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.

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.].

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.

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 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.

CVOT Summit Report 2023: new cardiovascular, kidney, and metabolic outcomes.

The 9th Cardiovascular Outcome Trial (CVOT) Summit: Congress on Cardiovascular, Kidney, and Metabolic Outcomes was held virtually on November 30-December 1, 2023. This reference congress served as a platform for in-depth discussions and exchange on recently completed outcomes trials including dapagliflozin (DAPA-MI), semaglutide (SELECT and STEP-HFpEF) and bempedoic acid (CLEAR Outcomes), and the advances they represent in reducing the risk of major adverse cardiovascular events (MACE), improving metabolic outcomes, and treating obesity-related heart failure with preserved ejection fraction (HFpEF). A broad audience of endocrinologists, diabetologists, cardiologists, nephrologists and primary care physicians participated in online discussions on guideline updates for the management of cardiovascular disease (CVD) in diabetes, heart failure (HF) and chronic kidney disease (CKD); advances in the management of type 1 diabetes (T1D) and its comorbidities; advances in the management of CKD with SGLT2 inhibitors and non-steroidal mineralocorticoid receptor antagonists (nsMRAs); and advances in the treatment of obesity with GLP-1 and dual GIP/GLP-1 receptor agonists. The association of diabetes and obesity with nonalcoholic steatohepatitis (NASH; metabolic dysfunction-associated steatohepatitis, MASH) and cancer and possible treatments for these complications were also explored. It is generally assumed that treatment of chronic diseases is equally effective for all patients. However, as discussed at the Summit, this assumption may not be true. Therefore, it is important to enroll patients from diverse racial and ethnic groups in clinical trials and to analyze patient-reported outcomes to assess treatment efficacy, and to develop innovative approaches to tailor medications to those who benefit most with minimal side effects. Other keys to a successful management of diabetes and comorbidities, including dementia, entail the use of continuous glucose monitoring (CGM) technology and the implementation of appropriate patient-physician communication strategies. The 10th Cardiovascular Outcome Trial Summit will be held virtually on December 5-6, 2024 ( http://www.cvot.org ).

No evidence for association between rs10191329 severity locus and longitudinal disease severity in 1813 relapse-onset multiple sclerosis patients from the MSBase registry.

BACKGROUND: The International Multiple Sclerosis Genetics Consortium and MultipleMS Consortium recently reported a genetic variant associated with multiple sclerosis (MS) severity. However, it remains unclear if these variants remain associated with more robust, longitudinal measures of disease severity. METHODS: We examined the top variant, rs10191329, from Harroud et al.'s study in 1813 relapse-onset MS patients from the MSBase Registry to assess association with longitudinal disease severity. RESULTS: Our analysis revealed no significant association between rs10191329 genotype and longitudinal binary disease severity (p > 0.05). CONCLUSION: These findings highlight the complexity of genetic factors mediating long-term MS outcomes and the need for further research.

The immune cell transcriptome is modulated by vitamin D3 supplementation in people with a first demyelinating event participating in a randomized placebo-controlled trial.

Vitamin D deficiency is a risk factor for developing multiple sclerosis. The PrevANZ trial was conducted to determine if vitamin D3 supplementation can prevent recurrent disease activity in people with a first demyelinating event. As a sub-study of this trial, we investigated the effect of supplementation on peripheral immune cell gene expression. Participants were randomized to 1000, 5000 or 10,000 international units daily of vitamin D3 or placebo. Peripheral blood was collected at baseline and 12 weeks and sent for ribonucleic acid sequencing. Datasets from 55 participants were included. Gene expression was modulated by high dose supplementation. Antigen presentation and viral response pathways were upregulated. Oxidative phosphorylation and immune signaling pathways, including tumor necrosis factor-alpha and interleukin-17 signaling, were downregulated. Overall, vitamin D3 supplementation for 12 weeks modulated the peripheral immune cell transcriptome with induction of anti-inflammatory gene expression profiles. Our results support a dose-dependent effect of vitamin D3 supplementation on immune gene expression.

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.

School-based interventions TO Prevent Dating and Relationship Violence and Gender-Based Violence: STOP-DRV-GBV systematic review.

Background: Schools have a duty of care to prevent violence between students but a significant amount of dating and relationship violence and gender-based violence occurs in schools. These are important public health issues with important longitudinal consequences for young people. Objectives: To understand functioning and effectiveness of school-based interventions for the prevention of dating and relationship violence and gender-based violence. Review methods: We undertook a mixed-methods systematic review to synthesise different types of evidence relating to school-based interventions for the prevention of dating and relationship violence and gender-based violence to understand if, how and in what ways these interventions are effective. We searched 21 databases and 2 trial registers and undertook forwards and backwards citation chasing, author contact and other supplementary search methods. Searches identified all literature published to June 2021. All screening was undertaken in duplicate and independently, and we quality appraised all included studies. Results: We included 247 reports (68 outcome evaluations, 137 process evaluations). Synthesis of intervention components produced an intervention typology: single-component, curricular, multicomponent, and multilevel programmes. Synthesis of intervention theories suggested that interventions aiming to increase students' sense of school belonging and sense of safety in the school building could encourage increased learning of prosocial skills and increased prosocial peer norms, and so potentially reducing dating and relationship violence and gender-based violence. Synthesis of factors affecting delivery highlighted school organisation and leaders who believed in the importance of addressing dating and relationship violence/gender-based violence, along with time and resources to deliver the interventions. The ease with which the intervention could be delivered and modified was also important. Meta-analysis found stronger evidence for intervention effectiveness in reducing dating and relationship violence than for gender-based violence, with significant long-term impacts on dating and relationship violence victimisation and perpetration, and some evidence that interventions in high-income countries could be effective for reducing victimisation and perpetration of gender-based violence in the long-term. Impacts on knowledge and attitudes were primarily short-term. Network meta-analysis did not suggest superiority of any intervention type. Moderation evidence suggested interventions reduced dating and relationship violence perpetration in boys more than girls, but reduced gender-based violence perpetration more in girls. Metaregression by intervention component did not explain heterogeneity in effectiveness, but qualitative comparative analysis suggested that reducing perpetration was important to reducing victimisation, and that perpetration could be reduced via focus on interpersonal skills, guided practice and (for gender-based violence) implementation of social structural components. Limitations: Despite an exhaustive search, trials may have been missed and risk of publication bias was high for several analyses. Conclusions: This is the most comprehensive systematic review of school-based interventions for dating and relationship violence and gender-based violence to date. It is clear that the prevention of dating and relationship violence and gender-based violence in schools will require longer-term investment to show benefit. Future work: Future research is needed to understand why intervention effectiveness appears stronger for dating and relationship violence than gender-based violence. Study registration: The study is registered as PROSPERO CRD42020190463. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme (NIHR award ref: NIHR130144) and is published in full in Public Health Research; Vol. 12, No. 3. See the NIHR Funding and Awards website for further award information.

Schools are places where dating and relationship violence and gender-based violence occur. Therefore, interventions conducted within schools are ideally placed to prevent and reduce dating and relationship violence and gender-based violence. We reviewed existing research on these interventions, exploring how they were expected to work, what factors affected their implementation in practice, how they had an impact on dating and relationship violence and gender-based violence, and what specific parts of the interventions were most effective and in what contexts. We defined what sort of evidence to include in the review, carried out a comprehensive search and found 247 reports on school-based interventions to prevent dating and relationship violence or gender-based violence, most of which were conducted in North America. Most interventions aimed to provide students with the knowledge, attitudes and skills needed to prevent perpetration and victimisation. They varied in complexity; some had one activity, others had multiple activities, some were integrated into the existing school curricula and others were complex in that they sought to change how schools as a whole respond to dating and relationship violence or gender-based violence. We theorised that complex interventions would bring about greater and more sustainable change, but this was not supported by our findings. The implementation of interventions was affected by factors such as school organisation and leaders who believed in the importance of addressing dating and relationship violence/gender-based violence, along with time and resources to deliver the interventions. The ease with which the intervention could be delivered and modified was also important. There was stronger evidence for intervention effectiveness in reducing dating and relationship violence than for gender-based violence, with significant long-term impacts on dating and relationship violence victimisation and perpetration. There was some evidence that interventions in high-income countries could be effective for reducing victimisation and perpetration of gender-based violence in the long-term. More complicated interventions were not more effective, and interventions tended to reduce dating and relationship violence perpetration in boys more than in girls. We have also been able to identify where there are gaps in available evidence, which may provide avenues for future research.