating Scale. Those who suffered from a serious illness in the previous 12 months were more likely to have an FDE (odds ratio (OR) = 2.35 (1.36, 4.06), p = 0.002), and when we limited our reference group to those who had no stressful life events, the magnitude of effect became stronger (OR = 5.41 (1.80, 16.28)). The total stress number and stress load were not convincingly associated with the risk of an FDE. Cases were more likely to report a serious illness in the previous 12 months, which could suggest that a non-specific illness provides an additional strain to an already predisposed immune system.
Publisher: SAGE Publications
Date: 13-05-2013
Abstract: Lifestyle factors prior to a first clinical demyelinating event (FCD), a disorder often preceding the development of clinically definite multiple sclerosis (MS), have not previously been examined in detail. Past tobacco smoking has been consistently associated with MS. This was a multicentre incident case-control study. Cases ( n = 282) were aged 18–59 years with an FCD and resident within one of four Australian centres (from latitudes 27°S to 43°S), from 1 November 2003 to 31 December 2006. Controls ( n = 558) were matched to cases on age, sex and study region, without CNS demyelination. Exposures measured included current and past tobacco and marijuana, alcohol and beverage use, physical activity patterns, blood pressure and physical anthropometry. A history of smoking ever was associated with FCD risk (AOR 1.89 (95%CL 1.82, 3.52)). Marijuana use was not associated with FCD risk after adjusting for confounders such as smoking ever but the estimates were imprecise because of a low prevalence of use. Alcohol consumption was common and not associated with FCD risk. No case-control differences in blood pressure or physical anthropometry were observed. Past tobacco smoking was positively associated with a risk of FCD but most other lifestyle factors were not. Prevention efforts against type 2 diabetes and cardiovascular disease by increasing physical activity and reducing obesity are unlikely to alter MS incidence, and more targeted c aigns will be required.
Publisher: Elsevier
Date: 2015
Publisher: Wiley
Date: 20-05-2021
DOI: 10.1111/ENE.14887
Abstract: This study was undertaken to identify clinically meaningful comorbidity patterns and their associations with the demographic/clinical characteristics of people with multiple sclerosis (MS). We conducted latent class analysis to identify clinically distinct comorbidity patterns in MS using the 15 most common comorbidities among 1518 Australian Multiple Sclerosis Longitudinal Study participants. The associations between demographic/clinical characteristics and comorbidity patterns were examined using log‐binomial and multinomial logistic regression. Five distinct comorbidity patterns were identified: “minimally diseased class” (30.8%), consisting of participants with no or one comorbidity “metabolic class” (22.7%) “mental health–allergy class” (21.7%) “nonmetabolic class” (7.6%) and “severely diseased class” (7.0%), consisting of participants with higher prevalence of these comorbidities. The relative probabilities of being assigned to comorbidity classes compared to the minimally diseased class were significantly increased for participants who were older (metabolic: relative risk ratio [RRR] = 1.09, 95% confidence interval [CI] = 1.06–1.11 nonmetabolic: RRR = 1.07, 95% CI = 1.04–1.11 severely diseased: RRR = 1.04, 95% CI = 1.01–1.08), female (nonmetabolic: RRR = 5.35, 95% CI = 1.98–14.42 severely diseased: RRR = 2.21, 95% CI = 1.02–4.77), and obese (metabolic: RRR = 4.06, 95% CI = 2.45–6.72 mental health–allergy: RRR = 1.57, 95% CI = 1.00–2.46 severely diseased: RRR = 4.53, 95% CI = 2.21–9.29) and who had moderate disability (mental health–allergy: RRR = 2.32, 95% CI = 1.47–3.64 severely diseased: RRR = 2.65, 95% CI = 1.16–6.04). Comorbidity patterns exist in MS. Women, people who were older, people who were obese, and people who had higher disability levels were more likely to be in classes with higher levels of comorbidity. These findings may offer opportunities for designing more personalised approaches to comorbidity prevention and treatment.
Publisher: Hindawi Limited
Date: 07-02-2017
DOI: 10.1111/ANE.12597
Publisher: Springer Science and Business Media LLC
Date: 09-03-2015
Publisher: BMJ
Date: 20-11-2010
Abstract: 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. 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. 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. 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.
Publisher: Oxford University Press (OUP)
Date: 25-02-2014
DOI: 10.1093/AJE/KWT446
Abstract: The Quantitative Assessment of Solar UV [ultraviolet] Exposure for Vitamin D Synthesis in Australian Adults (AusD) Study aimed to better define the relationship between sun exposure and serum 25-hydroxyvitamin D (25(OH)D) concentration. Cross-sectional data were collected between May 2009 and December 2010 from 1,002 participants aged 18-75 years in 4 Australian sites spanning 24° of latitude. Participants completed the following: 1) questionnaires on sun exposure, dietary vitamin D intake, and vitamin D supplementation 2) 10 days of personal ultraviolet radiation dosimetry 3) a sun exposure and physical activity diary and 4) clinical measurements and blood collection for 25(OH)D determination. Our multiple regression model described 40% of the variance in 25(OH)D concentration modifiable behavioral factors contributed 52% of the explained variance, and environmental and demographic or constitutional variables contributed 38% and 10%, respectively. The amount of skin exposed was the single strongest contributor to the explained variance (27%), followed by location (20%), season (17%), personal ultraviolet radiation exposure (8%), vitamin D supplementation (7%), body mass index (weight (kg)/height (m)(2)) (4%), and physical activity (4%). Modifiable behavioral factors strongly influence serum 25(OH)D concentrations in Australian adults. In addition, latitude was a strong determinant of the relative contribution of different behavioral factors.
Publisher: Wiley
Date: 09-03-2017
DOI: 10.1002/BRB3.670
Publisher: SAGE Publications
Date: 12-11-2017
Abstract: While cigarette and passive smoking have been identified as modifiable risk factors for multiple sclerosis (MS), there is no report regarding Waterpipe smoking–MS association. We examined the association of Waterpipe, tobacco, and passive smoking with MS. Population-based incident case–control study in Iran with 547 incident cases and 1057 general population controls (7 August 2013–17 February 2015). Logistic regression model was used. Multiplicative along with additive interaction was assessed using product term and Synergy Index (SI), respectively, and the population attributable fractions (PAFs) were calculated. Having ever smoked Waterpipe, tobacco, or being exposed to passive smoking were all significantly associated with MS (odds ratio (OR) = 1.77 (1.36–2.31), OR = 1.69 (1.24–2.31), and OR = 1.85 (1.48–2.32), respectively). Clear dose–response associations were observed with the duration exposed ( p 0.001 for all three) and the amount smoked ( p 0.001 for Waterpipe and tobacco). Those who had all three types of smoking had an odds that was 4.1 times higher than those without any type. The three types of smoking jointly contributed to 30.9% of the MS incidence. We identified Waterpipe smoking as a novel risk factor for MS. Given the global increase in Waterpipe smoking, especially among young adults, this finding reinforces the need for public health interventional and educational programs to combat this global increase.
Publisher: Elsevier BV
Date: 30-05-2008
Publisher: Wiley
Date: 02-2010
DOI: 10.1002/ANA.21849
Publisher: BMJ
Date: 28-07-2022
Abstract: Little is known about the comparative effectiveness of multiple sclerosis (MS) disease-modifying therapies (DMTs) on patient-reported outcomes in MS. We compared the effects of natalizumab to other DMTs in relation to MS symptom severity, quality of life, disability, disease progression and employment outcomes using real-world data. We included 2817 observations in 2015, 2016 and 2017 from 1382 participants in the Australian MS Longitudinal Study. Information on treatment, health and employment outcomes was prospectively collected by questionnaires. Marginal structural models with interaction terms for DMT×time were used to compare natalizumab and other comparator treatment groups. Natalizumab was associated with improvements over time, or general trends of improvement, in the severity of many symptoms and work productivity loss. Compared with any other DMTs, natalizumab was associated with superior effects over time for 8 of 23 patient-reported outcomes, with similar directions of effect observed for another 6, demonstrating consistency. There were no differences in effect for spasticity, fatigue, pain, feelings of depression, disability, European quality of life five dimension index, presenteeism and work status. Natalizumab did not perform significantly worse over time compared with any other DMTs for any of the outcomes. Natalizumab was associated with superior outcomes over time for many patient-reported health and employment outcomes when compared with other DMTs in this large prospective cohort study. These findings may influence treatment selection in clinical practice and future treatment cost-effectiveness analyses.
Publisher: SAGE Publications
Date: 02-2014
Abstract: It is now well established that both genetic and environmental factors contribute to and interact in the development of multiple sclerosis (MS). However, the currently described causal genetic variants do not explain the majority of the heritability of MS, resulting in ‘missing heritability’. Epigenetic mechanisms, which principally include DNA methylation, histone modifications and microRNA-mediated post-transcriptional gene silencing, may contribute a significant component of this missing heritability. As the development of MS is a dynamic process potentially starting with inflammation, then demyelination, remyelination and neurodegeneration, we have reviewed the dynamic epigenetic changes in these aspects of MS pathogenesis and describe how environmental risk factors may interact with epigenetic changes to manifest in disease.
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.MSARD.2019.101486
Abstract: Due to the considerable burden of multiple sclerosis (MS)-related symptoms and the need to identify effective interventions to prevent disease progression, various nutraceutical interventions have been trialed as adjunctive treatments. The aim of this review was to investigate the efficacy and safety of nutraceutical interventions for clinical and biological outcomes in people with MS. In accordance with PRISMA reporting guidelines, a systematic literature search was conducted using three electronic literature databases. Risk of bias was assessed using the Jadad scale. Thirty-seven randomized controlled trials, investigating fourteen nutraceuticals, were included in the review. Trials that investigated alpha lipoic acid (n = 4/6), ginkgo biloba (n = 3/5), vitamin A (n = 2/2), biotin (n = 1/2), carnitine (n = 1/2), green tea (n = 1/2), coenzyme Q10 (n = 1/1), probiotics (n = 1/1), curcumin (n = 1/1), Andrographis paniculata (n = 1/1), ginseng (n = 1/1), and lemon verbena (n = 1/1) were reported to improve biological (e.g. MRI brain volume change, antioxidant capacity) and/or clinical (e.g. fatigue, depression, Expanded Disability Status Scale) outcomes in multiple sclerosis compared to control. However, most trials were relatively small (average study s le size across included studies, n = 55) and there were few replicate studies per nutraceutical to validate the reported results. Furthermore, some nutraceuticals (e.g. green tea and inosine) should be used with caution due to reported adverse events. Risk of bias across most studies was low, with 31 studies receiving a score between 4 and 5 (out of 5) on the Jadad Scale. The existing literature provides preliminary support for the use of a number of nutraceutical interventions in MS. However, sufficiently powered long-term trials are required to expand the currently limited literature and to investigate unexplored nutraceuticals that may target relevant pathways involved in MS such as the gut microbiome and mitochondrial dysfunction. Prospero ID: CRD42018111736.
Publisher: Oxford University Press (OUP)
Date: 13-10-2006
DOI: 10.1111/J.1365-2249.2006.03235.X
Abstract: Higher sibling exposure is associated with a reduced risk of asthma and other T helper 2 (Th2)-type disorders, possibly through a beneficial effect of higher infection load. The effect on Th1 disorders such as multiple sclerosis (MS) is less clear. Here we examine the association between asthma and MS, taking into account early life sibling exposure. A population-based case–control study in Tasmania, Australia based on 136 cases of magnetic resonance imaging (MRI)-confirmed MS and 272 community controls, matched on sex and year of birth. Study measures include cumulative exposure to total, older or younger siblings by age 6 years, history of doctor-diagnosed asthma and serological IgG responses to herpes viruses. MS cases were more likely (P = 0·02) than controls to have asthma which began before age of onset of MS symptoms compared to the corresponding age for controls. The absence of younger sibling exposure by age 6 years potentiated (P = 0·04) the association between asthma and MS. Compared to those with younger sibling exposure and no asthma, the adjusted odds ratio for MS for those with asthma and no younger sibling exposure was 7·22 (95% CI: 2·52, 20·65). Early life sibling exposure was associated with altered IgG serological responses to Epstein–Barr virus (EBV) and herpes simplex virus 1 (HSV1) in adulthood. Reduced early life sibling exposure appeared to contribute to the excess of asthma among MS cases by the time of MS onset. MS development may reflect factors that relate to a general immuno-inflammatory up-regulation of immune activity as well as disease specific factors. The link between early life sibling exposure and the immune response to herpes group viral antigens is consistent with a protective role for early life infections.
Publisher: SAGE Publications
Date: 18-02-2010
Abstract: Increasing prevalence and variable geographic patterns of occurrence of multiple sclerosis suggest an environmental role in causation. There are few descriptive, population-level, data on whether such variability applies to first demyelinating events (FDEs). We recruited 216 adults (18—59 years), with a FDE between 1 November 2003 and 31 December 2006 in a multi-center incident case-control study in four locations on the south-eastern and eastern seaboard of Australia, spanning latitudes 27° south to 43° south. Population denominators were obtained from the Australian Bureau of Statistics censuses of 2001 and 2006. Age and sex adjusted FDE incidence rates increased by 9.55% (95% confidence interval (CI) 7.37—11.78, p 0.001) per higher degree of latitude. The incidence rate gradient per higher degree of latitude varied by gender (male: 14.69% (95% CI 9.68—19.94, p 0.001) female 8.13% (95% CI 5.69—10.62, p 0.001)) and also by the presenting FDE type: optic neuritis 11.39% (95% CI 7.15—15.80, p 0.001) brainstem/cerebellar syndrome 9.47% (95% CI 5.18—13.93, p 0.001) and spinal cord syndrome 5.36% (95% CI 1.78—9.06, p = 0.003). Differences in incidence rate gradients were statistically significant between males and females ( p = 0.02) and between optic neuritis and spinal cord syndrome ( p = 0.04). The male to female ratio varied from 1 : 6.7 at 27° south to 1 : 2.5 at 43° south. The study establishes a positive latitudinal gradient of FDE incidence in Australia. The latitude-related factor(s) influences FDE incidence variably according to subtype and gender, with the strongest influence on optic neuritis presentations and for males. These descriptive case analyses show intriguing patterns that could be important for understanding the etiology of multiple sclerosis.
Publisher: Springer Science and Business Media LLC
Date: 11-04-2007
DOI: 10.1007/S00415-006-0315-8
Abstract: Adequate 25(OH)D levels are required to prevent adverse effects on bone health. Population-based data on factors associated with 25(OH)D levels of people with MS have been lacking. To examine the prevalence and determinants of vitamin D insufficiency in a population-based s le of MS cases and controls, and to compare 25(OH)D status between MS cases and controls, taking into account case disability. We conducted a population based case-control study in Tasmania, Australia (latitude 41-43 degrees S) on 136 prevalent cases with MS confirmed by magnetic resonance imaging and 272 community controls, matched on sex and year of birth. Measurements included serum 25(OH)D, sun exposure, skin type, dietary vitamin D intake and disability including EDSS. A high prevalence of vitamin D insufficiency was found in MS cases and controls. Among MS cases, increasing disability was strongly associated with lower levels of 25(OH)D and with reduced sun exposure. Cases with higher disability (EDSS > 3) were more likely to have vitamin D insufficiency than controls (OR = 3.07 (1.37, 6.90) for 25(OH)D </= 40 nmol/l), but cases with low disability were not (OR = 0.87 (0.41, 1.86)). The strong associations between disability, sun exposure and vitamin D status indicate that reduced exposure to the sun, related to higher disability, may contribute to the high prevalence of vitamin D insufficiency found in this population-based MS case s le. Active detection of vitamin D insufficiency among people with MS and intervention to restore vitamin D status to adequate levels should be considered as part of the clinical management of MS.
Publisher: Springer Science and Business Media LLC
Date: 29-08-2022
DOI: 10.1007/S11136-022-03214-Y
Abstract: 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. A large representative s le 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. 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. 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.
Publisher: Springer Science and Business Media LLC
Date: 10-11-2018
DOI: 10.1007/S10072-017-3177-1
Abstract: Despite extensive studies focusing on the changes in expression of microRNAs (miRNAs) in multiple sclerosis (MS) compared to healthy controls, few studies have evaluated the association of genetic variants of miRNAs with MS clinical course. We investigated whether a functional polymorphism in the MS associated miR-146a gene predicted clinical course (hazard of conversion to MS and of relapse, and annualized change in disability), using a longitudinal cohort study of persons with a first demyelinating event followed up to their 5-year review. We found the genotype (GC+CC) of rs2910164 predicted relapse compared with the GG genotype (HR=2.09 (95% CI 1.42, 3.06), p=0.0001), as well as a near-significant (p=0.07) association with MS conversion risk. Moreover, we found a significant additive interaction between rs2910164 and baseline anti-EBNA-1 IgG titers predicting risk of conversion to MS (relative excess risk due to interaction [RERI] 2.39, p=0.00002) and of relapse (RERI 1.20, p=0.006). Supporting these results, similar results were seen for the other EBV-correlated variables: anti-EBNA-2 IgG titers and past history of infectious mononucleosis. There was no association of rs2910164 genotype for disability progression. Our findings provide evidence for miR-146a and EBV infection in modulating MS clinical course.
Publisher: Wiley
Date: 24-09-2018
DOI: 10.1111/ENE.13786
Abstract: 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. 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. 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. 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.
Publisher: SAGE Publications
Date: 14-07-2020
Abstract: We need high-quality data to assess the determinants for COVID-19 severity in people with MS (PwMS). Several studies have recently emerged but there is great benefit in aligning data collection efforts at a global scale. Our mission is to scale-up COVID-19 data collection efforts and provide the MS community with data-driven insights as soon as possible. Numerous stakeholders were brought together. Small dedicated interdisciplinary task forces were created to speed-up the formulation of the study design and work plan. First step was to agree upon a COVID-19 MS core data set. Second, we worked on providing a user-friendly and rapid pipeline to share COVID-19 data at a global scale. The COVID-19 MS core data set was agreed within 48 hours. To date, 23 data collection partners are involved and the first data imports have been performed successfully. Data processing and analysis is an on-going process. We reached a consensus on a core data set and established data sharing processes with multiple partners to address an urgent need for information to guide clinical practice. First results show that partners are motivated to share data to attain the ultimate joint goal: better understand the effect of COVID-19 in PwMS.
Publisher: American Physical Society (APS)
Date: 10-10-2013
Publisher: Society of Exploration Geophysicists
Date: 09-2012
Publisher: Wiley
Date: 19-02-2013
DOI: 10.1111/PHP.12044
Abstract: Spatio-temporal patterns in sun exposure underlie variations in skin cancer incidence and vitamin D deficiency, indicate effectiveness of sun protection programs and provide insights into future health risks. From 558 adults across four regions of Australia (Brisbane (27°S), Newcastle (33°S), Geelong and the Western Districts of Victoria (37°S) and Tasmania (43°S)), we collected: self-report data on time-in-the-sun from age 6 years natural skin color and ethnicity silicone skin casts (for cumulative skin damage) and serum for vitamin D status. Ambient ultraviolet radiation (UVR) at the location of residence, with time-in-the-sun, was used to calculate a "UVR dose" for each year of life. In iduals maintained their ranking compared to their peers for time-in-the-sun in summer compared to winter and across ages (Spearman rho 0.24-0.84, all P < 0.001). Time-in-the-sun decreased with age in all birth cohorts, and over calendar time. Summer time-in-the-sun increased with increasing latitude (P < 0.001). Seasonal variation in vitamin D status had greater litude and vitamin D deficiency increased with increasing latitude. Temporal patterns are consistent with effectiveness of sun protection programs. Higher relative time-in-the-sun persists from childhood through adulthood. Lower summer time-in-the-sun in the warmest location may have implications for predictions of UVR-related health risks of climate change.
Publisher: SAGE Publications
Date: 22-06-2013
Abstract: Anxiety, depression and fatigue are commonly reported by persons with multiple sclerosis (PwMS). We estimated the prevalence of each factor in a representative s le 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. 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). 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, - 0.05). All three factors occurred contemporaneously at cohort entry in a higher proportion of the cohort than expected by chance (p<0.001). 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.
Publisher: American Association for Cancer Research (AACR)
Date: 08-2006
DOI: 10.1158/1055-9965.EPI-05-0969
Abstract: Background: Measurement of past sun exposure through recall by adults has the potential for measurement error. We aimed to investigate aspects of validity and reliability of self-reported past sun exposure. Methods: A population-based case-control study was conducted in Tasmania on 136 cases with multiple sclerosis and 272 age- and sex-matched community controls. Repeat interviews on 52 cases and 52 controls were done on average 11 weeks after the initial interview. Sun exposure was assessed by questionnaire and lifetime calendar. Other measurements included serum 25-hydroxyvitamin D, actinic damage, and skin phenotype. Results: There was an association between recent sun exposure and serum vitamin D (time in the sun: r = 0.22, P & 0.01 activities outside: r = 0.31, P & 0.01 for controls) and between lifetime sun exposure and actinic damage [correlation between 0.34 (P & 0.01) and 0.17 (P = 0.01) for controls]. The test-retest weighted κ statistic of self-reported sun exposure ranged from 0.43 to 0.74. Recall of childhood/adolescent sun exposure by standardized questioning was no less reproducible than recall of recent adult sun exposure and no less reliable when made with the calendar method. Comparing the questionnaire and calendar method, the measures of childhood/adolescent sun exposure had a similar predictive validity for multiple sclerosis. Conclusions: The results of this study provide further evidence that adults are able to recall past sun exposure with shown validity and reliability and present information about the possible reasons for the good reliability of recalled sun exposure measures. (Cancer Epidemiol Biomarkers Prev 2006 (8):1538–44)
Publisher: Wiley
Date: 20-12-2016
Abstract: Patients presenting with clinically isolated syndrome (CIS) may proceed to clinically definite multiple sclerosis (CDMS). Midsagittal corpus callosum area (CCA) is a surrogate marker for callosal atrophy, and can be obtained from a standard MRI study. This study explores the relationship between CCA measured at CIS presentation (baseline) and at 5 years post presentation, with conversion from CIS to CDMS. The association between CCA and markers of disability progression is explored. Corpus callosum area was measured on MRI scans at presentation and 5-year review following diagnosis of a first demyelinating event, or evidence of progressive MS, in 143 participants in the Ausimmune/AusLong Study. Relationships between CCA (at baseline and follow-up) and clinical outcomes were assessed. Mean CCA at baseline study was 6.63 cm Baseline CCA obtained from standard MRI protocols may be compared with subsequent MRI examinations as a surrogate for neurodegeneration and cerebral atrophy in patients with MS. This study demonstrates an association between CCA and disability in in iduals presenting with CIS who convert to MS.
Publisher: Frontiers Media SA
Date: 20-03-2018
Publisher: Wiley
Date: 23-03-2023
DOI: 10.1002/HPJA.716
Abstract: Evaluated the impact of the Understanding Multiple Sclerosis (MS) massive open online course, which was intended to increase understanding and awareness about MS, on self‐reported health behaviour change 6 months after course completion. Observational cohort study evaluating precourse(baseline) and postcourse (immediately postcourse and six‐month follow‐up) survey data. The main study outcomes were self‐reported health behaviour change change type and measurable improvement. We also collected participant characteristic data (eg, age, physical activity). We compared participants who reported health behaviour change at follow‐up to those who did not and compared those who improved to those who did not using χ 2 and t tests. Participant characteristics, change types and change improvement were described descriptively. Consistency between changes reported immediately postcourse and at the 6‐month follow‐up was assessed using χ 2 tests and textual analysis. N = 303 course completers were included in this study. The study cohort included MS community members (eg, people with MS, healthcare providers) and nonmembers. N = 127 (41.9%) reported behaviour change in ≥1 area at follow‐up. Of these, 90 (70.9%) reported a measured change, and of these, 57 (63.3%) showed improvement. The most reported change types were knowledge, exercise hysical activity and diet. N = 81 (63.8% of those reporting a change) reported a change in both immediately and 6 months after course completion, with 72.0% of those that described both changes giving similar responses each time. Understanding MS encourages health behaviour change among course completers up to 6 months after course completion. An online education intervention can effectively encourage health behaviour change over a 6‐month follow‐up period, suggesting a transition from acute change to maintenance. The primary mechanisms underpinning this effect are information provision, including both scientific evidence and lived experience, and goal‐setting activities and discussions.
Publisher: BMJ
Date: 10-2022
DOI: 10.1136/BMJOPEN-2022-062703
Abstract: Generic multiattribute utility instruments (MAUIs) are efficient tools for determining and enumerating health-related quality of life. MAUIs accomplish this by generating health state utilities (HSUs) via algorithms. Minimal important differences (MIDs) assist with the interpretation of HSUs by estimating minimum changes that are clinically significant. The overall goal of the proposed systematic review and meta-analysis is the development of comprehensive guidelines for MID estimation. This protocol defines a systematic review and meta-analysis of MIDs for generic MAUIs. The proposed research will involve a comprehensive investigation of 10 databases (EconLit, IDEAs database, INAHTA database, Medline, PsycINFO, Embase, Emcare, JBIEBP and CINAHL) from 1 June 2022 to 7 June 2022, and will be performed and reported in accordance with several validated guidelines, principally the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The quality of papers, considered for inclusion in the review, will be appraised using the COnsensus-based Standards for the selection of health Measurement INstruments, inter alia. Narrative analysis will involve identifying the characteristics of MIDs including methods of calculation, sources of heterogeneity, and validation. Meta-analysis will also be conducted. The descriptive element of meta-analysis will involve the generation of I 2 statistics and Galbraith plots of MID heterogeneity. Together with narrative analysis, this will allow sources of MID heterogeniety to be identified. A multilevel mixed model, estimated via restricted maximum likelihood estimation, will be constructed for the purposes of meta-regression. Meta-regression will attempt to enumerate the effects of sources of heterogeneity on MID estimates. Meta-analysis will be concluded with pooling of MIDs via a linear random-effects model. Ethics approval is not required for this review, as it will aggregate data from published literature. Methods of dissemination will include publication in a peer-reviewed journal, as well as presentation at conferences and seminars. CRD42021261821.
Publisher: BMJ
Date: 03-11-2016
Abstract: Age at onset (AAO) in multiple sclerosis (MS) is an important marker of disease severity and may have prognostic significance. Understanding what factors can influence AAO may shed light on the aetiology of this complex disease, and have applications in the diagnostic process. The study cohort of 22 162 eligible patients from 21 countries was extracted from the MSBase registry. Only patients with MS aged ≥16 years were included. To reduce heterogeneity, only centres of largely European descent were included for analysis. AAO was defined as the year of the first symptom suggestive of inflammatory central nervous system demyelination. Predictors of AAO were evaluated by linear regression. Compared with those living in lower latitudes (19.0-39.9°), onset of symptoms was 1.9 years earlier for those at higher latitudes (50.0-56.0°) (p=3.83×10 An earlier AAO in higher latitude regions was found in this worldwide European-descent cohort and correlated inversely with variation in latitudinal UVR. These results suggest that environmental factors which act at the population level may significantly influence disease severity characteristics in genetically susceptible populations.
Publisher: Elsevier BV
Date: 09-2021
Publisher: Wiley
Date: 13-08-2023
DOI: 10.1111/ENE.16016
Abstract: 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 in iduals with a first clinical diagnosis of central nervous system demyelination (FCD). 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. 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. 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 in iduals with a greater disability and a higher relapse count are at higher risk of losing employment.
Publisher: Elsevier BV
Date: 12-2002
DOI: 10.1016/S0300-483X(02)00257-3
Abstract: This review examines the epidemiological evidence that suggests ultraviolet radiation (UVR) may play a protective role in three autoimmune diseases: multiple sclerosis, insulin-dependent diabetes mellitus and rheumatoid arthritis. To date, most of the information has accumulated from population studies that have studied the relationship between geography or climate and autoimmune disease prevalence. An interesting gradient of increasing prevalence with increasing latitude has been observed for at least two of the three diseases. This is most evident for multiple sclerosis, but a similar gradient has been shown for insulin-dependent diabetes mellitus in Europe and North America. Seasonal influences on both disease incidence and clinical course and, more recently, analytical studies at the in idual level have provided further support for a possible protective role for UVR in some of these diseases but the data are not conclusive. Organ-specific autoimmune diseases involve Th1 cell-mediated immune processes. Recent work in photoimmunology has shown ultraviolet B (UVB) can specifically attenuate these processes through several mechanisms which we discuss. In particular, the possible contribution of an UVR-induced increase in serum vitamin D (1,25(OH)2D3) levels in the beneficial immunomodulation of these diseases is discussed.
Publisher: Informa UK Limited
Date: 20-09-2021
DOI: 10.1080/14737175.2021.1978843
Abstract: Environmental factors play a significant role in the pathogenesis and progression of multiple sclerosis (MS), either acting alone or by interacting with other environmental or genetic factors. This cumulative exposure to external risk factors is highly complex and highly variable between in iduals. We narratively review the current evidence on the role of environment-specific risk factors in MS onset and progression, as well as the effect of gene-environment interactions and the timing of exposure We have reviewed the latest literature, by Ovid Medline, retrieving the most recently published systematic reviews and/or meta-analyses and more recent studies not previously included in meta-analyses or systematic reviews. There is some good evidence supporting the impact of some environmental risk factors in increasing the risk of developing MS. Tobacco smoking, low vitamin D levels and/or low sun exposure, Epstein Barr Virus (EBV) seropositivity and a history of infectious mononucleosis may increase the risk of developing MS. Additionally, there is some evidence that gene-smoking, gene-EBV, and smoking-EBV interactions additively affect the risk of MS onset. However, the evidence for a role of other environmental factors in MS progression is limited. Finally, there is some evidence that tobacco smoking, insufficient vitamin D levels and/or sun exposure have impacts on MS phenotypes and various markers of disease activity including relapse, disability progression and MRI findings. Clearly the effect of environmental factors on MS disease course is an area that requires significantly more research.
Publisher: Elsevier
Date: 2020
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1093/JN/NXZ089
Abstract: The evidence associating diet and risk of multiple sclerosis (MS) is inconclusive. The aim of this study was to investigate associations between a Mediterranean diet and risk of a first clinical diagnosis of central nervous system demyelination (FCD), a common precursor to MS. We used data from the 2003-2006 Ausimmune Study, an Australian multicenter, case-control study examining environmental risk factors for FCD, with participants matched on age, sex, and study region (282 cases, 558 controls 18-59 y old 78% female). The alternate Mediterranean diet score (aMED) was calculated based on data from a food-frequency questionnaire. We created a modified version of the aMED (aMED-Red) where ∼1 daily serving (65 g) of unprocessed red meat received 1 point. All other components remained the same as aMED. Conditional logistic regression (254 cases, 451 controls) was used to test associations between aMED and aMED-Red scores and categories and risk of FCD, adjusting for history of infectious mononucleosis, serum 25-hydroxyvitamin D concentrations, smoking, education, total energy intake, and dietary underreporting. There was no statistically significant association between aMED and risk of FCD [per 1-SD increase in aMED score: adjusted odds ratio (aOR): 0.89 95% CI: 0.75, 1.06 P = 0.181]. There was evidence of a nonlinear relation between aMED-Red and risk of FCD when a quadratic term was used (P = 0.016). Compared with the lowest category of aMED-Red, higher categories were significantly associated with reduced risk of FCD, corresponding to a 37% (aOR: 0.63 95% CI: 0.41, 0.98 P = 0.039), 52% (aOR: 0.48 95% CI: 0.28, 0.83 P = 0.009), and 42% (aOR: 0.58 95% CI: 0.35, 0.96 P = 0.034) reduced risk of FCD in categories 2, 3, and 4, respectively. A Mediterranean diet, including unprocessed red meat, was associated with reduced risk of FCD in this Australian adult population. The addition of unprocessed red meat to a Mediterranean diet may be beneficial for those at high risk of MS.
Publisher: BMJ
Date: 02-08-2017
Abstract: People with multiple sclerosis (PwMS) commonly use complementary and alternative medicines (CAM), but an understanding of their efficacy is lacking. Here, we quantitatively review the class I and class II studies of treatment efficacy for multiple sclerosis from January 2001 to January 2017, in order to assess the modern evidence for CAM use. The 38 studies included in this review are ided across five CAM types (cannabis, diet, exercise, psychological approaches and other). We found little evidence to support CAM efficacy. The studies contained little replication in intervention, primary outcomes or study design. Six of 16 CAMs included in this review were only researched in a single study. Future work in this area should build consensus around study methodologies and primary outcomes.
Publisher: American Medical Association (AMA)
Date: 04-05-2005
Publisher: American Medical Association (AMA)
Date: 04-05-2005
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-07-2011
Publisher: Wiley
Date: 28-12-2020
DOI: 10.1111/JGH.14924
Abstract: The prevalence of primary biliary cholangitis (PBC) reported in different countries varies significantly and in some parts of the world appears to be increasing. The aim of this study was to determine the 2013 prevalence of PBC in Victoria, Australia, and to determine the time trend by comparing it with previous studies undertaken in 1991 and 2002. Four case-finding methods were used to identify cases of PBC in Victoria: (1) physicians' survey (2) tertiary hospital search (3) liver transplant database search and (4) private pathology antimitochondrial antibody search. The prevalence of PBC in Victoria, Australia, is 189.0 per million using all four methods. The average annual increase in prevalence from 1991 to 2013 was 7.7 per million per year. Using the same case-finding methods as the 1991 Victorian prevalence study (methods 1 and 2), the prevalence of PBC increased from 19.1 per million in 1991 to 49.4 per million in 2002 (P < 0.001) and to 80.7 per million in 2013 (P < 0.001). The current prevalence of PBC in Victoria is significantly higher than previously reported. The use of private pathology-based case-finding methods is important in identifying the maximum number of PBC cases.
Publisher: Springer Science and Business Media LLC
Date: 02-09-2021
Publisher: Wiley
Date: 2008
DOI: 10.1002/PDS.1593
Abstract: 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. This longitudinal prospective study followed a population-based cohort (n = 199) of definite MS patients in Southern Tasmania (January 2002 to April 2005, source population 226 559) every 6 months. Baseline factors (demographic, clinical, psychological and cognitive) affecting adherence were examined by logistic regression and a longitudinal analysis (generalized estimating equation (GEE)). Of the 97 patients taking an IMD (mean follow-up = 2.4 years), 73% (71/97) missed doses, with 1 in 10 missing > 10 doses in any 6-month period. Missed doses were positively associated with alcohol amount consumed per session (p = 0.008). A history of missed doses predicted future missed doses (p < 0.0005). Over one-quarter (27/97) stopped their current IMD, which was associated with lower education levels (p = 0.032) and previous relapses (p = 0.05). No cognitive or psychological test predicted adherence. There were few strong predictors of missed doses, although people with MS consuming more alcoholic drinks per session are at a higher risk of missing doses. Divergent factors influenced the two levels of non-adherence indicating the need for a multifaceted approach to improving IMD adherence. In addition, missed doses should be assessed and incorporated into clinical trial design and clinical practice as poor adherers could impact on clinical outcomes.
Publisher: Bentham Science Publishers Ltd.
Date: 06-02-2018
DOI: 10.2174/1573406413666170921143600
Abstract: Multiple sclerosis (MS) is a progressive, demyelinating condition of the central nervous system, manifesting in loss or alterations in function of sensory, motor and cognitive function. Of the various environmental and behavioural risk factors identified as playing a role in MS onset and progression, perhaps none has been as consistent as vitamin D. In this review, we will endeavour to present a general background on the role of vitamin D in human health and particularly in MS, as well as the substantial epidemiological evidence in support of vitamin D's role in MS. Initially identified via the oft-noted latitudinal gradient in MS prevalence and incidence, vitamin D has since been demonstrated to have a strong and consistent inverse association with MS risk and clinical course. Cases have much lower levels of the diagnostic metabolite of vitamin D, 25- hydroxyvitamin D (25(OH)D) compared to healthy controls, while those with more active disease have lower levels of 25(OH)D than other cases with less active disease. These case-control and crosssectional study results led the way to cohort studies which indicated significant inverse associations between serum 25(OH)D and clinical activity in MS. The combined weight of indirect and direct observational evidence have been the impetus for completed and ongoing randomised trials of vitamin D supplementation, alone or in addition to standard immunomodulatory medications, as an intervention in MS onset and clinical course. Moreover, in addition to being a distinct factor in MS aetiology, vitamin D has been demonstrated to interact with a variety of other risk factors, from genetic predictors like HLA-DR1 genotype to behavioural factors like smoking. There is an abundance of epidemiological evidence, both direct and indirect, as well as significant biological plausibility substantiating a role for vitamin D in the onset and progression of multiple sclerosis.
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.MSARD.2016.08.015
Abstract: There exists inconsistent evidence regarding animals including pets as risk factors for the development of Multiple Sclerosis (MS). We investigated the association between farm animals and pets as possible environmental factors in MS development. Population based case-control study with 136 clinically definite MS cases and 272 controls randomly chosen from the community matched on sex and age. Data was collected from both questionnaire and a lifetime calendar detailing residence, occupation and pet/animal exposure over the course of participant's lives. Exposure to farming, livestock, specific farm animals and remoteness of residence showed no significant association with MS risk. Exposure to cats prior to disease onset was associated with a greater risk of MS (Adjusted Odds Ratio 2.46 (1.17-5.18)) but without a clear dose-response (test for trend, p=0.76). In contrast to other literature, farming and exposure to farm animals were not associated with MS. While we identified an association between cat exposure and MS, there was no dose-response relationship, and previous studies showed inconsistent results, leaving us to conclude that there is no strong evidence that exposure to cats is associated with MS.
Publisher: BMJ
Date: 26-10-2023
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-08-2008
DOI: 10.1212/01.WNL.0000323928.57408.93
Abstract: Low past sun exposure, fair skin type, and polymorphisms of the MC1R gene have been associated with multiple sclerosis (MS) risk. We aimed to investigate the interplay between melanocortin 1 receptor gene variants, red hair/fair skin phenotype, and past environmental sun exposure in MS. Population-based case-control study in Tasmania, Australia, involving 136 cases with MS and 272 controls randomly drawn from the community and matched on sex and year of birth. Measures included past sun exposure by calendar and questionnaire, spectrophotometric skin type, and MC1R genotype, with any MC1R Arg151Cys, Arg160Trp, or Asp294His alleles present denoted as red hair color (RHC) variant. The association between RHC variant genotype and MS was more evident for women (odds ratio 2.02 [1.15-3.54]) than for men (odds ratio 0.65 [0.27-1.57]) (difference in effect, p = 0.03). The RHC variant genotype was associated with behavioral sun avoidance. In addition, increasing summer sun exposure at ages 6 through 10 years was associated with reduced MS risk among those with no RHC variant (p = 0.03), but not among those with RHC variant genotype (p = 0.15 difference in effect, p = 0.02). Similar findings were evident for other past sun exposure measures and when the s le was restricted to women only. The interplay between red hair color variant genotype, red hair/fair skin phenotype, and multiple sclerosis (MS) is complex. The modification of past sun exposure by MC1R genotype provides further support that ultraviolet radiation or derivatives such as vitamin D may be causally related to a reduced MS risk.
Publisher: BMJ
Date: 19-06-2018
Abstract: The direct comparative evidence on treatment effects of available multiple sclerosis (MS) disease-modifying therapies (DMTs) is limited, and few studies have examined the benefits of DMTs on employment outcomes. We compared the effects of DMTs used in the previous 5 years on improving the work attendance, amount of work and work productivity of people with MS. The Australian MS Longitudinal Study collected data from participants on DMTs usage from 2010 to 2015 and whether DMTs contributed to changes in employment outcomes. We classified 11 DMTs into three categories based on their clinical efficacy (β-interferons and glatiramer acetate as category 1 teriflunomide and dimethyl fumarate as category 2 fingolimod, natalizumab, alemtuzumab and mitoxantrone as category 3). Each DMT used by a participant was treated as one observation and analysed by log-multinomial regression. Of the 874 participants included, 1384 observations were generated. Those who used category 3 (higher efficacy) DMTs were 2–3 times more likely to report improvements in amount of work, work attendance and work productivity compared with those who used category 1 (classical injectable) DMTs. Natalizumab was associated with superior beneficial effects on patient-reported employment outcomes than fingolimod (RR=1.76, 95% CI 1.02 to 3.03 for increased work attendance and RR=1.46, 95% CI 1.02 to 2.10 for increased work productivity). Those using the higher efficacy (category 3) DMTs, particularly fingolimod and natalizumab, reported significant increases in amount of work, work attendance and work productivity, suggesting they have important beneficial effects on work life in people with MS.
Publisher: Elsevier BV
Date: 09-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-03-2012
Publisher: SAGE Publications
Date: 24-11-2017
Abstract: Previous studies have documented far lower employment participation rates for people with multiple sclerosis (PwMS) compared to the general population. In a large national s le of PwMS, we examined employment status, longitudinal changes in employment and the provision of modifications to work role/environment from 2010 to 2013. Employment data were collected through the Australian MS Longitudinal Study from 2010 to 2013, with 1260 people responding to all four surveys. Employment rates were compared with the Australian general population. The survey included questions on the provision of modifications to employees’ work role and work environment. Employment (full- and part-time) increased from 48.8% in 2010 to 57.8% in 2013, mainly due to increases in male full-time employment. The employment gap between PwMS and the general population fell from 14.3% in 2010 to 3.5% in 2013. Male employment rates, however, remain significantly lower than the general population. The majority of PwMS who required adjustments to either their work role or environment received them. The gap in employment between PwMS and the general population has substantially reduced from 2010 to 2013, with organisations responding positively to requests for work role/environment adjustments.
Publisher: Informa UK Limited
Date: 12-2012
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.MSARD.2021.103428
Abstract: While a number of studies have examined associations between dietary factors and risk of multiple sclerosis (MS), little is known about intakes of inflammation-modulating foods and nutrients and risk of MS. To test associations between the Dietary Inflammatory Index (DII®) and risk of a first clinical diagnosis of central nervous system (CNS) demyelination (FCD) (267 cases, 507 controls) using data from the Ausimmune Study. The 2003-2006 Ausimmune Study was a multicentre, matched, case-control study examining environmental risk factors for an FCD, a common precursor to MS. The DII is a well-recognised tool that categorises in iduals' diets on a continuum from maximally anti-inflammatory to maximally pro-inflammatory. The DII score was calculated from dietary intake data collected using a food frequency questionnaire. Conditional logistic regression models were used to estimate the association between DII and FCD separately for men and women. In women, a higher DII score was associated with increased likelihood of FCD, with a 17% increase in likelihood of FCD per one-unit increase in DII score (adjusted odds ratio 1.17, 95% confidence interval 1.04-1.33). There was no association between DII and FCD in men (adjusted odds ratio 0.88, 95% confidence interval 0.73-1.07). These findings suggest that a pro-inflammatory diet is associated with an increased likelihood of FCD in women.
Publisher: Hindawi Limited
Date: 14-10-2015
DOI: 10.1111/ANE.12315
Abstract: To investigate whether those genes involved in the vitamin D pathway modulate the relationship between 25-hydroxyvitamin D (25(OH)D) and IFN-β, the relationship between IFN-β and sun in predicting 25(OH)D, and the interaction between IFN-β and 25(OH)D in modulating relapse risk in patients with MS. Prospective cohort study of 169 participants with MS and genotype data followed 2002-2005. Gene-IFN-β and gene-IFN-β-sun interactions predicting 25(OH)D evaluated by multilevel mixed-effects linear regression. Gene-IFN-β interactions with 25(OH)D in modulating in relapse risk assessed using survival analysis. 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-β-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-β in predicting 25(OH)D by level of rs10767935, although this did not reach statistical significance. No SNPs modified the interaction between IFN-β and 25(OH)D in predicting relapse. We have demonstrated that two-independent SNPs (rs10767935 and rs5030244) in WT1 modified the IFN-β-25(OH)D association in patients with MS. Some evidence was shown for a difference in the sun-IFN-β-25(OH)D association by level of rs10767935. These findings indicate that WT1 variants may play a role in altering the effects of IFN-β on vitamin D in MS.
Publisher: SAGE Publications
Date: 11-11-2020
Abstract: High-quality epidemiologic data worldwide are needed to improve our understanding of disease risk, support health policy to meet the erse needs of people with multiple sclerosis (MS) and support advocacy efforts. The Atlas of MS is an open-source global compendium of data regarding the epidemiology of MS and the availability of resources for people with MS reported at country, regional and global levels. Country representatives reported epidemiologic data and their sources via survey between September 2019 and March 2020, covering prevalence and incidence in males, females and children, and age and MS type at diagnosis. Regional analyses and comparisons with 2013 data were conducted. A total of 2.8 million people are estimated to live with MS worldwide (35.9 per 100,000 population). MS prevalence has increased in every world region since 2013 but gaps in prevalence estimates persist. The pooled incidence rate across 75 reporting countries is 2.1 per 100,000 persons/year, and the mean age of diagnosis is 32 years. Females are twice as likely to live with MS as males. The global prevalence of MS has risen since 2013, but good surveillance data is not universal. Action is needed by multiple stakeholders to close knowledge gaps.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-04-2010
Publisher: Public Library of Science (PLoS)
Date: 26-11-2013
Publisher: SAGE Publications
Date: 18-06-2019
Abstract: Little is known about the work productivity loss in multiple sclerosis (MS). To quantify the MS-related work productivity loss and to compare factors associated with labour force participation and work productivity loss. 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. 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. 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.
Publisher: SAGE Publications
Date: 08-2007
Abstract: Rising multiple sclerosis incidence over the last 50 years and geographic patterns of occurrence suggest an environmental role in the causation of this multifactorial disease. Design options for epidemiological studies of environmental causes of multiple sclerosis are limited by the low incidence of the disease, possible diagnostic delay and budgetary constraints. We describe scientific and methodological issues considered in the development of the Australian Multicentre Study of Environment and Immune Function (the Ausimmune Study), which seeks, in particular, to better understand the causes of the well-known MS positive latitudinal gradient. A multicentre, case-control design down the eastern seaboard of Australia allows the recruitment of sufficient cases for adequate study power and provides data on environmental exposures that vary by latitude. Cases are persons with an incident first demyelinating event (rather than prevalent multiple sclerosis), sourced from a population base using a two tier notification system. Controls, matched on sex, age (within two years) and region of residence, are recruited from the general population. Biases common in case-control studies, eg, prevalence-incidence bias, admission-rate bias, non-respondent bias, observer bias and recall bias, as well as confounding have been carefully considered in the study design and conduct of the Ausimmune Study. Multiple Sclerosis 2007 13 : 827—839. msj.sagepub.com
Publisher: SAGE Publications
Date: 04-2004
DOI: 10.1191/1352458504MS1006OA
Abstract: Evolving information techno logy has raised the possibility of new methods of data collection in multiple sclerosis (MS) research. A n anonymous, self-report, Internet-based survey was developed, which asked people with MS their opinion on how various extrinsic factors affected their condition. From September 2001 to July 2002, a total of 2529 people completed the questionnaire. The demographic and clinical profiles of the anonymous respondents indicated that most were likely to have MS. C ommon factors reported as beneficial were cannabis, cold baths, meditation and dietar y factors. C ommon adverse factors reported were high stress, exposure to high temperatures and viral infections. There was an increasing report of high temperatures as being adverse with increasing respondent age (test for trend, P B-0.001). The adverse report of high temperatures correlated significantly with the report of strong sunlight apparently making MS worse (r =0.35, P B-0.0001). In A ustralia, high temperatur es were more likely to be reported as adverse in warmer, lower latitude regions. The association between strong sunlight as adverse and age or region did not persist after adjustment for high temperatures. Thus, this apparent adverse factor appeared to relate to solar heat, not solar light. People with MS may risk vitamin D deficiency because of sun avoidance due to heat-related fatigue or intolerance. This is of clinical significance not only for bone health but because vitamin D may have beneficial immunomodulatory properties. The present study provides new information from people with MS on factors that may influence symptoms or clinical course. This information will now be used in the design of formal epidemiological cohort studies.
Publisher: Elsevier BV
Date: 05-2018
DOI: 10.1016/J.MSARD.2018.03.022
Abstract: Although low sun exposure, low vitamin D, and smoking are established risk factor of multiple sclerosis (MS), there is less evidence on the role of the other lifestyle factors. We examined the association of sun exposure, physical activity, drug abuse, and alcohol intake with MS. This was population-based incident case-control study in Iran with 547 incident cases and 1057 general population controls (7/8/2013-17/2/2015). Logistic regression was used to analyse the data. Higher sun exposure during adolescence was associated with a reduced risk of MS, both in summer (test for trend p < 0.001) and winter (P < 0.001), while physical activity was not associated with MS (test for trend p = 0.712). Lifetime drug abuse (OR for ever use 2.93 (1.83-4.70)), with a dose-response association (test for trend p < 0.001), and alcohol intake (OR for ever use 1.49 (1.05-2.12)) was significantly associated with an increased risk of MS. In a middle-eastern setting, we found that sun exposure during adolescence, drug abuse, and alcohol use were all associated with MS. Increasing sun exposure and reducing drug abuse and the use of alcohol through educational programs is likely to reduce the rate of MS.
Publisher: American Society of Civil Engineers
Date: 18-06-2013
Publisher: Informa UK Limited
Date: 06-06-2023
DOI: 10.1080/09638288.2022.2082564
Abstract: Physical activity (PA) participation offers many benefits for persons with multiple sclerosis (MS). Persons with MS are significantly less active than the general population however, there is insufficient evidence regarding the association between geographical remoteness and PA participation in persons with MS. We identify PA levels across levels of rurality in an Australian MS population. The Australian MS Longitudinal Study collects regular survey data from persons with MS in Australia, including demographic, clinical, and health behavioural data. Physical activity engagement was identified with the International Physical Activity Questionnaire-short form and geographical remoteness was identified from participants' postcode using the Access and Remoteness Index for Australia. Hurdle regression analysis examined the relationship between remoteness and PA participation, and level of PA, after controlling for confounding. Data from 1260 respondents showed that 24% of persons with MS did not participate in any PA. Remoteness was not associated with the participation in any PA (OR 1.04 89% highest density probability interval (HDPI) estimate 0.88, 1.22). Amongst those with any PA ( Physical activity promotion does not need to differ based on geographical location. Implications for rehabilitationAlmost one quarter of persons with MS in our study recorded no participation in any physical activity (PA).Healthcare practitioners are encouraged to include the promotion of PA as part of MS management.Physical activity participation is similar for persons with MS across different geographical locations.Physical activity promotion does not need to differ based on geographical location.
Publisher: S. Karger AG
Date: 2001
DOI: 10.1159/000054783
Abstract: The aim of this study was to conduct an ecological analysis of the extent to which ultraviolet radiation (UVR) levels might explain the regional variation of multiple sclerosis (MS) in Australia. MS prevalence data for six Australian regions were compared with UVR levels of the largest city in each region, with some other climatic variables and with the melanoma incidence in the same regions. A close association was found between the theoretical MS prevalence predicted from UVR levels and the actual prevalence. Furthermore, the negative correlation between UVR and MS prevalence (r = –0.91, p = 0.01) was higher than the positive correlation observed for UVR and malignant melanoma incidence (r = 0.75, p = 0.15 for males and r = 0.80, p = 0.10 for females). This study demonstrated that the regional variation in MS prevalence in the continent of Australia could be closely predicted by regional UVR levels. It is consistent with the hypothesis that UVR exposure may reduce the risk of MS possibly via T-lymphocyte-mediated immunosuppression. Analytical epidemiology studies are required to investigate this specific hypothesis.
Publisher: SAGE Publications
Date: 26-07-2019
Abstract: 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. 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 iding 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. 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. Consistent with global trends, Australia’s MS prevalence has increased this probably reflecting decreased mortality, increased longevity and increased incidence.
Publisher: Springer Science and Business Media LLC
Date: 12-2014
DOI: 10.1039/C4PP00322E
Abstract: 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.
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.JNS.2014.11.019
Abstract: We reviewed the evidence for the co-occurrence of type 1 diabetes mellitus (T1D) and multiple sclerosis (MS), and assessed the clinical significance of this association and the shared aetiological features of the two diseases. T1D and MS contribute considerably to the burden of autoimmune diseases in young adults. The co-occurrence of MS and T1D has been reported by a number of studies, suggesting that the two conditions share one or more aetiological components. Both conditions have been associated with distinct human leukocyte antigen (HLA) haplotypes but share a number of similarities in clinical, epidemiological and immunological features, leading to suggestions of possible common mechanisms of development. While underlying genetic factors may be important for the co-occurrence of both conditions, some evidence suggests that environmental factors such as vitamin D deficiency may also modulate an in idual's risk for the development of both conditions. Evidence on whether the co-occurrence of the two autoimmune conditions will affect the disease course and severity of MS is merely absent. Further studies need to be conducted to ascertain whether the neuropathology associated with T1D might influence the disease course and contribute to the severity of MS.
Publisher: Society of Exploration Geophysicists
Date: 07-2015
Abstract: A key objective of stage 2 of the Cooperative Research Centre for Greenhouse Gas Technologies (CO2CRC) Otway Project is to explore the ability of the seismic reflection method to detect and monitor injection of a small amount of greenhouse gas into a saline formation. Development of a seismic monitoring program requires an understanding of expected time-lapse (TL) seismic signals. Hence, before such an injection experiment is undertaken, we assessed the feasibility of seismic monitoring in a modeling study. Considering realistic gas distributions inferred from reservoir simulations, we analyzed the influence of various factors (injection volume, time after injection, and realizations of the reservoir flow model) on the TL seismic signal. However, the applicability of seismic monitoring depends not only on the strength of the TL seismic signal but also on the noise level of the seismic data. Hence, to estimate the detectability of gas in the subsurface, we have developed a workflow that integrated actual data repeatability observed at the Otway test site into the seismic feasibility study. Although we observed differences between the considered scenarios, all of the scenarios indicated a high likelihood of successful plume detection with the observed noise level and surface 4D seismic acquisition geometry used in stage 1 of the CO2CRC Otway Project at the same site. However, a thin layer of gas spreading out from the edges of the main plume below the seal in all scenarios would be a challenge for surface seismic monitoring.
Publisher: Wiley
Date: 08-2010
DOI: 10.1002/ANA.22043
Abstract: 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. 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. 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 10 nmol/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 10 nmol/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 10 nmol/l increase (p = 0.001). Adjusting for potential confounders did not alter these findings. 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 10 nmol/l increase in 25-OH-D resulting in up to a 12% reduction in risk of relapse. Clinically, raising 25-OH-D levels by 50 nmol/l could halve the hazard of a relapse.
Publisher: BMJ
Date: 24-08-2016
Abstract: The genetic drivers of multiple sclerosis (MS) clinical course are essentially unknown with limited data arising from severity and clinical phenotype analyses in genome-wide association studies. Prospective cohort study of 127 first demyelinating events with genotype data, where 116 MS risk-associated single nucleotide polymorphisms (SNPs) were assessed as predictors of conversion to MS, relapse and annualised disability progression (Expanded Disability Status Scale, EDSS) up to 5-year review (ΔEDSS). Survival analysis was used to test for predictors of MS and relapse, and linear regression for disability progression. The top 7 SNPs predicting MS/relapse and disability progression were evaluated as a cumulative genetic risk score (CGRS). We identified 2 non-human leucocyte antigen (HLA rs12599600 and rs1021156) and 1 HLA (rs9266773) SNP predicting both MS and relapse risk. Additionally, 3 non-HLA SNPs predicted only conversion to MS 1 HLA and 2 non-HLA SNPs predicted only relapse and 7 non-HLA SNPs predicted ΔEDSS. The CGRS significantly predicted MS and relapse in a significant, dose-dependent manner: those having ≥5 risk genotypes had a 6-fold greater risk of converting to MS and relapse compared with those with ≤2. The CGRS for ΔEDSS was also significant: those carrying ≥6 risk genotypes progressed at 0.48 EDSS points per year faster compared with those with ≤2, and the CGRS model explained 32% of the variance in disability in this study cohort. These data strongly suggest that MS genetic risk variants significantly influence MS clinical course and that this effect is polygenic.
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.JNEUROIM.2016.05.020
Abstract: We evaluated the effects of calcitriol and interferon-β on in vitro PBMC cytokine production from a cohort of 22 healthy adults not on medication. PBMCs were incubated with calcitriol and/or 100 or 400IU interferon-β or nothing, followed by stimulation with concanavalin A. When combined, calcitriol and interferon-β appeared to potentiate the effects of one another on reducing IL-6. Calcitriol significantly reduced the production of IL-2, IL-4, IL-6, and IFN-γ, while interferon-β significantly reduced production of IL-6 and TNF-α, and increased IL-10. This is the first study to evaluate the effects of combined calcitriol and interferon-β on cytokine production in PBMCs in vitro, demonstrating novel synergetic effects.
Publisher: S. Karger AG
Date: 12-12-2013
DOI: 10.1159/000355439
Abstract: b i Background: /i /b 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. b i Methods: /i /b 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. b i Results: /i /b 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. b i Conclusions: /i /b 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.
Publisher: SAGE Publications
Date: 14-11-2011
Abstract: 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 s les 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 rogression 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.
Publisher: SAGE Publications
Date: 14-05-2014
Abstract: There is accumulating data suggesting an association between serum lipids, apolipoproteins and disability in multiple sclerosis (MS). To investigate the associations between serum lipids, apolipoproteins and disability in MS. A cohort of 178 participants with clinically-definite MS in southern Tasmania, Australia were prospectively followed from 2002 – 2005, and serum s les were obtained at study entry and at each biannual review, to measure lipid profile and apolipoprotein levels. Associations with disability and annual change in disability were evaluated using linear regression and multilevel mixed-effects linear regression. In the unadjusted analyses, nearly all lipid-related variables were positively associated with Expanded Disability Status Scale (EDSS). After adjustment for confounders, total cholesterol (TC) ( p = 0.037), apolipoprotein B (ApoB) ( p = 0.003), and the apolipoprotein B to apolipoprotein A-I ratio (ApoB/ApoA-I ratio) ( p = 0.018) were independently associated with a higher EDSS. Higher body mass index (BMI) was also independently associated with higher EDSS ( p = 0.013). With the progression analysis, the total cholesterol to high density lipoprotein (HDL) ratio (TC/HDL ratio) ( p = 0.029) was prospectively associated with subsequent change in EDSS. In this prospective population-based cohort study, an adverse lipid profile was associated with high levels of MS disability and disease progression. Improving serum lipids may be beneficial for MS patients, to potentially improve clinical outcomes and vascular comorbidities.
Publisher: Wiley
Date: 22-03-2016
DOI: 10.1111/PHP.12582
Abstract: Sun exposure is the most important source of vitamin D, but is also a risk factor for skin cancer. This study investigated attitudes toward vitamin D, and changes in sun-exposure behavior due to concern about adequate vitamin D. Participants (n = 1002) were recruited from four regions of Australia and completed self- and interviewer-administered surveys. Chi-square tests were used to assess associations between participants' latitude of residence, vitamin D-related attitudes and changes in sun-exposure behaviors during the last summer. Multivariate logistic regression analyses were used to model the association between attitudes and behaviors. Overall, people who worried about their vitamin D status were more likely to have altered sun protection and spent more time in the sun people not concerned about vitamin D. Concern about vitamin D was also more common with increasing latitude. Use of novel item response theory analysis highlighted the potential impact of self-reported behavior change on skin cancer predisposition due concern to vitamin. This cross-sectional study shows that the strongest determinants of self-reported sun-protection behavior changes due to concerns about vitamin D were attitudes and location, with people at higher latitudes worrying more.
Publisher: Hindawi Limited
Date: 24-06-2019
DOI: 10.1111/ANE.13132
Abstract: Modifiable lifestyle factors are implicated in multiple sclerosis (MS) symptoms but their role in mood is unclear. This study aimed to investigate associations between lifestyle and depression and anxiety in Australian participants with MS. Self-reported data from the Australian Multiple Sclerosis Longitudinal Study included the Hospital Anxiety and Depression Scale (HADS) and lifestyle measurements from 1500 participants. SNAP score (range 0-5) was the sum of non-smoking, sufficient fruit/vegetable intake, non-hazardous alcohol consumption, sufficient physical activity and healthy BMI. Analyses by log-binomial and linear regression were adjusted for confounding. Symptoms of depression and anxiety were prevalent in 27% and 40%, respectively 20% had both. Mean SNAP score was 2.7/5 only 3% met all healthy lifestyle recommendations. Only 10% reported adequate fruit/vegetable intake, and 22% reported a combination of unhealthy BMI, inadequate physical activity and inadequate nutrition. A healthier SNAP score was associated with lower depression prevalence (adjusted prevalence ratio 0.83 [95% CI 0.75, 0.92] per unit increase) and depression severity (adjusted β-0.44 [95% CI -0.64, -0.24]), but not with anxiety. Modifiable lifestyle factors are associated with lower frequency and severity of depression, but not anxiety, in Australian people with multiple sclerosis. The associations between a healthier SNAP score and lower depression are likely bi-directional. SNAP risk factor prevalence and co-occurrence, especially inadequate nutrition and low physical activity, were high among Australians with MS.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-11-2021
DOI: 10.1212/WNL.0000000000012753
Abstract: People with multiple sclerosis (MS) are a vulnerable group for severe coronavirus disease 2019 (COVID-19), particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international s le of people with MS. Data from 12 data sources in 28 countries were aggregated (sources could include patients from 1–12 countries). Demographic (age, sex), clinical (MS phenotype, disability), and DMT (untreated, alemtuzumab, cladribine, dimethyl fumarate, glatiramer acetate, interferon, natalizumab, ocrelizumab, rituximab, siponimod, other DMTs) covariates were queried, along with COVID-19 severity outcomes, hospitalization, intensive care unit (ICU) admission, need for artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression adjusted for age, sex, MS phenotype, and Expanded Disability Status Scale (EDSS) score. Six hundred fifty-seven (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19 were analyzed. Among suspected plus confirmed and confirmed-only COVID-19, 20.9% and 26.9% were hospitalized, 5.4% and 7.2% were admitted to ICU, 4.1% and 5.4% required artificial ventilation, and 3.2% and 3.9% died. Older age, progressive MS phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl fumarate, ocrelizumab and rituximab were associated with hospitalization (adjusted odds ratio [aOR] 1.56, 95% confidence interval [CI] 1.01–2.41 aOR 2.43, 95% CI 1.48–4.02) and ICU admission (aOR 2.30, 95% CI 0.98–5.39 aOR 3.93, 95% CI 1.56–9.89), although only rituximab was associated with higher risk of artificial ventilation (aOR 4.00, 95% CI 1.54–10.39). Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalization (aOR 1.75, 95% CI 1.29–2.38 aOR 2.76, 95% CI 1.87–4.07) and ICU admission (aOR 2.55, 95% CI 1.49–4.36 aOR 4.32, 95% CI 2.27–8.23), but only rituximab was associated with artificial ventilation (aOR 6.15, 95% CI 3.09–12.27). Compared to natalizumab, ocrelizumab and rituximab were associated with hospitalization (aOR 1.86, 95% CI 1.13–3.07 aOR 2.88, 95% CI 1.68–4.92) and ICU admission (aOR 2.13, 95% CI 0.85–5.35 aOR 3.23, 95% CI 1.17–8.91), but only rituximab was associated with ventilation (aOR 5.52, 95% CI 1.71–17.84). Associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Stratification by age, MS phenotype, and EDSS score found no indications that DMT associations with COVID-19 severity reflected differential DMT allocation by underlying COVID-19 severity. Using the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalization, ICU admission, and need for artificial ventilation and of ocrelizumab with hospitalization and ICU admission. Despite the cross-sectional design of the study, the internal and external consistency of these results with prior studies suggests that rituximab/ocrelizumab use may be a risk factor for more severe COVID-19.
Publisher: Public Library of Science (PLoS)
Date: 12-08-2015
Publisher: SAGE Publications
Date: 30-11-2018
Publisher: Elsevier BV
Date: 09-2021
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.MSARD.2022.103910
Abstract: Many people with multiple sclerosis (MS) modify their dietary intake post diagnosis, but there is little evidence that dietary modifications influence MS outcomes. 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. 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: β=-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: β=-1.61,95%CI=-2.76,-0.46,p=0.01, Depression: β=-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: β=-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. 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.
Publisher: SAGE Publications
Date: 16-02-2021
Abstract: While employment rates have increased in people with multiple sclerosis (PwMS), little is known about the longitudinal trends of work productivity. To describe the longitudinal patterns of work productivity and examine the factors associated with annual change of work productivity of PwMS. 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-in idual variations in MS symptoms are associated with changes in work productivity. 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. In idual 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.
Publisher: Elsevier BV
Date: 2018
Publisher: SAGE Publications
Date: 13-08-2021
DOI: 10.1177/13524585211035948
Abstract: 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. 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). 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. 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. 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.
Publisher: Elsevier BV
Date: 07-2020
Publisher: Oxford University Press (OUP)
Date: 22-03-2013
DOI: 10.1093/AJE/KWS322
Abstract: 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.
Publisher: BMJ
Date: 08-04-2011
Abstract: There is a striking latitudinal gradient in multiple sclerosis (MS) prevalence, but exceptions in Mediterranean Europe and northern Scandinavia, and some systematic reviews, have suggested that the gradient may be an artefact. The authors sought to evaluate the association between MS prevalence and latitude by meta-regression. Studies were sourced from online databases, reference mining and author referral. Prevalence estimates were age-standardised to the 2009 European population. Analyses were carried out by means of random-effects meta-regression, weighted with the inverse of within-study variance. The authors included 650 prevalence estimates from 321 peer-reviewed studies 239 were age-standardised, and 159 provided sex-specific data. The authors found a significant positive association (change in prevalence per degree-latitude) between age-standardised prevalence (1.04, p<0.001) and latitude that diminished at high latitudes. Adjustment for prevalence year strengthened the association with latitude (2.60, p<0.001). An inverse gradient in the Italian region reversed on adjustment for MS-associated HLA-DRB1 allele distributions. Adjustment for HLA-DRB1 allele frequencies did not appreciably alter the gradient in Europe. Adjustment for some potential sources of bias did not affect the observed associations. This, the most comprehensive review of MS prevalence to date, has confirmed a statistically significant positive association between MS prevalence and latitude globally. Exceptions to the gradient in the Italian region and northern Scandinavia are likely a result of genetic and behavioural-cultural variations. The persistence of a positive gradient in Europe after adjustment for HLA-DRB1 allele frequencies strongly supports a role for environmental factors which vary with latitude, the most prominent candidates being ultraviolet radiation (UVR)/vitamin D.
Publisher: Springer Science and Business Media LLC
Date: 03-09-2021
Publisher: BMJ
Date: 02-02-2023
Abstract: There are currently no specific biomarkers for multiple sclerosis (MS). Identifying robust biomarkers for MS is crucial to improve disease diagnosis and management. 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. 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 in iduals 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 ). These findings support investigating serine as an important candidate biomarker for MS onset and disability progression.
Publisher: SAGE Publications
Date: 06-09-2019
Abstract: More work is needed to understand the burden of comorbidities in people with multiple sclerosis (MS). To assess prevalence of 30 comorbidities and impacts of comorbidities on employment outcomes in a working-aged MS cohort. 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). 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. 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.
Publisher: Frontiers Media SA
Date: 02-2018
Publisher: Oxford University Press (OUP)
Date: 1998
Abstract: Hand dermatitis is common in workers in the horticultural industry. This study determined the prevalence of hand dermatitis in workers of Alstroemeria cultivation, investigated how many workers had been sensitized by tulipalin A (the allergen in Alstroemeria) and took stock of a wide range of determinants of hand dermatitis. The 12-month period prevalence of major hand dermatitis amounted to 29.5% whereas 7.4% had minor dermatitis. Of these workers, 52.1% were sensitized for tulipalin A. Several personal and work-related determinants played a role in the multifactorial aetiology of hand dermatitis. Factors which showed a significant relationship with major hand dermatitis were: female sex, atopic dermatitis, chapped hands and the frequency of washing hands. It may be concluded that the Alstroemeria workers are a population at risk of developing contact dermatitis and it might be useful to carry out an educational c aign to lower the high prevalence.
Publisher: Hindawi Limited
Date: 12-01-2016
DOI: 10.1111/ANE.12554
Abstract: 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). 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). 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. 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.
Publisher: BMJ
Date: 24-07-2017
Abstract: Due to the lack of prospective studies with longitudinal data on relapse, past genetic studies have not attempted to identify genetic factors that predict relapse risk (the primary endpoint of many pivotal clinical trials testing the efficacy of multiple sclerosis (MS) disease-modifying drugs) at a genome-wide scale. We conducted a genome-wide association analysis (GWAS) to identify genetic variants that predict MS relapse risk, using a three-stage approach. First, GWAS was conducted using the southern Tasmania MS Longitudinal Study with 141 cases followed prospectively for a mean of 2.3 years. Second, GWAS was conducted using the Ausimmune Longitudinal Study with 127 cases having a classic first demyelinating event followed for 5 years from onset. Third, the top hits with p<5.0×10 In the pooled results, using these three unique longitudinal MS cohorts, we discovered one novel locus ( The finding of a genetic locus that has extensive effects on neuronal development and repair is of interest as a potential modulator of MS disease course.
Publisher: American Geophysical Union (AGU)
Date: 07-2011
DOI: 10.1029/2011GL046959
Publisher: Elsevier BV
Date: 12-2005
Publisher: Wiley
Date: 28-06-2016
Publisher: Hindawi Limited
Date: 13-06-2013
DOI: 10.1111/ANE.12155
Abstract: 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. 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. Personal reported sun exposure was inversely associated with depression scores (β -0.26 (95%CI -0.40, -0.12) P ≤ 0.001) and fatigue scores (β -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 (β -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. 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.
Publisher: American Association for Cancer Research (AACR)
Date: 11-2009
DOI: 10.1158/1055-9965.EPI-09-0191
Abstract: Past sun exposure is linked to a wide range of disease outcomes but is difficult to measure accurately. Silicone skin casts measure skin damage, but some studies show that age rather than sun exposure is the most important determinant of cast score. We examined skin damage scores from silicone casts of the back of the hand in a large adult s le (n = 534) with a broad range of past cumulative UV radiation (UVR) doses. Participants were ages 18 to 61 years and resided in one of four locations down the eastern Australian seaboard, spanning 27-43°S. Data were collected by questionnaire and during a nurse-led interview and examination. Silicone casts were graded from 1 to 6, where higher score represents greater damage. Higher skin damage score was associated with lighter skin pigmentation [adjusted odds ratio (AOR), 4.51 95% confidence interval (95% CI), 2.33-8.75], fairer natural hair color, particularly red hair (AOR, 11.31 95% CI, 4.08-31.36), and blue/gray eyes (AOR, 1.72 95% CI, 1.14-2.59). Higher cumulative UVR dose, particularly before age 18 years, was associated with higher skin damage score (AOR, 2.06 95% CI, 1.15-2.67 per 1,000 KJ/m2), as was number of sunburns, even after adjustment for cumulative UVR dose (AOR, 2.86 95% CI, 1.50-5.43 for & sunburns ever compared with no sunburns ever). Silicone casts of the dorsum of the hand provide a measure of cumulative UVR dose and number of sunburns over the lifetime, which persists after adjustment for chronological age. They can be used as an objective measure of cumulative past sun exposure in epidemiologic studies, but other determinants of skin damage, such as skin pigmentation, should be concurrently evaluated. (Cancer Epidemiol Biomarkers Prev 2009 (11):2887–94)
Publisher: SAGE Publications
Date: 26-02-2019
Abstract: 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). 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. 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). 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.
Publisher: Wiley
Date: 12-2012
Abstract: Multiple sclerosis (MS) is a debilitating disease that causes significant morbidity within a young demographic. Diagnostic guidelines for MS have evolved, and imaging has played an increasingly important role in diagnosis over the last two decades. For imaging to contribute to diagnosis in a meaningful way, it must be reproducible. Consensus guidelines for MRI in MS exist to define correct sequence type and imaging technique, but it is not clear to what extent they are followed. This study reviewed MRI studies performed on Australian in iduals presenting with a first clinical diagnosis of central nervous system demyelination (FCD) for adherence to published guidelines and discussed practical implementation of MS guidelines in light of recent updates. The Ausimmune study was a prospective case control study of Australian participants presenting with FCD from 2003 to 2006. Baseline cranial and spinal cord MRI studies of 226 case participants from four separate Australian regions were reviewed. MRI sequences were classified according to anatomical location, slice plane, tissue weighting and use of gadolinium-containing contrast media. Results were compared with the 2003 Consortium of Multiple Sclerosis Centres MRI protocol for the diagnosis of MS. The composition of core cranial MRI sequences performed varied across the 226 scans. Of the studies, 91% included sagittal fluid attenuated inversion recovery (FLAIR) sequences. Cranial axial T2-weighted, axial FLAIR and axial proton density-weighted sequences were performed in 88%, 60% and 16% (respectively) of scans. Only 25% of the studies included a T1-weighted contrast-enhanced sequence. Concordance with the guidelines in all sequences was very low (2). Only a small number of MRI investigations performed included all of the sequences stipulated by consensus guidelines. This is likely due to poor awareness in the imaging community of the guidelines and the rationale behind certain sequences. Radiologists with a sub-speciality interest in neuroradiology should take ownership of this issue and ensure that recommended imaging guidelines are followed.
Publisher: Consortium of Multiple Sclerosis Centers
Date: 11-2021
DOI: 10.7224/1537-2073.2021-006
Abstract: One of the major objectives of the Multiple Sclerosis Data Alliance (MSDA) is to enable better discovery of multiple sclerosis (MS) real-world data (RWD). We implemented the MSDA Catalogue, which is available worldwide. The current version of the MSDA Catalogue collects descriptive information on governance, purpose, inclusion criteria, procedures for data quality control, and how and which data are collected, including the use of e-health technologies and data on collection of COVID-19 variables. The current cataloguing procedure is performed in several manual steps, securing an effective catalogue. Herein we summarize the status of the MSDA Catalogue as of January 6, 2021. To date, 38 data sources across five continents are included in the MSDA Catalogue. These data sources differ in purpose, maturity, and variables collected, but this landscaping effort shows that there is substantial alignment on some domains. The MSDA Catalogue shows that personal data and basic disease data are the most collected categories of variables, whereas data on fatigue measurements and cognition scales are the least collected in MS registries/cohorts. The Web-based MSDA Catalogue provides strategic overview and allows authorized end users to browse metadata profiles of data cohorts and data sources. There are many existing and arising RWD sources in MS. Detailed cataloguing of MS RWD is a first and useful step toward reducing the time needed to discover MS RWD sets and promoting collaboration.
Publisher: Springer Science and Business Media LLC
Date: 02-02-2021
Publisher: SAGE Publications
Date: 31-10-2020
Abstract: The Multiple Sclerosis Severity Score (MSSS) is a widely used measure of the disability progression rate. However, the global MSSS may not be the best basis for comparison between all patient groups. We evaluated sex-specific and onset phenotype-specific MSSS matrices to determine if they were more effective than the global MSSS as a basis for comparison within these subsets. Using a large international dataset of multiple sclerosis (MS) patient records and the original MSSS algorithm, we constructed global, sex-specific and onset phenotype-specific MSSS matrices. We compared matrices using permutation analysis. Our final dataset included 30,203 MS cases, with 28.9% males and 6.5% progressive-onset cases. Our global MSSS matrix did not differ from previously published data ( The differences in the disability accrual rate between progressive- and relapsing-onset MS have a significant effect on MSSS. An onset-specific MSSS should be used when comparing the rate of disability progression among progressive-onset cases and for mixed cohorts.
Publisher: Society of Exploration Geophysicists
Date: 05-2020
Abstract: Seismic waves may exhibit significant dispersion and attenuation in reservoir rocks due to pore-scale fluid flow. Fluid flow at the microscopic scale is referred to as squirt flow and occurs in very compliant pores, such as grain contacts or microcracks, that are connected to other stiffer pores. We have performed 3D numerical simulations of squirt flow using a finite-element approach. Our 3D numerical models consist of a pore space embedded into a solid grain material. The pore space is represented by a flat cylinder (a compliant crack) whose edge is connected with a torus (a stiff pore). Grains are described as a linear isotropic elastic material, whereas the fluid phase is described by the quasistatic linearized compressible Navier-Stokes momentum equation. We obtain the frequency-dependent effective stiffness of a porous medium and calculate dispersion and attenuation due to fluid flow from a compliant crack to a stiff pore. We compare our numerical results against a published analytical solution for squirt flow and analyze the effects of its assumptions. Previous interpretation of the squirt flow phenomenon based mainly on analytical solutions is verified, and some new physical effects are identified. The numerical and analytical solutions agree only for the simplest model in which the edge of the crack is subjected to zero fluid pressure boundary condition while the stiff pore is absent. For the more realistic model that includes the stiff pore, significant discrepancies are observed. We identify two important aspects that need improvement in the analytical solution: the calculation of the frame stiffness moduli and the frequency dependence of attenuation and dispersion at intermediate frequencies.
Publisher: SAGE Publications
Date: 23-04-2018
Abstract: In the general population, variation in the serotonin-transporter-linked polymorphic region ( 5-HTTLPR) has been shown to modify the association between stressful events and depression/anxiety. This has not been examined in people with multiple sclerosis (MS). We examined the interaction between significant life events (SLE), 5-HTTLPR and depression/anxiety. A population-based longitudinal cohort of 198 people with MS was followed biannually for 2.5 years. Depression and anxiety symptoms were measured at each review using the Hospital Anxiety and Depression Scale (HADS). SLEs were assessed using a questionnaire based on the Social Readjustment Rating Scale. We found an interaction between SLE load in the previous 12 months and functional variation in the 5-HTTLPR allele type in predicting depression, with the association between SLE load and depression being stronger for those with S/S allele type (β = 0.21 (95% confidence interval (CI): 0.09–0.33) per 10-unit increase) and S/L (β = 0.14 (95% CI: 0.05–0.24)) compared to L/L allele type (β = 0.04 (95% CI: −0.05 to 0.24) p interaction 0.001). No convincing evidence of an interaction was found with anxiety. We found that the association between SLE load and MS depression severity was stronger among those with one or two copies of the short allele of the 5-HTTLPR. The identification of a gene–environment interaction between SLEs and depression in a population where depression is partly disease-driven is novel.
Publisher: SAGE Publications
Date: 10-04-0100
Abstract: The measurement of health state utility values (HSUVs) for a representative s le of Australian people with multiple sclerosis (MS) has not previously been performed. Our main aim was to quantify the HSUVs for different levels of disease severities in Australian people with MS. HSUVs were calculated by employing a ‘judgement-based’ method that essentially creates EQ-5D-3L profiles based on WHOQOL-100 responses and then applying utility weights to each level in each dimension. A stepwise linear regression was used to evaluate the relationship between HSUVs and disease severity, classified as mild (Expanded Disability Status Scale (EDSS) levels: 0–3.5), moderate (EDSS levels: 4–6) and severe (EDSS levels: 6.5–9.5). Mean HSUV for all people with MS was 0.53 (95% confidence interval (CI): 0.52–0.54). Utility decreased with increasing disease severity: 0.61 (95% CI: 0.60–0.62), 0.51 (95% CI: 0.50–0.52) and 0.40 (95% CI: 0.38–0.43) for mild, moderate and severe disease, respectively. Adjusted differences in mean HSUV between the three severity groups were statistically significant. For the first time in Australia, we have quantified the impact of increasing severity of MS on health utility of people with MS. The HSUVs we have generated will be useful in further health economic analyses of interventions that slow progression of MS.
Publisher: Elsevier BV
Date: 04-2021
Publisher: Elsevier BV
Date: 10-2021
Publisher: Society of Exploration Geophysicists
Date: 11-2013
Abstract: The Cranfield field in southwest Mississippi has been under continuous [Formula: see text] injection by Denbury Onshore LLC since 2008. Two 3D seismic surveys were collected in 2007 and 2010. An initial 4D seismic response was characterized after three years of injection, where more than three million tons of [Formula: see text] remain in the subsurface. This interpretation showed coherent seismic litude anomalies in some areas that received large amounts of [Formula: see text] but not in others. To understand these effects better, we performed Gassmann substitution modeling at two wells: the 31F-2 observation well and the 28-1 injection well. We aimed to predict a postinjection saturation curve and acoustic impedance (AI) change through the reservoir. Seismic volumes were cross-equalized, well ties to seismic were performed, and AI inversions were subsequently carried out. Inversion results showed that the change in AI is higher than Gassmann substitution predicted for the 28-1 injection well. The time-lapse AI difference predicted by the inversion is similar in magnitude to the difference inferred from a time delay along a marker horizon below the reservoir.
Publisher: BMJ
Date: 11-09-2012
DOI: 10.1136/PRACTNEUROL-2012-000276
Abstract: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Improved prevention and treatment will depend on a greater understanding of the causes and mechanisms involved in its onset and progression. MS is clearly driven by both environmental and genetic factors. Established contributory environmental factors include lower ultraviolet radiation exposure and lower vitamin D levels, Epstein-Barr virus and smoking. Our current understanding of MS genetics is undergoing a major upgrade as new genetic technologies are applied to large MS studies. In this article, we review the current literature describing a genetic contribution to MS susceptibility and review the methods to detect genetic variants that may underlie the genetic contribution to MS. We also consider how reporting of genetic discoveries in MS in the lay press has caused some confusion among patients and their families, who, not surprisingly, think that these discoveries can be translated into an available genetic test to diagnose MS or recognise family members at risk of developing MS. We review the current limited clinical use of genetics in the diagnosis and management of MS.
Publisher: SAGE Publications
Date: 23-10-2018
Abstract: Transition probabilities are the engine within many health economics decision models. However, the probabilities of progression of disability due to multiple sclerosis (MS) have not previously been estimated in Australia. To estimate annual probabilities of changing disability levels in Australians with relapsing-remitting MS (RRMS). Combining data from Ausimmune/Ausimmune Longitudinal (2003–2011) and Tasmanian MS Longitudinal (2002–2005) studies ( n = 330), annual transition probabilities were obtained between no/mild (Expanded Disability Status Scale (EDSS) levels 0–3.5), moderate (EDSS 4–6.0) and severe (EDSS 6.5–9.5) disability. From no/mild disability, 6.4% (95% confidence interval (CI): 4.7–8.4) and 0.1% (0.0–0.2) progressed to moderate and severe disability annually, respectively. From moderate disability, 6.9% (1.0–11.4) improved (to no/mild state) and 2.6% (1.1–4.5) worsened. From severe disability, 0.0% improved to moderate and no/mild disability. Male sex, age at onset, longer disease duration, not using immunotherapies greater than 3 months and a history of relapse were related to higher probabilities of worsening. We have estimated probabilities of changing disability levels in Australians with RRMS. Probabilities differed between various subgroups, but due to small s le sizes, results should be interpreted with caution. Our findings will be helpful in predicting long-term disease outcomes and in health economic evaluations of MS.
Publisher: BMJ
Date: 05-2015
Abstract: Altered reactivity of peripheral blood mononuclear cells (PBMC) and their production of cytokines may affect multiple sclerosis (MS) clinical course. We assessed the relationship of stimulated PBMC-produced IFN-γ, TNF-α, IL-4 and IL-10 in modulating relapse risk using a prospective cohort with established relapsing-remitting MS. Cytokine production from PBMCs taken in summer and winter was measured by ELISA. Predictors of cytokines assessed by multilevel mixed-effects linear regression. Predictors of relapse assessed by survival analysis. Increasing IFN-γ was associated with increasing relapse risk, while increasing TNF-α reduced relapse risk after adjusting for IFN-γ. IL-10 and IL4 were not consistently associated with relapse risk. IFN-γ's effects on relapse were greatly attenuated by immunomodulatory therapies, by summer season and by higher serum vitamin D, whereas TNF-α's inverse association with relapse was only present in these circumstances. The TNF-α inverse association with relapse was only present among persons carrying the wild-type of the functional SNP rs1800693 in TNFRSF1A that has been previously associated with MS risk. We found strong effects of IFN-γ and TNF-α on relapse risk, these differing by immunomodulatory therapy, season, and serum vitamin D, as well as by genotype. These results indicate altered reactivity of immune cells modulate MS disease.
Publisher: American Medical Association (AMA)
Date: 26-01-2005
Abstract: The "hygiene hypothesis" has implicated sibship as a marker of infection load during early life and suggests that exposure or reexposure to infections can influence the developing immune system. Viral infection has also been implicated in the pathogenesis of multiple sclerosis (MS). To evaluate whether exposure to infant siblings in early life is associated with the risk of MS, and to explore the possible mechanism for any apparent protective effect, including altered Epstein-Barr virus (EBV) infection patterns. Population-based case-control study in Tasmania, Australia, from 1999 to 2001 based on 136 cases of magnetic resonance imaging-confirmed MS and 272 community controls, matched on sex and year of birth. Risk of MS by duration of contact with younger siblings aged less than 2 years in the first 6 years of life. Increasing duration of contact with a younger sibling aged less than 2 years in the first 6 years of life was associated with reduced MS risk (adjusted odds ratios [AORs]: <1 infant-year, 1.00 [reference] 1 to <3 infant-years, 0.57 [95% confidence interval {CI}, 0.33-0.98] 3 to or =5 infant-years, 0.12 [95% CI, 0.02-0.88] test for trend, P = .002). A history of exposure to infant siblings was associated with a reduced IgG response to EBV among controls. Controls with at least 1 infant-year contact had a reduced risk of infectious mononucleosis and a reduced risk of very high composite EBV IgG titers (AOR, 0.33 95% CI, 0.11-0.98) compared with other controls. The inverse association between higher infant contact and MS was independent of EBV IgG titer. Higher infant sibling exposure in the first 6 years of life was associated with a reduced risk of MS, possibly by altering childhood infection patterns and related immune responses.
Publisher: Oxford University Press (OUP)
Date: 18-04-2013
DOI: 10.1111/CEI.12077
Abstract: 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’.
Publisher: Elsevier BV
Date: 05-2013
DOI: 10.1016/J.JOCN.2012.10.005
Abstract: The role of vitamin D supplementation in preventing multiple sclerosis (MS) and/or treating MS progression is an area of significant research interest. We detail the current status of the ongoing research in this field, and note the lack of class 1 evidence from well-conducted, large, double-blind, placebo-controlled studies of vitamin D supplementation in the prevention and/or treatment of MS. We have been able to provide some guidelines for practitioners based on the substantial burden of supportive evidence for the use of vitamin D in MS as summarised here. These guidelines may provide some support to those clinicians who treat people with MS and their families.
Publisher: Environmental Health Perspectives
Date: 08-2007
DOI: 10.1289/EHP.9937
Publisher: Elsevier BV
Date: 08-2017
Publisher: Hindawi Limited
Date: 03-06-2014
DOI: 10.1111/ANE.12268
Abstract: 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. 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. 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 s les, 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 in idual. 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.
Publisher: Springer Science and Business Media LLC
Date: 26-08-2016
Publisher: S. Karger AG
Date: 2016
DOI: 10.1159/000442203
Abstract: b i Background: /i /b 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. b i Methods: /i /b 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. b i Results: /i /b 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. b i Conclusions: /i /b 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.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2003
No related grants have been discovered for Ingrid van der Mei.