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.

The key role of specific DSM-5 diagnostic criteria in the early development of alcohol use disorder: Findings from the RADAR prospective cohort study.

BACKGROUND: Prevention and early intervention of alcohol use disorder (AUD) is a public health priority, yet there are gaps in our understanding of how AUD emerges, which symptoms of AUD come first, and whether there are modifiable risk factors that forecast the development of the disorder. This study investigated potential early-warning-sign symptoms for the development of AUD. METHODS: Data were from the RADAR study, a prospective cohort study of contemporary emerging adults across Australia (n = 565, mean age = 18.9, range = 18-21 at baseline, 48% female). Participants were interviewed five times across a 2.5-year period. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) AUD criteria and diagnoses were assessed by clinical psychologists using the Structured Clinical Interview for DSM-IV (SCID-IV), modified to cover DSM-5 criteria. Hazard analyses modeled the time from first alcoholic drink to the emergence of any AUD criteria and determined which first-emergent AUD criteria were associated with a faster transition to disorder. RESULTS: By the final time point, 54.8% of the sample had experienced at least one DSM-5 AUD criterion and 26.1% met criteria for DSM-5 AUD. The median time from first AUD criterion to a diagnosis of AUD was 4 years. Social problems from drinking (hazard ratio [HR] = 3.24, CI95 = 2.14, 4.92, p < 0.001), major role (HR = 2.53, CI95 = 1.58, 4.06, p < 0.001), and drinking larger amounts/for longer than intended (HR = 2.04, CI95 = 1.20, 3.46, p = 0.008) were first-onset criteria associated with a faster transition to AUD. CONCLUSION: In the context of a prospective general population cohort study of the temporal development of AUD, alcohol-related social problems, major role problems, and using more or for longer than intended are key risk factors that may be targeted for early intervention.

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.

The association of diet quality and physical activity with cardiovascular disease and mortality in 85,545 older Australians: A longitudinal study.

BACKGROUND: A quality diet and an active lifestyle are both important cornerstones of cardiovascular disease (CVD) prevention. However, despite their interlinked effects on metabolic health, the 2 behaviors are rarely considered jointly, particularly within the context of CVD prevention. We examined the independent, interactive, and joint associations of diet and physical activity with CVD hospitalization, CVD mortality, and all-cause mortality. METHODS: CVD-free Australian participants aged 45-74 years (n = 85,545) reported physical activity, diet, and sociodemographic and lifestyle characteristics at baseline (2006-2009) and follow-up (2012-2015), and data were linked to hospitalization and death registries (03/31/2019 for CVD hospitalization and all-cause mortality and 12/08/2017 for CVD mortality). Diet quality was categorized as low, medium, and high based on meeting dietary recommendations. Physical activity was operationalized as (a) total moderate-to-vigorous physical activity (MVPA) as per guidelines, and (b) the composition of MVPA as the ratio of vigorous-intensity physical activity (VPA) to total MVPA. We used a left-truncated cause-specific Cox proportional hazards model using time-varying covariates. RESULTS: During a median of 10.7 years of follow-up, 6576 participants were admitted to the hospital for CVD and 6581 died from all causes (876 from CVD during 9.3 years). A high-quality diet was associated with a 17% lower risk of all-cause mortality than a low-quality diet, and the highest MVPA category (compared with the lowest) was associated with a 44% and 48% lower risk of CVD and all-cause mortality, respectively. Multiplicative interactions between diet and physical activity were non-significant. For all outcomes, the lowest risk combinations involved a high-quality diet and the highest MVPA categories. Accounting for total MVPA, some VPA was associated with further risk reduction of CVD hospitalization and all-cause mortality. CONCLUSION: For CVD prevention and longevity, one should adhere to both a healthy diet and an active lifestyle and incorporate some VPA when possible.

Physical activity across midlife and health-related quality of life in Australian women: A target trial emulation using a longitudinal cohort.

BACKGROUND: There is little long-term causal evidence on the effect of physical activity on health-related quality of life. This study aimed to examine the associations between longitudinal patterns of physical activity over 15 years and health-related quality of life in both the physical and mental health domains, in a cohort of middle-aged Australian women. METHODS AND FINDINGS: We used data collected at 3-year intervals (1998 to 2019) from 11,336 participants in the Australian Longitudinal Study on Women's Health (ALSWH) (1946 to 1951 birth cohort). Primary outcomes were the physical (PCS) and mental health component summary (MCS) scores (range from 0 to 100; higher scores indicate higher perceived physical/mental health) from the SF-36 in 2019 (when women aged 68 to 73 years). Using target trial emulation to imitate a randomized controlled trial (RCT), we tested 2 interventions: (1) meeting the World Health Organization (WHO) physical activity guidelines consistently throughout the 15-year "exposure period" (2001 to 2016; when women aged 50-55 to 65-70 years; physical activity assessed every 3 years); and (2) not meeting the guidelines at the beginning of the exposure period but starting to first meet the guidelines at age 55, 60, or 65; against the control of not meeting the guidelines throughout the exposure period. Analysis controlled for confounding using marginal structural models which were adjusted for sociodemographic and health variables and conditions. Consistent adherence to guidelines during the exposure period (PCS: 46.93 [99.5% confidence interval [CI]: 46.32, 47.54]) and first starting to meet the guidelines at age 55 (PCS: 46.96 [99.5% CI: 45.53, 48.40]) were associated with three-point higher PCS (mean score difference: 3.0 [99.5% CI: 1.8, 4.1] and 3.0 [99.5% CI:1.2, 4.8]) than consistent non-adherence (PCS: 43.90 [99.5% CI: 42.79, 45.01]). We found a similar pattern for most SF-36 subscales but no significant effects of the interventions on MCS. The main limitations of the study were that it may not account for all underlying health conditions and/or other unmeasured or insufficiently measured confounders, the use of self-reported physical activity and that findings may not be generalizable to all mid-age women. CONCLUSIONS: Results from the emulated RCT suggest women should be active throughout mid-age, ideally increasing activity levels to meet the guidelines by age 55, to gain the most benefits for physical health in later life.

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.

Reach, acceptability and impact of an online parent healthy lifestyle intervention during the COVID-19 lockdown: A pilot study.

ISSUE ADDRESSED: There is growing evidence that online parent-focused child healthy lifestyle interventions can improve healthy eating practices and food environments in the home. Greater understanding of whether and how parents engage with these online interventions is needed. This study evaluated the reach, acceptability and impacts of an online parent healthy lifestyle intervention. METHODS: A pilot study was conducted in New South Wales during the COVID-19 pandemic when stay-at-home public health orders were in place (July-August 2021). A concurrent mixed methods design was adopted. Data collection measures were: an online participant survey at baseline, post-intervention and 3-month follow-up; two online post-intervention focus groups; and web metrics at post-intervention and 3-month follow-up. RESULTS: There were 181 intervention participants, primarily mothers with high education levels and living in advantaged areas: 43 (24%) completed surveys post-intervention; and of these, 35 (81%; 19% of participants) completed surveys at follow-up. Sixteen mothers participated in focus groups. Parents' knowledge, self efficacy, role modelling and behaviours improved, but there were no significant differences detected over time. Metrics and survey data indicated webinar recordings, particularly the topics of 'Fussy Eating' and 'Screen time and sleep', had the greatest engagement and most perceived them as useful (93% and 96%, respectively). CONCLUSIONS: An online healthy lifestyle intervention to support parents in providing opportunities for their children to engage in healthier lifestyle behaviours was appealing and acceptable to mothers and has the potential to improve families' healthy lifestyle behaviours. Enhancing intervention reach amongst fathers and priority populations, as well as incorporating design elements to enhance engagement will be important. SO WHAT?: An online healthy lifestyle intervention reached and engaged parents, despite being faced with additional parenting challenges arising from COVID-19 stay-at-home orders.

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.

Clinical Observation, Management and Function Of low back pain Relief Therapies (COMFORT): A cluster randomised controlled trial protocol.

INTRODUCTION: Low back pain (LBP) is commonly treated with opioid analgesics despite evidence that these medicines provide minimal or no benefit for LBP and have an established profile of harms. International guidelines discourage or urge caution with the use of opioids for back pain; however, doctors and patients lack practical strategies to help them implement the guidelines. This trial will evaluate a multifaceted intervention to support general practitioners (GPs) and their patients with LBP implement the recommendations in the latest opioid prescribing guidelines. METHODS AND ANALYSIS: This is a cluster randomised controlled trial that will evaluate the effect of educational outreach visits to GPs promoting opioid stewardship alongside non-pharmacological interventions including heat wrap and patient education about the possible harms and benefits of opioids, on GP prescribing of opioids medicines dispensed. At least 40 general practices will be randomised in a 1:1 ratio to either the intervention or control (no outreach visits; GP provides usual care). A total of 410 patient-participants (205 in each arm) who have been prescribed an opioid for LBP will be enrolled via participating general practices. Follow-up of patient-participants will occur over a 1-year period. The primary outcome will be the cumulative dose of opioid dispensed that was prescribed by study GPs over 1 year from the enrolment visit (in morphine milligram equivalent dose). Secondary outcomes include prescription of opioid medicines, benzodiazepines, gabapentinoids, non-steroidal anti-inflammatory drugs by study GPs or any GP, health services utilisation and patient-reported outcomes such as pain, quality of life and adverse events. Analysis will be by intention to treat, with a health economics analysis also planned. ETHICS AND DISSEMINATION: The trial received ethics approval from The University of Sydney Human Research Ethics Committee (2022/511). The results will be disseminated via publications in journals, media and conference presentations. TRIAL REGISTRATION NUMBER: ACTRN12622001505796.

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.

Sixteen-year trends in multiple lifestyle risk behaviours by socioeconomic status from 2004 to 2019 in New South Wales, Australia.

Few studies have examined trends in inequalities related to lifestyle risk behaviours. This study examined 1) 16-year (2004-2019) trends of individual lifestyle risk factors and a combined lifestyle risk index and 2) trends in socioeconomic inequalities in these risk factors, in New South Wales (NSW; Australia) adults. Data was sourced from the NSW Adult Population Health Survey, an annual telephone survey of NSW residents aged ≥16 years, totalling 191,905 completed surveys. Excessive alcohol consumption, current smoking, insufficient physical activity, insufficient fruit and/or vegetable consumption, sugar-sweetened beverage [SSB] consumption, and a combined lifestyle risk index (overall high-risk lifestyle defined as total number of lifestyle risk behaviours ≥2) were examined. Socioeconomic status was assessed using education attainment, postal area-level disadvantage measured by Index of Relative Socioeconomic Disadvantage (IRSD), and remoteness based on Accessibility-Remoteness Index of Australia Plus (ARIA+). Socioeconomic inequalities were examined as prevalence difference for absolute inequalities and prevalence ratio for relative inequalities. The prevalence of lifestyle behaviours by levels of each socioeconomic status variable were estimated using predicted probabilities from logistic regression models. After adjusting for covariates, there was a decrease in prevalence over time for most lifestyle risk behaviours. Between 2004 and 2019, the prevalence decreased for current smoking from 21.8% to 17.1%, insufficient physical activity from 39.1% to 30.9%, excessive alcohol consumption from 15.4% to 13.7%, daily SSB consumption from 29.9% to 21.2%, and overall high-risk lifestyle from 50.4% to 43.7%. Socioeconomic inequalities, based on one or more of the socioeconomic variables, increased over time for current smoking, insufficient physical activity, daily SSB consumption, and an overall high-risk lifestyle. Overall, the health behaviours of the NSW population improved between 2004 and 2019. However, some socioeconomic inequalities increased during this time, highlighting the need for effective public health strategies that seek to improve health behaviours among the most socioeconomically disadvantaged.

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.