The Vertebrate Breed Ontology: Towards Effective Breed Data Standardization.

Background ­: Limited universally adopted data standards in veterinary science hinders data interoperability and therefore integration and comparison; this ultimately impedes application of existing information-based tools to support advancement in veterinary diagnostics, treatments, and precision medicine. Hypothesis/Objectives ­: Creation of a Vertebrate Breed Ontology (VBO) as a single, coherent logic-based standard for documenting breed names in animal health, production and research-related records will improve data use capabilities in veterinary and comparative medicine. Animals ­: No live animals were used in this study. Methods ­: A list of breed names and related information was compiled from relevant sources, organizations, communities, and experts using manual and computational approaches to create VBO. Each breed is represented by a VBO term that includes all provenance and the breed's related information as metadata. VBO terms are classified using description logic to allow computational applications and Artificial Intelligence-readiness. Results ­: VBO is an open, community-driven ontology representing over 19,000 livestock and companion animal breeds covering 41 species. Breeds are classified based on community and expert conventions (e.g., horse breed, cattle breed). This classification is supported by relations to the breeds' genus and species indicated by NCBI Taxonomy terms. Relationships between VBO terms, e.g. relating breeds to their foundation stock, provide additional context to support advanced data analytics. VBO term metadata includes common names and synonyms, breed identifiers/codes, and attributed cross-references to other databases. Conclusion and clinical importance ­: Veterinary data interoperability and computability can be enhanced by the adoption of VBO as a source of standard breed names in databases and veterinary electronic health records.

Effectiveness of a universal, school-based, online programme for the prevention of anxiety, depression, and substance misuse among adolescents in Australia: 72-month outcomes from a cluster-randomised controlled trial.

BACKGROUND: The CSC study found that the universal delivery of a school-based, online programme for the prevention of mental health and substance use disorders among adolescents resulted in improvements in mental health and substance use outcomes at 30-month follow-up. We aimed to compare the long-term effects of four interventions-Climate Schools Combined (CSC) mental health and substance use, Climate Schools Substance Use (CSSU) alone, Climate Schools Mental Health (CSMH) alone, and standard health education-on mental health and substance use outcomes among adolescents at 72-month follow-up into early adulthood. METHODS: This long-term study followed up adolescents from a multicentre, cluster-randomised trial conducted across three states in Australia (New South Wales, Queensland, and Western Australia) enrolled between Sept 1, 2013, and Feb 28, 2014, for up to 72 months after baseline assessment. Adolescents (aged 18-20 years) from the original CSC study who accepted contact at 30-month follow-up and provided informed consent at 60-month follow-up were eligible. The interventions were delivered in school classrooms through an online delivery format and used a mixture of peer cartoon storyboards and classroom activities that were focused on alcohol, cannabis, anxiety, and depression. Participants took part in two web-based assessments at 60-month and 72-month follow-up. Primary outcomes were alcohol use, cannabis use, anxiety, and depression, measured by self-reported surveys and analysed by intention to treat (ie, in all students who were eligible at baseline). This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12613000723785), including the extended follow-up study. FINDINGS: Of 6386 students enrolled from 71 schools, 1556 (24·4%) were randomly assigned to education as usual, 1739 (27·2%) to CSSU, 1594 (25·0%) to CSMH, and 1497 (23·4%) to CSC. 311 (22·2%) of 1401 participants in the control group, 394 (26·4%) of 1495 in the CSSU group, 477 (37·%) of 1289 in the CSMH group, and 400 (32·5%) of 1232 in the CSC group completed follow-up at 72 months. Adolescents in the CSC group reported slower year-by-year increases in weekly alcohol use (odds ratio 0·78 [95% CI 0·66-0·92]; p=0·0028) and heavy episodic drinking (0·69 [0·58-0·81]; p<0·0001) than did the control group. However, significant baseline differences between groups for drinking outcomes, and no difference in the predicted probability of weekly or heavy episodic drinking between groups were observed at 72 months. Sensitivity analyses increased uncertainty around estimates. No significant long-term differences were observed in relation to alcohol use disorder, cannabis use, cannabis use disorder, anxiety, or depression. No adverse events were reported during the trial. INTERPRETATION: We found some evidence that a universal online programme for the prevention of anxiety, depression, and substance use delivered in early adolescence is effective in reducing the use and harmful use of alcohol into early adulthood. However, confidence in these findings is reduced due to baseline differences, and we did not see a difference in the predicted probability of drinking between groups at 72-month follow-up. These findings suggest that a universal prevention programme in adolescence is not sufficient to have lasting effects on mental health and substance use disorders in the long term. In addition to baseline differences, substantial attrition warrants caution in interpretation and the latter factor highlights the need for future long-term follow-up studies to invest in strategies to increase engagement. FUNDING: Australian National Health and Medical Research Council.

Alcohol initiation before age 15 predicts earlier hazardous drinking: A survival analysis of a 7-year prospective longitudinal cohort of Australian adolescents.

BACKGROUND AND AIMS: Early alcohol use may predict later alcohol problems, but the magnitude of this effect and impact of delayed onset remain uncertain. This study measured age-based differences in progression from first full alcoholic drink to hazardous drinking in one of the largest and most recent prospective cohorts of Australian adolescents. DESIGN, SETTINGS, PARTICIPANTS AND MEASUREMENT: A 7-year (2012-19) prospective longitudinal cohort of 2082 Australian adolescents was established from the Climate and Preventure (cohort 1) and Climate Schools Combined (cohort 2) studies. Participants completed surveys annually from ages 13 to 20 years. Interval censored survival analyses were conducted with first episode of hazardous drinking [three or more on proxy Alcohol Use Disorders Identification Test (AUDIT-C)] as the survival end-point, controlling for age, sex and mental health symptomatology. Onset of hazardous drinking was expressed as hazard ratios (HRs), and median survival time (years) was used to model first onset of hazardous alcohol use in survival curves. FINDINGS: Compared with those aged 15 or older, those who had their first full drink at 12 or younger had significantly elevated risk of hazardous drinking onset during the study period [log (HR): 9.3; 95% confidence interval (CI) = 7.0-12.0, P < 0.001]. Compared with those who had their first full drink at ages 13-14, those who delayed until 15 or older had significantly later onset of hazardous drinking; 1.63 years for males (95% CI = 1.31-1.92, P < 0.001) and 1.50 for females (95% CI = 1.15-1.81, P < 0.001), resulting in a median age of onset of hazardous drinking of > 19 for both sexes (male: 19.05 years, 95% CI = 18.74-19.38; female: 19.47 years, 95% CI = 19.19-19.75). First drink at ages 13-14 was associated with the earliest onset of hazardous drinking (males: 17.43 years; females: 17.98 years). CONCLUSIONS: In Australia, alcohol initiation prior to age 15 appears to be associated with an earlier onset of hazardous drinking than initiation after age 15.

Cancer sleep symptom-related phenotypic clustering differs across three cancer specific patient cohorts.

Specific sleep disorders have been linked to disease progression in different cancers. We hypothesised sleep symptom clusters would differ between cancer types. The aim of this study was to compare sleep symptom clusters in post-treatment melanoma, breast and endometrial cancer patients. Data were collected from 124 breast cancer patients (1 male, 60 ± 15 years, 28.1 ± 6.6 kg/m2 ), 82 endometrial cancer patients (64.0 ± 12.5 years, 33.5 ± 10.4 kg/m2 ) and 112 melanoma patients (59 male, 65.0 ± 18.0 years, 29.1 ± 6.6 kg/m2 ). All patients completed validated questionnaires to assess sleep symptoms, including the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10). Snoring, tiredness, observed apneas, age, BMI, and gender data were also collected. Binary values (PSQI, ISI, FOSQ), or continuous variables for sleepiness (ESS) and perceived sleep quality (PSQI), were created and sleep symptom clusters were identified and compared across cancer cohorts. Four distinct sleep symptom clusters were identified: minimally symptomatic (n = 152, 47.7%); insomnia-predominant (n = 87, 24.9%); very sleepy with upper airway symptoms (n = 51, 16.3%), and severely symptomatic with severe dysfunction (n = 34, 11.1%). Breast cancer patients were significantly more likely to be in the insomnia predominant or severely symptomatic with severe dysfunction clusters, whereas melanoma patients were more likely to be minimally symptomatic or sleepy with upper airway symptoms (p <0.0001). Endometrial cancer patients were equally distributed across symptom clusters. Sleep symptom clusters vary across cancer patients. A more personalised approach to the management of sleep-related symptoms in these patients may improve the long term quality of life and survival.

A national effectiveness trial of an eHealth program to prevent alcohol and cannabis misuse: responding to the replication crisis.

BACKGROUND: The burden of disease attributable to alcohol and other drug (AOD) use in young people is considerable. Prevention can be effective, yet few programs have demonstrated replicable effects. This study aimed to replicate research behind Climate Schools: Alcohol and Cannabis course among a large cohort of adolescents. METHODS: Seventy-one secondary schools across three States participated in a cluster-randomised controlled trial. Year 8 students received either the web-based Climate Schools: Alcohol and Cannabis course (Climate, n = 3236), or health education as usual (Control, n = 3150). Outcomes were measured via self-report and reported here for baseline, 6- and 12-months for alcohol and cannabis knowledge, alcohol, cannabis use and alcohol-related harms. RESULTS: Compared to Controls, students in the Climate group showed greater increases in alcohol- [standardised mean difference (SMD) 0.51, p < 0.001] and cannabis-related knowledge (SMD 0.49, p < 0.001), less increases in the odds of drinking a full standard drink[(odds ratio (OR) 0.62, p = 0.014], and heavy episodic drinking (OR 0.49, p = 0.022). There was no evidence for differences in change over time in the odds of cannabis use (OR 0.57, p = 0.22) or alcohol harms (OR 0.73, p = 0.17). CONCLUSIONS: The current study provides support for the effectiveness of the web-based Climate Schools: Alcohol and Cannabis course in increasing knowledge and reducing the uptake of alcohol. It represents one of the first trials of a web-based AOD prevention program to replicate alcohol effects in a large and diverse sample of students. Future research and/or adaptation of the program may be warranted with respect to prevention of cannabis use and alcohol harms.

The 7-Year Effectiveness of School-Based Alcohol Use Prevention From Adolescence to Early Adulthood: A Randomized Controlled Trial of Universal, Selective, and Combined Interventions.

OBJECTIVE: Alcohol use is a leading cause of burden of disease among young people. Prevention strategies can be effective in the short-term; however little is known about their longer-term effectiveness. The aim of this study was to examine the sustainability of universal, selective, and combined alcohol use prevention across the critical transition period from adolescence into early adulthood. METHOD: In 2012, a total of 2190 students (mean age, 13.3 years) from 26 Australian high schools participated in a cluster randomized controlled trial and were followed up for 3 years post baseline. Schools were randomly assigned to deliver the following: (1) universal Web-based prevention for all students (Climate Schools); (2) selective prevention for high-risk students (Preventure); (3) combined universal and selective prevention (Climate Schools and Preventure [CAP]); or (4) health education as usual (control). This study extends the follow-up period to 7-years post baseline. Primary outcomes were self-reported frequency of alcohol consumption and binge drinking, alcohol-related harms, and hazardous alcohol use, at the 7-year follow-up. RESULTS: At 7-year follow-up, students in all 3 intervention groups reported reduced odds of alcohol-related harms compared to the control group (odds ratios [ORs] = 0.13-0.33), and the Climate (OR = 0.04) and Preventure (OR = 0.17) groups reported lower odds of hazardous alcohol use. The Preventure group also reported lower odds of weekly alcohol use compared to the control group (OR = 0.17), and the Climate group reported lower odds of binge drinking (OR = 0.12), holding mean baseline levels constant. CONCLUSION: This study demonstrated that both universal and selective preventive interventions delivered in schools can have long-lasting effects and reduce risky drinking and related harms into adulthood. No added benefit was observed by delivering the combined interventions. CLINICAL TRIAL REGISTRATION INFORMATION: The CAP Study: Evaluating a Comprehensive Universal and Targeted Intervention Designed to Prevent Substance Use and Related Harms in Australian Adolescents; https://www.anzctr.org.au/; ACTRN12612000026820.

Irregular Sleep/Wake Patterns Are Associated With Reduced Quality of Life in Post-treatment Cancer Patients: A Study Across Three Cancer Cohorts.

Background: Cancer patients often describe poor sleep quality and sleep disruption as contributors to poor quality of life (QoL). In a cross-sectional study of post-treatment breast, endometrial, and melanoma cancer patients, we used actigraphy to quantify sleep regularity using the sleep regularity index (SRI), and examined relationships with reported sleep symptoms and QoL. Methods: Participants were recruited post-primary treatment (35 diagnosed with breast cancer, 24 endometrial cancer, and 29 melanoma) and wore an actigraphy device for up to 2 weeks and SRI was calculated. Self-report questionnaires for cancer-related QoL [European Organization for Research and Treatment of Cancer EORTC (QLQ-C30)] were completed. Data were compared using analysis of variance (ANOVA) or Chi-Square tests. Multivariate linear regression analysis was used to determine independent variable predictors for questionnaire-derived data. Results: Age distribution was similar between cohorts. Endometrial and breast cancer cohorts were predominantly female, as expected, and body mass index (BMI) was higher in the endometrial cancer cohort, followed by breast and melanoma. There were no differences between tumor groups in: total sleep time, sleep onset latency, bedtime, and SRI (breast 80.9 ± 8.0, endometrial 80.3 ± 12.2, and melanoma 81.4 ± 7.0) (all p > 0.05). A higher SRI was associated with both better functional and symptom scores, including increased global QoL, better physical functioning, less sleepiness and fatigue, better sleep quality, and associated with less nausea/vomiting, dyspnea, and diarrhea (all p < 0.05). Conclusion: In cancer patients post-treatment, greater sleep regularity is associated with increased global QoL, as well as better physical functioning and fewer cancer related symptoms. Improving sleep regularity may improve QoL for cancer patients.

It's the Content That Counts: Longitudinal Associations between Social Media Use, Parental Monitoring, and Alcohol Use in an Australian Sample of Adolescents Aged 13 to 16 Years.

(1) Background: More time spent on social media has been linked to increased alcohol use, with exposure to peer alcohol-related content on social media (content exposure) named as a critical factor in this relationship. Little is currently known about whether early content exposure may have lasting effects across adolescent development, or about the capacity of parental monitoring of social media use to interrupt these links. (2) Methods: These gaps were addressed in both cross-sectional and longitudinal contexts among a longitudinal sample of Australian secondary school students (n = 432) across the ages of 13-16. (3) Results: Evidence was found for links between social media use and alcohol use frequency in early development. Social media time at age 13 was significantly associated with concurrent alcohol use frequency. At age 13, alcohol use frequency was significantly higher among those who reported content exposure compared to those who reported no exposure. Longitudinally, the frequency of alcohol use over time increased at a faster rate among participants who reported content exposure at age 13. In terms of parental monitoring, no longitudinal effects were observed. However, parental monitoring at age 13 did significantly reduce the concurrent relationship between alcohol use frequency and content exposure. (4) Conclusion: The impact of social media content exposure on alcohol use in adolescence may be more important than the time spent on social media, and any protective effect of parental monitoring on content exposure may be limited to the time it is being concurrently enacted.

The long-term effectiveness of universal, selective and combined prevention for alcohol use during adolescence: 36-month outcomes from a cluster randomized controlled trial.

AIM: To compare the long-term universal outcomes of the Climate Schools programme, the selective preventure programme and their combined implementation to standard substance use education in reducing the uptake of alcohol use, engagement in binge drinking and alcohol-related harms over a 3-year period. DESIGN: A cluster-randomized controlled trial. SETTING AND PARTICIPANTS: Substance use prevention programmes delivered in Australian secondary schools. Students from 26 Australian secondary schools (n = 2190), mean age at baseline 13.3 years (standard deviation = 0.48), 57.4% male. Schools were recruited between September 2011 and February 2012. INTERVENTIONS: Schools were block-randomized to one of four groups: universal prevention (climate; 12 × 40-minute lessons); selective prevention (preventure; 2 × 90-minute sessions); combined prevention (climate and preventure; CAP); or health education as usual (control). The climate intervention delivered 12 × 40-minute lessons aimed at reducing alcohol and cannabis use and related harms. The preventure intervention delivered 2 × 90-minute group sessions to high-risk students. The CAP group implemented the climate programme to the entire year group and the preventure programme to the high-risk students. MEASUREMENTS: Participants were all consenting 8th grade students (in 2012) assessed at baseline, post-intervention (6-9 months post-baseline) and at 12, 24 and 36 months post-baseline on measures of alcohol use, knowledge and related harms. Primary outcomes were alcohol use, binge drinking (five or more standard drinks) and alcohol-related harms, obtained from all students regardless of whether or not they received intervention. Intervention effects at 36 months post-baseline were estimated from generalized multi-level mixed models using data from all time-points and accounting for school-level clustering. Exploratory analyses examined intervention effects among low- and high-risk adolescents. FINDINGS: Compared with students in the control condition, students in the climate, preventure and CAP groups demonstrated significantly slower increases in their likelihood to drink any alcohol [odds ratio (OR) = 0.64, 95% confidence interval (CI) = 0.50-0.82 for climate; OR = 0.55, 95% CI = 0.43-0.71 for preventure and OR = 0.67, 95% CI = 0.53-0.84 for CAP] to engage in binge drinking (OR = 0.60, 95% CI = 0.44-0.82 for climate; OR = 0.59, 95% CI = 0.44-0.80 for preventure and OR = 0.68, 95% CI = 0.51-0.92 for CAP) and to experience alcohol harms (OR = 0.63, 95% CI = 0.49-0.82 for climate; OR = 0.55, 95% CI = 0.43-0.71 for preventure and OR = 0.64, 95% CI = 0.50-0.81 for CAP). There was no strong evidence that the combined approach showed advantages over universal prevention. The direction and magnitude of effects were consistent in low- and high-risk adolescents. CONCLUSIONS: The universal Climate Schools programme and the selective preventure programme were effective in reducing alcohol consumption and alcohol problems compared with standard Australian health education, when trialled individually and together over a 3-year period.

Combined prevention for substance use, depression, and anxiety in adolescence: a cluster-randomised controlled trial of a digital online intervention.

BACKGROUND: Substance use, depression, and anxiety in adolescence are major public health problems requiring new scalable prevention strategies. We aimed to assess the effectiveness of a combined online universal (ie, delivered to all pupils) school-based preventive intervention targeting substance use, depression, and anxiety in adolescence. METHODS: We did a multicentre, cluster-randomised controlled trial in secondary schools in Australia, with pupils in year 8 or 9 (aged 13-14 years). Participating schools were randomly assigned (1:1:1:1) to one of four intervention conditions: (1) Climate Schools-Substance Use, focusing on substance use only; (2) Climate Schools-Mental Health, focusing on depression and anxiety only; (3) Climate Schools-Combined, focusing on the prevention of substance use, depression, and anxiety; or (4) active control. The interventions were delivered in school classrooms in an online delivery format and used a mixture of peer cartoon storyboards and classroom activities that were focused on alcohol, cannabis, anxiety, and depression. The interventions were delivered for 2 years and primary outcomes were knowledge related to alcohol, cannabis, and mental health; alcohol use, including heavy episodic drinking; and depression and anxiety symptoms at 12, 24, and 30 months after baseline. This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12613000723785) and an extended follow-up is underway. FINDINGS: Between Sept 1, 2013, and Feb 28, 2014, we recruited 88 schools (12 391 pupils), of whom 71 schools and 6386 (51·5%) pupils were analysed (17 schools dropped out and 1308 pupils declined to participate). We allocated 18 schools (1739 [27·25%] pupils; 1690 [97·2%] completed at least one follow-up) to the substance use condition, 18 schools (1594 [25·0%] pupils; 1560 [97·9%] completed at least one follow-up) to the mental health condition, 16 schools (1497 [23·4%] pupils; 1443 [96·4%] completed at least one follow-up) to the combined condition, and 19 schools (1556 [23·4%] pupils; 1513 [97·2%] completed at least one follow-up) to the control condition. Compared with controls, the combined intervention group had increased knowledge related to alcohol and cannabis at 12, 24, and 30 months (standardised mean difference [SMD] for alcohol 0·26 [95% CI 0·14 to 0·39] and for cannabis 0·17 [0·06 to 0·28] at 30 months), increased knowledge related to mental health at 24 months (0·17 [0·08 to 0·27]), reduced growth in their odds of drinking and heavy episodic drinking at 12, 24, and 30 months (odds ratio for drinking 0·25 [95% CI 0·12 to 0·51], and for heavy episodic drinking 0·15 [0·04 to 0·58] at 30 months), and reduced increases in anxiety symptoms at 12 and 30 months (SMD -0·12 [95% CI -0·22 to -0·01] at 30 months). We found no difference in symptoms or probable diagnosis of depression. The combined intervention group also showed improvement in alcohol use outcomes compared with the substance use and mental health interventions and improvements in anxiety outcomes when compared with the mental health intervention only. INTERPRETATION: Combined online prevention of substance use, depression, and anxiety led to increased knowledge of alcohol, cannabis, and mental health, reduced increase in the odds of any drinking and heavy episodic drinking, and reduced symptoms of anxiety over a 30-month period. These findings provide the first evidence of the effectiveness of an online universal school-based preventive intervention targeting substance use, depression, and anxiety in adolescence. FUNDING: Australian National Health and Medical Research Council.

Evaluating the differential effectiveness of social influence and personality-targeted alcohol prevention on mental health outcomes among high-risk youth: A novel cluster randomised controlled factorial design trial.

OBJECTIVE: This study examined the secondary mental health outcomes of two contrasting alcohol prevention approaches, whereby one intervention targets common underlying personality risk for alcohol use and mental health problems (Preventure) and the other targets alcohol- and drug-related behaviours and cognitions (Climate Schools). METHODS: A 2 × 2 cluster randomised controlled factorial design trial was conducted in 26 Australian schools randomised to the following 4 conditions: Climate Schools (n = 6), Preventure (n = 7), combined Climate Schools and Preventure (CAP; n = 6) or treatment as usual (TAU; n = 7). Participants completed questionnaires at baseline, 6, 12, 24 and 36 months post-baseline including the Brief Symptom Inventory anxiety and depression scales and hyperactivity and conduct scales of the Strengths and Difficulties Questionnaire. Analyses focused on students who were at high-risk based on personality traits (n = 947; Mage = 13.3). The effectiveness of each approach in reducing symptoms of internalising and externalising problems was assessed using multi-level mixed effects analysis. RESULTS: Main effects for each intervention relative to not receiving that intervention revealed significant main effects of Preventure in reducing anxiety symptoms (d = -0.27, 95% confidence interval [CI] = [-0.53, -0.01], p < 0.05) and a marginal effect in reducing depressive symptoms (d = -0.24, 95% CI = [-0.49, 0.01], p = 0.06) over 3 years. Interaction effects revealed that when delivered alone, Preventure significantly reduced conduct problems (d = -0.45, 95% CI = [-0.78, -0.11], p < 0.05) and hyperactivity symptoms (d = -0.38, 95% CI = [-0.70,-0.07], p < 0.05) compared to TAU. CONCLUSION: This study is the first to report the effectiveness of personality-targeted alcohol prevention in reducing internalising and externalising symptoms relative to an active control, providing evidence in favour of its specificity in preventing concurrent substance use and mental health problems among high-risk youth.

Correction: Evaluating the Long-Term Effectiveness of School-Based Depression, Anxiety, and Substance Use Prevention Into Young Adulthood: Protocol for the Climate School Combined Study.

[This corrects the article DOI: 10.2196/11372.].

Evaluating the Long-Term Effectiveness of School-Based Depression, Anxiety, and Substance Use Prevention Into Young Adulthood: Protocol for the Climate School Combined Study.

BACKGROUND: Mental health and substance use disorders are the leading causes of global disability in children and youth. Both tend to first onset or escalate in adolescence and young adulthood, calling for effective prevention during this time. The Climate Schools Combined (CSC) study was the first trial of a Web-based combined universal approach, delivered through school classes, to prevent both mental health and substance use problems in adolescence. There is also limited evidence for the cost-effectiveness of school-based prevention programs. OBJECTIVE: The aim of this protocol paper is to describe the CSC follow-up study, which aims to determine the long-term efficacy and cost-effectiveness of the CSC prevention program for depression, anxiety, and substance use (alcohol and cannabis use) up to 7 years post intervention. METHODS: A cluster randomized controlled trial (the CSC study) was conducted with 6386 participants aged approximately 13.5 years at baseline from 2014 to 2016. Participating schools were randomized to 1 of 4 conditions: (1) control (health education as usual), (2) Climate Substance Use (universal substance use prevention), (3) Climate Mental Health (universal mental health prevention), or (4) CSC (universal substance use and mental health prevention). It was hypothesized that the CSC program would be more effective than conditions (1) to (3) in reducing alcohol and cannabis use (and related harms), anxiety, and depression symptoms as well as increasing knowledge related to alcohol, cannabis, anxiety, and depression. This long-term study will invite follow-up participants to complete 3 additional Web-based assessments at approximately 5, 6, and 7 years post baseline using multiple sources of locator information already provided to the research team. The primary outcomes include alcohol and cannabis use (and related harms) and mental health symptoms. An economic evaluation of the program will also be conducted using both data linkage as well as self-report resource use and quality of life measures. Secondary outcomes include self-efficacy, social networks, peer substance use, emotion regulation, and perfectionism. Analyses will be conducted using multilevel mixed-effects models within an intention-to-treat framework. RESULTS: The CSC long-term follow-up study is funded from 2018 to 2022 by the Australian National Health and Medical Research Council (APP1143555). The first follow-up wave commences in August 2018, and the results are expected to be submitted for publication in 2022. CONCLUSIONS: This is the first study to provide a long-term evaluation of combined universal substance use and mental health prevention up to 7 years post intervention. Evidence of sustained benefits into early adulthood would provide a scalable, easy-to-implement prevention strategy with the potential for widespread dissemination to reduce the considerable harms, burden of disease, injury, and social costs associated with youth substance use and mental disorders. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/11372.

Universal cannabis outcomes from the Climate and Preventure (CAP) study: a cluster randomised controlled trial.

BACKGROUND: The Climate and Preventure (CAP) study was the first trial to assess and demonstrate the effectiveness of a combined universal and selective approach for preventing alcohol use and related harms among adolescents. The current paper reports universal effects from the CAP study on cannabis-related outcomes over three years. METHODS: A cluster randomized controlled trial was conducted with 2190 students from twenty-six Australian high schools (mean age: 13.3 yrs., SD 0.48). Participants were randomised to one of four conditions; universal prevention for all students (Climate); selective prevention for high-risk students (Preventure); combined universal and selective prevention (Climate and Preventure; CAP); or health education as usual (Control). Participants were assessed at baseline, post intervention (6-9 months post baseline), and at 12-, 24- and 36-months, on measures of cannabis use, knowledge and related harms. This paper compares cannabis-related knowledge, harms and cannabis use in the Control, Climate and CAP groups as specified in the protocol, using multilevel mixed linear models to assess outcomes. RESULTS: Compared to Control, the Climate and CAP groups showed significantly greater increases in cannabis-related knowledge initially (p <  0.001), and had higher knowledge at the 6, 12 and 24-month follow-ups. There was no significant difference between the Climate and CAP groups. While no differences were detected between Control and the CAP and Climate groups on cannabis use or cannabis-related harms, the prevalence of these outcomes was lower than anticipated, possibly limiting power to detect intervention effects. Additional Bayesian analyses exploring confidence in accepting the null hypothesis showed there was insufficient evidence to conclude that the interventions had no effect, or to conclude that they had a meaningfully large effect. CONCLUSIONS: Both the universal Climate and the combined CAP programs were effective in increasing cannabis-related knowledge for up to 2 years. The evidence was inconclusive regarding whether the interventions reduced cannabis use and cannabis-related harms. A longer-term follow-up will ascertain whether the interventions become effective in reducing these outcomes as adolescents transition into early adulthood. TRIAL REGISTRATION: This trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12612000026820) on the 6th of January 2012, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=347906&isReview=true.

Clustering of Multiple Risk Behaviors Among a Sample of 18-Year-Old Australians and Associations With Mental Health Outcomes: A Latent Class Analysis.

INTRODUCTION: Risk behaviors commonly co-occur, typically emerge in adolescence, and become entrenched by adulthood. This study investigated the clustering of established (physical inactivity, diet, smoking, and alcohol use) and emerging (sedentary behavior and sleep) chronic disease risk factors among young Australian adults, and examined how clusters relate to mental health. METHODS: The sample was derived from the long-term follow-up of a cohort of Australians. Participants were initially recruited at school as part of a cluster randomized controlled trial. A total of 853 participants (Mage = 18.88 years, SD = 0.42) completed an online self-report survey as part of the 5-year follow-up for the RCT. The survey assessed six behaviors (binge drinking and smoking in the past 6 months, moderate-to-vigorous physical activity/week, sitting time/day, fruit and vegetable intake/day, and sleep duration/night). Each behavior was represented by a dichotomous variable reflecting adherence to national guidelines. Exploratory analyses were conducted. Clusters were identified using latent class analysis. RESULTS: Three classes emerged: "moderate risk" (moderately likely to binge drink and not eat enough fruit, high probability of insufficient vegetable intake; Class 1, 52%); "inactive, non-smokers" (high probabilities of not meeting guidelines for physical activity, sitting time and fruit/vegetable consumption, very low probability of smoking; Class 2, 24%), and "smokers and binge drinkers" (high rates of smoking and binge drinking, poor fruit/vegetable intake; Class 3, 24%). There were significant differences between the classes in terms of psychological distress (p = 0.003), depression (p < 0.001), and anxiety (p = 0.003). Specifically, Class 3 ("smokers and binge drinkers") showed higher levels of distress, depression, and anxiety than Class 1 ("moderate risk"), while Class 2 ("inactive, non-smokers") had greater depression than the "moderate risk" group. DISCUSSION: Results indicate that risk behaviors are prevalent and clustered in 18-year old Australians. Mental health symptoms were significantly greater among the two classes that were characterized by high probabilities of engaging in multiple risk behaviors (Classes 2 and 3). An examination of the clustering of lifestyle risk behaviors is important to guide the development of preventive interventions. Our findings reinforce the importance of delivering multiple health interventions to reduce disease risk and improve mental well-being.

Pathways to prevention: protocol for the CAP (Climate and Preventure) study to evaluate the long-term effectiveness of school-based universal, selective and combined alcohol misuse prevention into early adulthood.

BACKGROUND: Alcohol use and associated harms are among the leading causes of burden of disease among young people, highlighting the need for effective prevention. The Climate and Preventure (CAP) study was the first trial of a combined universal and selective school-based approach to preventing alcohol misuse among adolescents. Initial results indicate that universal, selective and combined prevention were all effective in delaying the uptake of alcohol use and binge drinking for up to 3 years following the interventions. However, little is known about the sustainability of prevention effects across the transition to early adulthood, a period of increased exposure to alcohol and other drug use. This paper describes the protocol for the CAP long-term follow-up study which will determine the effectiveness of universal, selective and combined alcohol misuse prevention up to 7 years post intervention, and across the transition from adolescence into early adulthood. METHODS: A cluster randomized controlled trial was conducted between 2012 and 2015 with 2190 students (mean age: 13.3 yrs) from 26 Australian high schools. Participants were randomized to receive one of four conditions; universal prevention for all students (Climate); selective prevention for high-risk students (Preventure); combined universal and selective prevention (Climate and Preventure; CAP); or health education as usual (Control). The positive effect of the interventions on alcohol use at 12-, 24- and 36-month post baseline have previously been reported. This study will follow up the CAP study cohort approximately 5- and 7-years post baseline. The primary outcome will be alcohol use and related harms. Secondary outcomes will be cannabis use, alcohol and other drug harms including violent behavior, and mental health symptomatology. Analyses will be conducted using multi-level, mixed effects models within an intention-to-treat framework. DISCUSSION: This study will provide the first ever evaluation of the long-term effectiveness of combining universal and selective approaches to alcohol prevention and will examine the durability of intervention effects into the longer-term, over a 7-year period from adolescence to early adulthood. TRIAL REGISTRATION: This trial was registered in the Australian New Zealand Clinical Trials Registry ( ACTRN12612000026820 ) on January 6th 2012.

Motor-evoked potentials reveal functional differences between dominant and non-dominant motor cortices during response preparation.

Transcranial magnetic stimulation (TMS) of the motor cortex produces motor-evoked potentials (MEPs) in contralateral muscles. The amplitude of these MEPs can be used to measure the excitability of the corticospinal tract during motor planning. In two experiments, we investigated learning-related changes in corticospinal excitability as subjects prepared to respond in a choice reaction-time task. Subjects responded with their left or right hand to a left or right arrow, and on some trials the arrow was immediately preceded by a warning cue that signaled which response would be required. TMS was applied to the motor cortex during the warning cues, and MEPs were measured in the dominant or non-dominant hand. We observed changes in corticospinal excitability during the warning cue, but these depended on which hand the subject was preparing to respond with, and how experienced they were with the task. When subjects prepared to respond with the non-dominant hand, excitability increased in the non-dominant hemisphere and decreased in the dominant hemisphere. These changes became stronger with task experience, and were accompanied by behavioral improvements in the task. When subjects were preparing a dominant-hand response, the non-dominant hemisphere was suppressed, but this effect disappeared as subjects gained experience with the task. There were no changes in the dominant hemisphere before dominant-hand responses. We conclude that preparing to respond with the non-dominant hand involves temporarily reversing an asymmetry in excitability that normally favors the dominant hemisphere, and that this pattern is enhanced by learning during the task.

Unmasking latent inhibition in humans.

Presentations of a to-be-conditioned stimulus (CS) on its own impairs subsequent learning when that CS is paired with an unconditioned stimulus (US). Evidence for this latent inhibition (LI) effect in humans is said to require a "masking task" that diverts attention from the CS during preexposure. We present three experiments that demonstrate LI in humans without masking. Subjects performed a computerised task, making speeded responses to an imperative cue (the US) presented within a continuous stream of stimuli. During preexposure, a to-be-CS was presented 20 times among other stimuli, but excluding the US. Instructions ensured subjects actively monitored all stimuli at this time. This was immediately followed by the training phase, which included the US, the preexposed CS, and a novel CS. Both CSs were reliably followed by the US, but these associations were incidental to the instructed task. Nonetheless, some subjects learned the CS-US associations, responding faster when the US followed a CS than when it was unsignalled. All three experiments also found evidence for LI, in that subjects learned the novel CS-US association sooner than the preexposed CS-US association. We conclude that humans can show LI even when actively attending to the CS during preexposure.