Burden of Mental Disorders and Suicide Attributable to Childhood Maltreatment.

Importance: The proportion of mental disorders and burden causally attributable to childhood maltreatment is unknown. Objective: To determine the contribution of child maltreatment to mental health conditions in Australia, accounting for genetic and environmental confounding. Design, Setting, and Participants: This meta-analysis involved an epidemiological assessment accounting for genetic and environmental confounding between maltreatment and mental health and 3 cross-sectional national surveys: the Australian Child Maltreatment Study (ACMS) 2023, National Study of Mental Health and Well-being 2020-2022, and Australian Burden of Disease Study 2023. Causal estimates were derived on the association between childhood maltreatment and mental health conditions from a meta-analysis of quasi-experimental studies. This was combined with the prevalence of maltreatment from the ACMS to calculate the population attributable fraction (PAF). The PAF was applied to the number and burden of mental health conditions in Australia, sourced from 2 population-based, nationally representative surveys of Australians aged 16 to 85 years, to generate the number and associated burden of mental disorders attributable to child maltreatment. Exposure: Physical abuse, sexual abuse, emotional abuse, or neglect prior to age 18 years. Main Outcomes and Measures: Proportion and number of cases, years of life lost, years lived with disability, and disability-adjusted life-years of mental health conditions (anxiety, depression, harmful alcohol and drug use, self-harm, and suicide attempt) attributable to childhood maltreatment. Results: Meta-analytic estimates were generated from 34 studies and 54 646 participants and applied to prevalence estimates of childhood maltreatment generated from 8503 Australians. Childhood maltreatment accounted for a substantial proportion of mental health conditions, ranging from 21% (95% CI, 13%-28%) for depression to 41% (95% CI, 27%-54%) of suicide attempts. More than 1.8 million cases of depressive, anxiety, and substance use disorders could be prevented if childhood maltreatment was eradicated. Maltreatment accounted for 66 143 years of life lost (95% CI, 43 313-87 314), primarily through suicide, and 184 636 disability-adjusted life-years (95% CI, 109 321-252 887). Conclusions and Relevance: This study provides the first estimates of the causal contribution of child maltreatment to mental health in Australia. Results highlight the urgency of preventing child maltreatment to reduce the population prevalence and burden of mental disorders.

BE-WEL trial (breast: evaluation of weight and exercise for lymphoedema) testing weight control and exercise programmes for women with breast cancer related lymphoedema: a feasibility trial.

PURPOSE: A combined body weight loss and upper body/arm exercise programme is a potential strategy for managing Breast cancer related lymphoedema (BCRL), but there is limited data on the best method for delivery or its potential efficacy. METHODS: Fifty-seven women with overweight/obesity and BCRL were randomised to a 12 week supervised (n = 12) or home-based combined weight loss and upper body/arm exercise programme (n = 16), a home-based upper-body arm exercise only programme (n = 17) or standard care (n = 12). Primary outcomes were uptake, retention and changes in weight and change in Relative Arm Volume Increase (RAVI) using analysis of covariance (ANCOVA). RESULTS: Sixteen percent of women invited joined the study and 49 completed the trial (85% retention). Reductions in weight occurred in the supervised and home-based weight control and exercise programmes; Mean (95% CI) change compared to standard care - 1.68 (- 4.36 to - 1.00), - 2.47(- 4.99 to - 0.04) Kg. Reductions in perometer assessed RAVI were seen in the supervised and home-based combined weight control and arm exercise groups and the weight stable home-based arm exercise only group: mean (95% CI) change compared to standard care - 2.4 (- 5.0 to + 0.4),- 1.8 (- 4.3 to + 0.7), - 2.5(- 4.9 to - 0.05)%. CONCLUSION: Women with BCRL and overweight and obesity engaged in diet and exercise weight loss programmes. Both weight loss/arm exercise programmes led to modest changes in weight and BCRL. Comparable reductions in BCRL were reported in the weight stable group undertaking arm exercise only. The independent and combined effects of weight loss and exercise on BCRL need further study. TRIAL REGISTRATION: ISRCTN86789850 https://doi.org/10.1186/ISRCTN86789850 , registered 2011.

It's time for change: inequities and determinants of health-related quality of life among gender and sexually diverse young people in Australia.

PURPOSE: This study was guided by three research aims: firstly, to examine the longitudinal trends of health-related quality of life (HR-QoL) among gender and sexuality diverse (LGBTQA2S+) young people through adolescence (ages 14-19); secondly, to assess longitudinal associations between poor mental health and HR-QoL among LGBTQA2S+ young people through adolescence; and thirdly, to examine differences in HR-QoL among LGBTQA2S+ young people during early adolescence (ages 14 and 15) depending on select school-, peer-, and parent-level factors. METHODS: This study used three of nine available waves of data from a large population-level, probability sample-based, longitudinal cohort study, namely the K' cohort: children aged 4-5 years old at time of study enrolment followed-up biennially (~ 61% retention rate). HR-QoL weighted means and standard deviations were calculated using Child Health Utility 9D (CHU-9D) scores for LGBTQA2S+ participants at ages 14 and 15 (Wave 6), ages 16 and 17 (Wave 7), and ages 18 and 19 (Wave 8). To strategically identify policy-relevant modifiable behavioural factors suitable for prevention and early intervention, non-parametric Wilcoxon signed-rank tests tested differences in mean CHU-9D ranks at ages 14 and 15 (Wave 6) between groups (gender identity: trans vs. cis; identity-level sexuality: gay, lesbian, bisexual, or other diverse sexuality vs. heterosexual; group-level sexuality: sexually diverse vs. not sexually diverse) and selected school factors (school acceptance, belonging, freedom of expression), peer factors (peer relationship quality, trust, respect), and family factors (parental acceptance, understanding, trust), with Hedge's g correction statistics computed for effect sizes. Longitudinal associations between gender, sexuality, and poor mental health (depressive symptoms, anxiety, symptoms, self-harm thoughts/behaviour, and suicidal thoughts/behaviour) and HR-QoL were tested using mixed-effects models with random intercepts and random slopes for nested clustering (participants within postcodes). RESULTS: HR-QoL disparities disproportionately affecting LGBTQA2S+ groups relative to their cisgender, heterosexual peers, were well-established by age 14 to 15 relatively steeper reductions in HR-QoL were observed throughout adolescence among all LGBTQA2S+ groups, with HR-QoL widening the most for trans participants. Poor mental health was significantly associated with HR-QoL declines. LGBTQA2S+ participants with positive school- and parent factors related to feelings of acceptance, belonging, and freedom of self-expression, reported significantly higher HR-QoL during early adolescence. CONCLUSION: Evidence-based public health policy responses are required to address the dire HR-QoL inequities among LGBTQA2S+ young people, particularly trans young people. Prioritising the promotion of school- and family-based interventions which foster LGBTQA2S+ inclusivity, acceptance, and a sense of belonging from early adolescence through young adulthood, represents a feasible, evidence-based, and cost-effective response to address these HR-QoL disparities.

The long-term effectiveness of a personality-targeted substance use prevention program on aggression from adolescence to early adulthood.

BACKGROUND: Addressing aggressive behavior in adolescence is a key step toward preventing violence and associated social and economic costs in adulthood. This study examined the secondary effects of the personality-targeted substance use preventive program Preventure on aggressive behavior from ages 13 to 20. METHODS: In total, 339 young people from nine independent schools (M age = 13.03 years, s.d. = 0.47, range = 12-15) who rated highly on one of the four personality traits associated with increased substance use and other emotional/behavioral symptoms (i.e. impulsivity, anxiety sensitivity, sensation seeking, and negative thinking) were included in the analyses (n = 145 in Preventure, n = 194 in control). Self-report assessments were administered at baseline and follow-up (6 months, 1, 2, 3, 5.5, and 7 years). Overall aggression and subtypes of aggressive behaviors (proactive, reactive) were examined using multilevel mixed-effects analysis accounting for school-level clustering. RESULTS: Across the 7-year follow-up period, the average yearly reduction in the frequency of aggressive behaviors (b = -0.42; 95% confidence interval [CI] -0.64 to -0.20; p < 0.001), reactive aggression (b = -0.22; 95% CI 0.35 to -0.10; p = 0.001), and proactive aggression (b = -0.14; 95% CI -0.23 to -0.05; p = 0.002) was greater for the Preventure group compared to the control group. CONCLUSIONS: The study suggests a brief personality-targeted intervention may have long-term impacts on aggression among young people; however, this interpretation is limited by imbalance of sex ratios between study groups.

Effect of a selective personality-targeted prevention program on 7-year illicit substance related outcomes: A secondary analysis of a cluster randomized controlled trial.

BACKGROUND: This study evaluated the efficacy of the selective personality-targeted PreVenture program in reducing cannabis and stimulant use over a 7-year period spanning adolescence and early adulthood. METHODS: A cluster randomized controlled trial was conducted in 14 Australian schools. Schools were randomized to PreVenture, a brief personality-targeted selective intervention, comprising two 90-minute facilitator-led sessions delivered one week apart, or a control group (health education as usual). Only students who scored highly on one of four personality traits (anxiety sensitivity, negative thinking, impulsivity, sensation seeking) were included. Students completed online self-report questionnaires between 2012 and 2019: at baseline; post-intervention; 1-, 2-, 3-, 5.5- and 7-years post-baseline. Outcomes were past 6-months cannabis use, stimulant use (MDMA, methamphetamine or amphetamine) and cannabis-related harms. RESULTS: The sample comprised 438 adolescents (Mage=13.4 years; SD=0.47) at baseline. Retention ranged from 51% to 79% over the 7-years. Compared to controls, the PreVenture group had significantly reduced odds of annual cannabis-related harms (OR=0.78, 95% CI=0.65-0.92). However, there were no significant group differences in the growth of cannabis use (OR=0.84, 95% CI=0.69-1.02) or stimulant use (OR=1.07, 95% CI=0.91-1.25) over the 7-year period. CONCLUSIONS: PreVenture was effective in slowing the growth of cannabis-related harms over time, however owing to missing data over the 7-year trial, replication trials may be warranted to better understand the impact of the PreVenture intervention on cannabis and stimulant use among young Australians. Alternative implementation strategies, such as delivering the intervention in later adolescence and/or providing booster sessions, may be beneficial.

The impact of arts-inclusive programs on young children's mental health and wellbeing: a rapid review.

BACKGROUND: This review evaluated the existing literature exploring the effects of arts-inclusive programs (AIPs) on the mental health and wellbeing of young children. AIPs include activities, programs, or interventions containing creative arts. METHODS: Literature searches were conducted across three databases (SCOPUS, psycINFO, and ERIC). The search was restricted to studies reporting outcomes of children 0-6 years. RESULTS: Nine studies were included in the review (3,671 participants). Three key themes were identified: music-related (n = 4); artmaking (n = 3); and storytelling/drama (n = 2). All included studies reported positive outcomes on children's wellbeing following engagement in AIPs. DISCUSSION: This review found emerging evidence demonstrating positive impacts of arts engagement on the wellbeing of children aged 0-6. However, most studies were low quality and used varying outcome measures. The review is one of the first to highlight the lack of high-quality studies on the relationship between AIPs and wellbeing in young children.

A recently collected Xanthomonas translucens isolate encodes TAL effectors distinct from older, less virulent isolates.

Xanthomonas translucens, the causal agent of bacterial leaf streak disease (BLS) in cereals, is a re-emerging pathogen that is becoming increasingly destructive across the world. While BLS has caused yield losses in the past, there is anecdotal evidence that newer isolates may be more virulent. We observed that two X. translucens isolates collected from two sites in Colorado, USA, are more aggressive on current wheat and barley varieties compared to older isolates, and we hypothesize that genetic changes between recent and older isolates contribute to the differences in isolate aggressiveness. To test this, we phenotyped and genetically characterized two X. translucens isolates collected from Colorado in 2018, which we designated CO236 (from barley) and CO237 (from wheat). Using pathovar-specific phenotyping and PCR primers, we determined that CO236 belongs to pathovar translucens (Xtt) and CO237 belongs to pathovar undulosa (Xtu). We sequenced the full genomes of the isolates using Oxford Nanopore long-read sequencing, and compared their whole genomes against published X. translucens genomes. This analysis confirmed our pathovar designations for Xtt CO236 and Xtu CO237, and showed that, at the whole-genome level, there were no obvious genomic structural changes between Xtt CO236 and Xtu CO237 and other respective published pathovar genomes. Focusing on pathovar undulosa (Xtu CO237), we then compared putative type III effectors among all available Xtu isolate genomes and found that they were highly conserved. However, there were striking differences in the presence and sequence of various transcription activator-like effectors between Xtu CO237 and published undulosa genomes, which correlate with isolate virulence. Here, we explore the potential implications of the differences in these virulence factors, and provide possible explanations for the increased virulence of recently emerged isolates.

What set some young adults apart during the COVID-19 pandemic? Mental health trajectories, risk and protective factors in an Australian longitudinal study.

OBJECTIVE: Evidence suggests that young adults (aged 18-34) were disproportionately impacted by the COVID-19 pandemic, but little is known about their longer-term mental health changes beyond the early pandemic period. This article investigates heterogeneous trajectories of mental health among Australian young adults across 2 years of the pandemic and identifies a broad range of associated risk and protective factors. METHOD: Young adults (N = 653, Mage = 27.8 years) from the longitudinal Alone Together Study were surveyed biannually between July 2020 and June 2022. Measures assessed anxiety (7-item Generalised Anxiety Disorder scale) and depression (9-item Patient Health Questionnaire) symptoms at Waves 1-4, as well as demographic, psychological, adversity and COVID-19 factors at baseline. RESULTS: Four and three distinct trajectories of anxiety and depressive symptoms, respectively, were identified through growth mixture modelling. The proportion of participants in each anxiety trajectory were Asymptomatic (45.9%), Mild Stable (17.9%), Moderate-Severe Stable (31.1%) and Initially Severe/Recovering (5.1%). For depression, Mild Stable (58.3%), Moderate-Severe Stable (30.5%) and Reactive/Recovering (11.2%). Baseline factors associated with severe symptom trajectories included a lifetime mental health disorder, pre-pandemic stressful events, identifying as LGBTQIA+ and/or female, and experiencing one or more infection-control measures. Higher household income was protective. CONCLUSION: Most young adults demonstrated stable trajectories of low or high symptoms during the pandemic, with smaller groups showing initially severe or reactive symptoms followed by marked improvements over time. Vulnerable subgroups (gender- or sexuality-diverse, those with prior adversity or pre-existing mental ill-health) may face ongoing impacts and require targeted psychosocial supports to assist their mental health recovery post-COVID-19 and in the event of future crises.

Mental ill-health and substance use among sexuality diverse adolescents: The critical role of school climate and teacher self-efficacy.

INTRODUCTION: Mental ill-health, substance use and their co-occurrence among sexuality diverse young people during earlier adolescence is relatively understudied. The preventive utility of positive school climate for sexuality diverse adolescents' mental health is also unclear, as well as the role of teachers in conferring this benefit. METHOD: Using Wave 8 'B Cohort' data from the Longitudinal Study of Australian children (N = 3127, Mage = 14.3), prevalence ratios and odds ratios were used to assess prevalence and disparities in mental ill-health and substance use, and multinomial logistic regression for co-occurring outcomes, among sexuality diverse adolescents relative to heterosexual peers. Logistic regression was used to assess associations between school climate and teacher self-efficacy with sexuality diverse adolescents' mental health. RESULTS: Mental ill-health prevalence ranged from 22% (suicidal thoughts/behaviour) to 46% (probable depressive disorders) and substance use between 66% (cigarette use) and 97% (alcohol use). Sexuality diverse participants were significantly more likely to report self-harm and high levels of emotional symptoms in co-occurrence with cigarette, alcohol and/or cannabis use. For each 1-point increase in school climate scores as measured by the Psychological Sense of School Membership scale, there was 10% reduction in sexuality diverse adolescents reporting high levels of emotional symptoms, probable depressive disorder, self-harm thoughts/behaviour and suicidal thoughts/behaviour. For each 1-point increase in lower perceived (worse) teacher self-efficacy scores as measured by four bespoke teacher self-efficacy items, odds of sexuality diverse adolescent-reported suicidal thoughts/behaviour increased by 80%. DISCUSSION: Mental ill-health, substance use and especially their co-occurrence, are highly prevalent and pose significant and inequitable health and well-being risks. Schools represent a potential site for focusing future prevention efforts and educating and training teachers on sexuality diversity is a promising pathway towards optimising these.

Minority stressors, traumatic events, and associations with mental health and school climate among gender and sexuality diverse young people in Australia: Findings from a nationally representative cohort study.

INTRODUCTION: Population-level, nationally representative data on the prevalence of minority stressors and traumatic events, mental ill-health effects, and the preventative utility of school climate, among gender and sexuality diverse young people in Australia, is significantly lacking. In this study, we estimated the prevalence and distribution of minority stressors and traumatic events among young people by sexuality identity (gay/lesbian, bisexual, other sexuality, heterosexual), sexuality diversity (sexuality diverse, not sexuality diverse), and gender identity (transgender, cisgender) and assessed associations with mental ill-health and the moderating role of school climate factors. METHODS: Using Wave 8 (2018) follow-up data from a population-level, nationally representative longitudinal cohort study, the sample comprised 3037 young people aged 17-19 years in Australia. Prevalence ratios for minority stressors and traumatic events were calculated for gender and sexuality diverse categories using logistic regression models. Linear regression models were used to test associations between traumatic events and minority stressors, and mental ill-health. Multivariate linear regression tested school climate factors as effect modifier between minority stressors and mental ill-health among sexuality diverse young people. RESULTS: Rates of traumatic events and minority stressors were highest among bisexual and gay/lesbian young people and were significantly associated with mental ill-health among all gender and sexuality diverse young people. Highest mental ill-health effects were observed among trans young people. Among sexuality diverse young people, positive and negative feelings toward school climate were associated with decreased and increased mental ill-health, respectively. After accounting for sexuality diversity, positive overall school climate appeared protective of mental ill-health effects of sexuality-based discrimination. DISCUSSION: Minority stressors, traumatic events, and associated mental ill-health are prevalent among gender and sexuality diverse young people in Australia, especially trans, bisexual, and gay/lesbian young people. Promotion of affirmative, safe, and inclusive school climate demonstrates significant promise for the prevention and early intervention of mental ill-health among gender and sexuality diverse young people.

Self-compassion and avoidant coping as mediators of the relationship between childhood maltreatment and mental health and alcohol use in young adulthood.

BACKGROUND: Exposure to childhood maltreatment increases the risk of mental health and substance use problems. Understanding the mechanisms linking maltreatment to these problems is critical for prevention. OBJECTIVE: To examine whether self-compassion and avoidant coping mediate the relationship between childhood maltreatment and mental ill-health and alcohol use. PARTICIPANTS AND SETTING: Australians aged 18-20 years at baseline were recruited through social media and professional networks. METHODS: Participants (n = 568) completed an online survey, and were followed up annually for two subsequent surveys. Mediation models were conducted with the SPSS PROCESS macro. Maltreatment was the predictor; Wave 2 self-compassion and avoidant coping as mediators; Wave 3 mental health and alcohol use as outcomes. RESULTS: Childhood maltreatment predicted greater mental health symptoms (b = 0.253, 95 % CI = 0.128-0.378), and alcohol use (b = 0.057, 95 % CI = 0.008-0.107). Both self-compassion (b = 0.056, 95 % CI = 0.019-0.093) and avoidant coping (b = 0.103, 95 % CI = 0.024-0.181) mediated the relationship between maltreatment and mental health. Additionally, avoidant coping, but not self-compassion, mediated the relationship (b = 0.040, 95 % CI 0.020-0.061) with alcohol use. However, when controlling for pre-existing mental health and substance use, neither self-compassion nor avoidant coping mediated the relationship with mental health. Only avoidant coping mediated the link with alcohol use (b = 0.010, 95 % CI = 0.001-0.020). CONCLUSIONS: Findings suggests that by adulthood, self-compassion and avoidant coping may not explain future change in mental health symptoms; however, avoidant coping accounts for change in alcohol use across early adulthood. Reducing avoidant coping may prevent hazardous alcohol use across young adulthood among people exposed to childhood maltreatment.

Mental health and wellbeing outcomes of youth participation: A scoping review protocol.

There is growing recognition that young people should be given opportunities to participate in the decisions that affect their lives, such as advisory groups, representative councils, advocacy or activism. Positive youth development theory and sociopolitical development theory propose pathways through which youth participation can influence mental health and wellbeing outcomes. However, there is limited empirical research synthesising the impact of participation on youth mental health and/or wellbeing, or the characteristics of activities that are associated with better or worse mental health and/or wellbeing outcomes. This scoping review seeks to address this gap by investigating the scope and nature of evidence detailing how youth participation initiatives can influence mental health and/or wellbeing outcomes for participants. To be eligible, literature must describe youth (aged 15-24) in participation activities and the impact of this engagement on participant mental health and/or wellbeing outcomes. A systematic scoping review of peer-reviewed and grey literature will be conducted using Scopus, PsycINFO, Embase, Medline and grey literature databases. The scoping review will apply established methodology by Arksey and O'Malley, Levac and colleagues and the Joanna Briggs Institute. Title, abstract, and full text screening will be completed by two reviewers, data will be extracted by one reviewer. Findings will be reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR), including a qualitative summary of the characteristics of youth participation and their influence on youth mental health outcomes. Youth advisory group members will be invited to deliver governance on the project from the outset; participate in, and contribute to, all stages of the review process; reflect on their own experiences of participation; and co-author the resulting publication. This scoping review will provide essential knowledge on how participation activities can be better designed to maximise beneficial psychosocial outcomes for involved youth.

Profiles of resilient psychosocial function during three isolated ski expeditions in the High Arctic.

To successfully complete a Polar expedition individuals and teams must respond resiliently to the environmental, psychological, and social demands they face. In this study we examined profiles of resilient function in seven people from three expeditions in the High Arctic. Using a structured daily diary, participants reported on experiences of physical health (morning and evening), affect, team cohesion, performance, and potential explanatory factors including sleep, demand appraisals, events, and coping strategies. Notable intra- and inter-individual variability was observed in daily reports and all profiles could be interpreted as representing resilient function. A number of significant relationships were found between markers of resilient physical and psychosocial function and potential explanatory variables. For example, there was much more daily variability in an individual's reporting of positive affect than prior research might imply, and what prior research designs could capture. Further, while negative affect tended to remain low and stable, our findings reveal that even minor and infrequent increases in negative emotions were significantly associated with other variables in the network. Finally, across the expedition period individual coping resources consistently exceeded demands, suggesting that individuals viewed the expedition as a challenge and not a threat. More broadly, these findings inform efforts to monitor, and maintain resilience when operating in Polar and other extreme settings.

Associations Between Personality Traits and Energy Balance Behaviors in Emerging Adulthood: Cross-Sectional Study.

BACKGROUND: Internalizing and externalizing personality traits are robust risk factors for substance use and mental health, and personality-targeted interventions are effective in preventing substance use and mental health problems in youth. However, there is limited evidence for how personality relates to other lifestyle risk factors, such as energy balance-related behaviors, and how this might inform prevention efforts. OBJECTIVE: This study aimed to examine concurrent cross-sectional associations between personality traits (ie, hopelessness, anxiety sensitivity, impulsivity, and sensation seeking) and sleep, diet, physical activity (PA), and sedentary behaviors (SB), 4 of the leading risk factors for chronic disease, among emerging adults. METHODS: Data were drawn from a cohort of young Australians who completed a web-based, self-report survey in 2019 during early adulthood. A series of Poisson and logistic regressions were conducted to examine the concurrent associations between the risk behaviors (sleep, diet, PA, and sitting and screen time) and personality traits (hopelessness, anxiety sensitivity, impulsivity, and sensation seeking) among emerging adults in Australia. RESULTS: A total of 978 participants (mean age 20.4, SD 0.5 years) completed the web-based survey. The results indicated that higher scores on hopelessness were associated with a greater daily screen (risk ratio [RR] 1.12, 95% CI 1.10-1.15) and sitting time (RR 1.05, 95% CI 1.0-1.08). Similarly, higher scores on anxiety sensitivity were associated with a greater screen (RR 1.04, 95% CI 1.02-1.07) and sitting time (RR 1.04, 95% CI 1.02-1.07). Higher impulsivity was associated with greater PA (RR 1.14, 95% CI 1.08-1.21) and screen time (RR 1.06, 95% CI 1.03-1.08). Finally, higher scores on sensation seeking were associated with greater PA (RR 1.08, 95% CI 1.02-1.14) and lower screen time (RR 0.96, 95% CI 0.94-0.99). CONCLUSIONS: The results suggest that personality should be considered when designing preventive interventions for lifestyle risk behaviors, particularly in relation to SB, such as sitting and screen time. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612000026820; https://tinyurl.com/ykwcxspr.

Corrigendum to "The school-led Preventure study: Protocol of a cluster-randomised controlled trial of effectiveness to prevent adolescent alcohol misuse, internalising problems, and externalising problems through a personality-targeted intervention delivered by school staff", preventive medicine" [Reports 21 (2021) 101286/PMID: 33384915; PMCID: PMC7772564].

[This corrects the article DOI: 10.1016/j.pmedr.2020.101286.].

X-linked hydrocephalus genes: Their proximity to telomeres and high A + T content compared to Parkinson's disease.

Proximity to telomeres (i) and high adenine and thymine (A + T) content (ii) are two factors associated with high mutation rates in human chromosomes. We have previously shown that >100 human genes when mutated to cause congenital hydrocephalus (CH) meet either factor (i) or (ii) at 91% matching, while two factors are poorly satisfied in human genes associated with familial Parkinson's disease (fPD) at 59%. Using the sets of mouse, rat, and human chromosomes, we found that 7 genes associated with CH were located on the X chromosome of mice, rats, and humans. However, genes associated with fPD were in different autosomes depending on species. While the contribution of proximity to telomeres in the autosome was comparable in CH and fPD, high A + T content played a pivotal contribution in X-linked CH (43% in all three species) than in fPD (6% in rodents or 13% in humans). Low A + T content found in fPD cases suggests that PARK family genes harbor roughly 3 times higher chances of methylations in CpG sites or epigenetic changes than X-linked genes.

Effect of proximal blood flow arrest during endovascular thrombectomy (ProFATE): Study protocol for a multicentre randomised controlled trial.

BACKGROUND: Observational studies have demonstrated improved outcomes with the adjunctive use of balloon guide catheters (BGC) during endovascular thrombectomy (EVT) for anterior circulation acute ischaemic stroke (AIS). However, the lack of high-level evidence and global practice heterogeneity justifies a randomised controlled trial (RCT) to investigate the effect of transient proximal blood flow arrest on the procedural and clinical outcomes of patients with AIS following EVT. HYPOTHESIS: Proximal blood flow arrest in the cervical internal carotid artery during EVT for proximal large vessel occlusion is superior to no flow arrest in achieving complete vessel recanalisation. METHODS: ProFATE is an investigator-initiated, pragmatic, multicentre RCT with blinding of participants and outcome assessment. An estimated 124 participants with an anterior circulation AIS due to large vessel occlusion, an NIHSS of ⩾2, ASPECTS ⩾ 5 and eligible for EVT using a first-line combined technique (contact aspiration and stent retriever) or contact aspiration only will be randomised (1:1) to receive BGC balloon inflation or no inflation during EVT. OUTCOMES: The primary outcome is the proportion of patients achieving near-complete/complete vessel recanalisation (eTICI 2c-3) at the end of the EVT procedure. Secondary outcomes include the functional outcome (modified Rankin Scale at 90 days), new or distal vascular territory clot embolisation rate, near-complete/complete recanalisation after the first pass, symptomatic intracranial haemorrhage, procedure-related complications and death at 90 days. DISCUSSION: This is the first RCT to investigate the effect of proximal blood flow arrest during EVT using a BGC on the procedural and clinical outcomes of patients with AIS due to large vessel occlusion.

Off-World Mental Health: Considerations for the Design of Well-being-Supportive Technologies for Deep Space Exploration.

During future long-duration space exploration missions, humans will be exposed to combinations of extreme physical, psychological, and interpersonal demands. These demands create risks for the safety, performance, health, and well-being of both individuals and crew. The communication latency in deep space means that explorers will increasingly have to operate independently and take responsibility for their own self-care and self-management. At present, several research programs are focused on developing and testing digital technologies and countermeasures that support the effective functioning of deep space crews. Although promising, these initiatives have been stimulated mostly by technological opportunity rather than cogent theory. In this perspective, we argue that digital technologies developed for spaceflight should be informed by well-being-supportive design principles and be cognizant of broader conversations around the development and use of digital health applications, especially pertaining to issues of autonomy, privacy, and trust. These issues are important for designing potentially mission-critical health technologies and may be determining factors in the safe and successful completion of future off-world endeavors.

Olutasidenib (FT-2102) induces durable complete remissions in patients with relapsed or refractory IDH1-mutated AML.

Olutasidenib (FT-2102) is a potent, selective, oral, small-molecule inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1). Overall, 153 IDH1 inhibitor-naive patients with mIDH1R132 relapsed/refractory (R/R) acute myeloid leukemia (AML) received olutasidenib monotherapy 150 mg twice daily in the pivotal cohort of this study. The median age of participants was 71 years (range, 32-87 years) and the median number of prior regimens received by patients was 2 (1-7). The rate of complete remission (CR) plus CR with partial hematologic recovery (CRh) was 35%, and the overall response rate was 48%. Response rates were similar in patients who had, and who had not, received prior venetoclax. With 55% of patients censored at the time of data cut-off, the median duration of CR/CRh was 25.9 months. The median duration of overall response was 11.7 months, and the median overall survival was 11.6 months. Of 86 patients who were transfusion dependent at baseline, a 56-day transfusion independence was achieved in 29 (34%), which included patients in all response groups. Grade 3 or 4 treatment-emergent adverse events (≥10%) were febrile neutropenia and anemia (n = 31; 20% each), thrombocytopenia (n = 25; 16%), and neutropenia (n = 20; 13%). Differentiation syndrome adverse events of special interest occurred in 22 (14%) patients, with 14 (9%) grade ≥3 and 1 fatal case reported. Overall, olutasidenib induced durable remissions and transfusion independence with a well-characterized and manageable side effect profile. The observed efficacy represents a therapeutic advance in this molecularly defined, poor-prognostic population of patients with mIDH1 R/R AML. This trial was registered at www.clinicaltrials.gov as #NCT02719574.