A phase 3 randomised double-blind placebo-controlled trial of mirtazapine as a pharmacotherapy for methamphetamine use disorder: a study protocol for the Tina Trial.

BACKGROUND: There are no approved pharmacotherapies for methamphetamine use disorder. Two preliminary phase 2 randomised controlled trials have found mirtazapine, a tetracyclic antidepressant, to be effective in reducing methamphetamine use. The proposed Tina Trial is the first phase 3 placebo-controlled randomised trial to examine the effectiveness and safety of mirtazapine as an outpatient pharmacotherapy for methamphetamine use disorder. METHODS: This is a multi-site phase 3 randomised, double-blind, placebo-controlled parallel trial. Participants are randomly allocated (1:1) to receive either mirtazapine (30 mg/day for 12 weeks) or matched placebo, delivered as a take-home medication. The target population is 340 people aged 18-65 years who have moderate to severe methamphetamine use disorder. The trial is being conducted through outpatient alcohol and other drug treatment clinics in Australia. The primary outcome is measured as self-reported days of methamphetamine use in the past 4 weeks at week 12. Secondary outcomes are methamphetamine-negative oral fluid samples, depressive symptoms, sleep quality, HIV risk behaviour and quality of life. Other outcomes include safety (adverse events), tolerability, and health service use. Medication adherence is being monitored using MEMS® Smart Caps fitted to medication bottles. DISCUSSION: This trial will provide information on the safety and effectiveness of mirtazapine as a pharmacotherapy for methamphetamine use disorder when delivered as an outpatient medication in routine clinical practice. If found to be safe and effective, this trial will support an application for methamphetamine use disorder to be included as a therapeutic indication for the prescription of mirtazapine. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12622000235707. Registered on February 9, 2022.

Effect of retirement on loneliness: a longitudinal comparative analysis across Australia, China and the USA.

BACKGROUND: There is evidence that the transition to retirement can bring social challenges and may increase loneliness. Few studies have examined the impact of retirement on loneliness; most have been conducted in Western countries. It is important to examine the differences in loneliness postretirement across countries to identify patterns and risk factors that might influence the health and well-being of older adults. We aimed to examine the effect of retirement on loneliness among older adults in Australia, China and the USA. METHODS: Longitudinal analysis of data from population-based samples of Australian, Chinese and American adults over 50. Lagged and fully lagged adjusted models were applied. Social engagement was examined as an effect modifier and a sensitivity analysis was conducted among urban participants. RESULTS: Retirees had a higher predicted prevalence of loneliness than non-retirees in Australia (19.4% (95% CI 18.0% to 20.9%) vs 17.0% (95% CI 15.7% to 18.4%)) and in the USA (19.3% (95% CI 17.5% to 21.1%) vs 15.7% (95% CI 14.3% to 17.3%)). These differences were significant only in the USA. In China, loneliness was significantly lower in those who had retired (10.0% (95% CI 7.9% to 12.5%) vs 17.1% (95% CI 15.7% to 18.5%)). In Australia and the USA, voluntary retirees had the lowest loneliness and involuntary retirees had the highest. Social engagement did not modify the association between retirement and loneliness. CONCLUSIONS: Our findings imply that the effect of retirement should be considered within a cultural context to inform suitable and effective strategies to alleviate loneliness.

Transitions to polysubstance use: Prospective cohort study of adolescents in Australia.

BACKGROUND AND AIMS: Adolescent polysubstance use has been associated with adverse social and health outcomes. Our aim was to measure rates and transitions to polysubstance use during adolescence and identify factors associated with initiation and discontinuation of polysubstance use. DESIGN: Prospective cohort study. Multistate Markov modelling was used to estimate rates and identify correlates of transitions between substance use states. SETTING AND PARTICIPANTS: Adolescent-parent dyads (n = 1927; adolescents in grade 7, age ≈13 years) were recruited from Australian schools during 2010/11 (Wave 1). Adolescents were surveyed annually until 2016/17 (n = 1503; age ≈19 years; Wave 7) and parents were surveyed annually until 2014/15 (Wave 5). MEASUREMENTS: Alcohol, tobacco, cannabis and 3,4-methylenedioxymethamphetamine (MDMA) use outcomes were collected at Waves 3-7. Potential confounders were collected at Waves 1-6 and consisted of sex, anxiety and depression symptoms and externalizing problems, parental monitoring, family conflict and cohesion, parental substance use and peer substance use. Covariates were age and family socioeconomic status. FINDINGS: Few adolescents engaged in polysubstance use at earlier waves (Wave 3: 5%; Wave 4: 8%), but proportions increased sharply across adolescence (Waves 5-7: 17%, 24%, 36%). Rates of transitioning to polysubstance use increased with age, with few (<9%) adolescents transitioning out. More externalizing problems (odds ratio [OR] = 1.10; 99.6% confidence interval [CI] = 1.07-1.14), parental heavy episodic drinking (OR = 1.22; 99.6% CI = 1.07-1.40), parental illicit substance use (OR = 3.56; 99.6% CI = 1.43-8.86), peer alcohol use (OR = 5.68; 99.6% CI = 1.59-20.50) and peer smoking (OR = 4.18; 99.6% CI = 1.95-8.81) were associated with transitioning to polysubstance use. CONCLUSIONS: Polysubstance use in Australia appears to be rare during early adolescence but more common in later adolescence with low rates of transitioning out. Externalizing problems and greater parental and peer substance use are risk factors for adolescent polysubstance use that may be suitable intervention targets.

Sport Participation for Academic Success: Evidence From the Longitudinal Study of Australian Children.

BACKGROUND: We aimed to identify long-term patterns of sport participation (overall, team, and individual sport) from childhood into adolescence, and to examine the association between these patterns and academic outcomes. METHODS: This cohort study used data from the Longitudinal Study of Australian Children in wave 3 (4-5 y) to wave 9 (20-21 y). The participants were a nationally representative sample of 4241 children. We conducted latent class analyses to identify sport participation trajectories and assessed the association between these trajectories and academic outcomes. RESULTS: Continued sport participation was associated with lower odds of being absent from school (OR = 0.44; 95% confidence intervals [CIs], 0.26 to 0.74), better performance on attention (B = -0.010; 95% CIs, -0.019 to -0.002) and working memory (B = -0.013; 95% CIs, -0.023 to -0.003), higher numeracy (B = 20.21; 95% CIs, 14.56 to 25.86) and literacy scores (B = 9.42; 95% CIs, 2.82 to 16.02), higher end of school academic performance (B = 3.28; 95% CIs, 1.47 to 5.09), and higher odds of studying at university (OR = 1.78; 95% CIs, 1.32 to 2.40). Team sport participation was associated with reduced absenteeism, better performance on attention and working memory, and being awarded the Higher School Certificate. Whereas individual sport participation was associated with higher literacy scores and end of school academic performance. CONCLUSIONS: Team and individual sport participation both benefit academic outcomes, but differently. Given the decline in sport participation during adolescence, these findings highlight the need to develop educational policies to establish an environment that promotes sport participation, which in turn could improve academic outcomes.

Health Care Utilization Following Interventions to Improve Social Well-Being: A Systematic Review and Meta-analysis.

Importance: It has been suggested that interventions that aim to improve social well-being may contribute to decreased health care use; however, such evidence has not been fully systematically synthesized. Objective: To systematically review and meta-analyze available evidence on the associations between psychosocial interventions and health care utilization. Data Sources: Medline, Embase, PsycInfo, Cumulated Index to Nursing and Allied Health Literature, Cochrane, Scopus, Google Scholar, and reference lists of systematic reviews were searched from inception until November 31, 2022. Study Selection: Included studies were randomized clinical trials reporting on both health care utilization and social well-being outcomes. Data Extraction and Synthesis: The reporting of the systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Full-text and quality assessments were conducted by 2 reviewers independently. Multilevel random-effects meta-analyses were used to synthesize the data. Subgroup analyses were conducted to examine the characteristics associated with decreased health care use. Main Outcomes and Measures: The outcome of interest was health care utilization, including primary, emergency, inpatient, and outpatient care services. Social well-being was measured as social support, social participation, social relationships, community support, social integration, or loneliness. Results: A total of 41 studies were retrieved from 18 969 citations; 37 studies were eligible for meta-analysis. Data were analyzed for 7842 participants, including 2745 older adults, 1579 young women considered to be at risk of social and mental health disadvantages, 1118 people with chronic illnesses, 1597 people with mental illnesses, and 803 caregivers. The odds ratio (OR) random-effects model showed an overall reduction in health care use (OR, 0.75; 95% CI, 0.59 to 0.97), but the standardized mean difference (SMD) random effect model showed no association. An improvement in health care utilization was observed in association with social support interventions (SMD, 0.25; 95% CI, 0.04 to 0.45) but not in loneliness interventions. Subgroup analysis indicated a reduced length of inpatient visits (SMD, -0.35; 95% CI, -0.61 to -0.09) and number of emergency care visits (OR, 0.64; 95% CI, 0.43 to 0.96) following the intervention. However, an increase in outpatient care associated with psychosocial interventions was observed (SMD, 0.34; 95% CI, 0.05 to 0.62). The largest reductions in health care use were associated with interventions among caregivers (OR, 0.23; 95% CI, 0.07 to 0.71) and individuals with mental illnesses (OR, 0.31; 95% CI, 0.13 to 0.74). Conclusions: These findings suggest that psychosocial interventions were associated with most measures of health care utilization. As the association differed by participant and intervention delivery characteristics, these characteristics should be considered in the design of future interventions.

Have Middle-Aged and Older Americans Become Lonelier? 20-Year Trends From the Health and Retirement Study.

OBJECTIVES: Despite media and public dialog portraying loneliness as a worsening problem, little is known about how the prevalence of loneliness has changed over time. Our study aims to identify (a) temporal trends in episodic and sustained loneliness (lonely in 1 wave vs consistently lonely in 3 consecutive waves); (b) trends across sociodemographic subgroups by sex, race/ethnicity, birth cohort, education, employment status, marital status, and living alone; and (c) longitudinal predictors of loneliness in middle-aged and older Americans (≥50 years). METHODS: Based on Waves 3 (1996) to 14 (2018) of the Health and Retirement Study (n = 18,841-23,227), we conducted a series of lagged mixed-effects Poisson regression models to assess trends of episodic and sustained loneliness in the overall and sociodemographic subgroup samples (by sex, race/ethnicity, birth cohort, education, employment, relationship, and living alone status). To examine the predictors of episodic and sustained loneliness, we used a multivariate mixed-effects Poisson regression model with all sociodemographic variables entered into the same model. RESULTS: Episodic loneliness prevalence decreased from 20.1% to 15.5% and sustained loneliness from 4.6% to 3.6%. Trends were similar across most subgroups. Males, Caucasians, those born in 1928-1945, with university education, working, married/partnered, and those not living alone reported lower episodic and sustained loneliness, although associations with sustained loneliness were stronger. DISCUSSION: Contrary to common perceptions, loneliness has decreased over 20 years of follow-up in middle-aged and older Americans. Several sociodemographic subgroups have been identified as having a higher risk of loneliness, prompting targeted public health attention.

How does a family history of psychosis influence the risk of methamphetamine-related psychotic symptoms: Evidence from longitudinal panel data.

AIMS: To determine whether the risk of psychotic symptoms during weeks of methamphetamine use was dependent on, increased by, or independent of having a family history of psychosis. DESIGN: Secondary analysis of 13 contiguous 1-week periods of data (1370 weeks). A risk modification framework was used to test each scenario. SETTING: Geelong, Wollongong and Melbourne, Australia. PARTICIPANTS: Participants in a randomized controlled trial of treatment for methamphetamine dependence (n = 148) who did not have a primary psychotic disorder on enrolment. MEASUREMENTS: Psychotic symptoms in the previous week were defined as a score of 3+ on any of the Brief Psychiatric Rating Scale items of hallucinations, unusual thought content or suspiciousness. Any (vs no) methamphetamine use in the previous week was assessed using the Timeline Followback method. Self-reported family history of psychosis was assessed using the Diagnostic Interview for Psychosis. FINDINGS: The risk of psychotic symptoms in the past week was independently associated with methamphetamine use in that week (relative risk [RR] = 2.3, 95% CI = 1.3-4.3) and with having a family history of psychosis (RR = 2.4, 95% CI = 0.9-7.0); the joint risk among participants with a family history of psychosis during weeks when they were using methamphetamine was large (RR = 4.0, 95% CI = 2.0-7.9). There was no significant interaction between a family history of psychosis and methamphetamine use in predicting psychotic symptoms (interaction RR = 0.7 95% CI = 0.3-1.8), but there was a small non-significant excess risk due to the interaction (0.20 95% CI = -1.63 to 2.03). CONCLUSIONS: Among people dependent on methamphetamine, the relative risk of psychotic symptoms during weeks of methamphetamine use does not appear to be dependent on, or increased by, having a family history of psychosis. However, a family history of psychosis does appear to be an independent risk factor that contributes to the absolute risk of psychotic symptoms in this population.

Changes in mental health and help-seeking among young Australian adults during the COVID-19 pandemic: a prospective cohort study.

BACKGROUND: Young people may have elevated risk for poorer mental health during the coronavirus disease 2019 (COVID-19) pandemic, yet longitudinal studies documenting this impact are lacking. This study assessed changes in mental health and help-seeking since COVID-19 restrictions in young Australians, including gender differences. METHODS: Data were drawn from a recent subsample (n = 443; 60% female; Mage = 22.0) of a prospective cohort originally recruited in secondary school to complete annual surveys. The subsample completed an additional COVID-19 survey during COVID-19 restrictions (May-June 2020), which was compared to responses from their latest annual survey (August 2019-March 2020). Mixed effect models with time and gender as the primary predictors were conducted for: (i) scores on the Patient Health Questionnaire Depression 9-item (PHQ-9) and Generalised Anxiety Disorder 7-item (GAD-7) modules assessed before and during COVID-19 restrictions, and (ii) self-reported help-seeking from a health professional in February 2020, and the month preceding May-June 2020. RESULTS: Mean symptom scores increased from before to during COVID-19 restrictions on the PHQ-9 (coefficient: 1.29; 95% CI 0.72-1.86) and GAD-7 (0.78; 95% CI 0.26-1.31), but there was no increase in help-seeking over time (odds ratio 0.50; 95% CI 0.19-1.32). There was no evidence of differential changes by gender. CONCLUSIONS: This study found increases in depression and anxiety symptoms but not greater help-seeking among young Australian adults during the first wave of the pandemic. Increasing availability and awareness of accessible treatment options and psychoeducation is critical, as well as further research into risk and protective factors to help target treatment to this vulnerable age group.

E-cigarette use by people who smoke or have recently quit, New South Wales, 2016-2020.

OBJECTIVE: To examine e-cigarette use by adults who smoke or have recently quit, and demographic characteristics associated with their use; to assess reasons for using e-cigarettes. DESIGN: The Cancer Institute NSW Tobacco Tracking Survey (CITTS) is an ongoing, serial, cross-sectional telephone survey study (40 interviews each week). This report is based on interviews during 4 January 2016 - 31 December 2020. SETTING, PARTICIPANTS: Randomly selected New South Wales adults who are current smokers (smoked cigarettes, pipes, or other tobacco products daily, weekly, or less often) or recent quitters (smoked tobacco products in the past twelve months but who no longer smoked). MAIN OUTCOMES: E-cigarette use by age group; reasons for using e-cigarettes. RESULTS: CITTS callers rang 1 494 233 randomly selected numbers; in 203 203 answered calls (13.6%), 11 125 people were eligible for the survey (5.5% of answered calls), of whom 10 004 completed the survey interview, including the question about whether they used e-cigarettes (89.9%). Overall e-cigarette use increased from 6.6% of respondents in 2016 to 13.0% in 2020 (adjusted odds ratio, 1.86; 95% confidence interval [CI], 1.47-2.36). The proportion of respondents aged 18-24 years who reported e-cigarette use increased from 18.4% (95% CI, 12.9-23.9%) in 2018 to 27.2% (95% CI, 20.5-33.9%) in 2020, a larger proportion than for any other age group. The leading reasons offered for e-cigarette use were "to help me quit smoking" (33%; 95% CI, 30-37%) and "to cut down on the number of cigarettes I smoke" (25%; 95% CI, 22-28%). CONCLUSION: The increase between 2016 and 2020 in the proportions of young adults who smoke or have recently quit who use e-cigarettes undermines claims that these products are designed for older smokers who have struggled to quit using other methods.

Trends in pharmaceutical opioid consumption in the WHO Eastern Mediterranean Region, 2010-2019.

Background: Pharmaceutical opioid consumption has been increasing worldwide, but disparities in access to these medications exist. Few countries of the WHO Eastern Mediterranean Region have well defined pain management policies. Aims: This study presents trends in the consumption of pharmaceutical opioids in the 22 countries in the Eastern Mediterranean Region from 2010 to 2019, with comparative intra- and extra-regional analyses; the correlation between pharmaceutical opioid consumption and human development index rankings; and pharmaceutical opioids use in the region. Methods: We calculated the defined daily doses for statistical purposes (S-DDD) per million inhabitants per day of pharmaceutical opioids from 2010 to 2019, and used the mixed effects models to assess changes in consumption. We used regression analyses to establish the strength of associations between human development index level and consumption in the region and elsewhere. Results: Pharmaceutical opioid use has fluctuated in the region since 2010, with a mean sum of S-DDD of 2547 for 2010-2019. Consumption is relatively low in the region irrespective of the human development index. The highest-consuming country reported 369 S-DDD in 2019 and the lowest reported 1 S-DDD. The most used pharmaceutical opioids in the region were fentanyl, morphine, pethidine, oxycodone, and codeine. Conclusion: Consumption could be considered inadequate in several countries of the region. Supporting these countries to improve collection and reporting of consumption data, and providing humanitarian assistance to enhance access to pain relief, should be a priority for the international community.

Vigorous physical activity, incident heart disease, and cancer: how little is enough?

AIMS: Vigorous physical activity (VPA) is a time-efficient way to achieve recommended physical activity levels. There is a very limited understanding of the minimal and optimal amounts of vigorous physical activity in relation to mortality and disease incidence. METHODS AND RESULTS: A prospective study in 71 893 adults [median age (IQR): 62.5 years (55.3, 67.7); 55.9% female] from the UK Biobank cohort with wrist-worn accelerometry. VPA volume (min/week) and frequency of short VPA bouts (≤2 min) were measured. The dose-response associations of VPA volume and frequency with mortality [all-cause, cardiovascular disease (CVD) and cancer], and CVD and cancer incidence were examined after excluding events occurring in the first year. During a mean post-landmark point follow-up of 5.9 years (SD ± 0.8), the adjusted 5-year absolute mortality risk was 4.17% (95% confidence interval: 3.19%, 5.13%) for no VPA, 2.12% (1.81%, 2.44%) for >0 to <10 min, 1.78% (1.53%, 2.03%) for 10 to <30 min, 1.47% (1.21%, 1.73%) for 30 to <60 min, and 1.10% (0.84%, 1.36%) for ≥60 min. The 'optimal dose' (nadir of the curve) was 53.6 (50.5, 56.7) min/week [hazard ratio (HR): 0.64 (0.54, 0.77)] relative to the 5th percentile reference (2.2 min/week). There was an inverse linear dose-response association of VPA with CVD mortality. The 'minimal' volume dose (50% of the optimal dose) was ∼15 (14.3, 16.3) min/week for all-cause [HR: 0.82 (0.75, 0.89)] and cancer [HR: 0.84 (0.74, 0.95)] mortality, and 19.2 (16.5, 21.9) min/week [HR: 0.60 (0.50, 0.72)] for CVD mortality. These associations were consistent for CVD and cancer incidence. There was an inverse linear association between VPA frequency and CVD mortality. 27 (24, 30) bouts/week was associated with the lowest all-cause mortality [HR: 0.73 (0.62, 0.87)]. CONCLUSION: VPA of 15-20 min/week were associated with a 16-40% lower mortality HR, with further decreases up to 50-57 min/week. These findings suggest reduced health risks may be attainable through relatively modest amounts of VPA accrued in short bouts across the week.

Definition matters: assessment of tolerance to the effects of alcohol in a prospective cohort study of emerging adults.

BACKGROUND AND AIMS: Tolerance to the effects of alcohol is an important element in the diagnosis of alcohol use disorders (AUD); however, there is ongoing debate about its utility in the diagnosis AUD in adolescents and young adults. This study aimed to refine the assessment of tolerance in young adults by testing different definitions of tolerance and their associations with longitudinal AUD outcomes. DESIGN: Prospective cohort study. SETTINGS: Australia. PARTICIPANTS: A contemporary cohort of emerging adults across Australia (n = 565, mean age = 18.9, range = 18-21 at baseline). MEASUREMENTS: Clinician-administered Structured Clinical Interview for DSM-IV Research Version (SCID-IV-RV) assessed for AUD criteria across five interviews, at 6-month intervals over 2.5 years. Tolerance definitions were operationalized using survey-type response (yes/no), clinician judgement (SCID-IV-RV), different initial drinking quantity and percentage increase thresholds and average heavy consumption metrics. AUD persistence was operationalized by the number of times AUD was present across the 2.5-year study period (n = 491), and new-onset AUD was operationalized as any new incidence of AUD during the follow-up period (n = 461). FINDINGS: The (i) SCID-IV-RV clinician judgement [odds ratio (OR) = 2.50, P = 0.005], (ii) an initial drinking quantity threshold of four to five drinks and 50% minimum increase (OR = 2.48, P = 0.007) and (iii) 50% increase only (OR = 2.40, P = 0.005) were the tolerance definitions more strongly associated with any new onset of AUD throughout the four follow-up time-points than other definitions. However, these definitions were not associated with persistent AUD (Ps > 0.05). Average heavy consumption definitions of tolerance were most strongly associated with persistent AUD (OR = 6.66, P = 0.001; OR = 4.65, P = 0.004) but not associated with new-onset AUD (Ps > 0.05). CONCLUSIONS: Initial drink and percentage change thresholds appear to improve the efficacy of change-based tolerance as an indicator for new-onset alcohol use disorder diagnosis in self-report surveys of young adults. When predicting persistent alcohol use disorder, average heavy consumption-based indicators appear to be a better way to measure tolerance than self-reported change-based definitions.

Physical activity, diet quality and all-cause cardiovascular disease and cancer mortality: a prospective study of 346 627 UK Biobank participants.

OBJECTIVES: To examine independent and interactive associations of physical activity and diet with all-cause, cardiovascular disease (CVD) and physical activity, diet and adiposity-related (PDAR) cancer mortality. METHODS: This population-based prospective cohort study (n=346 627) is based on the UK Biobank data with linkage to the National Health Service death records to 30 April 2020. A left-truncated Cox proportional hazards model was fitted to examine the associations between exposures (self-reported total moderate-to-vigorous intensity physical activity (MVPA), vigorous-intensity physical activity (VPA) and a diet quality index (score ranged 0-3)) and outcomes (all-cause, CVD and PDAR cancer mortality). RESULTS: During a median follow-up of 11.2 years, 13 869 participants died from all causes, 2650 from CVD and 4522 from PDAR cancers. Compared with quartile 1 (Q1, 0-210 min/week), Q2-Q4 of MVPA were associated with lower risks of all-cause (HR ranged from 0.87 (95% CI: 0.83 to 0.91) to 0.91 (95% CI: 0.87 to 0.96)), CVD (HR ranged from 0.85 (95% CI: 0.76 to 0.95) to 0.90 (95% CI: 0.81 to 1.00)) and PDAR cancer mortality (HR ranged from 0.86 (95% CI: 0.79 to 0.93) to 0.94 (95% CI: 0.86 to 1.02)). Compared with no VPA, any VPA was associated with lower risk for all-cause and CVD mortality (HR ranged from 0.85 (95% CI: 0.80 to 0.89) to 0.88 (95% CI: 0.84 to 0.93) and from 0.75 (95% CI: 0.68 to 0.83) to 0.90 (95% CI: 0.80 to 1.02), respectively). Although not reaching statistical significance for all-cause and CVD mortality, being in the best dietary category (diet quality index=2-3) was associated with a reduction in PDAR cancer mortality (HR=0.86, 95% CI: 0.78 to 0.93). No additive or multiplicative interactions between physical activity categories and dietary quality was found. When comparing across physical activity and diet combinations, the lowest risk combinations consistently included the higher levels of physical activity and the highest diet quality score. CONCLUSIONS: Adhering to both quality diet and sufficient physical activity is important for optimally reducing the risk of mortality from all causes, CVD and PDAR cancers.

Trajectories of parental and peer supply of alcohol in adolescence and associations with later alcohol consumption and harms: A prospective cohort study.

BACKGROUND: Supply of alcohol to adolescents is associated with increased alcohol consumption and harms including alcohol use disorder (AUD). We aimed to identify: (1) trajectories of alcohol supply to adolescents; (2) sociodemographic characteristics associated with supply trajectory; (3) patterns of alcohol consumption by supply trajectory; and (4) supply trajectory associations with adverse alcohol outcomes. METHODS: We used Australian longitudinal survey data (N = 1813) to model latent trajectories of parent and peer alcohol supply over five annual follow-ups (Waves 2-6; Mage 13.9-17.8 years). Regression models assessed associations between supply trajectories and Wave 1 (Mage=12.9 years) sociodemographic factors and associations between supply trajectories and Wave 7 (Mage=18.8 years) alcohol outcomes. RESULTS: We identified five alcohol supply classes: (1) minimal supply (n = 739, 40.8%); (2) early parent sips, late peer/parent whole drinks (n = 254, 14.0%); (3) late peer/parent whole drinks (n = 419, 23.1%); (4) early parent sips, mid peer/parent whole drinks (n = 293, 16.2%); (5) early peer/parent whole drinks (n = 108, 6.0%). Compared to minimal supply, the other classes were 2.7-12.9 times as likely to binge drink, 1.6-3.0 times as likely to experience alcohol-related harms, and 2.1-8.6 times as likely to report AUD symptoms at age 19. CONCLUSION: Earlier supply of whole drinks, particularly from peers, was associated with increased risk of early adulthood adverse alcohol outcomes. While minimal supply represented the lowest risk, supplying sips only in early-mid adolescence and delaying supply of whole drinks until late adolescence is likely to be less risky than earlier supply of whole drinks.

Trends in risk factors and management strategies used by people with type 2 diabetes in New South Wales, Australia.

Adopting healthy lifestyle behaviours is an important component of Type 2 diabetes (T2D) self-management, which can lower risks of further health complications. Monitoring lifestyle risk factors including overweight or obesity, healthy diet and physical activity behaviours, alcohol consumption, smoking and psychological distress remain important. This study examined prevalence trends in these factors and adoption of three diabetes lifestyle self-management strategies in adults (aged 40+) with T2D in New South Wales (NSW), Australia. Analyses were conducted on NSW Adult Population Health Survey data, 2004-2019 (n = 142,168), using predicted probabilities from generalised linear models, weighted to population estimates. Throughout the study period overweight or obesity prevalence remained higher amongst those with T2D (83.1% to 81.7%) compared to those without diabetes (61.0 to 61.2%); only 8.9% of those with T2D were trying to lose weight. During the study period, there were declines in the proportions of those with T2D reporting sufficient fruit consumption [63.9% to 50.1%], moderate vegetable consumption (3 serves) [49.0% to 37.7%], and achieving sufficient physical activity [40.0% to 34.0%]. There were also declines in those reporting they manage their diabetes through following a special diet [73.6% to 55.9%] and exercising most days [33.5% to 22.2%]. This study highlights potential gaps in T2D secondary prevention and suggests more targeted diabetes education services are needed to address lifestyle risks. Increased understanding of why fewer people with T2D adopt these lifestyle management strategies is needed to inform policy and practice.

The experience of physiological and psychosocial alcohol-related harms across adolescence and its association with alcohol use disorder in early adulthood: A prospective cohort study.

BACKGROUND: Different forms of alcohol-related harm (e.g., hangovers, fighting) may confer differential risk of clinically relevant alcohol problems. We examine: (i) patterns of transition in experiencing alcohol-related harms across adolescence; (ii) whether factors in early adolescence predict transition patterns; and (iii) whether transition patterns predict later alcohol use disorder (AUD) symptoms. METHODS: We used a longitudinal Australian cohort (n = 1828) to model latent class transition patterns of alcohol-related harms across three timepoints (Mage  = 13.9, 16.8, 18.8 years). Regression models assessed whether child, peer, and parent factors in early adolescence (Mage  = 12.9) predicted harms transition patterns and whether these patterns predicted AUD symptoms in early adulthood (Mage  = 19.8). RESULTS: Five transition patterns characterized most of the cohort (n ≈ 1609, 88.0%): (i) minimal harms (n ≈ 381, 20.8%); (ii) late physiological harms (n ≈ 702, 38.4%); (iii) early physiological harms (n ≈ 226, 12.4%); (iv) late all harms (n ≈ 131, 7.2%); and (v) gradual all harms (n ≈ 169, 9.2%). With late physiological harms as the reference, females had increased risk of experiencing early physiological harms (relative risk [RR]: 2.15; 99.5% CI: 1.19, 3.90). Late all harms (RR: 1.71; CI: 1.19, 2.47) and gradual all harms (RR: 1.84; CI: 1.37, 2.47) were each associated with increased odds of meeting criteria for AUD, even when patterns of alcohol consumption are considered. CONCLUSIONS: Adolescents display heterogeneous transition patterns across physiological and psychosocial alcohol-related harms. Females are at greater risk of experiencing early physiological harms. Experience of both physiological and psychosocial harms in late adolescence is an important and potentially modifiable precursor to clinically relevant alcohol problems in early adulthood.

Gender differences in the supply of alcohol to adolescent daughters and sons.

Background: Parents are the main supplier of alcohol to children but it is not known whether mothers and fathers equally contribute to the supply of alcohol to their female and male children as these children transition to adulthood.Objectives: i) to determine whether the gender of the parent is associated with the gender of the adolescent offspring when alcohol is supplied and ii) whether the gender of the parent supplying is associated with gender differences in adolescent binge drinking and alcohol related harms.Methods: Longitudinal cohort of 1,927 (males = 1052) Australian adolescents (mean age 12.9 years), recruited in 2010/11 from schools in Australia and surveyed annually for six years. We assessed the association between adolescent and parent gender related to subsequent adolescent drinking, binge drinking (>4 standard drinks), and alcohol-related harms.Results: At mean age of 12.9 years about one in ten children report parental supply of alcohol which increases to about four in ten children by 17.8 years. Mothers consistently more often supply their daughters with alcohol than their sons, [Wave 5 OR 1.77 (1.53,2.05)], while mothers less often supply sons than their daughters, [Wave 5 OR 0.82 (0.71,0.95)]. Mothers' supply of alcohol to daughters predicts substantially increased odds of daughters binge drinking, [OR 1.67 (1.10,2.53)] and experiencing alcohol related harms, [OR 1.65 (1.10,2.48)].Conclusion: There is a need to involve both mothers and fathers and to equally target female and male children in programs to reduce the harmful consequences of parental supply of alcohol to their children.

N-acetylcysteine (NAC) for methamphetamine dependence: A randomised controlled trial.

BACKGROUND: Methamphetamine dependence is a significant global health concern for which there are no approved medications. The cysteine prodrug, N-acetylcysteine (NAC), has been found to ameliorate glutamate dysregulation in addiction, and to reduce craving for methamphetamine and other drugs. We evaluated the efficacy and safety of NAC as a pharmacotherapy for methamphetamine dependence. METHODS: A parallel double-blind randomised placebo-controlled trial of people dependent on methamphetamine recruited from Geelong, Melbourne and Wollongong, Australia, between July 2018 and December 2019. Participants were randomised to receive either 12 weeks of oral NAC (2400 mg/day) or matched placebo, delivered as a take-home medication. The primary outcome was methamphetamine use, measured in two ways: (a) change in days of use in the past 4 weeks from baseline to weeks 4, 8 and 12, assessed using the Timeline Followback; and (b) methamphetamine-positive oral fluid samples taken weekly. Analyses were intention-to-treat and based on imputed data. Secondary outcomes were craving, severity of dependence, withdrawal severity and psychiatric symptoms (depression, suicidality, hostility and psychotic symptoms). Significance levels were p < 0.025 for primary outcomes and p < 0.01 for secondary outcomes. Adverse events were compared between groups by system organ class. The study was prospectively registered, ACTRN12618000366257. RESULTS: Participants (N = 153; 59% male, mean [SD] age 38 [8]) were randomised to placebo (n = 77) or NAC (n = 76). Both groups had a median (IQR) of 24 (15-28) days of methamphetamine use in the 4 weeks prior to baseline. Both groups significantly reduced methamphetamine use (mean [SE] reduction of 7.3 [1.2]) days for placebo, 6.8 [1.2] for NAC) but NAC did not reduce days of methamphetamine use more than placebo (group difference of 0.5 days, 97.5% CI -3.4-4.3). There was no significant effect of NAC on methamphetamine-positive oral fluid samples (placebo 79%, NAC 76%; mean difference -2.6, 97.5% CI -12.6-7.4). NAC did not significantly reduce craving, severity of dependence, withdrawal, suicidality, depression, hostility or psychotic symptoms relative to placebo. Adverse events did not differ significantly between placebo and NAC groups. INTERPRETATION: These findings suggest that take-home oral NAC has no significant effect on methamphetamine use or most clinically related outcomes amongst people who are dependent on the drug.

Alcohol use among young Australian adults in May-June 2020 during the COVID-19 pandemic: a prospective cohort study.

AIMS: To estimate change in young people's alcohol consumption during COVID-19 restrictions in Australia in early-mid 2020, and test whether those changes were consistent by gender and level of consumption prior to the pandemic. DESIGN: Prospective longitudinal cohort. SETTING: Secondary schools in New South Wales, Tasmania and Western Australia. PARTICIPANTS: Subsample of a cohort (n = 443) recruited in the first year of secondary school in 2010-11. Analysis data included three waves collected in September 2017-July 2018, September 2018-May 2019 and August 2019-January 2020), and in May-June 2020. MEASUREMENTS: The primary predictors were time, gender and level of consumption prior to the pandemic. Outcome variables, analysed by mixed-effects models, included frequency and typical quantity of alcohol consumption, binge drinking, peak consumption, alcohol-related harm and drinking contexts. FINDINGS: Overall consumption (frequency × quantity) during the restrictions declined by 17% [incidence rate ratio (IRR) = 0.83; 95% confidence interval (CI) = 0.73, 0.95] compared to February 2020, and there was a 35% decline in the rate of alcohol-related harms in the same period (IRR = 0.66; 95% CI = 0.54, 0.79). Changes in alcohol consumption were largely consistent by gender. CONCLUSIONS: From a survey of secondary school students in Australia, there is evidence for a reduction in overall consumption and related harms during the COVID-19 restrictions.

Pharmaceutical Opioid Use Patterns and Indicators of Extramedical Use and Harm in Adults With Chronic Noncancer Pain, 2012-2018.

Importance: Despite concern about harms related to long-term prescribed opioid use among individuals with chronic noncancer pain (CNCP), no study has examined whether the same patients engage in a risky pattern of use consistently for the long term. Objective: To examine the prevalence, incidence, persistence, and cessation of a range of opioid behaviors, indicators of extramedical use, and harm among individuals who are prescribed opioids. Design, Setting, and Participants: This 5-year prospective cohort study in communities across Australia included 1514 adults who were prescribed opioids for CNCP. Data collection took place from August 2012 to December 2018, and data analysis took place from February to November 2020. Exposure: Prescription opioid use. Main Outcomes and Measures: High-dose opioid use (≥200 oral morphine equivalent [OME] mg/d); requesting an increase in opioid dose; requesting an early prescription renewal; tampering with opioid medication; diversion of medication to others; and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision opioid dependence. Cessation of opioid use was also assessed. Results: Of the 1514 participants, 672 (44.39%) were men, the mean (SD) age was 58 (19) years, and 737 (48.68%) were unemployed. At each annual interview, approximately 1 in 8 people (10.98% [95% CI, 10.33%-11.63%] to 14.73% [95% CI, 13.98%-15.48%] at any given interview) were taking more than 200 OME mg/d; comparatively more had requested an increased dosage in the previous 3 months (8.46% [95% CI, 7.89%-9.03%] to 23.77% [95% CI, 22.82%-24.73%]); and fewer asked for an early prescription renewal (4.61% [95% CI, 4.19%-5.03%] to 13.97% [95% CI, 13.24%-14.70%]). In any given interview, between 3.06% (95% CI, 2.72%-3.40%) and 7.86% (95% CI, 7.31%-8.41%) of respondents reported tampering and between 0.47% (95% CI, 0.33%-0.60%) and 1.39% (95% CI, 1.16%-1.62%) reported diversion to others. Between 8.28% (95% CI, 7.71%-8.84%) and 13.06% (95% CI, 12.35%-13.77%) met criteria for opioid dependence at each interview. Opioid cessation increased across interviews, from year 1 (9.15% [95% CI, 8.55%-9.74%]) to year 5 (20.02% [19.14%-20.89%]). There was considerable incidence and cessation in all behaviors from 1 interview to the next: most who engaged in any of these behaviors only did so at only 1 interview. For pharmaceutical opioid dependence, between 55.26% (95% CI, 53.81%-56.71%) and 64.44% (95% CI, 62.87%-66.00%) of cases in 1 interview did not meet dependence criteria in the following interview. Conclusions and Relevance: These findings suggest considerable fluidity in opioid use, extramedical behaviors, and opioid dependence among people with CNCP. This reinforces the need for reassessment of the effectiveness and safety of prescription opioid use over time.