Estimation of Transition Probabilities from a Large Cohort (> 6000) of Australians Living with Multiple Sclerosis (MS) for Changing Disability Severity Classifications, MS Phenotype, and Disease-Modifying Therapy Classifications.

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune/neurodegenerative disease associated with progressing disability affecting mostly women. We aim to estimate transition probabilities describing MS-related disability progression from no disability to severe disability. Transition probabilities are a vital input for health economics models. In MS, this is particularly relevant for pharmaceutical agency reimbursement decisions for disease-modifying therapies (DMTs). METHODS: Data were obtained from Australian participants of the MSBase registry. We used a four-state continuous-time Markov model to describe how people with MS transition between disability milestones defined by the Expanded Disability Status Scale (scale 0-10): no disability (EDSS of 0.0), mild (EDSS of 1.0-3.5), moderate (EDSS of 4.0-6.0), and severe (EDSS of 6.5-9.5). Model covariates included sex, DMT usage, MS-phenotype, and disease duration, and analysis of covariate groups were also conducted. All data were recorded by the treating neurologist. RESULTS: A total of N = 6369 participants (mean age 42.5 years, 75.00% female) with 38,837 person-years of follow-up and 54,570 clinical reviews were identified for the study. Annual transition probabilities included: remaining in the no, mild, moderate, and severe states (54.24%, 82.02%, 69.86%, 77.83% respectively) and transitioning from no to mild (42.31%), mild to moderate (11.38%), and moderate to severe (9.41%). Secondary-progressive MS was associated with a 150.9% increase in the hazard of disability progression versus relapsing-remitting MS. CONCLUSIONS: People with MS have an approximately 45% probability of transitioning from the no disability state after one year, with people with progressive MS transitioning from this health state at a much higher rate. These transition probabilities will be applied in a publicly available health economics simulation model for Australia and similar populations, intended to support reimbursement of a plethora of existing and upcoming interventions including medications to reduce progression of MS.

Longitudinal epidemiology of multiple sclerosis over 60 years in Newcastle, Australia: 1961 to 2021.

INTRODUCTION: Newcastle, Australia, has been serially studied for MS epidemiology since 1961, showing consistently increasing prevalence estimates and incidence rates, including to our 2011 study. OBJECTIVES: To assess the 2011-2021 epidemiology of MS in Newcastle and to compare with previous measures. METHODS: Demographic and clinical data were extracted from medical records of MS cases residing in Newcastle, as identified by public and private clinicians. Prevalence (2011 and 2021) and incidence rates (2011-2021, from onset and from diagnosis) and mortality rate (2011-2021) were estimated and age-standardised to the 2021 Australian population. RESULTS: The 2021 prevalence was 173.1/100,000 (age-standardised = 178.7/100,000, F/M-sex-ratio = 3.3), a 42.2 % increase from 2011 (F/M-sex-ratio = 3.1), 175.0 % from 1996 (F/M-sex-ratio = 2.6), and 831.0 % from 1961 (F/M-sex-ratio = 1.2). The 2011-21 age-standardised onset incidence rate was 3.5/100,000 person-years (F/M-sex-ratio = 2.8), a 68.7 % increase from 1971 to 81 (F/M-sex-ratio = 1.1) and 44.5 % from 1986 to 96 (F/M-sex-ratio = 2.3). The age-standardised diagnosis incidence rate was 6.1/100,000 (F/M-sex-ratio = 2.2), statistically unchanged from that in 2001-2011 (6.8/100,000, F/M-sex-ratio = 3.2). The 2011-21 mortality rate was 2.1/100,000 person-years (2.2 age-standardised, F/M-sex-ratio = 1.4), with a standardised mortality ratio of 1.6. CONCLUSION: The Newcastle region continues to be a high frequency zone for MS. The incidence rate from onset is significantly increased from previous estimates, but incidence rate from diagnosis is stable. Prevalence and incidence sex ratios have stabilised at roughly 3.0, similar to other Australian sites.

Significantly increasing multiple sclerosis prevalence in Australia from 2010 to 2021.

BACKGROUND: Multiple sclerosis (MS) prevalence is increasing globally. OBJECTIVES: To determine whether increased prevalence is continuing within Australia using our validated prescription-based ascertainment method. METHODS: We used methods employed in our 2010 and 2017 prevalence estimates. Disease-modifying therapy (DMT) prescriptions were extracted from Australia's Pharmaceutical Benefits Scheme data for January-December 2021. DMT penetrance was calculated using data from the Australian MS Longitudinal Study. We divided the total number of monthly prescriptions by 12 or 2 (except alemtuzumab), adjusted for DMT penetrance and Australian population estimates. Prevalences in Australian states/territories were age-standardised. 2021 prevalence estimates were compared with 2010 and 2017 prevalence estimates using Poisson regression. RESULTS: Number of people with MS in Australia in 2021 was 33,335; an increase of 7728 from 2017 (30.2%) and 12,092 from 2010 (56.6%) and increasing at a faster rate than population change (+10.1%, +14.1%). Age-standardised prevalence was 136.1/100,000 (increased from 103.7/100,000 in 2017). The previously demonstrated positive latitudinal gradient in 2010 and 2017 persisted in 2021, with Tasmania (southernmost state) having the highest prevalence (age-standardised: 203.5/100,000) while northernmost states had the lowest. CONCLUSIONS: In line with global trends, MS prevalence is escalating in Australia, particularly in higher-latitude states. MS prevention is crucial to halt this disturbing trend.

Low intensity repetitive transcranial magnetic stimulation enhances remyelination by newborn and surviving oligodendrocytes in the cuprizone model of toxic demyelination.

In people with multiple sclerosis (MS), newborn and surviving oligodendrocytes (OLs) can contribute to remyelination, however, current therapies are unable to enhance or sustain endogenous repair. Low intensity repetitive transcranial magnetic stimulation (LI-rTMS), delivered as an intermittent theta burst stimulation (iTBS), increases the survival and maturation of newborn OLs in the healthy adult mouse cortex, but it is unclear whether LI-rTMS can promote remyelination. To examine this possibility, we fluorescently labelled oligodendrocyte progenitor cells (OPCs; Pdgfrα-CreER transgenic mice) or mature OLs (Plp-CreER transgenic mice) in the adult mouse brain and traced the fate of each cell population over time. Daily sessions of iTBS (600 pulses; 120 mT), delivered during cuprizone (CPZ) feeding, did not alter new or pre-existing OL survival but increased the number of myelin internodes elaborated by new OLs in the primary motor cortex (M1). This resulted in each new M1 OL producing ~ 471 µm more myelin. When LI-rTMS was delivered after CPZ withdrawal (during remyelination), it significantly increased the length of the internodes elaborated by new M1 and callosal OLs, increased the number of surviving OLs that supported internodes in the corpus callosum (CC), and increased the proportion of axons that were myelinated. The ability of LI-rTMS to modify cortical neuronal activity and the behaviour of new and surviving OLs, suggests that it may be a suitable adjunct intervention to enhance remyelination in people with MS.

Racial discrimination and mental health in the context of anti-Asian xenophobia: An intersecting approach of race, ethnicity, nativity, and socioeconomic status.

The COVID-19 pandemic, polarized politics, and heightened stigma and discrimination are salient drivers for negative mental health outcomes, particularly among marginalized racial and ethnic minoritized groups. Intersectionality of race, ethnicity, foreign-born status, and educational attainment may distinctively shape an individual's experience of discrimination and mental health during such unprecedented time. The present study examines the differential associations of racial discrimination and mental health based on an individual's race, ethnicity, foreign-born status, and educational attainment during the COVID-19 pandemic. Analyses were based on a nationally representative sample of U.S. adults collected between October and November 2021 (n = 6276). We utilized multivariable linear regressions to identify the multiplicative effects of race, ethnic, foreign-born status and self-reported racial discrimination on mental health, stratified by educational attainment. Among individuals with lower educational attainment, associations between racial discrimination and poor mental health were stronger among Asians (US-born: ß = -2.07, p = 0.03; foreign-born: ß = -3.18, p = 0.02) and US-born multiracial individuals (ß = -1.96, p = 0.02) than their White counterparts. Among individuals with higher educational attainment, foreign-born Hispanics (ß = -3.66, p < 0.001) and US-born Asians (ß = -2.07, p = 0.01) reported worst mental health when exposed to racial discrimination out of all other racial, ethnic and foreign-born groups. Our results suggest that association of racial discrimination and mental health varies across racial, ethnic, foreign-born, and education subgroups. Using an intersectional approach to address the widening inequities in racial discrimination and mental health during the COVID-19 pandemic contextualizes unique experience of discrimination and provides crucial insight on the patterns of mental health among marginalized groups.

Exploring the workplace factors and their influence on the employment outcomes for people with multiple sclerosis.

BACKGROUND: High unemployment rate of people with multiple sclerosis (PwMS) is associated with substantial economic costs. Whilst the impact of MS symptoms and other disease-related factors on employment outcomes of PwMS has been assessed, limited evidence exists on the impacts of workplace factors. OBJECTIVE: To investigate the most common individual and group workplace factors associated with unemployment or a perceived risk of unemployment in PwMS, and to identify patient subgroups that are more susceptible to changes in employment status due to such factors. METHODS: Data from the Australian MS Longitudinal Study (AMSLS) on employment status and workplace factors were used. Fifteen workplace factors were classified under four groups: organisational, commuting, moving around at work, and equipment usage factors. Participants answered 'Yes' to each factor if it related to their unemployment and/or perceived risk of becoming unemployed and a group factor was considered "Yes" if at least one individual factor within it was answered as "Yes". The proportions of "Yes" responses were calculated for both individual and group factors. Total number of individual factors was calculated and descriptive analyses and ordered logistic regression were used to summarize the total number of factors affecting each participant, and their association with participants' occupations, sex, disability severity and disease duration. RESULTS: Common workplace factors influencing employment were organisational (39.8 % perceived risk, 44.0 % lost employment), commuting (28.9 % perceived risk) and equipment usage difficulty (30.9 % lost employment). Common individual factors included inflexible working conditions, lack of suitable work, commuting difficulties, architectural barriers, and requirement to stand for long periods to use equipment. Professionals, blue-collar workers, and those with moderate/severe disability were more likely to report a higher number of workplace factors risking their employment. CONCLUSIONS: Workplace factors undermine PwMS employment, with variations among subgroups based on occupation and disability severity. Understanding these barriers is crucial for supporting PwMS in the workforce.

Pointing Fingers: Who US Adults Blame for the Opioid Overdose Epidemic.

BACKGROUND: Over 3 million Americans have an opioid use disorder (OUD), and only a fraction receive treatment. Public opinion is crucial in enacting evidence-based policies. Few studies have examined the public's perception of blame for the ongoing opioid overdose epidemic directed at distinct groups. We assessed US adults' perceived blameworthiness for the epidemic and examined factors that may influence the perceived blameworthiness. METHODS: We conducted a national survey in 2022 using the AmeriSpeak® panel to assess US adults' perception of blame toward individuals with an OUD and external contributors. Of the 3335 eligible panel members invited to participate, 1233 (37%) completed the survey. We developed a measure of knowledge and understanding of OUD, with a higher value indicating a greater understanding of the nature of OUD and recovery-including knowledge and beliefs on evidence-based treatment and relapse. We analyzed the relationships between sources of blame, knowledge, and understanding of OUD, and individual-level correlates. RESULTS: Higher score of knowledge and understanding of OUD was associated with lower odds of blaming individuals with OUD (odds ratio [OR] = 0.73, 95% confidence interval [CI] = [0.51, 1.05]) and greater odds of blaming external contributors: healthcare providers (OR = 1.49, 95% CI = [1.05, 2.12]), pharmaceutical companies (OR = 2.17, 95% CI = [1.50, 3.15]), and health insurance companies (OR = 1.42, 95% CI = [0.97, 2.09]). Those who are female, non-Hispanic White, Democrat, have higher education, or have friends or family who misused opioids tended to score higher in knowledge and understanding of OUD. CONCLUSIONS: Perceived blameworthiness for the opioid overdose epidemic is related to knowledge and understanding of OUD. Public health campaigns with a bipartisan agenda to increase evidence-informed knowledge about OUD targeting people of color and with lower education may help reduce the blame toward people with an OUD, which in turn may increase support for evidence-informed policies.

Knowledge, Attitudes, and Beliefs About Opioid Use Disorder Treatment in Primary Care.

This survey study assesses the US public's perception and awareness regarding medication for opioid use disorder and its availability in primary care settings.

The association of comorbidities with sleep quality among Australians with multiple sclerosis: Insights from the Australian Multiple Sclerosis Longitudinal Study.

BACKGROUND: Comorbidities and poor sleep quality are prevalent among individuals with multiple sclerosis (MS). Our understanding of the effects of comorbidities on sleep quality in MS remains limited. OBJECTIVES: The objectives were to investigate whether the number and presence of specific comorbidities have associations with sleep quality and to assess the relative contribution of comorbidity groups to sleep quality. METHODS: We collected data on sleep quality (using Pittsburgh Sleep Quality Index (PSQI)) and presence of comorbidities in people with MS (n = 1597). Associations between comorbidities and sleep quality were examined using linear regression and dominance analysis. RESULTS: Having more comorbidities was associated with poorer sleep quality (p for trend < 0.001). All 13 groups of comorbidities explained 12.9% of the variance in PSQI from which half of the variance was contributed by mental health disorders. In total, 16 of the 28 comorbidities were associated with significantly worse sleep quality, with the strongest associations seen for 'other autoimmune diseases' (ß = 1.98), depression (ß = 1.76), anxiety (ß = 1.72) and rheumatoid arthritis (ß = 1.62). CONCLUSIONS: Many individual comorbidities are associated with poorer sleep quality, with mental health disorders making the largest relative contribution. Optimal management of comorbidities that make the greatest contributions could have the largest benefit for improving sleep in MS.

Low-intensity repetitive transcranial magnetic stimulation is safe and well tolerated by people living with MS - outcomes of the phase I randomised controlled trial (TAURUS).

Background: Low-intensity repetitive transcranial magnetic stimulation (rTMS), delivered as a daily intermittent theta burst stimulation (iTBS) for four consecutive weeks, increased the number of new oligodendrocytes in the adult mouse brain. Therefore, rTMS holds potential as a remyelinating intervention for people with multiple sclerosis (MS). Objective: Primarily to determine the safety and tolerability of our rTMS protocol in people with MS. Secondary objectives include feasibility, blinding and an exploration of changes in magnetic resonance imaging (MRI) metrics, patient-reported outcome measures (PROMs) and cognitive or motor performance. Methods: A randomised (2:1), placebo controlled, single blind, parallel group, phase 1 trial of 20 rTMS sessions (600 iTBS pulses per hemisphere; 25% maximum stimulator output), delivered over 4-5 weeks. Twenty participants were randomly assigned to 'sham' (n = 7) or active rTMS (n = 13), with the coil positioned at 90° or 0°, respectively. Results: Five adverse events (AEs) including one serious AE reported. None were related to treatment. Protocol compliance was high (85%) and blinding successful. Within participant MRI metrics, PROMs and cognitive or motor performance were unchanged over time. Conclusion: Twenty sessions of rTMS is safe and well tolerated in a small group of people with MS. The study protocol and procedures are feasible. Improvement of sham is warranted before further investigating safety and efficacy.

Protocol for a pragmatic randomised controlled feasibility study of MS WorkSmart: an online intervention for Australians with MS who are employed.

INTRODUCTION: Multiple sclerosis (MS) causes a wide variety of symptoms. Loss of income due to sickness and early retirement comprise one-third of the total cost of MS in Australia. An intervention that maximises work productivity and keeps people with MS in the workforce for longer could provide a large societal cost saving and improve quality of life. The aim is to test the feasibility of delivering and evaluating a 10-week digitally delivered intervention called 'MS WorkSmart'. Findings will provide insights into participant profiles and address key methodological and procedural uncertainties (recruitment, retention, intervention adherence and engagement, and selection of primary outcome) in preparation for a subsequent definitive trial. METHODS AND ANALYSIS: A parallel-arm randomised controlled feasibility study, comparing those randomised to receive the MS WorkSmart package plus usual care (n=20) to those receiving usual care only (n=20). Australians with MS, aged 18-60 years, who are employed, and self-report work instability will be recruited from the Australian MS Longitudinal Study. Online surveys, at baseline and 1-month postintervention, will include MS-related work productivity loss and risk of job loss, MS work behaviour self-efficacy, health-related quality of life, fatigue severity, MS symptom impact on work, intention to retire due to MS, MS-related work difficulties, and awareness and readiness for change at work. Qualitative feedback will be obtained via a semistructured survey following the intervention (for participants) and via interviews (coaches). Analyses will be primarily descriptive and focus on the feasibility and acceptability of the intervention and study procedures. Progression criteria will guide decisions around whether to progress to a full trial. ETHICS AND DISSEMINATION: The study has been approved by the University of Tasmania Human Research Ethics Committee (H0024544). Findings will be disseminated via publication in peer-reviewed journals, conference presentations and community presentations. TRIAL REGISTRATION NUMBER: ACTRN12622000826741.

Corrigendum to "Stigma towards persons who use methamphetamine: Results from a nationally representative survey of U.S. Adults" [Pre. Med. Rep. 36 (2023) 102496].

[This corrects the article DOI: 10.1016/j.pmedr.2023.102496.].

Changes in Partner-Seeking and Sexual Behavior Among US Adults During the First 2 Years of the COVID-19 Pandemic.

BACKGROUND: The COVID-19 pandemic may have influenced partner-seeking and sexual behaviors of adults. METHODS: We examined cross-sectional survey data collected at the end of the first year (n = 1161) and second year (n = 1233) of the COVID-19 pandemic by the National Opinion Research Center's nationally representative, probability-based AmeriSpeak panel. Data were analyzed to (1) quantify behavioral changes across pandemic years, (2) examine changes of in-person dating prevalence during year 2, and (3) assess risk perception for acquiring COVID-19 or HIV/STIs through new partnerships during year 2. Weighted percentages were calculated for responses; univariate relationships between demographic characteristics and outcomes were assessed. RESULTS: Prevalence of new partners for dating remained stable across pandemic years (year 1: n = 1157 [10%]; year 2: n = 1225 [12%]). The prevalence of in-person sex with new partners was also stable (year 1: n = 1157 [7%], year 2: n = 1225 [6%]), marking a decline from a prepandemic estimate (2015-2016: 16%). Partner-seeking experiences varied by age and sexual identity in both years, and by race/ethnicity during year 2. Reports of in-person dating fluctuated throughout year 2, without clear relationship to viral variants. Respondents who met new partners in person during year 2 generally reported greater concern and preparedness for reducing risks associated with HIV/STIs than COVID-19. CONCLUSIONS: The prevalence of US adults seeking new partners for dating or sex remained stable across pandemic years. During future public health emergencies, public health officials are encouraged to offer guidance for reducing disease risks in partnerships, while emphasizing sexual health and providing tailored messaging for persons more susceptible to infection.

The quality of life impact of the COVID-19 pandemic and lockdowns for people living with multiple sclerosis (MS): evidence from the Australian MS Longitudinal Study.

PURPOSE: People living with multiple sclerosis (PwMS) in metropolitan Victoria, Australia, experienced a 112-day, COVID-19-related lockdown in mid-2020. Contemporaneously, Australian PwMS elsewhere experienced minimal restrictions, resulting in a natural experiment. This study investigated the relationships between lockdowns, COVID-19-related adversity, and health-related quality of life (HRQoL). It also generated health state utilities (HSU) representative of changes in HRQoL. METHODS: Data were extracted from Australian MS Longitudinal Study surveys, which included the Assessment of Quality of Life-Eight Dimensions (AQoL-8D) instrument and a COVID-19 questionnaire. This COVID-19 questionnaire required participants to rank their COVID-19-related adversity across seven health dimensions. Ordered probits were used to identify variables contributing to adversity. Linear and logit regressions were applied to determine the impact of adversity on HRQoL, defined using AQoL-8D HSUs. Qualitative data were examined thematically. RESULTS: N = 1666 PwMS (average age 58.5; 79.8% female; consistent with the clinical presentation of MS) entered the study, with n = 367 (22.0%) exposed to the 112-day lockdown. Lockdown exposure and disability severity were strongly associated with higher adversity rankings (p < 0.01). Higher adversity rankings were associated with lower HSUs. Participants reporting major adversity, across measured health dimensions, had a mean HSU 0.161 (p < 0.01) lower than participants reporting no adversity and were more likely (OR: 2.716, p < 0.01) to report a clinically significant HSU reduction. Themes in qualitative data supported quantitative findings. CONCLUSIONS: We found that COVID-19-related adversity reduced the HRQoL of PwMS. Our HSU estimates can be used in health economic models to evaluate lockdown cost-effectiveness for people with complex and chronic (mainly neurological) diseases.

Police Use of Discretion in Encounters with People with Opioid Use Disorder: a Study of Illinois Police Officers.

Police frequently encounter people with opioid use disorder (OUD), having a profound effect on their risk environment and health outcomes. Officers retain significant discretionary authority in their response to these encounters. To explore the factors that underlie these decisions, we surveyed a sample of Illinois police officers. We administered an online survey to Illinois police departments using a random sampling strategy, stratified by agency size and the rurality of their service areas. Our final sample was 248 police officers from 27 departments. We surveyed officers' beliefs about (1) influences and control over their decision making; (2) the approval of other actors in making referrals to treatment for addiction, and (3) the potential impacts of medication-assisted treatment (MAT). We analyzed the survey data using descriptive statistics and regression analyses. Most officers were highly influenced by the expectations of their supervisors when responding to subjects who appeared to have an OUD, and about half would take direction from addiction treatment providers. Police in urban departments perceived greater support for MAT and were more likely to believe MAT could reduce the need for future arrests. Our findings suggest ways police officers can be influenced to make discretionary decisions that improve the health outcomes of their encounters with people with OUD: (1) Supervisors should serve as champions to promote referrals to treatment for substance use disorders; (2) collaboration between law enforcement and community addiction treatment providers should be strengthened, and (3) MAT should be supported and expanded in rural areas.

The Saturation- and Dose-Dependent Effects of a Teen Sexual Harassment Prevention Program: Findings from a Randomized Controlled Trial.

Using a randomized controlled trial, we investigated changes in both sexual harassment (SH) perpetration and victimization of 2104 middle school students in New York City who received divergent saturation and dosage levels of Shifting Boundaries, an SH prevention program, which was represented by the length of the program. We assessed the saturation effect of the program by comparing the outcomes across respondents from 26 schools in which there were varying percentages of students enrolled in the program. The data suggested that, overall, the program was effective in reducing sexual harassment victimization but achieved a null effect against respondents' SH perpetration and that neither the length nor the school-saturation level of the program exerted a significant effect on SH perpetration. Although the data indicated a significant difference in SH victimization between the treatment and control group, when comparing subgroups who received treatment with divergent saturation and dosage levels, no statistically significant difference was identified. Our results suggested that the program effect was not contingent on the portion of students in a school who enrolled in the program, nor was it contingent on the dosage.

High School Follow-Up of the Dating Matters® RCT: Effects on Teen Dating Violence and Relationship Behaviors.

Teen dating violence (TDV) is a significant public health problem that can have lifelong consequences. Using a longitudinal, cluster randomized controlled trial (RCT), this study examines whether the Dating Matters comprehensive prevention model, implemented in middle school, prevented TDV and negative relationship behaviors and promoted positive relationship behaviors in high school (9th-11th grades), when compared with a standard of care intervention. Dating Matters includes programs for sixth to eighth grade youth and their parents, training for school staff, a youth communications program, and policy and data activities implemented in the community. Self-report survey data were collected from students in 46 middle schools that were randomly assigned to condition within site. Students completed two surveys (fall and spring) in each middle school grade and a single survey in the spring of each high school grade. This study examined self-reported TDV perpetration and victimization, use of negative conflict resolution strategies, and positive relationship skills in the high school follow-up. While varying patterns emerged, latent panel models demonstrated significant program effects for all outcomes. Dating Matters students reported 19% reduced risk for TDV perpetration, 24% reduced risk for TDV victimization, 7% reduced risk for use of negative conflict strategies, and 3% more use of positive relationship skills, on average across time and cohort, than standard of care students. On average, Dating Matters, implemented in middle school, continued to be more effective at reducing TDV perpetration, TDV victimization, and use of negative conflict resolution strategies in high school than an evidence-based comparison program.Trial Registration: clinicaltrials.gov Identifier: NCT01672541.