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 cannabisrelated 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

The validity of the Substance Use Risk Profile Scale (SURPS) among Australian adolescents

Aims: This study investigated the validity of a brief personality screening measure for substance use in adolescents, the Substance Use Risk Profile Scale (SURPS), among Australian adolescents. Design and participants: A total of 527 adolescents (mean age: 13.38 years, SD=0.43) from seven Australian schools were assessed at two time points 24 months apart. The concurrent and predictive validity of the SURPS was determined using a series of linear and logistic regressions, and was compared to the results in a United Kingdom (UK) sample. SURPS subscale scores for the Australian population were also reported and compared to those in the UK. Findings: Overall, the SURPS subscale scores for Australian adolescents were similar to those for adolescents from the UK. Tests of concurrent and predictive validity in the Australian sample demonstrated that the all four personality profiles - Hopelessness (H), Anxiety Sensitivity (AS), Impulsivity (IMP), and Sensation Seeking (SS) - were related to measures of substance use and other behavioural and emotional characteristics. In addition, all the predicted specific prospective relationships between the personality profiles and particular substance use and other behavioural problems were confirmed except that H was not associated with illicit drug use. Overall, the results were similar between the Australian and UK samples. Conclusions: The SURPS is a valid and useful measure for identifying Australian adolescents at high-risk for substance use and other emotional and behavioural problems. Implications for prevention are discussed

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

Early Treatment with Fumagillin, an Inhibitor of Methionine Aminopeptidase-2, Prevents Pulmonary Hypertension in Monocrotaline-Injured Rats

Pulmonary Hypertension (PH) is a pathophysiologic condition characterized by hypoxemia and right ventricular strain. Proliferation of fibroblasts, smooth muscle cells, and endothelial cells is central to the pathology of PH in animal models and in humans. Methionine aminopeptidase-2 (MetAP2) regulates proliferation in a variety of cell types including endothelial cells, smooth muscle cells, and fibroblasts. MetAP2 is inhibited irreversibly by the angiogenesis inhibitor fumagillin. We have previously found that inhibition of MetAP2 with fumagillin in bleomycin-injured mice decreased pulmonary fibrosis by selectively decreasing the proliferation of lung myofibroblasts. In this study, we investigated the role of fumagillin as a potential therapy in experimental PH. In vivo, treatment of rats with fumagillin early after monocrotaline injury prevented PH and right ventricular remodeling by decreasing the thickness of the medial layer of the pulmonary arteries. Treatment with fumagillin beginning two weeks after monocrotaline injury did not prevent PH but was associated with decreased right ventricular mass and decreased cardiomyocyte hypertrophy, suggesting a direct effect of fumagillin on right ventricular remodeling. Incubation of rat pulmonary artery smooth muscle cells (RPASMC) with fumagillin and MetAP2-targeting siRNA inhibited proliferation of RPASMC in vitro. Platelet-derived growth factor, a growth factor that is important in the pathogenesis of PH and stimulates proliferation of fibroblasts and smooth muscle cells, strongly increased expression of MetP2. By immunohistochemistry, we found that MetAP2 was expressed in the lesions of human pulmonary arterial hypertension. We propose that fumagillin may be an effective adjunctive therapy for treating PH in patients

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Online school-based prevention for alcohol and other drugs: a systematic review.

This poster presents the results of a review of 10 online school-based prevention programs. Aim: To identify Internet and computer-based prevention programs for alcohol and other drugs delivered in schools, and to determine the efficacy of these programs. Conclusion: The present results, together with the implementation advantages and high fidelity associated with new technology, suggest that programs facilitated by the Internet offer a promising delivery method for school-based prevention

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

IntroductionRisk 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.MethodsThe 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.ResultsThree 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 &lt; 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.DiscussionResults 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

The Reliability and validity of the Australian moral disengagement scale

Background: The present study explored the reliability, validity, and factor structure of a modified version of the Moral Disengagement Scale (MDS), which comprehensively assesses proneness to disengage from different forms of conduct specific to Australian adolescents. Methods: A sample of 452 students (Mage = 12.79; SD = 1.93) completed the modified MDS and the Australian Self-Report Delinquency Scale. A multistep approach was used to evaluate the factor structure of the MDS. The sample was divided into exploratory (n = 221) and cross-validation samples (n = 231). Principal component analysis was conducted with the exploratory sample and multiple factor solutions compared to determine the optimal factor structure of the modified MDS. The final factor solution was confirmed in the cross-validation sample using confirmatory factor analysis. Internal consistency of the final scale and convergent validity with the delinquency questionnaire was also assessed. Results: Analyses resulted in a 22-item MDS for use in Australia, with four factors mapping onto the four conceptual categories of moral disengagement. The individual subscales demonstrated adequate to good internal consistency, and the total scale also demonstrated high internal consistency (α = 0.87). Convergent validity of the scale was established. Conclusions: The 22-item Australian MDS is a reliable and valid instrument for use within an Australian population.14 page(s

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

Adolescents’ trajectories of depression and anxiety symptoms prior to and during the COVID-19 pandemic and their association with healthy sleep patterns

The COVID-19 pandemic has seen a rise in anxiety and depression among adolescents. This study aimed to investigate the longitudinal associations between sleep and mental health among a large sample of Australian adolescents and examine whether healthy sleep patterns were protective of mental health in the context of the COVID-19 pandemic. We used three waves of longitudinal control group data from the Health4Life cluster-randomized trial (N= 2781, baseline Mage= 12.6, SD= 0.51; 47% boys and 1.4% ‘prefer not to say’). Latent class growth analyses across the 2 years period identifed four trajectories of depressive symptoms: low-stable (64.3%), average-increasing (19.2%), high-decreasing (7.1%), moderate-increasing (9.4%), and three anxiety symptom trajectories: lowstable (74.8%), average-increasing (11.6%), high-decreasing (13.6%). We compared the trajectories on sociodemographic and sleep characteristics. Adolescents in low-risk trajectories were more likely to be boys and to report shorter sleep latency and wake after sleep onset, longer sleep duration, less sleepiness, and earlier chronotype. Where mental health improved or worsened, sleep patterns changed in the same direction. The subgroups analyses uncovered two important fndings: (1) the majority of adolescents in the sample maintained good mental health and sleep habits (low-stabletrajectories), (2) adolescents with worsening mental health also reported worsening sleep patterns and vice versa in the improving mental health trajectories. These distinct patterns of sleep and mental health would not be seen using mean-centred statistical approaches