ORCID Profile
0000-0001-6521-3056
Current Organisations
Sunnybrook Research Institute
,
Menzies Research Institute Tasmania, University of Tasmania
,
University of Melbourne
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Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.NUTRES.2018.05.004
Abstract: Oil tea has traditionally been used in minority populations in China for treating various ailments in traditional Chinese medicine. In idually, green tea and ginger, which are the main ingredients of oil tea, have demonstrated antidiabetic effects however, whether oil tea exerts antidiabetic effects remains unknown. In addition, aberrant gut microbiota structure is associated with diabetic status, and research indicates that there may be beneficial effects of tea on gut microbiota. Therefore, we hypothesized that oil tea exerts antidiabetic effects and induces alteration in gut microbiota. To test our hypothesis, we first examined the nutrition composition of oil tea. Then, db/db mice were randomly ided into 3 groups and orally gavaged with saline, metformin, and oil tea for 8 weeks. Fasting blood glucose (FBG), oral glucose tolerance test (OGTT), and lipid levels were tested during the experiment. 16S rRNA genes were sequenced and changes in gut microbiota in response pre ost treatment were examined. Our experiments showed that oil tea contains high concentrations of tea polyphenols (246.35 mg/100 g) and [6]-gingerol (2.98 mg/100 g). It appeared that oil tea treatment significantly suppressed the postprandial blood glucose elevation and lowered the levels of FBG, total cholesterol, triglycerides, and LDL-cholesterol (P < .05). The composition of gut microbiota changed significantly in response to oil tea treatment, Lachnospiraceae were significantly enriched (q 3.5). Redundancy analysis identified 155 oil tea-modulating family level phylotypes, where Lachnospiraceae significantly correlated with FBG, total cholesterol, and LDL-cholesterol (P < .05). Our findings demonstrate that oil tea improved glucose and lipid levels and modulated gut microbiota in db/db mice.
Publisher: Hindawi Limited
Date: 20-04-2015
DOI: 10.1111/ANE.12405
Abstract: We sought to determine the prevalence of MS on the Isle of Man in 2006 and 2011, and the incidence and mortality rates over this interval. Cases were identified by hospital medical record review, General Practitioners and the local MS Society. The significance of the change in prevalence over time and the significance of differences in frequencies by sex and place of birth were assessed by Poisson regression. The 2006 prevalence was 153.64 per 100,000 persons and the 2011 prevalence was 179.89. The prevalence was higher among females and persons born in the Isle of Man at both time points. The 2006-2011 incidence rate was 6.86 per 100,000 person-years, much higher among females and persons born in the Isle of Man. The prevalence sex ratios in 2006 and 2011, 2.77 and 2.59, respectively, and the incidence sex ratio, 2.19, are similar to others found in the region. The mortality rate over the study period was 2.84 per 100,000 person-years, this solely among persons born overseas. This is the first study of MS epidemiology in the Isle of Man, finding this area to be of high prevalence and to have one of the highest incidence rates in the UK region.
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.PLACENTA.2009.12.008
Abstract: Workshops are an important part of the annual meeting of the International Federation of Placenta Associations (IFPA). At IFPA Meeting 2009 erse topics were discussed in twelve themed workshops. Topics covered included: immune response to pregnancy signaling between fetus and placenta bioactive lipids in placenta placenta in agricultural species epigenetics and placentation trophoblast deportation glucocorticoids and placental function endothelium placental transport genes and placenta uteroplacental blood flow and placental stem cells. This report is a full summary of the various topics covered.
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.CANEP.2016.04.001
Abstract: Anal cancer is a human papillomavirus (HPV)-mediated neoplasia of the anal squamous epithelium. Anal cancer is much more common among women, particularly those with a previous high-grade gynaecological neoplasia. Cross-sectional study of women with a previous HPV-mediated gynaecological neoplasia in Tasmania, Australia. Women presenting for follow-up gynaecological care had anal swab s les taken for anal cytology by Hologic Liquid ThinPrep, followed by HPV genotyping. Women with abnormal anal cytology were invited for high-resolution anoscopy. Potential risk factors, including post-toilet wiping behaviours, were queried by questionnaire while clinical covariates were extracted from medical records. Covariates of anal outcomes evaluated by log-binomial and log-multinomial regression. From 163 women enrolled in the study, 65 (39.9%) had abnormal cytology, with 46 (28.2%) being high-grade. Of the 50 women with abnormal anal cytology having high-resolution anoscopy, 32 (64.0%) had abnormal histology with 13 (26.0%) being high-grade. Of the 123 women tested for HR-HPV DNA, 48 (39.0%) had HR-HPV detected, the most common genotypes being 16 and 51 (14/123, 11.4% for both). In addition to some known anal cancer risk factors, we found front-to-back wiping was associated with significantly increased (Prevalence ratio (PR) range: 1.99-3.60) prevalence of cytological and histological abnormality and HR-HPV carriage/co-carriage, while dabbing post-toilet was significantly associated with decreased prevalences (PR range: 0.50-0.62). Post-toilet wiping behaviours were significantly associated with the prevalence of anal cytological, histological and HR-HPV carriage outcomes. This suggests a biologically plausible mechanism for HR-HPV introduction and the higher frequencies of anal neoplasia in women.
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: 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: 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: Ovid Technologies (Wolters Kluwer Health)
Date: 27-05-2022
DOI: 10.1212/NXG.0000000000200005
Abstract: Advances in genome sequencing technologies have unlocked new possibilities in identifying disease-associated and causative genetic markers, which may in turn enhance disease diagnosis and improve prognostication and management strategies. With the capability of examining genetic variations ranging from single-nucleotide mutations to large structural variants, whole-genome sequencing (WGS) is an increasingly adopted approach to dissect the complex genetic architecture of neurologic diseases. There is emerging evidence for different structural variants and their roles in major neurologic and neurodevelopmental diseases. This review first describes different structural variants and their implicated roles in major neurologic and neurodevelopmental diseases, and then discusses the clinical relevance of WGS applications in neurology. Notably, WGS-based detection of structural variants has shown promising potential in enhancing diagnostic power of genetic tests in clinical settings. Ongoing WGS-based research in structural variations and quantifying mutational constraints can also yield clinical benefits by improving variant interpretation and disease diagnosis, while supporting biomarker discovery and therapeutic development. As a result, wider integration of WGS technologies into health care will likely increase diagnostic yields in difficult-to-diagnose conditions and define potential therapeutic targets or intervention points for genome-editing strategies.
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: BMJ
Date: 02-2023
Abstract: We previously reported an association between household chemical exposures and an increased risk of paediatric-onset multiple sclerosis. Using a case–control paediatric multiple sclerosis study, gene–environment interaction between exposure to household chemicals and genotypes for risk of paediatric-onset multiple sclerosis was estimated. Genetic risk factors of interest included the two major HLA multiple sclerosis risk factors, the presence of DRB1*15 and the absence of A*02, and multiple sclerosis risk variants within the metabolic pathways of common household toxic chemicals, including IL-6 (rs2069852), BCL-2 (rs2187163) and NFKB1 (rs7665090). 490 paediatric-onset multiple sclerosis cases and 716 controls were included in the analyses. Exposures to insect repellent for ticks or mosquitos (OR 1.47, 95% CI 1.06 to 2.04, p=0.019), weed control products (OR 2.15, 95% CI 1.51 to 3.07, p .001) and plant/tree insect or disease control products (OR 3.25, 95% CI 1.92 to 5.49, p .001) were associated with increased odds of paediatric-onset multiple sclerosis. There was significant additive interaction between exposure to weed control products and NFKB1 SNP GG (attributable proportions (AP) 0.48, 95% CI 0.10 to 0.87), and exposure to plant or disease control products and absence of HLA-A*02 (AP 0.56 95% CI 0.03 to 1.08). There was a multiplicative interaction between exposure to weed control products and NFKB1 SNP GG genotype (OR 2.30, 95% CI 1.00 to 5.30) but not for other exposures and risk variants. No interactions were found with IL-6 and BCL-2 SNP GG genotypes. The presence of gene–environment interactions with household toxins supports their possible causal role in paediatric-onset multiple sclerosis.
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: 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: 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: 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: MDPI AG
Date: 15-08-2020
Abstract: Health communication offers an important means for patients to make informed decisions for illness self-management. We assessed how the level of engagement with selected health information at baseline is associated with the adoption and maintenance of lifestyle behaviours at a 5-year follow-up in people with multiple sclerosis (MS). Non-engagers were compared to engagers of information delivered online and print (medium), and with engagers who additionally attended a live-in workshop (high). Engagement was assessed against lifestyle behaviours by log-binomial regression. Information engagers had higher education, and were less likely to have severe disability, clinically significant fatigue, or obesity. Medium and high baseline engagement was associated with adopting healthy behaviours for omega 3 supplementation (RR = 1.70 95%CI: 1.02–2.84), physical activity (RR = 2.16 95%CI: 1.03–4.55), and dairy non-consumption (RR = 3.98 95%CI: 1.85–8.56) at 5 years associations were stronger among high engagers. Only high baseline engagement was associated with maintaining behaviours from baseline to 5 years, specifically for omega-3 (RR = 1.26 95%CI: 1.06–1.49) and vitamin D supplementation (RR = 1.26 95%CI: 1.04–1.54) and dairy non-consumption (RR = 1.47 95%CI: 1.03–2.10). Health communication that includes face-to-face information delivery and practical tools for implementation in daily living may be optimal for adopting and maintaining lifestyle behaviours in people with MS.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-06-2012
Publisher: BMJ
Date: 13-05-2021
Publisher: Frontiers Media SA
Date: 08-06-2018
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: 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: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.MSARD.2019.02.014
Abstract: Depression is highly prevalent among people with MS, and determinants thereof would be useful. We examined the relationship of demographic and clinical factors with positive depression-screen and change in depression over 2.5 years in people with MS. Positive depression-screen assessed by Patient Health Questionnaire (PHQ)-2 and PHQ-9. Associations of demographic and clinical factors with depression-screen and change thereof assessed using multivariable regression models, adjusted for age, sex, disability, fatigue, antidepressant use, and baseline PHQ-2, as appropriate. Overweight/obese BMI, comorbidity number, fatigue, and disability were associated with positive depression-screen, while married artnered state, being employed, higher perceived socioeconomic status, and greater education were inversely associated with depression-screen. After adjustment, only marital status, socioeconomic status, antidepressant medication use, and fatigue were associated with risk of newly positive depression-screen. MS type, relapse number and immunomodulatory medication use were not associated with depression-screen after controlling for disability and fatigue. In a large prospective cohort study of depression in people with MS, we substantiated several potential determinants of a positive depression-screen and depression trajectory, particularly fatigue. Given that fatigue is the most common and most significant clinical symptom for people with MS, efforts to reduce fatigue may have follow-on benefits for reducing depression.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2021
DOI: 10.1161/HYPERTENSIONAHA.121.17267
Abstract: Preecl sia is a hypertensive disorder of pregnancy that is a major cause of maternal-fetal morbidity and mortality worldwide. Severe preecl sia (sPE) is mediated by pathology of the placental villi resulting in repressed PIGF (placental growth factor) production and hyper-secretion of sFLT1 (soluble fms-like tyrosine kinase 1), the net effect being wide-spread maternal endothelial dysfunction. Villous trophoblast differentiation is under control of the PPARγ (peroxisome proliferator-activated receptor γ) and GCM1 (glial cell missing 1) axis which is dysregulated in sPE. We hypothesized that disruption of trophoblast differentiation via the PPARγ-GCM1 axis is a major contribution to excess production of sFLT1 and pharmacological activation of PPARγ in the sPE placenta could reduce sFLT1 to normal levels. sPE, age-matched control placentas and first-trimester villous explants, were used to investigate the molecular relationships between PPARγ-GCM1 and sFLT1. We modulated this pathway by pharmacological activation/inhibition of PPARγ using Rosiglitazone and T0070907, respectively, and through siRNA repression of GCM1. PPARγ and GCM1 protein expressions are reduced in the sPE placenta while FLT1 protein and sFLT1 secretion are increased. GCM1 reduction in the first trimester explants significantly increased sFLT1 secretion, suggesting GCM1 as a key player in this pathway. Activation of PPARγ restored GCM1 and significantly reduced sFLT1 expression and release in first trimester and sPE placental villi. Functional integrity of the PPARγ-GCM1 axis in the villous trophoblast is critical for normal pregnancy development and is disrupted in the sPE placenta to favor excessive production of sFLT1. Pharmacological manipulation of PPARγ activity has the potential to rescue the antiangiogenic state of sPE and thereby prolong pregnancy and deliver improved clinical outcomes.
Publisher: Frontiers Media SA
Date: 12-12-2018
Publisher: Wiley
Date: 26-08-2021
DOI: 10.1111/ENE.15066
Abstract: Modifiable lifestyle factors, including diet, may affect clinical outcomes in multiple sclerosis (MS). This study assessed the relationships between diet, and disability, fatigue, and depression risk in people with MS. Participants from the Health Outcomes and Lifestyle In a S le of people with Multiple sclerosis (HOLISM) international cohort were assessed over 2.5 years. Dietary data were obtained using a modified Diet Habits Questionnaire (DHQ), disability using the calculated Patient‐determined MS Severity Score (P‐MSSS), fatigue using the Fatigue Severity Scale, and depression risk using the Patient Health Questionnaire‐2. Participants reported whether they were experiencing symptoms due to a recent relapse. Cross‐sectional and prospective relationships of diet and disease outcomes were explored, adjusted for relevant confounders. Among 1,346 participants, higher DHQ scores showed significant dose‐dependent associations with lower frequencies of severe disability, fatigue, and depression risk, cross‐sectionally. Prospectively, higher baseline DHQ scores were associated with a lower risk of increasing disability, those above the median having 41% and 36% lower risk of increasing disability, and 0.30 P‐MSSS points less disability progression, but were not associated with fatigue or depression risk. Meat consumption was associated with 0.22 P‐MSSS points higher disability cross‐sectionally, while prospectively, baseline meat consumption was associated with 76% higher risk of increasing disability and 0.18 P‐MSSS points higher disability progression. Dairy consumption showed mixed associations cross‐sectionally and prospectively. These results show that better quality of diet, as well as not consuming meat, were associated with reduced disability progression in people with MS. Substantiation of these findings in other settings may inform opportunities to manage disability progression in people with MS using dietary modifications.
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: 20-07-2023
DOI: 10.1111/ENE.15980
Abstract: Modifiable lifestyle factors, including diet, have been implicated in multiple sclerosis (MS) progression, but prospective evidence is limited. The aim of this study was to examine prospective relationships between quality of diet and subsequent disability over 7.5 years in an international cohort of people living with MS (pwMS). Data from 602 participants in the HOLISM (Health Outcomes and Lifestyle In a S le of people with Multiple sclerosis) study were analysed. Quality of diet was assessed using the modified Diet Habits Questionnaire (DHQ). Disability was assessed using the Patient‐determined MS Severity Score (P‐MSSS). Characteristics of disability were assessed by log‐binomial, log‐multinomial and linear regression, adjusted for demographic and clinical covariates, as appropriate. Higher baseline total DHQ scores ( –89, %) were associated with lower risks of increased P‐MSSS at 7.5 years (adjusted risk ratio [aRR] 0.46, 95% confidence interval [CI] 0.23, 0.91 and aRR 0.48, 95% CI 0.26, 0.89, respectively), and with less P‐MSSS accrual (aβ = −0.38, 95% CI −0.78, 0.01 and aβ = −0.44, 95% CI −0.81, −0.06). Of the DHQ domains, fat subscore was most strongly associated with subsequent disability. Participants with reducing baseline‐to‐2.5‐ years total DHQ scores had greater risk of increased P‐MSSS at 7.5 years (aRR 2.77, 95% CI 1.18, 6.53) and higher P‐MSSS accrual (aβ = 0.30, 95% CI 0.01, 0.60). Participants reporting baseline meat and dairy consumption had greater risk of increased P‐MSSS at 7.5 years (aRR 2.06, 95% CI 1.23, 3.45 and aRR 2.02, 95% CI 1.25, 3.25) and higher P‐MSSS accrual (aβ = 0.28, 95% CI 0.02, 0.54 and aβ = 0.43, 95% CI 0.16, 0.69, respectively). However, reported meat consumption was confounded by quality of diet. Changes in meat or dairy consumption from baseline were inconsistently associated with subsequent disability. We show for the first time robust long‐term associations between quality of diet and subsequent disability progression in pwMS. Subject to replication, dietary modification may represent a point of intervention for reducing disability in pwMS.
Publisher: Springer Science and Business Media LLC
Date: 29-08-2013
Publisher: Elsevier BV
Date: 04-2022
DOI: 10.1016/J.MSARD.2022.103710
Abstract: There is increasing interest in the role of diet in multiple sclerosis (MS) progression and whether a healthier diet may lead to improved health and wellbeing in people living with MS (plwMS). To assess the prospective relationship of the quality of dietary intakes with quality of life (QoL) in an international cohort of plwMS followed over 7.5 years. Data from the Health Outcomes and Lifestyle In a S le of people with Multiple sclerosis (HOLISM) cohort from baseline to 7.5-year review were analysed. Quality of the diet was assessed using the Diet Habits Questionnaire (DHQ). QoL was measured by the MSQOL-54, including physical and mental health composite scores and multiple subdomains. Linear regression was used to determine cross-sectional and prospective relationships with QoL, adjusted for clinical and demographic covariates. Amongst 948 participants, median physical- and mental-health QoL scores at 7.5-year review were 66.9 and 78.2, respectively. Baseline total DHQ was positively associated with subsequent change in physical-QoL to 7.5-year review, such that participants in the top two quartiles of baseline DHQ had 0.65 and 0.64 higher physical-QoL per year, though a similar association with mental-QoL did not persist on adjustment. Baseline meat consumption was associated with 0.38 lower physical-QoL per year, while baseline dairy consumption was associated with 0.50 and 0.41 lower physical- and mental-QoL per year, respectively. These results suggest efforts to improve the quality of dietary intake could be beneficial to the wellbeing of plwMS. Subject to replication, this aspect of lifestyle could be a useful intervention in better managing MS.
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: JMIR Publications Inc.
Date: 04-02-2021
Abstract: igital health interventions have revolutionized multiple sclerosis (MS) care by supporting people with MS to better self-manage their disease. It is now understood that the technological elements that comprise this category of digital health interventions can influence participant engagement in self-management programs, and people with MS can experience significant barriers, influenced by these elements, to remaining engaged during a period of learning. It is essential to explore the influence of technological elements in mitigating attrition. his study aimed to examine the study design and technological elements of documented digital health interventions targeted at people with MS—digital health interventions that were intended to support a program of engagement over a defined period—and to explore how these correlated with attrition among participants of randomized controlled trials (RCTs). e conducted a systematic review and meta-analysis of RCTs (n=32) describing digital health self-management interventions for people with MS. We analyzed attrition in included studies, using a random-effects model and meta-regression to measure the association between potential moderators. here were no measured differences in attrition between the intervention and control arms however, some of the heterogeneity observed was explained by the composite technological element score. The pooled attrition rates for the intervention and control arms were 14.7% and 15.6%, respectively. his paper provides insight into the technological composition of digital health interventions designed for people with MS and describes the degree of attrition in both study arms. This paper will aid in the design of future studies in this area, particularly for digital health interventions of this type.
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: 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: MDPI AG
Date: 31-10-2022
DOI: 10.3390/NU14214568
Abstract: Understanding the dietary characteristics of people living with multiple sclerosis (plwMS) may assist in the planning of nutrition interventions for multiple sclerosis yet dietary assessment methods in existing studies are not well established. The aim of this study was to validate the psychometric properties (construct validity and internal consistency) of the Dietary Habits Questionnaire (DHQ) against repeated online 24-h recall dietary assessments. The DHQ is a 24-item tool that is scored using ten dietary sub-scores. Total DHQ scores can range from 20–100 and are considered indicative of the quality of dietary intake with higher scores reflecting increased quality. People living with a relapsing-remitting MS phenotype who had completed a modified DHQ were recruited from the international Health Outcomes and Lifestyle In a S le of people with Multiple sclerosis (HOLISM) cohort. Repeated 24-h recall via the online Automated Self-administered Assessment-24 (ASA-24) tool were modelled to reflect usual dietary intakes using the Multiple Source Method. DHQ scores of eight sub-scores: three key nutrients, three food groups and two food preparation practices, were calculated and statistically compared with ASA-24 usual intake data. Principal component analysis of the ASA-24 data was undertaken to understand dietary patterns of the s le. Of the 105 participants, valid 24-h recall data were available for 96 plwMS (n = 66 1 day, n = 30 ≥ 2 day). The median total DHQ score was 84.50 (IQR: 77.04, 91.83) points. The highest absolute correlations were between the DHQ scores and ASA-24 data for cereal (r = 0.395, p 0.001), fruit and vegetables (r = 0.436, p 0.001), and total dietary fiber (r = 0.482, p 0.001). Five dietary patterns emerged from the data explaining 42.12% variance and reflecting exposure of plwMS to the influence of ‘MS diets’. The DHQ appears to be appropriate for screening participants with relapsing-remitting MS. Evidence-based dietary models focusing on food are required to monitor the quality of an overall dietary pattern and set priorities for the planning nutrition interventions for plwMS.
Publisher: Elsevier BV
Date: 03-2008
DOI: 10.1016/J.CHROMA.2007.11.001
Abstract: On-line preconcentration is one of the aspects of analytical method development using capillary electrophoretic techniques. The choice of the s le matrix alone can significantly alter both method sensitivity and separation efficiency. The recent trend to detect s les in narrower separation vessels also necessitates the need to improve detection sensitivity. The desire to detect very low levels of analytes using limited amounts of s le from biological specimens and the high separation efficiency obtainable using very large injections compared to classical small size injections also adds to this list. Indeed, one of the rich areas of research in the capillary electrophoresis field is on on-line s le preconcentration. More than 400 published research articles gathered from the www.webofscience.com from the year 2000 described a form of on-line preconcentration in capillary electrophoresis. This review provides a comprehensive table listing the applications of on-line preconcentration in capillary electrophoresis.
Publisher: Hindawi Limited
Date: 07-02-2017
DOI: 10.1111/ANE.12597
Publisher: Hindawi Limited
Date: 08-2019
DOI: 10.1111/HSC.12822
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-2011
DOI: 10.1161/HYPERTENSIONAHA.111.172627
Abstract: Preecl sia is a multisystemic disorder of pregnancy characterized by hypertension, proteinuria, and maternal endothelial dysfunction. It is a major cause of maternal and perinatal morbidity and mortality and is thought to be attributable, in part, to inadequate trophoblast invasion. Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a ligand-activated transcription factor expressed in trophoblasts, and the vasculature of which activation has been shown to improve endothelium-dependent vasodilatation in hypertensive conditions. We investigated the effects of the administration of a PPAR-γ agonist using the reduced uterine perfusion pressure (RUPP) rat model of preecl sia. The selective PPAR-γ agonist, rosiglitazone, was administered to pregnant rats that had undergone RUPP surgery. To investigate whether any observed beneficial effects of PPAR-γ activation were mediated by the antioxidant enzyme, heme oxygenase 1, rosiglitazone was administered in combination with the heme oxygenase 1 inhibitor tin-protoporphyrin IX. RUPP rats were characterized by hypertension, endothelial dysfunction, and elevated microalbumin:creatinine ratios. Rosiglitazone administration ameliorated hypertension, improved vascular function, and reduced the elevated microalbumin:creatinine ratio in RUPP rats. With the exception of microalbumin:creatinine ratio, these beneficial effects were abrogated in the presence of the heme oxygenase 1 inhibitor. Administration of a PPAR-γ agonist prevented the development of several of the pathophysiological characteristics associated with the RUPP model of preecl sia, via a heme oxygenase 1–dependent pathway. The findings from this study provide further insight into the underlying etiology of preecl sia and a potential therapeutic target for the treatment of preecl sia.
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: Wiley
Date: 09-2015
DOI: 10.1111/IMJ.12841
Abstract: Hyperglycaemia has been associated with adverse outcomes in several different hospital populations. The aim of this study was to investigate the relationship between admission blood glucose level (BGL) and outcomes in all patients admitted through the emergency department. This study was a retrospective observational cohort study from an Australian tertiary referral hospital. Patients admitted in the first week of each month from April to October 2012 had demographic data, co-morbidities, BGL, intensive care unit admission, length of stay and dates of death recorded. Factors associated with outcomes were assessed by multi-level mixed-effects linear regression. Admission BGL was recorded for 601 admissions with no diagnosis of diabetes and for 219 admissions diagnosed with type 2 diabetes (T2DM). In patients with no diagnosis of diabetes, admission BGL was associated with in-hospital and 90-day mortality (P < 0.001). After multivariate analysis, BGL greater than 11.5 mmol/L was significantly associated with increased mortality at 90 days (P < 0.05). In patients with T2DM increased BGL on admission was not associated with in-hospital or 90-day mortality but was associated with length of hospital stay (β: 0.22 days/mmol/L 95% confidence interval 0.09-0.35 P < 0.001), although this association was lost on multivariable analysis. In patients with T2DM, increased coefficient of variation of BGL was also positively associated with length of hospital stay in an almost dose-dependent fashion (P < 0.001). Admission BGL was independently associated with increased mortality in patients with no diagnosis of diabetes. Glycaemic variability was associated with increased length of hospital stay in patients with T2DM.
Publisher: Wiley
Date: 09-03-2017
DOI: 10.1002/BRB3.670
Publisher: JMIR Publications Inc.
Date: 27-02-2022
Abstract: odification of lifestyle-related risk factors for multiple sclerosis (MS) has been associated with improved health outcomes when compared with standard medical management alone. Based on an existing evidence-based lifestyle education program offered as a residential workshop, the MS Online Course (MSOC) was developed to translate the face-to-face program into an online educational intervention. We performed a preliminary small randomised controlled trial (RCT), to quantitatively and qualitatively assess the feasibility of the MSOC. This paper reports qualitative aspects of participant involvement in this preliminary study. s part of an assessment of feasibility, to explore participants’ motivations, expectations, and experiences of the MSOC. SOC trial participants were recruited via online advertisements through MS society websites of Canada, New Zealand, and the United States, and an Australian MS Facebook group. Consenting participants were randomised to one of two arms: the MSOC standard care course, containing material relating to MS and lifestyle sourced from public facing MS websites or the MSOC intervention course, based on a face-to-face lifestyle modification program. Following completion of the respective courses, participants were invited to undertake semi-structured interviews. Reflexive thematic analysis of interviews was performed to identify themes related to participants’ motivations, expectations, and experiences of the MSOC. f 31 eligible participants, 17 people completed the MSOC feasibility RCT and 14 agreed to be interviewed. Four themes were identified: 1) “Wanting to help others” (helping through volunteering, contributing to knowledge base and spreading the word 2) “Obtaining knowledge to help better manage MS” (reassurance and confirmation of existing knowledge new credible knowledge and evidence) 3) “Doing whatever I can to help myself” (understanding lifestyle modification, changing my lifestyle, and remaining well and high-functioning) and 4) “Developing new attitudes” (finding positivity and feeling more confident and in control). articipants were motivated to undertake the MSOC to help others with MS through participation in research, to help themselves by improving their knowledge and to find ways in which they could manage their own MS. Expectations included the obtaining of credible, reliable information to substantiate their existing knowledge, and to further understand lifestyle modification. Participants’ experiences varied from experiencing little to no impact, to confirming existing knowledge, obtaining new knowledge, and early implementation of new or modified lifestyle behaviours. Although not identified as an expectation prior to undertaking the MSOC, some participants experienced improved positivity, confidence, and a greater sense of control. These insights surrounding participants’ motivations, expectations and experiences may assist in recruitment strategies, course redevelopment and outcome measures for future studies. Identification of participants’ changing attitudes, which they considered a high priority in their lives, suggests outcome measures should include measures of confidence and agency his study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ID: ACTRN12621000245897).
Publisher: MDPI AG
Date: 17-11-2021
DOI: 10.3390/JPM11111218
Abstract: Multiple sclerosis (MS), a neuroinflammatory disorder, occurs as non-progressive or progressive phenotypes both forms present with erse symptoms that may reduce quality of life (QoL). Adherence to healthy lifestyle behaviors has been associated with higher QoL in people with MS whether these associations differ based on MS phenotype is unknown. Cross-sectional self-reported observational data from 1108 iConquerMS participants were analysed. Associations between lifestyle behaviors and QoL were assessed by linear regression, and phenotype differences via moderation analyses. Diet, wellness, and physical activity, but not vitamin D or omega-3 supplement use, were associated with QoL. Specifically, certain diet types were negatively associated with QoL in relapsing-remitting MS (RRMS), and positively associated in progressive MS (ProgMS). Participation in wellness activities had mixed associations with QoL in RRMS but was not associated in ProgMS. Physical activity was positively associated with QoL in RRMS and ProgMS. Phenotype differences were observed in diet and wellness with physical QoL, and physical activity with most QoL subdomains. Our findings show lifestyle behaviors are associated with QoL and appear to differ based on MS phenotype. Future studies assessing timing, duration, and adherence of adopting lifestyle behaviors may better inform their role in MS management.
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: 10-2022
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: Cold Spring Harbor Laboratory
Date: 10-02-2021
DOI: 10.1101/2021.02.08.21251316
Abstract: People with multiple sclerosis (MS) are a vulnerable group for severe 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. Demographic and clinical covariates were queried, alongside COVID-19 clinical severity outcomes, hospitalisation, admission to ICU, requiring artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression. 657 (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19 were analysed. 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 hospitalisation (aOR=1.56,95%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), though 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 hospitalisation (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 with artificial ventilation (aOR=6.15,95%CI=3.09-12.27). Compared to natalizumab, ocrelizumab and rituximab were associated with hospitalisation (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 with ventilation (aOR=5.52,95%CI=1.71-17.84). Importantly, associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Using the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalisation, ICU admission, and requiring artificial ventilation, and ocrelizumab with hospitalisation and ICU admission, suggesting their use may be a risk factor for more severe COVID-19.
Publisher: Elsevier BV
Date: 10-2020
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: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2011
DOI: 10.1161/HYPERTENSIONAHA.111.179440
Abstract: Preecl sia, a major cause of maternal and perinatal mortality and morbidity, is thought to be attributed, in part, to impaired trophoblast invasion. Peroxisome proliferator-activated receptors are ligand-activated transcription factors expressed in trophoblasts, which regulate the expression of a number of genes involved in cell differentiation and proliferation. We investigated the effect of the administration of a peroxisome proliferator-activated receptor-γ antagonist during uncomplicated pregnancy in rats. Using an intraperitoneal miniosmotic pump, healthy pregnant rats were administered either vehicle or the peroxisome proliferator-activated receptor-γ–specific antagonist, T0070907 (1 mg/kg per day from gestational days 11–15). Rats treated with T0070907 developed key features of preecl sia, including elevated mean arterial blood pressure, proteinuria, endothelial dysfunction, reduced pup weight, and increased platelet aggregation. T0070907-treated rats had reduced plasma vascular endothelial growth factor and increased plasma soluble fms-like tyrosine kinase 1. Furthermore, increases in total placental soluble fms-like tyrosine kinase 1 mRNA and fms-like tyrosine kinase 1 protein were also demonstrated, suggesting the placenta as the main contributor to the increased circulating levels of soluble fms-like tyrosine kinase 1. The labyrinthine trophoblast in the placentas of T0070907-treated rats were less differentiated, had increased cellular proliferation, and were strongly immunopositive for CD-31 staining, indicating adaptive angiogenesis. The present study suggests that peroxisome proliferator-activated receptor-γ may play a pivotal role in the progression of a healthy pregnancy and may critically regulate the risk of preecl sia. These findings have important implications regarding the underlying etiology of preecl sia and potential therapeutic targets.
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: 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: 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: SAGE Publications
Date: 23-02-2022
DOI: 10.1177/13524585211069068
Abstract: Over the recent years, the treatment of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) has evolved very rapidly and a large number of disease-modifying treatments (DMTs) are now available. However, most DMTs are associated with adverse events, the most frequent of which being infections. Consideration of all DMT-associated risks facilitates development of risk mitigation strategies. An international focused workshop with expert-led discussions was sponsored by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and was held in April 2021 to review our current knowledge about the risk of infections associated with the use of DMTs for people with MS and NMOSD and corresponding risk mitigation strategies. The workshop addressed DMT-associated infections in specific populations, such as children and pregnant women with MS, or people with MS who have other comorbidities or live in regions with an exceptionally high infection burden. Finally, we reviewed the topic of DMT-associated infectious risks in the context of the current SARS-CoV-2 pandemic. Herein, we summarize available evidence and identify gaps in knowledge which justify further research.
Publisher: Wiley
Date: 14-09-2018
DOI: 10.1111/ENE.13784
Publisher: SAGE Publications
Date: 19-04-2021
DOI: 10.1177/13524585211004422
Abstract: Genome-wide association studies (GWAS) have succeeded in identifying over 200 susceptibility loci for multiple sclerosis (MS). However, the potential functional variants and the mechanisms by which these loci affect MS risk remain largely unexplained. We used summary data-based Mendelian randomisation to prioritise risk genes and infer potential biological mechanisms for MS risk loci. The data used consisted of DNA methylation ( n = 1980) QTL (mQTL) and gene expression ( n = 31,684) QTL (eQTL) derived from whole blood as well as MS GWAS summary statistics (14,802 cases, 26,703 controls). The findings were further evaluated using data derived from independent brain mQTL ( n = 1160) and eQTL ( n = 1194). In whole blood, we identified two independent genomic loci (lincRNA: RP11-326C3.13 and TNFSF14) with consistent genome-wide significant pleiotropic associations across different omics layers. In brain tissue, a similar effect for the RP11-326C3.13 locus was observed but not for TNFSF14, indicating a potential tissue-specific effect for the TNFSF14 locus. We provide in silico evidence for the putative biological mechanisms by which the identified DNA methylation sites and target genes are functionally relevant to MS development in different tissues. Future research targeting these genes and DNA methylation sites will determine their roles in the pathophysiology of MS.
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: 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: Frontiers Media SA
Date: 02-11-2018
Publisher: BMJ
Date: 26-10-2023
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: SAGE Publications
Date: 06-05-2023
DOI: 10.1177/13524585231167739
Abstract: A pro-inflammatory diet has been posited to induce chronic inflammation within the central nervous system (CNS), and multiple sclerosis (MS) is an inflammatory disease of the CNS. We examined whether Dietary Inflammatory Index (DII ®) ) scores are associated with measures of MS progression and inflammatory activity. A cohort with a first clinical diagnosis of CNS demyelination was followed annually (10 years, n = 223). At baseline, 5- and 10-year reviews, DII and energy-adjusted DII (E-DII TM ) scores were calculated (food frequency questionnaire) and assessed as predictors of relapses, annualised change in disability (Expanded Disability Status Scale) and two magnetic resonance imaging measures fluid-attenuated inversion recovery (FLAIR) lesion volume and black hole lesion volume. A more pro-inflammatory diet was associated with a higher relapse risk (highest vs. lowest E-DII quartile: hazard ratio = 2.24, 95% confidence interval (CI) = −1.16, 4.33, p = 0.02). When we limited analyses to those assessed on the same manufacturer of scanner and those with a first demyelinating event at study entry (to reduce error and disease heterogeneity), an association between E-DII score and FLAIR lesion volume was evident (β = 0.38, 95% CI = 0.04, 0.72, p = 0.03). There is a longitudinal association between a higher DII and a worsening in relapse rate and periventricular FLAIR lesion volume in people with MS.
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: Informa UK Limited
Date: 02-03-2202
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: Frontiers Media SA
Date: 30-10-2018
Publisher: BMJ
Date: 04-2023
DOI: 10.1136/BMJNO-2023-000407
Abstract: In 2015/2016, annual national expenditure on neurological conditions exceeded $A3 billion. However, a comprehensive study of the Australian neurological workforce and supply/demand dynamics has not previously been undertaken. Current neurological workforce was defined using neurologist survey and other sources. Workforce supply modelling used ordinary differential equations to simulate neurologist influx and attrition. Demand for neurology care was estimated by reference to literature regarding incidence and prevalence of selected conditions. Differences in supply versus demand for neurological workforce were calculated. Potential interventions to increase workforce were simulated and effects on supply versus demand estimated. Modelling of the workforce from 2020 to 2034 predicted an increase in neurologist number from 620 to 896. We estimated a 2034 capacity of 638 024 Initial and 1 269 112 Review encounters annually, and deficits against demand estimated as 197 137 and 881 755, respectively. These deficits were proportionately greater in regional Australia, which has 31% of Australia’s population (Australian Bureau of Statistics) but is served by only 4.1% of its neurologists as determined by our 2020 survey of Australia and New Zealand Association of Neurologists members. Nationally, simulated additions to the neurology workforce had some effect on the review encounter supply deficit (37.4%), but in Regional Australia, this impact was only 17.2%. Modelling of the neurologist workforce in Australia for 2020–2034 demonstrates a significant shortfall of supply relative to current and projected demand. Interventions to increase neurologist workforce may attenuate this shortfall but will not eliminate it. Thus, additional interventions are needed, including improved efficiency and additional use of support staff.
Publisher: MDPI AG
Date: 30-09-2016
Publisher: BMJ
Date: 14-11-2019
Publisher: SAGE Publications
Date: 13-05-2022
DOI: 10.1177/13524585221089900
Abstract: People with multiple sclerosis face significant employment-related challenges, with little known of the drivers of these outcomes. We examined prospective trajectories of employment-related outcomes up to 11 years following a first episode of central nervous system (CNS) demyelination (FCD). Participants were aged 18–59 years, at FCD, with at least two observations and were employed at study entry or anytime during follow-up ( n = 207). Outcomes were employment status (full-time, part-time and unemployed), average workhours per week and disability support pension (DSP receiving/not receiving). We used group-based trajectory modelling to identify groups with common trajectories. Factors associated with trajectory membership were explored using log-multinomial regression. Distinct trajectories were identified for employment (4), workhours (4) and DSP (2). Compared with stable full-time, female sex was strongly associated with being in the stable part-time trajectory (risk ratio (RR): 5.35 95% confidence interval (CI) = 2.56–11.20 p 0.001). A greater level of disability at 5-year review (RR: 1.35 95% CI = 1.19–1.53) and having more than two comorbidities at baseline (RR: 2.77 95% CI = 1.37–5.64) were associated with being in early and late deteriorated employment trajectories, respectively. Compared with the increased part-time trajectory, every additional relapse during the 5 years post-FCD was associated with a 10% increased risk of being in the reduced part-time trajectory (RR = 1.10 95%CI = 1.00–1.22). For every additional EDSS point at 5-year review, the risk of being in the DSP trajectory increased (RR = 1.21 95% CI = 1.05–1.41). These trajectories indicate substantial heterogeneity and the complex impact of MS on employment from its earliest timepoints. Understanding these trends could enable better targeting of interventions to facilitate workforce retention, particularly for females, those with a higher number of comorbidities, more frequent relapses and greater rate of disability accrual.
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: SAGE Publications
Date: 25-03-2013
Abstract: Surveying volunteer members of a multiple sclerosis registry is a very cost-effective way of assessing the impact of the disease on life outcomes. However, whether the data from such a study can be generalised to the whole population of persons living with MS in a country or region is unclear. Here we compare the demographic and disease characteristics of participants in one such study, the Australian Multiple Sclerosis Longitudinal Study (AMSLS), with two well-characterised MS prevalence studies with near-complete ascertainment of MS in their study regions. Although some differences were found, these largely represented the effects of geography (sex ratios) and local factors (national immunomodulatory therapy prescribing requirements), and the cohorts were otherwise comparable. Overall, despite comprising only 12–16% of MS cases in Australia, the AMSLS is highly representative of the MS population. Therefore with some minor caveats, the AMSLS data can be generalised to the whole Australasian MS population. Volunteer disease registries such as this can be highly representative and provide an excellent convenience s le when studying rare conditions such as MS.
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: SAGE Publications
Date: 15-04-2013
Abstract: The purpose of this study was to determine the prevalence of multiple sclerosis (MS) in Australia in 2010 using a novel method based on Australia-wide prescription data for MS-specific disease modifying agents. The results obtained were validated against two other prevalence estimates. We obtained the total number of scripts for medications that were used exclusively for the treatment of MS written in Australia for the period January–December 2010. The percentage of MS patients using medications (42–55%) was taken from state-specific surveys of MS Society clients. To estimate prevalence we ided the annual number of scripts dispensed by 12 and adjusted for penetration of medications by state. The prevalence of MS in Australia in 2010 calculated using the prescription method was 21,283 people (95.5/100,000). This compared to 21,200 people (95.2/100,000) obtained from the Australian Bureau of Statistics (ABS) Survey of Disability, Ageing and Carers (SDAC) survey of 2009 and 20,471 people (91.9/100,000) using MS Society client numbers. Prevalence increased with increasing latitude, with the prevalence for Tasmania over seven times that of the Northern Territory. Results were sensitive to the percentage of people with MS being treated. Calculation of prevalence of MS using nation-wide prescription data is a novel method that generates results similar to other potentially more resource-intensive methods.
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: 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: 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: 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: 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: 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: SAGE Publications
Date: 30-11-2018
Publisher: Elsevier BV
Date: 09-2023
Publisher: Elsevier BV
Date: 2018
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.MATURITAS.2017.10.005
Abstract: Vitamin D deficiency has been associated with cognitive decline and dementia in older adults. However, there is a paucity of studies assessing whether this association manifests from midlife. Given the long prodromal stage of dementia, we investigated the association between midlife vitamin D and cognition 10 years later. 252 participants (aged 55-67 years) from the Women's Healthy Ageing Project had baseline (2002) vitamin D and neuropsychological measures assessed. Of these, 170 (aged 65-77 years) had follow-up neuropsychological testing (2012). Serum 25-hydroxyvitamin D (25[OH]D) was measured using an automated chemiluminescence system. The neuropsychological tests used were: Consortium to Establish a Registry for Alzheimer's Disease (CERAD), California Verbal Learning Test Second Edition (CVLT-II), verbal fluency and Trail Making Test-B (TMT-B). Composite scores for verbal episodic memory (CERAD and CVLT-II) and executive function (verbal fluency and TMT-B) were obtained by summating standardized scores for each test. Analyses were adjusted for age, education and body mass index (BMI). Further adjustment for physical activity, depression, vascular risk factors, supplementation and APOE4-genotype did not materially change the results. At baseline, those with vitamin D>25nmol/L performed better on verbal fluency (β=2.46, 95%CI=0.53,4.40) and TMT-B time (β=-18.23, 95%CI=-32.86,-3.61), with higher executive function (β=1.40, 95%CI=0.44,2.37). These relationships persisted 10 years later for TMT-B (β=-15.38, 95%CI=-30.82,0.07) and executive function (β=1.05, 95%CI=0.14,1.95). There were no associations with tests of verbal episodic memory. Midlife vitamin D>25nmol/L is associated with improved aspects of executive function in ageing. Findings highlight a potential therapeutic age window where midlife vitamin D repletion could be neuroprotective against cognitive decline.
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: Wiley
Date: 09-07-2023
DOI: 10.1111/ENE.15940
Abstract: People with multiple sclerosis (pwMS) report reduced quality of life (QoL). Engagement with healthy lifestyle behaviours, including consuming a healthy diet, regular physical activity, and adequate vitamin D exposure, is associated with higher QoL. We aim to assess whether in idual lifestyle behaviours are more beneficial to QoL than others, and whether there are additive benefits to QoL by engaging in multiple healthy behaviours concurrently. Data from pwMS who completed an online survey at baseline, and at 2.5‐, 5‐ and 7.5‐year follow‐up, were analysed. Behaviours assessed were consumption of a no‐meat/dairy‐plus‐omega‐3 supplementation diet, meditation practice, physical activity, non‐smoking, and vitamin D exposure. Mental QoL (mQoL) and physical QoL (pQoL) were assessed by the Multiple Sclerosis Quality of Life (MSQOL‐54) questionaire. Linear regression analyses were performed to assess associations of in idual behaviours at baseline and follow‐up time points with QoL, as well as between number of behaviours and QoL. At baseline, healthy diet and regular physical activity were associated with higher mQoL (5.3/100 and 4.0/100) and higher pQoL (7.8/100 and 6.7/100). Prospectively, diet was positively associated with mQoL, and physical activity with both mQoL and pQoL. At baseline, engagement with ≥3 behaviours was positively associated with mQoL and pQoL, with additive positive associations for each additional behaviour. Prospectively, engagement with ≥3 behaviours was positively associated with mQoL and pQoL, with strongest associations observed with engagement with five behaviours. Consumption of a healthy diet, and regular physical activity, are both potential interventions to improve QoL. Engagement with multiple lifestyle behaviours may provide additional benefits and should be encouraged and supported for multiple sclerosis management.
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: 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: Research Square Platform LLC
Date: 30-03-2021
DOI: 10.21203/RS.3.RS-319260/V1
Abstract: Background: Mastery is the extent to which an in idual perceives their life circumstances as being under their control and not predominantly influenced by external factors. The relationship of mastery with clinical outcomes in people with multiple sclerosis (pwMS) has not been well-researched. We assessed the relationships of mastery with fatigue, disability, relapse number, and depression risk among pwMS over 2.5 years’ follow-up. Methods: Data from the Health Outcomes and Lifestyle in a S le of people with Multiple sclerosis (HOLISM) study, among 839 participants who completed the 2.5 and 5-year reviews, were analysed. Mastery was measured by the Pearlin Mastery Scale, fatigue by Fatigue Severity Scale, depression risk by Patient Health Questionnaire-9, and disability by Patient-Determined Disease Steps, and diagnosed relapse number in the previous 12 months was queried. Cross-sectional and prospective analyses were undertaken by log-binomial, log-multinomial, and Poisson regression, as appropriate, adjusted for relevant confounders. Results: Cross-sectionally, pwMS with the highest quartile mastery ( /28) had 90% lower depression risk, 60% lower frequency of clinically significant fatigue, and 77% fewer with severe disability, all largely robust to adjustment. Prospectively, those in the top two quartiles of mastery ( -25, ) had 66% and 74% lower depression risk, robust to adjustment. No significant associations were seen prospectively for change in fatigue, disability, or relapse number, however, and no robust associations of mastery with relapse number. Conclusions: Prospectively, a protective relationship of mastery with subsequent risk of depression was observed, suggesting this may be a point of intervention to improve wellbeing in pwMS.
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: 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: SAGE Publications
Date: 11-2014
Publisher: Elsevier BV
Date: 2021
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: JMIR Publications Inc.
Date: 09-02-2022
DOI: 10.2196/27735
Abstract: Digital health interventions have revolutionized multiple sclerosis (MS) care by supporting people with MS to better self-manage their disease. It is now understood that the technological elements that comprise this category of digital health interventions can influence participant engagement in self-management programs, and people with MS can experience significant barriers, influenced by these elements, to remaining engaged during a period of learning. It is essential to explore the influence of technological elements in mitigating attrition. This study aimed to examine the study design and technological elements of documented digital health interventions targeted at people with MS—digital health interventions that were intended to support a program of engagement over a defined period—and to explore how these correlated with attrition among participants of randomized controlled trials (RCTs). We conducted a systematic review and meta-analysis of RCTs (n=32) describing digital health self-management interventions for people with MS. We analyzed attrition in included studies, using a random-effects model and meta-regression to measure the association between potential moderators. There were no measured differences in attrition between the intervention and control arms however, some of the heterogeneity observed was explained by the composite technological element score. The pooled attrition rates for the intervention and control arms were 14.7% and 15.6%, respectively. This paper provides insight into the technological composition of digital health interventions designed for people with MS and describes the degree of attrition in both study arms. This paper will aid in the design of future studies in this area, particularly for digital health interventions of this type.
Publisher: National Institute for Health and Care Research
Date: 2019
DOI: 10.3310/HTA23020
Abstract: Randomised controlled trials (RCTs) exploring the potential of vitamin D to prevent acute respiratory infections have yielded mixed results. In idual participant data (IPD) meta-analysis has the potential to identify factors that may explain this heterogeneity. To assess the overall effect of vitamin D supplementation on the risk of acute respiratory infections (ARIs) and to identify factors modifying this effect. MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, ClinicalTrials.gov and the International Standard Randomised Controlled Trials Number (ISRCTN) registry. Randomised, double-blind, placebo-controlled trials of supplementation with vitamin D 3 or vitamin D 2 of any duration having incidence of acute respiratory infection as a prespecified efficacy outcome were selected. Study quality was assessed using the Cochrane Collaboration Risk of Bias tool to assess sequence generation, allocation concealment, blinding of participants, personnel and outcome assessors, completeness of outcome data, evidence of selective outcome reporting and other potential threats to validity. We identified 25 eligible RCTs (a total of 11,321 participants, aged from 0 to 95 years). IPD were obtained for 10,933 out of 11,321 (96.6%) participants. Vitamin D supplementation reduced the risk of ARI among all participants [adjusted odds ratio (aOR) 0.88, 95% confidence interval (CI) 0.81 to 0.96 heterogeneity p 0.001]. Subgroup analysis revealed that protective effects were seen in in iduals receiving daily or weekly vitamin D without additional bolus doses (aOR 0.81, 95% CI 0.72 to 0.91), but not in those receiving one or more bolus doses (aOR 0.97, 95% CI 0.86 to 1.10 p = 0.05). Among those receiving daily or weekly vitamin D, protective effects of vitamin D were stronger in in iduals with a baseline 25-hydroxyvitamin D [25(OH)D] concentration of 25 nmol/l (aOR 0.30, 95% CI 0.17 to 0.53) than in those with a baseline 25(OH)D concentration of ≥ 25 nmol/l (aOR 0.75, 95% CI 0.60 to 0.95 p = 0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (aOR 0.98, 95% CI 0.80 to 1.20 p = 0.83). The body of evidence contributing to these analyses was assessed as being of high quality. Our study had limited power to detect the effects of vitamin D supplementation on the risk of upper versus lower respiratory infection, analysed separately. Vitamin D supplementation was safe, and it protected against ARIs overall. Very deficient in iduals and those not receiving bolus doses experienced the benefit. Incorporation of additional IPD from ongoing trials in the field has the potential to increase statistical power for analyses of secondary outcomes. This study is registered as PROSPERO CRD42014013953. The National Institute for Health Research Health Technology Assessment programme.
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: 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: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.MSARD.2019.01.037
Abstract: Differential treatment allocation may impact on clinical phenotype in MS and in turn upon quality of life (QoL). (a) Investigate the association between disease-modifying drugs (DMDs) use and relapse frequency, disability, clinically significant fatigue, and physical and mental health-related QoL among participants with MS residing in Australia and New Zealand (NZ) (b) assess whether these associations differed between Australia and NZ. Disability and fatigue were measured by PDDS and FSS, respectively. QoL was assessed by MSQOL-54. Associations were assessed by binomial and multinomial logistic regression, as appropriate. Multivariable models were adjusted for demographic and clinical covariates, as appropriate. 837 participants (627 from Australia 210 from NZ) were identified from an online cohort of people with MS. First- and second-generation DMD use was associated with higher adjusted-odds of fatigue and disability, though not with 12-month relapse number. DMD use was not independently associated with physical or mental QoL. The association of first-generation DMD use with moderate disability differed between nations, such that treatment was associated with lower odds in Australia but not in NZ a similar but a small difference was found for severe disability. No differences were seen in the DMD association with relapse number, nor with fatigue or QoL, between Australia and NZ. The differential treatment allocation associations in NZ are evident in the DMD-disability association, but there is no evidence that this treatment regimen has negative associations with fatigue, mood, or QoL.
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: Springer Science and Business Media LLC
Date: 23-02-2023
DOI: 10.1007/S11136-023-03361-W
Abstract: Health state utilities (HSU) are a subjective measure of an in idual's health-related quality of life (HRQoL), adjusted by societal or patient relative preference weights for living in different states of health-related quality of life (HRQoL), derived from patient-reported responses to multi-attribute utility instrument (MAUI), and can be used as inputs for cost-utility analyses and in clinical assessment. This research assessed associations of diet with subsequent HSU in a large international cohort of people living with multiple sclerosis (MS), a progressive autoimmune condition of the central nervous system. HSUs were generated from responses to Short-Form Six-Dimension (SF-6D) MAUI, and quality-of-the-diet by Diet Habits Questionnaire (DHQ). Cross-sectional, and short- and long-term prospective associations of DHQ with HSU evaluated by linear regression at 2.5- and 5-years. Pooled prospective associations between DHQ and HSU evaluated using linear and quantile regression. Analyses adjusted for relevant demographic and clinical covariates. Among 839 participants, baseline DHQ scores showed short- and long-term associations with subsequent HSU, each 10-unit increase in total DHQ score associated with 0.008–0.012 higher HSU (out of 1.00). These associations were dose-dependent, those in the top two quartiles of baseline DHQ scores having 0.01–0.03 higher HSU at follow-up, 0.03 being the threshold for a minimally clinically important difference. Fat, fiber, and fruit/vegetable DHQ subscores were most strongly and consistently associated with better HSU outcomes. However, baseline meat and dairy consumption were associated with 0.01–0.02 lower HSU at subsequent follow-up. A higher quality-of-the-diet showed robust prospective relationships with higher HSUs 2.5- and 5-years later, substantiating previous cross-sectional relationships in this cohort. Subject to replication, these results suggest interventions to improve the quality-of-the-diet may be effective to improve HRQoL in people living with MS.
Publisher: Springer Science and Business Media LLC
Date: 28-09-2023
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: 15-02-2017
DOI: 10.1136/BMJ.I6583
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: CSIRO Publishing
Date: 2012
DOI: 10.1071/SH11002
Abstract: Background Anal cancer is a rare cancer analogous to cervical cancer, largely caused by exposure to oncogenic human papillomavirus. We have sought to study this disease in the epidemiologically distinct population of Tasmania. Methods: Medical records at all tertiary and secondary referral centres in Tasmania were audited for records with corresponding International Classification of Diseases (ICD)-10 codes. Statistical significances of trends were evaluated using Fisher’s exact test, logistic regression or linear regression. Results: Of ~1350 screening records, 170 cases of anal cancer were found with patient presentation during 1973–2010, corresponding to 132 patients. This cohort was mostly female (66.7%), with squamous cell histology (81.8%) and anal canal primaries (72.0%). Most cases were detected at Stage II or below and the majority remained disease-free after treatment. Relatively few cases had documentation of typical risk factors for anal cancer, such as HIV seropositivity, a history of cancer or smoking. After 2000, there was a trend towards a lower stage at presentation, correlating with an increased 5-year survival. After 2000, no anal margin tumours presented beyond Stage II nearly half were detected in situ and none were fatal. For anal canal tumours, there was virtually no change in the mean stage at detection or in survival. Conclusion: This is the first case series of anal cancer in Tasmania. We find that in many ways, including symptoms and pathology at presentation, epidemiology is typical. However, our cohort is distinct in its paucity of known risk groups, including HIV-positive people, those with a history of cancer and smokers.
Publisher: CSIRO Publishing
Date: 2017
DOI: 10.1071/SH16135
Abstract: Background: It has previously been shown that there is a significant demographic variation in sexual health literacy (SHL) in university-level students in Tasmania, Australia. Aims: The aim of this study was to evaluate the effect of statistical adjustment for sexuality-related attitudes on this demographic variation in SHL. Methods: Iterated principal-factor analysis was used to evaluate latent variable grouping of responses to 21 attitudinal questions regarding sexuality and sexual behaviour. Linear regression was used to evaluate the distribution and determinants of attitudinal patterns and thence the relationship of these patterns to SHL. Results: Three patterns – conservative, anti-persons-living-with-HIV and sexually responsible – were identified as explaining variation in sexual attitudes the former two being associated with significantly lower SHL and the latter associated with significantly higher SHL. Adjustment for these patterns significantly attenuated much of the differences in SHL by birthplace/ethnicity and religion, including among South and South-East Asian and Protestant, Islamic and Hindu students. However, some differences in SHL persisted, suggesting they are partly or fully independent of the attitudinal questions. Conclusions: As hypothesised, differences in attitude significantly explained much of the demographic differences in SHL found previously. These results suggest that sexual education and orientation efforts need to bear cultural framing in mind to enhance uptake by students.
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: 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: Wiley
Date: 13-07-2021
DOI: 10.1111/ENE.14956
Abstract: Several modifiable lifestyle factors have been associated with the onset and health outcomes of multiple sclerosis (MS), including clinically significant fatigue. A combined lifestyle score approach represents one method of assessing their relationship with clinical outcomes. The aim was to examine the association of two lifestyle scores with clinically significant fatigue and change thereof over 2.5 years' follow‐up using inverse probability treatment weighting (IPTW). Data on sociodemographic, lifestyle, and clinical characteristics surveyed from an international cohort of people with MS at baseline and at 2.5‐year follow‐up were used. Fatigue was defined by the Fatigue Severity Scale (FSS ) and healthy lifestyle by the Healthy Lifestyle Index Score (HLIS) and the Smoking, Nutrition, Alcohol Consumption and Physical Activity (SNAP) score. Analyses were by IPTW accounting for age, sex, MS type, disability, treated comorbidity number, immunomodulatory medication use, prescription antifatigue medication use, and ongoing relapse symptoms. In total, 1268 participants completed the FSS at both time points approximately 62% had fatigue. Using doubly robust IPTW, high ( /20) HLIS (odds ratio [OR] 0.90, 95% confidence interval [CI] 0.81–0.98) and high ( /5) SNAP (OR 0.82, 95% CI 0.73–0.90) were each associated with lower risk of fatigue at follow‐up. Evaluating change in fatigue, a higher SNAP score was associated with a lower risk of fatigue (OR 0.89, 95% CI 0.80–0.97) but the score for HLIS did not reach statistical significance (OR 0.93, 95% CI 0.85–1.01). These results suggest a robust role for key lifestyle factors in preventing clinically significant fatigue and may represent a place for lifestyle modification in improving clinical outcomes in MS.
Publisher: Springer Science and Business Media LLC
Date: 23-11-2021
DOI: 10.1007/S11136-021-03033-7
Abstract: Mastery is the extent to which an in idual perceives their life circumstances as being under their control and not predominantly influenced by external factors. The relationship of mastery with clinical outcomes in people with multiple sclerosis (pwMS) has not been well-researched. We assessed the relationships of mastery with fatigue, disability, relapse number, and depression risk among pwMS over 2.5 years’ follow-up. Data from the Health Outcomes and Lifestyle in a S le of people with Multiple sclerosis study, among 839 participants who completed the 2.5 and 5-year reviews, were analysed. Mastery was measured by the Pearlin Mastery Scale, fatigue by Fatigue Severity Scale, depression risk by Patient Health Questionnaire-9, and disability by Patient-Determined Disease Steps, and diagnosed relapse number in the previous 12 months was queried. Cross-sectional and prospective analyses were undertaken by log-binomial, log-multinomial, and Poisson regression, as appropriate, adjusted for relevant confounders. Cross-sectionally, pwMS with the highest quartile mastery ( 25/28) had 90% lower frequency of depression risk, 60% lower frequency of clinically significant fatigue, and 77% fewer had severe disability, all largely robust to adjustment. Prospectively, those in the top two quartiles of mastery ( 21–25, 25/28) had 66% and 74% lower subsequent depression risk, robust to adjustment. No significant associations were seen prospectively for change in fatigue, disability, or relapse number, however, and no robust associations of mastery with relapse number were evident. Prospectively, a protective relationship of mastery with subsequent risk of depression was observed, suggesting this may be a point of intervention to improve wellbeing in pwMS.
Location: United States of America
Location: Australia
Location: United States of America
No related grants have been discovered for Steve Simpson-Yap.