This article reports results from the National Survey on Teen Relationships and Intimate Violence (STRiV) for 12- to 18-year-old youth (n = 1,804). STRiV provides the first nationally representative ...household survey focused on adolescent relationship abuse (ARA), covering perpetration and victimization. Among respondents (37%) reporting current- or past-year dating, 69% reported lifetime ARA victimization (63% lifetime ARA perpetration). Although psychological abuse was most common for these youth (more than 60%), the rates of sexual abuse (18%) and physical abuse victimization (18%), as well as 12% reporting perpetrating physical abuse and/or sexual abuse (12%) were substantial as well. Other than differences by age and gender, ARA rates were consistent by race/ethnicity, geographic region, urbanicity, and household characteristics, highlighting the importance of universal prevention programs. Compared with youth aged 15 to 18, those 12 to 14 years old reported lower rates of psychological and sexual ARA victimization. Similarly, we found lower ARA perpetration rates for those 12 to 14. We found no gender differences for ARA victimization but found that girls perpetrated more physical ARA than boys. Girls aged 15 to 18 reported perpetrating moderate threats/physical violence at more than twice the rate of younger girls and 3 times the rate compared with boys aged 15 to 18; girls aged 15 to 18 reported perpetrating more than 4 times the rate of serious psychological abuse than boys 15 to 18. Finally, these data document the significant positive correlation between ARA victimization and perpetration. Findings suggest that when working with youth in prevention services, interventions should not be designed for monolithic groups of “victims” or “perpetrators.”
T helper cells play an important role in the aetiology of Multiple Sclerosis (MS). Vitamin D has an anti-inflammatory effect on T helper cells and can affect onset and pathogenesis of MS. Two genes ...of the metabolic Vitamin D pathway expressed by activated T helper (Th) cells have been identified as MS risk genes by genome-wide association studies, CYP27B1 (25(OH)D3 1-alpha-hydroxylase) and CYP24A1 (1,25(OH)2D3 24-alpha-hydroxylase). Therefore, we hypothesize that the MS risk alleles around gene CYP27B1 and CYP24A1 are associated with the altered inflammatory profile of peripheral Th cells in PBMCs both ex vivo and in vitro potentially influencing the pathogenesis of MS. PBMCs from MS patients (41 RRMS patients in their remitting stage and 4 SPMS patients) and 12 healthy controls were collected, subpopulation of Th cells in PBMCs and cytokine profile were tested by Flow cytometry and Cytometric Bead Array (CBA), respectively. MS risk SNPs were genotyped by allele-specific PCR analysis. Data were analysed using nonparametric tests and linear regression for adjusting multiple factors. The proportion of Th17.1, Th17 and Th1 cells were all associated with MS while the proportions of Th2 (significant) and Th17 (near significant) cells were correlated with the expanded disability scale score of MS patients. Additionally, we found a MS-specific dysregulation in the IL-6 and TNF production of Th cells in Concanavalin A-stimulated PBMCs. Furthermore, the risk allele rs2248359-C (near gene CYP24A1) showed a consistent inhibitory effect on the proportions of Th1 and Th17.1 cells, and the presence of the homozygous risk allele rs703842-AA (near gene CYP27B1) reduced the production of IL-2. In conclusion, both MS disease and its risk alleles near Vitamin D metabolism genes influence the inflammatory profile of T helper cells in PBMCs.
Increasing evidence suggests the potential of Epstein-Barr virus (EBV) vaccination in preventing multiple sclerosis (MS). We aimed to explore the cost-effectiveness of a hypothetical EBV vaccination ...to prevent MS in an Australian setting.
A five-state Markov model was developed to simulate the incidence and subsequent progression of MS in a general Australian population. The model inputs were derived from published Australian sources. Hypothetical vaccination costs, efficacy and strategies were derived from literature. Total lifetime costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were estimated for two hypothetical prevention strategies versus no prevention from the societal and health system payer perspectives. Costs and QALYs were discounted at 5% annually. One-way, two-way and probabilistic sensitivity analyses were performed.
From societal perspective, EBV vaccination targeted at aged 0 and aged 12 both dominated no prevention (ie, cost saving and increasing QALYs). However, vaccinating at age 12 was more cost-effective (total lifetime costs reduced by $A452/person, QALYs gained=0.007, ICER=-$A64 571/QALY gained) than vaccinating at age 0 (total lifetime costs reduced by $A40/person, QALYs gained=0.003, ICER=-$A13 333/QALY gained). The probabilities of being cost-effective under $A50 000/QALY gained threshold for vaccinating at ages 0 and 12 were 66% and 90%, respectively. From health system payer perspective, the EBV vaccination was cost-effective at age 12 only. Sensitivity analyses demonstrated the cost-effectiveness of EBV vaccination to prevent MS under a wide range of plausible scenarios.
MS prevention using future EBV vaccinations, particularly targeted at adolescence population, is highly likely to be cost-effective.
Activation of the kynurenine pathway (KP) of tryptophan metabolism results from chronic inflammation and is known to exacerbate progression of neurodegenerative disease. To gain insights into the ...links between inflammation, the KP and multiple sclerosis (MS) pathogenesis, we investigated the KP metabolomics profile of MS patients. Most significantly, we found aberrant levels of two key KP metabolites, kynurenic acid (KA) and quinolinic acid (QA). The balance between these metabolites is important as it determines overall excitotoxic activity at the N-methyl-D-Aspartate (NMDA) receptor. We also identified that serum KP metabolic signatures in patients can discriminate clinical MS subtypes with high sensitivity and specificity. A C5.0 Decision Tree classification model discriminated the clinical subtypes of MS with a sensitivity of 91%. After validation in another independent cohort, sensitivity was maintained at 85%. Collectively, our studies suggest that abnormalities in the KP may be associated with the switch from early-mild stage MS to debilitating progressive forms of MS and that analysis of KP metabolites in MS patient serum may have application as MS disease biomarkers.
Over the course of a year, we developed and tested a 6-week massive open online course (MOOC) on multiple sclerosis (MS) in consultation with the MS community. The course targeted the MS community ...and interested laypeople and was titled Understanding MS. The primary purpose of the course was to improve MS knowledge, health literacy, and resilience among participants. The final version of the MOOC made available for open enrollment was ranked first among all MOOCs released in 2019 (n>2400) based on participant reviews.
The aim of this study was to present a detailed description and assessment of the development process of the Understanding MS MOOC.
The development process included a course development focus group; the creation of more than 50 content videos and related text, quizzes, activities, and discussion prompts; the creation of original images and animations; a pilot study; and collaborations with people living with MS, MS nurses, allied health care practitioners, and neurologists and researchers from 4 universities.
Overall, the process was efficient and effective. With a few small changes, we recommend this approach to those seeking to develop a similar course. This process led to the development of a highly reviewed MOOC with excellent user satisfaction.
We identified 5 key lessons from this process: (1) community support is essential, (2) stakeholder involvement improves content quality, (3) plan for research from the beginning, (4) coordination between the academic lead and project manager team ensures a consistent voice, and (5) a network of collaborators is a key resource.
Abstract
The strongest epidemiological clue that the environment at the population level has a significant impact on the risk of developing multiple sclerosis is the well established, and in many ...instances, increasing latitudinal gradient of prevalence, incidence and mortality globally, with prevalence increasing by up to 10-fold between the equator and 60° north and south. The drivers of this gradient are thought to be environmental with latitude seen as a proxy for ultraviolet radiation and thus vitamin D production; however, other factors may also play a role. Several important questions remain unanswered, particularly when in the life course is the gradient established, does lifetime migration mitigate or exacerbate previously reported latitude gradients at location of diagnosis, and do factors such as sex or multiple sclerosis disease phenotype influence the timing or significance of the gradient? Utilizing lifetime residence calendars collected as part of the New Zealand National Multiple Sclerosis Prevalence Study, we constructed lifetime latitudinal gradients for multiple sclerosis from birth to prevalence day in 2006 taking into account migration internally and externally and then analysed by sex and multiple sclerosis clinical course phenotype. Of 2917 individuals living in New Zealand on prevalence day, 7 March 2006, with multiple sclerosis, 2127 completed the life course questionnaire and of these, 1587 were born in New Zealand. All cohorts and sub-cohorts were representative of the overall multiple sclerosis population in New Zealand on prevalence day. We found that the prevalence gradient was present at birth and was, in fact, stronger than at census day, and the slope of the gradient persisted until the age of 12 before gradually declining. We found that internal and external migration into New Zealand had little, if any, effect on the gradient except to decrease the significance of the gradient somewhat. Finally, we found as we had reported previously, that the lifetime prevalence gradients were largely driven by females with relapse onset multiple sclerosis. These findings confirm for the first time the importance of early life environmental exposures in the risk of multiple sclerosis indicating strongly that exposures as early as in utero and at birth drive the latitudinal gradient. Consequently, prevention studies should be focused on high-risk individuals and populations from the earliest possible time points especially, when appropriate, on females.
Background:
The MS disease-modifying therapies (DMTs) prescribing landscape in Australia have changed over time.
Objectives:
This study evaluated the utilisation and cost trends of MS-related DMTs in ...Australia over 10 years and investigated differences between States/Territories.
Methods:
The prescription and costs of 16 DMTs were extracted from the Pharmaceutical Benefits Scheme for 2013–2022. Descriptive approaches analysed the total number of people prescribed DMTs and total DMT costs per 10,000 population, proportions of prescriptions/costs by DMT groups and the number of people prescribed each individual DMT and costs of each DMT over the 10-year period. All estimates were for Australia and each State/Territory individually.
Results:
The number of people prescribed DMT and costs per 10,000 population had substantial growth between 2013 and 2022: 125%/164% for Australia, and 94%–251%/129%–373% for individual States/Territories. Higher efficacy group accounted for 54% of total people prescribed DMTs in 2013 and 75% in 2022. Fingolimod was the most popular DMT until 2020, then was dominated by ocrelizumab. The trends of individual DMT prescriptions and costs differed between states particularly in Western Australia (WA), Tasmania and Northern Territory (NT).
Conclusion:
DMT prescriptions and costs continuously increased over the last decade, particularly for higher efficacy DMTs, and their trends differed between States/Territories.
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an inflammatory neuropathy, classically characterised by a slowly progressive onset and symmetrical, sensorimotor involvement. ...However, there are many phenotypic variants, suggesting that CIDP may not be a discrete disease entity but rather a spectrum of related conditions. While the abiding theory of CIDP pathogenesis is that cell-mediated and humoral mechanisms act together in an aberrant immune response to cause damage to peripheral nerves, the relative contributions of T cell and autoantibody responses remain largely undefined. In animal models of spontaneous inflammatory neuropathy, T cell responses to defined myelin antigens are responsible. In other human inflammatory neuropathies, there is evidence of antibody responses to Schwann cell, compact myelin or nodal antigens. In this review, the roles of the cellular and humoral immune systems in the pathogenesis of CIDP will be discussed. In time, it is anticipated that delineation of clinical phenotypes and the underlying disease mechanisms might help guide diagnostic and individualised treatment strategies for CIDP.
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