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Artificial intelligence (AI) tools used in employment decision-making cut across the multiple stages of job advertisements, shortlisting, interviews and hiring, and actual and potential bias can arise in each of these stages. One major challenge is to mitigate AI bias and promote fairness in opaque AI systems. This paper argues that the equal opportunity merit principle is an ethical approach for fair AI employment decision-making. Further, explainable AI can mitigate the opacity problem by placing greater emphasis on enhancing the understanding of reasonable users (employing organisations) and affected persons (employees and job candidates) as to the AI output. Both the equal opportunity merit principle and explainable AI should be integrated in the design and implementation of AI employment decision-making systems so as to ensure, as far as possible, that the AI output is arrived at through a fair process. [ABSTRACT FROM AUTHOR]

Randomized controlled trials (RCTs) are considered the gold standard for causal inference. With a sufficient sample size, randomization removes confounding up to the time of randomization and allows the treatment effect to be isolated. However, RCTs may have limited generalizability and transportability and are often not feasible in addiction research due to ethical or logistical constraints. The importance of observational studies from real‐world settings has been increasingly recognized in research on health. This paper provides an overview of modern approaches to designing observational studies that enable causal inference. It illustrates three key techniques, Directed Acyclic Graphs (DAGs), modified Disjunctive Cause Criterion and Target Trial Emulation, and discusses the strengths and limitations of their applications. [ABSTRACT FROM AUTHOR]

Background: Vaping is an increasingly popular mode of cannabis use. Few studies have characterized the role of flavors in cannabis e-liquids. Objectives: To explore the prevalence of flavored vaping liquids, including differences between countries and correlates of use. Methods: Data were from Wave 4 (2021) of the International Cannabis Policy Study with national samples aged 16-65 in Canada, the United States (US), Australia, and New Zealand. The sample comprised 52,938 respondents, including 6,265 who vaped cannabis e-liquids in the past 12-months (2,858 females, 3,407 males). Logistic regression models examined differences in the use of flavored e-liquids between countries and sociodemographic characteristics. Results: The prevalence of vaping cannabis e-liquids was highest in the US (15.3%) and Canada (10.7%) compared to Australia (4.0%) and New Zealand (3.7%). Among past 12-month cannabis consumers, 57.5% reported using flavored vaping liquids, 34.2% used unflavored vaping products and 8.3% did not know. People who vape in Australia were most likely to report using flavored liquids compared to New Zealand (OR = 2.29), Canada (OR = 3.14), and the US (OR = 3.14) (p < .05 for all). Fruit was the most reported vaping flavor (40.8%), followed by candy/dessert (20.4%) and vanilla (15.2%). Use of flavored vapes was greater among younger, ethnic minorities, female, higher education and income adequacy, and more frequent consumers (p < .05). Conclusion: Many cannabis consumers reported using flavored e-liquids, with highest levels among young people aged 16-35. Given the high prevalence of vaping in legal markets, regulators should consider the role of flavored vaping products in promoting cannabis use among this group. [ABSTRACT FROM AUTHOR]

Introduction In 2010, Australian tobacco excise (administered federally) increased by 25%, and by 12.5% annually from 2013 to 2020, with additional increases on roll-your-own (RYO) tobacco between 2017 and 2020. We estimated past year changes in smoking behavior among Australian adults who smoked (daily and non-daily) in the past year, and the association between consumer characteristics and stated motivations to change/attempt to change smoking behavior between 2007 and 2019. Methods Logistic regression analysis of combined data from national representative triennial cross-sectional surveys in Australia (N = 22 977). Results The main motivation cited for changing smoking behavior switched from health-related from 2007 to 2010 to cost-related from 2013 to 2019. Among those who quit between one and 12 months ago, living in a lower socioeconomic area (odds ratio (OR) = 1.61, 95% CI = 1.18% to –2.18%), was associated with reporting the cost of smoking motivated them to quit. Among those who reduced their smoking, smoking daily and >20 cigarettes/day vs. non-daily smoking (OR = 2.11, 95% CI = 1.60% to 2.78%), having high/very high psychological distress (OR = 1.33, 95% CI = 1.12% to 1.59%), and alcohol consumption (ORdaily drinking = 1.38, 95% CI = 1.05% to 1.81%) was associated with cost as a motivation. Exclusive (OR = 0.65, 95% CI = 0.53% to 0.80%) and non-exclusive (OR = 0.77, 95% CI = 0.65% to 0.91%) RYO use was associated with being less likely to report the cost of tobacco as motivation for cutting down. Conclusions The cost of smoking became the most cited motivator to change smoking behavior (eg, quitting and cutting down), particularly for those who lived in low socioeconomic areas, smoked more cigarettes per day, drank alcohol, and had high/very high psychological distress. Implications A change in the main federal tobacco control intervention implemented in Australia from mass-media campaigns to tobacco tax increases has likely led to cost, rather than health, being the main motivation cited for changing smoking behavior in Australia since 2013. Further monitoring is needed to ensure the harmonization in tax rates for RYO and factory-made cigarettes has effectively reduced the price difference between these products because the lower cost of RYO may have reduced the effectiveness of tax increases as a motivator to change smoking behavior. [ABSTRACT FROM AUTHOR]

Genetic alterations that activate protein kinase A (PKA) are found in many tumor types. Yet, their downstream oncogenic signaling mechanisms are poorly understood. We used global phosphoproteomics and kinase activity profiling to map conserved signaling outputs driven by a range of genetic changes that activate PKA in human cancer. Two signaling networks were identified downstream of PKA: RAS/MAPK components and an Aurora Kinase A (AURKA)/glycogen synthase kinase (GSK3) sub-network with activity toward MYC oncoproteins. Findings were validated in two PKA-dependent cancer models: a novel, patient-derived fibrolamellar carcinoma (FLC) line that expresses a DNAJ-PKAc fusion and a PKA-addicted melanoma model with a mutant type I PKA regulatory subunit. We identify PKA signals that can influence both de novo translation and stability of the proto-oncogene c-MYC. However, the primary mechanism of PKA effects on MYC in our cell models was translation and could be blocked with the eIF4A inhibitor zotatifin. This compound dramatically reduced c-MYC expression and inhibited FLC cell line growth in vitro. Thus, targeting PKA effects on translation is a potential treatment strategy for FLC and other PKA-driven cancers. [ABSTRACT FROM AUTHOR]

Introduction: This study examines age, time period and birth cohort trends in cannabis use intention and weekly use in Australia over a period in which medicinal cannabis was legalised. Methods: Hierarchical age‐period‐cohort models were used to analyse the National Drug Strategy Household Survey between 2001 and 2019, including 158,395 participants aged 18–79 years. Results: The hierarchical age‐period‐cohort model demonstrated a decrease in likelihood of intending to try cannabis as age increases. Similar age effects were found in intending to use cannabis as often or less often. There was broad‐based shift in attitudes for people wanting to try cannabis (2007: b = −0.51 [−0.82, −0.21]; 2019: b = 0.68 [0.38, 0.98]) or use cannabis more often (2007: b = −0.15 [−0.50, 0.20]; 2019: b = 0.83 [0.49, 1.18]). The population trend of weekly cannabis use decreased in the earlier periods but increased since 2013 (b = −0.13 [−0.25, −0.02] vs 2019: b = 0.06 [−0.09, 0.20]). This suggests that legalisation would increase uptake of cannabis and consumption among current consumers. There were distinctive inter‐generation variations: people born between 1950s and 1960s had more liberal views towards cannabis use than people born before or after (p < 0.05). There were indications that young people born in the 1990 s are catching up with the baby boomers in using cannabis more often if it was legal. Discussion and Conclusions: There has been a population‐based shift in Australia in favourable attitudes towards cannabis use, more so among those born in the 1950s to 1960s than other generations. Liberal attitudes and more frequent cannabis use may put certain cohorts at higher risks of cannabis dependence and related harms. [ABSTRACT FROM AUTHOR]

Understanding mental healthcare seeking and associated factors is essential for planning mental health services. This study aimed to assess treatment seeking and barriers to care for depressive symptoms and hazardous drinking in a community sample of Northwest Ethiopia. A cross-sectional study was conducted to screen 1,728 participants for depressive symptoms (n = 414) and hazardous drinking (n = 155). Participants were asked whether they had sought mental healthcare. We also assessed the barriers to seeking mental healthcare. Logistic regression was used to identify associated factors. Among people with depressive symptoms, 14.3%, 15.5%, and 19.6% sought treatment from healthcare settings, non-healthcare settings, or any sources, respectively. Religious places (39.5%) were the most helpful treatment sources. People with low levels of internalized stigma (adj OR = 3.00 [1.41, 6.42]) and positive attitudes towards mental illness (adj OR = 2.84 [1.33, 6.07]) were nearly threefold more likely to seek depression treatment. No participants with hazardous drinking sought treatment from healthcare settings, and only 1.3% had sought help from families/friends. Over 97% of participants with depressive symptoms and hazardous drinking reported at least one barrier to treatment-seeking from a healthcare setting. Religious and traditional healers were as important as healthcare settings for treatment-seeking. [ABSTRACT FROM AUTHOR]

Background: Mental health services are advocated to move from specialized care to more integrated and accessible primary care settings. The integration of mental health into primary health services is expanding in Ethiopia. However, there is a lack of research on the perspectives of health professionals on mental health services in Ethiopia. This study aimed to explore the perspectives, views, and experiences of health professionals regarding mental health services and the help-seeking behavior of people with mental illness in Northwest Ethiopia. Methods: This qualitative study included sixteen health professionals. The participants were interviewed using a semi-structured interview guide. Interviews were conducted in Amharic and translated into English. We analyzed the data using reflexive thematic analysis. Results: Five key themes were generated from the interview data: (1) Avoidance of mental healthcare; (2) Low literacy about mental illness; (3) Stigma as a hindrance to accessing mental health services; (4) The role of culture and religion in mental health services; and (5) Lack of government concern about mental health services. Conclusion: This study identified important factors related to mental health services in Northwest Ethiopia, from the perspectives of health professionals. Our findings highlighted that the government health agenda needs to prioritize mental health services. The role of religious and cultural healing places in the help-seeking pathway should be given due consideration to ensure success in mental health services provision and utilization. [ABSTRACT FROM AUTHOR]

Randomized controlled trials (RCTs) are the gold standard for making causal inferences, but RCTs are often not feasible in addiction research for ethical and logistic reasons. Observational data from real‐world settings have been increasingly used to guide clinical decisions and public health policies. This paper introduces the potential outcomes framework for causal inference and summarizes well‐established causal analysis methods for observational data, including matching, inverse probability treatment weighting, the instrumental variable method and interrupted time‐series analysis with controls. It provides examples in addiction research and guidance and analysis codes for conducting these analyses with example data sets. [ABSTRACT FROM AUTHOR]

Aim: To (i) estimate the prevalence of adolescent vaping in 47 lower‐middle, upper‐middle and high‐income countries, and (ii) test the association between implementation of World Health Organisation (WHO) tobacco control policies and adolescent e‐cigarette use (also known as vaping) in 44 countries where implementation data were available. Design: Cross‐sectional surveys. Settings A total of 47 lower‐middle, upper‐middle and high‐income countries. Participants: A total of 151 960 adolescents (typically ages 13–15) who participated in WHO's Global Youth Tobacco Survey between 2015 and 2018. Measurements Prevalence of past‐30‐day vaping and past 30‐day frequent vaping (≥10 days) were estimated from the surveys. Data on the implementation of six tobacco control measures including monitoring, smoke‐free policies, cessation programs, warning about the dangers of tobacco, advertising bans and taxation were taken from WHO's report on global tobacco epidemic. Findings The overall weighted prevalence of adolescent vaping and frequent vaping in the past 30 days was 8.6% (95% CI, 8.3‐8.9) and 1.7% (95% CI, 1.6‐1.8), respectively. For five of WHO's policies (monitoring, smoking‐free environment, cessation programs, health warning and advertising bans), their association with adolescent vaping was inconclusive because of large variation of their effects across countries. Higher tax on combustible tobacco products was associated with higher adolescent vaping (> = 75% tax vs < 25% tax; odds ratio = 2.58; 95% CI, 1.25‐5.21). Conclusion: In 47 lower‐middle, upper‐middle and high‐income countries from 2015 to 2018, ~1 in 12 (8.6%) adolescents reported vaping in the past 30 days, but prevalence of frequent vaping was low (1 in 60; 1.7%). A higher tobacco tax was associated with higher adolescent vaping. [ABSTRACT FROM AUTHOR]

Background: Vitamin D (VitD) supplementation is recommended by the American Academy of Pediatrics (AAP) for preterm infants to improve bone density. Complications of VitD supplementation include hypercalciuria and nephrocalcinosis (NC). NC has been reported in 7–64% infants < 32 weeks gestational age (GA) or < 1500 g birth weight (BW). The relationships between VitD supplementation, serum 25-hydroxy VitD levels, bone density, hypercalciuria and development of NC in preterm infants are not well established. Methods: Prospective, observational cohort study of 56 infants with GA ≤ 32 weeks or BW ≤ 1800 g. Demographics, dietary intakes, serum 25-hydroxy VitD levels and weekly urinalyses were collected until 40 weeks corrected GA or discharge. Bone mineral density (BMD) and content (BMC) were assessed using dual-energy X-ray absorptiometry (DEXA) scan. NC was identified by kidney ultrasound. Results: 56 infants received on average 447 IU/day of VitD with average serum 25-hydoxy VitD level 39.6 ng/mL. DEXA scan showed average BMD 0.13 g/cm2 and BMC 35.8 g. 23/56 (41%) infants were diagnosed with NC. Infants with NC had lower GA (p < 0.01) and BW (p < 0.01) and increased presence of calcium oxalate crystals (78% vs. 36%) (p = 0.002). There were no differences in VitD intake, urine calcium/creatinine ratios or BMD and BMC in infants with versus without NC. Conclusions: VitD supplementation per AAP guidelines resulted in acceptable serum 25-hydroxyVitD levels, but no improvement in BMD or BMC compared to previously reported values. However, infants receiving recommended amounts born at earlier GA and lower BW are at increased risk of NC. VitD supplementation and serum levels should be closely monitored in this high-risk population. A higher resolution version of the Graphical abstract is available as Supplementary information. [ABSTRACT FROM AUTHOR]

Aim: To test (1) if there was a change in self‐reported lifetime prevalence of meth/amphetamine use by birth cohort and (2) if the extent of under‐reporting of meth/amphetamine use was associated with the proportion of the population who nominated meth/amphetamine as a drug problem. Design Observational study using seven waves of repeated cross‐sectional nationally representative household surveys between 2001 and 2019. Setting: Australia. Participants: Participants were from three birth cohorts: 1951–60 (age 68–77 at the 2019 survey; n = 29 458; 55% female), 1961–1970 (age 58–67; n = 29 859; 57% female) and 1971–1980 (age 48–57; n = 28 758; 59% female). Data were weighted to align the sample to the Australian population. Measurements Past year meth/amphetamine use; under‐reporting of lifetime meth/amphetamine use in each birth cohort, year and survey stratum (operationalised as the difference between self‐reported lifetime prevalence in 2001 and that of each subsequent year); proportion of the population who nominated meth/amphetamine as a drug problem in each birth cohort, year and survey stratum. Under‐reporting was regressed on the proportion of people holding negative attitude towards meth/amphetamine. Survey year and birth cohort were adjusted for. Findings Between 2001 and 2019, the lifetime prevalence of meth/amphetamine decreased from 6.1% (95% CI = 5.3–6.9) to 1.7% (95% CI = 1.2–2.2) in the 1951–1960 birth cohort (p < 0.001), from 13.0% (95% CI = 12.0–14.1) to 4.4% (95% CI = 3.7–5.2) in the 1961–1970 birth cohort (p < 0.001) and from 21.4% (95% CI = 19.9–22.9) to 11.2% (95% CI = 10.0–12.4) in the 1971–1980 birth cohort (p < 0.001). The proportion who nominated meth/amphetamine as a 'drug problem' increased significantly in all three cohorts (all p < 0.001) and the degree of under‐reporting of meth/amphetamine use was significantly associated with proportion of people who nominated meth/amphetamine as the 'drug problem' (b = 0.09, SE = 0.01, p < 0.001). Conclusion: In Australia, the actual prevalence of lifetime meth/amphetamine use may be two‐ to fourfold higher than that estimated in the most recent national household surveys (2019). The level of under‐reporting is strongly associated with increasing negative attitudes towards methylamphetamine and d‐amphetamine use over the same period. [ABSTRACT FROM AUTHOR]

Aim: Type 2 diabetes (T2D) is associated with significant cardiovascular (CV) morbidity and mortality. A single‐nucleotide polymorphism (SNP) in the acetyl‐coenzyme A carboxylase beta (ACACB) gene, rs2268388, reproducibly associates with diabetic nephropathy (DN). ACACB regulates fatty‐acid oxidation. As such, we assessed whether ACACB SNP rs2268388 was associated with CV disease in Chinese individuals with T2D. Methods: Chinese individuals with T2D were genotyped for SNP rs2268388. Baseline demographics were recorded and clinical data regarding coronary, carotid, and peripheral arterial disease and congestive heart failure were retrieved from electronic patient records. Statistical analyses were performed to detect associations between the rs2268388 T risk allele with CV outcomes in the cohort. Results: A total of 596 Chinese individuals with T2D were genotyped. Their mean age was 66.8 ± 10.9 years at the time of data extraction. Genotyping revealed 59.7%, 33.2% and 7.1% of the study population were non‐carriers, heterozygous and homozygous carriers of the rs2268388 T risk allele in ACACB. No statistically significant correlations of the risk allele were observed with CV outcomes. Conclusion: These results did not demonstrate association between rs2268388 SNP in ACACB with CV outcomes in Chinese T2D patients. The ACACB gene and its role in CV risk susceptibility, via alterations in fatty acid oxidation, remains an interesting postulate and studies with larger cohort sizes and in different ethnic groups remain warranted. SUMMARY AT A GLANCE: In this study of Chinese patients with type 2 diabetes mellitus, a single nucleotide polymorphism in ACACB, which is known to be associated with type 2 diabetes, was not associated with cardiovascular outcomes. Although this gene has been implicated to have a role in the regulation of fatty‐acid oxidation and has the potential of mediating cardiovascular outcomes, the result of this study does not support such a relationship. [ABSTRACT FROM AUTHOR]

Rationale: There has been increasing attention on cannabis use for medical purposes, but there is currently a lack of data on its epidemiology. Objectives: To examine the epidemiology of self-reported cannabis use for medical purposes by (1) estimating its prevalence, (2) comparing gender and age differences, and (3) investigating what reasons they were used to manage. Methods: Participants included 27,169 respondents (aged 16–65) who completed Wave 1 of The International Cannabis Policy Study (ICPS) conducted across Canada and the USA in 2018 via online surveys. Cannabis policy conditions were "US legal–recreational" (legal for both recreational and medical uses), "US legal–medical only", "US illegal", and "Canada–medical only". Results: The overall prevalence of self-reported ever cannabis use for medical purposes was 27%, with similar rates by sex and the highest prevalence in young adults. Prevalence was higher in US legal–recreational states (34%) than US illegal states (23%), US legal–medical only states (25%), and Canada (25%). The most common physical health reasons include use to manage pain (53%), sleep (46%), headaches/migraines (35%), appetite (22%), and nausea/vomiting (21%). For mental health reasons, the most common were for anxiety (52%), depression (40%), and PTSD/trauma (17%). There were 11% who reported using cannabis for managing other drug or alcohol use and 4% for psychosis. Conclusions: A substantial proportion of the North American population self-reported cannabis use for medical purposes for a variety of medical reasons, including those living in jurisdictions without legal markets. Further research is needed to understand the safety and efficacy of these forms of medical cannabis use. [ABSTRACT FROM AUTHOR]

Background: Depression is considered a global crisis due to its high prevalence and associated disabilities. The burden posed by depression could be reduced by increasing access to timely treatment. Limited information is available on treatment rates of depression, particularly in low- and middle-income countries. This study aimed to estimate the treatment rates for depression in the general adult population by World Bank income classification.Methods: We searched PubMed, EMBASE, PsycINFO, and CINAHL, supplemented with hand-search of reference lists to identify community-based studies. The overall treatment rate for depression was estimated from studies that reported any treatment (behavioral or pharmacological treatments) in healthcare or informal non-healthcare settings. Data were pooled using a random-effects meta-analysis model. Subgroup analyses by income classification were completed. Meta-regression was conducted by study characteristics. The protocol was pre-registered at PROSPERO (CRD42020161683).Results: We included 65 studies comprising 1.1 million participants from 79 countries and territories. The global 12-month/lifetime pooled treatment rate was 34.8% (95% confidence interval: 29.9, 39.9%). The treatment rates were 48.3% (43.0, 53.6%) in high-income countries, 21.4% (15.1, 27.7%) in middle-income countries, and 16.8% (11.3, 23.0%) in low-income countries. Among the treated samples, 12-month minimally adequate treatment was estimated to be 40%.Limitation: We reported a substantial level of between-study heterogeneity, which was partially explained by study characteristics in the meta-regression.Conclusion: Globally, approximately one-third of people with depression receive treatment. Three in five treated people with depression did not receive minimally adequate treatment. Depression treatment rates are considerably lower in low-and middle-income countries. [ABSTRACT FROM AUTHOR]

Background: Human cytomegalovirus (HCMV) resides latently in cells of the myeloid compartment, including CD34+ hematopoietic progenitor cells and circulating monocytes. Healthy hosts maintain the virus latently, and this infection is, for the most part, asymptomatic. However, given the proper external cues, HCMV reactivates from latency, at which point the virus disseminates, causing disease. The viral and cellular factors dictating the balance between these phases of infection are incompletely understood, though a large body of literature support a role for viral-mediated manipulation of host cell signaling. Main body: To establish and maintain latency, HCMV has evolved various means by which it usurps host cell factors to alter the cellular environment to its own advantage, including altering host cell signaling cascades. As early as virus entry into myeloid cells, HCMV usurps cellular signaling to change the cellular milieu, and this regulation includes upregulation, as well as downregulation, of different signaling cascades. Indeed, given proper reactivation cues, this signaling is again altered to allow for transactivation of viral lytic genes. Conclusions: HCMV modulation of host cell signaling is not binary, and many of the cellular pathways altered are finely regulated, wherein the slightest modification imparts profound changes to the cellular milieu. It is also evident that viral-mediated cell signaling differs not only between these phases of infection, but also is myeloid cell type specific. Nonetheless, understanding the exact pathways and the means by which HCMV mediates them will undoubtedly provide novel targets for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Aims: To estimate the treatment rate for alcohol use disorders (AUDs) in the general adult population. Treatment rates were also considered in relation to economic differences. Methods: Systematic review and meta‐analysis. We searched PubMed, EMBASE, PsycINFO and CINAHL databases to identify studies that reported treatment rates for alcohol use disorders in the general population. Independent reviewers screened the articles based on predefined inclusion criteria. Data were extracted using a standardized data extraction form. We conducted quality assessments of the included studies. The overall treatment rates were estimated from studies that reported any treatment for AUDs from healthcare or informal non‐healthcare settings (any treatment). We estimated the separate treatment rates for each diagnostic category as reported in the primary studies: AUD as a single disorder, alcohol abuse and alcohol dependence. Data were pooled using a random‐effect model. Results: Thirty‐two articles were included to estimate the treatment rates (percentage treated among the total number of people with AUDs). The pooled estimate of people with AUDs who received any treatment were 14.3% (95% CI: 9.3–20.3%) for alcohol abuse, 16.5% (95% CI: 12–21.5%) for alcohol dependence and 17.3% (95% CI: 12.8–22.3%) for AUD. A subgroup analysis by World Bank economic classification of countries found that the treatment rate for AUD was 9.3% (95% CI: 4.0–15.7%) in low and lower‐middle‐income countries. Conclusion: Globally, approximately one in six people with AUDs receives treatment. Treatment rates for AUDs are generally low, with even lower rates in low and lower‐middle‐income countries. [ABSTRACT FROM AUTHOR]

Background and aims: Experience of alcohol‐induced memory blackouts in adolescence may be an important risk factor for later harms. This longitudinal study (i) modelled trajectories of alcohol‐related blackouts throughout adolescence, (ii) explored early‐adolescent predictors of blackout trajectories and (iii) examined the association between blackout trajectories and alcohol use disorder (AUD) symptoms. Design Longitudinal study in which data from six annual surveys of a longitudinal cohort of Australian adolescents were used to model latent class growth trajectories of blackouts, adjusting for alcohol consumption frequency and typical quantity. Regression models were used to determine whether parent, child and peer factors at baseline (mean age = 12.9) predicted profiles of blackout trajectory membership and whether blackout trajectories predicted meeting criteria for AUD in early adulthood (mean age = 19.8). Setting and participants: Australian adolescents (n = 1821; mean age = 13.9–18.8 years). Measurements Alcohol‐related blackouts, alcohol consumption frequency, typical consumption quantity and DSM‐5 AUD in early adulthood were all self‐reported. Findings We identified a three‐class solution: delayed alcohol initiation, rare blackouts (n = 701; 38.5%); early initiation, rare blackouts (n = 869; 47.7%); and early initiation, increasing blackouts (n = 251; 13.8%). Female sex was associated with increased risk of early initiation, increasing blackouts relative to delayed initiation, rare blackouts [relative risk ratio (RRR) = 3.90; 99.5% confidence interval (CI) = 1.96, 7.76] and relative to early initiation, rare blackouts (RRR = 2.89; 99.5% CI = 1.42, 5.87). Early initiation, rare blackouts [odds ratio (OR) = 1.96; 99.5% CI = 1.17, 3.29] and early initiation, increasing blackouts (OR = 4.93; 99.5% CI = 2.32, 10.48) were each associated with increased odds of meeting criteria for AUD in early adulthood relative to delayed initiation, rare blackouts. Early initiation, increasing blackouts was associated with increased odds of meeting criteria for AUD in early adulthood relative to early initiation, rare blackouts (OR = 2.51; 99.5% CI = 1.18, 5.38). Conclusions: Females in Australia appear to be at higher risk of adolescent alcohol‐related blackouts independent of alcohol consumption levels and age of initiation. Alcohol‐related blackouts may be associated with later alcohol use disorder. [ABSTRACT FROM AUTHOR]

Background: The International Gaming Study (IGS22) multi-country study recruited participants from a wide age range, providing an opportunity to explore gaming patterns and consequences in older adults, a hitherto under-assessed population. The aim of the present study was therefore to understand the impact of videogaming on the wellbeing of older adults. Method: The IGS22 is a cross-sectional survey of individuals who play video games weekly. This study included 955 participants aged 18-94 (M = 46.10 [16.19]; 55% female). We stratified our sample into five age categories: (i) 18-25 (10.3%), (ii) 26-35 (21.8%), (iii) 36-45 (20.1%), (iv) 46-65 (31.9%), and (v) >65 (15.8%). Results: Participants' play frequency did not differ across age (p = 0.151), but older adults were less likely than young adults (18-25: 73%, >=65: 24%, p < 0.001) to play for 4 hours or more on a typical day. Younger people were more likely than older people to play for 3 or more hours in one session (p < 0.001), with only a very small proportion of older adults playing for 6 or more hours in single session (>=65: 2.6% vs 18-25: 19.4%). In young adults aged 18-25, 27% met IGDT-10 cut-off, compared to only 2% in older adults aged >65 years (p < 0.001). Conclusions: Preliminary analyses showed that people across the lifespan engage in videogame play. Older individuals were less likely than to game for long sessions, and the majority did not meet the IGD-10 gaming disorder positive category. Analyses are underway to investigate if videogaming may be more harmoniously integrated into their lives. [ABSTRACT FROM AUTHOR]

Background: The ICD-11 diagnosis of Gaming Disorder (GD) requires the presence of impaired control over gaming, increasing priority over other activities, continued gaming despite adverse consequences, and demonstrable impairment. Tolerance and withdrawal, which are characteristic features of substance dependence, are not accepted as diagnostic features; instead they are noted as "additional clinical features". This study, part of IGS22, sought to examine whether tolerance and dependence are integral components of GD. Method: Data were from 803 participants (age <=65) in the IGS22. There were 76 items in the study measuring impaired control over gaming, increasing priority over other activities, continued gaming despite adverse consequences, e impairment, and tolerance and withdrawal. Results: Tolerance was reported by 32%, and withdrawal by 33.5%, compared with 33.7% reporting impaired control. Exploratory factor analysis (EFA) shows that both tolerance and withdrawal loaded on the same factor as impaired control. Increasing priority loaded on to a second factor and impairment on to a third. We then conducted two sets of confirmatory factor analysis, one with the 3-factor structure identified in the EFA and one with 6-factor with impaired control, tolerance and withdrawal loaded on separate factors. The 3-factor model fitted the data well (CFI=0.962, RMSEA=0.025); with substantially increased model complexity, the 6-factor model only marginally fitted the data better (CFI=0.973, RMSEA= 0.022). Conclusions: The constructs of tolerance and withdrawal largely overlap with impaired control. While they could be additional clinical features, they are unlikely to be necessary for diagnosis and screening for gaming disorder. [ABSTRACT FROM AUTHOR]

Introduction: This paper compares consequences of cannabis use initiated after high school with those of cannabis initiation in adolescence, with estimates of the proportion of adverse consequences accounted for by adult‐onset and adolescent‐onset cannabis users. Methods: A state‐representative sample in Victoria, Australia (n = 1792) participated in a 10‐wave longitudinal study and was followed from age 15 to 35 years. Exposure variable: Patterns of cannabis use across 20 years. Outcomes at age 35: Alcohol use, smoking, illicit drug use, relationship status, financial hardship, depression, anxiety and employment status. Results: Substantially more participants (13.6%) initiated regular use after high school (young‐adult onset) than in adolescence (7.7%, adolescent onset). By the mid‐30s, both young‐adult and adolescent‐onset regular users were more likely than minimal/non‐users (63.5%) to have used other illicit drugs (odds ratio [OR] > 20.4), be a high‐risk alcohol drinker (OR > 3.7), smoked daily (OR > 7.2) and less likely to be in relationships (OR < 0.4). As the prevalence of the young‐adult‐onset group was nearly double of the adolescent‐onset group, it accounted for a higher proportion of adverse consequences than the adolescent‐onset group. Discussion and Conclusions: Cannabis users who began regular use in their teens had poorer later life outcomes than non‐using peers. The larger group who began regular cannabis use after leaving high school accounted for most cannabis‐related harms in adulthood. Given the legalisation of cannabis use in an increasing number of jurisdictions, we should increasingly expect harms from cannabis use to lie in those commencing use in young adulthood. [ABSTRACT FROM AUTHOR]

Background and Aims: Studies have consistently found a longitudinal association between e‐cigarette use (vaping) and cigarette smoking. Many have interpreted such association as causal. This systematic review and meta‐analysis evaluated the plausibility of a causal interpretation by (1) estimating the effect of adolescent vaping on smoking initiation, adjusted for study quality characteristics, (2) evaluating the sufficiency of adjustment for confounding based on the social development model (SDM) and the social ecological model (SEM) and E‐value analyses and (3) investigating sample attrition and publication bias. Methods: Systematic review and meta‐analysis of longitudinal studies that examined the association between e‐cigarette use at baseline and smoking at follow‐up. Participants were non‐smokers aged < 18 at baseline. Results: Meta‐analysis of 11 studies showed a significant longitudinal association between vaping and smoking [adjusted odds ratio (aOR) = 2.93, 95% confidence interval (CI) = 2.22, 3.87]. Studies with sample sizes < 1000 had a significantly higher odds ratio (OR = 6.68, 95% CI = 3.63, 12.31) than studies with sample sizes > 1000 (OR = 2.49, 95% CI = 1.97, 3.15). Overall, the attrition rate was very high (median = 30%). All but one study reported results from complete sample analysis, despite those dropping out having higher risk profiles. Only two studies comprehensively adjusted for confounding. The median E‐value was 2.90, indicating that the estimates were not robust against unmeasured confounding. Conclusions: There is a longitudinal association between adolescent vaping and smoking initiation; however, the evidence is limited by publication bias, high sample attrition and inadequate adjustment for potential confounders. [ABSTRACT FROM AUTHOR]

Objective: Studies have noted an inconsistent risk of stillbirth in women with high BMI. There are no reports on obese women specifically selected without any pre-existing or current medical or obstetric conditions. We aimed to document the risk of stillbirth, specifically in this group of women.Methods: A retrospective cohort study of 182,362 singleton pregnancies at gestation ≥28 weeks in Queensland, Australia between 2008 and 2016 with no pre-existing or current medical or obstetric conditions.Results: We found no significant association on rates of stillbirth with increasing BMI ; odds ratios for stillbirth were 1.10, 95% CI; 0.90, 1.36 in overweight and 1.09, 95% CI; 0.87-1.37 in obese women compared to women with normal BMI. There was increasing trend in stillbirth from 37 weeks and more specifically after 40 weeks with increasing BMI. Independent of BMI, there was a statistically significant increased risk of stillbirth for women with poor antenatal care and current smokers.Conclusions: There is no firm evidence for an effect of BMI on stillbirth at ≥28 weeks gestation among women with uneventful pregnancies. Our care should focus on surveillance for early detection and monitoring of co-morbidities associated with obesity with consideration to birthing prior to 40 weeks gestation. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Adolescents often display heterogenous trajectories of alcohol use. Initiation and escalation of drinking may be important predictors of later harms, including alcohol use disorder (AUD). Previous conceptualizations of these trajectories lacked adjustment for known confounders of adolescent drinking, which we aimed to address by modeling dynamic changes in drinking throughout adolescence while adjusting for covariates. METHODS: Survey data from a longitudinal cohort of Australian adolescents (n = 1813) were used to model latent class alcohol use trajectories over 5 annual follow-ups (mean age = 13.9 until 17.8 years). Regression models were used to determine whether child, parent, and peer factors at baseline (mean age = 12.9 years) predicted trajectory membership and whether trajectories predicted self-reported symptoms of AUD at the final follow-up (mean age = 18.8 years). RESULTS: We identified 4 classes: abstaining (n = 352); late-onset moderate drinking (n = 503); early-onset moderate drinking (n = 663); and early-onset heavy drinking (n = 295). Having more alcohol-specific household rules reduced risk of early-onset heavy drinking compared with late-onset moderate drinking (relative risk ratio: 0.31; 99.5% confidence interval [CI]: 0.11-0.83), whereas having more substance-using peers increased this risk (relative risk ratio: 3.43; 99.5% CI: 2.10-5.62). Early-onset heavy drinking increased odds of meeting criteria for AUD in early adulthood (odds ratio: 7.68; 99.5% CI: 2.41-24.47). CONCLUSIONS: Our study provides evidence that parenting factors and peer influences in early adolescence should be considered to reduce risk of later alcohol-related harm. Early initiation and heavy alcohol use throughout adolescence are associated with increased risk of alcohol-related harm compared with recommended maximum levels of consumption (late-onset, moderate drinking). [ABSTRACT FROM AUTHOR]

Aim: To estimate the proportion of cannabis consumed in Australia by daily cannabis users. Design Monte Carlo simulation using parameters estimated from nationally representative and repeated cross‐sectional household surveys in 2007, 2010, 2013 and 2016. Setting: Australia Participants: Adult samples (mean age = 49.9; 55% females) from four National Drug Strategy Household Surveys (n = 92 243). Measurement Frequency of cannabis use (daily/weekly/about once a month/every few months/once or twice a year). The weighted estimated prevalence of users in each of these frequency levels was multiplied by population size to estimate the total number of users. Quantity of cannabis use was measured as number of joints consumed. The consumption of those who reported using bongs was converted into joints based on the bong to joint ratio estimated from the survey data. We estimated the proportion of cannabis consumed by daily users by Monte Carlo simulation using parameters estimated from the household surveys. We conducted 10 000 simulation trials, and in each trial we [1] simulated the number of users at each consumption level (stratum) based on estimated prevalence and population size[2], for each simulated individual, we simulated the number of days of cannabis use in a year based on frequency data[3], for each consumption day, we simulated the quantity consumed [4] and lastly we calculated the total joints consumed at each consumption level and estimated the proportion of joints consumed by daily users out of the total consumption. Findings The prevalence of past‐year cannabis use increased from 8.9% [95% confidence interval (CI) = 8.5–9.4] in 2007 to 10.5% (95% CI = 10.0–11.1) in 2016, 16% of whom were daily users. Between 2007 and 2016, daily users accounted for between 81.6 and 85.7% of all cannabis consumed. Weekly users accounted for an additional 12.1–15.9%. Conclusion: Between 2007 and 2016, only one in six Australian cannabis users were daily users, but they accounted for more than 80% of the estimated cannabis consumed in Australia. [ABSTRACT FROM AUTHOR]

Aim: Increased arterial stiffness is associated with progressive renal deterioration and poor clinical outcomes in patients with chronic kidney disease (CKD). Assessment of vascular age as derived from arterial stiffness parameters might be an important clinical marker of cardiovascular risks. The aim of the present study is to evaluate whether the difference (△age) between vascular age and chronological age can predict the risk of reaching dialysis or death in patients with known CKD. Methods: This longitudinal study enrolled 94 male Chinese CKD patients, aged 40–62 years. Vascular age was calculated by brachial‐ankle pulse wave velocity, and measured by an ankle‐brachial index‐form device. The study endpoints were the commencement of renal replacement therapy or death. Results: After a stepwise multivariate analysis, △age was associated independently with increased urine protein‐to‐creatinine ratio (β = 0.32; P = 0.001) and decreased baseline estimated glomerular filtration rate (β = −0.24; P = 0.008). During a median follow‐up period of 62 (interquartile range = 55–66) months, the 4‐year cumulative incidence of reaching the study endpoint in patients with △age = 0 and △age > 0 year was 4.9% and 25%, respectively (log–rank test, P = 0.009). Multivariate forward Cox regression analysis identified that higher △age (hazard ratio (HR) = 1.05; P = 0.027), lower baseline estimated glomerular filtration rate (HR = 0.93; P < 0.001), and history of cardiovascular disease (HR = 5.90; P = 0.031) were independently associated with progression to commencement of dialysis or death. Conclusion: Thus, the assessment of the difference between vascular age and chronological age may provide an alternative method to identify CKD patients at a high risk of progression to dialysis or death. SUMMARY AT A GLANCE: This longitudinal cohort study of 94 middle‐aged Chinese chronic kidney disease patients examined the relationship between vascular age and progression to end stage kidney disease/death. After adjustment for relevant confounders, the difference between vascular age (measured by brachial‐ankle pulse wave velocity) and chronological age was found to be independently associated with progression to commencement of dialysis or death. This study suggests an alternative method to prognosticate risk of progression of chronic kidney disease that will require further studies to examine its relevance to routine clinical practice. [ABSTRACT FROM AUTHOR]

Homogeneous populations of mature differentiated primary cell types can display variable responsiveness to extracellular stimuli, although little is known about the underlying mechanisms that govern such heterogeneity at the level of gene expression. In this article, we show that morphologically homogenous human endothelial cells exhibit heterogeneous expression of VCAM1 after TNF-α stimulation. Variability in VCAM1 expression was not due to stochasticity of intracellular signal transduction but rather to preexisting established heterogeneous states of promoter DNA methylation that were generationally conserved through mitosis. Variability in DNA methylation of the VCAM1 promoter resulted in graded RelA/p65 and RNA polymerase II binding that gave rise to a distribution of VCAM1 transcription in the population after TNF-α stimulation. Microarray analysis and single-cell RNA sequencing revealed that a number of cytokine-inducible genes shared this heterogeneous response pattern. These results show that heritable epigenetic heterogeneity is fundamental in inflammatory signaling and highlight VCAM1 as a metastable epiallele. [ABSTRACT FROM AUTHOR]

Aims: To (1) identify population‐level classes of polysubstance use among young Australians between 2004 and 2016, (2) test if these classes changed over the same period, in terms of class prevalence and probabilities of substance use within each class, and (3) identify demographic and health‐related correlates of polysubstance use. Design Repeated cross‐sectional nationally representative household surveys. Setting: All Australian states/territories. Participants: Young adult samples (aged 18–30 years; 58% females) from the National Drug Strategy Household Surveys (n = 20 350) Measurements Outcomes were the extent of past‐year use of 10 licit (e.g. alcohol), and illicit substances (e.g. cannabis) were used to derive polysubstance use classes. The correlates were gender, age, psychological distress, general health, language background, personal income, education level, remoteness of residence and socio‐economic index for area of residence. Findings Three polysubstance use classes were consistently identified between 2004 and 2016 (SSABIC: 188349): minimal users (MU, ~60%), mainly tobacco, alcohol and cannabis users (TAC, ~30%) and extended range polysubstance users (POLY, ~10%). There were substantial changes in use of different substances within each class over the study period. For example, smoking decreased in all classes (P < 0.05), while harmful alcohol use only decreased in the first two classes (P < 0.05). Factors associated with TAC and POLY were similar over the study period. These included: being male and having an English‐speaking background, a high level of psychological distress, suboptimal health and high personal income. Living in an affluent area was associated with reduced likelihood of being TAC, but an increased likelihood of being POLY. Conclusion: At the population‐level among young Australians between 2004 and 2016, six in 10 did not engage in polysubstance use; four in 10 used a limited range of substances (mainly alcohol, tobacco and cannabis) and one in 10 used an extended range of substances. Over time, the types of substance within the extended polysubstance use class changed substantially. [ABSTRACT FROM AUTHOR]

Aim: To assess (1) how far smoking patterns, depression and smoking‐related beliefs and intentions predict vaping uptake, current vaping and vaping frequency among daily smokers; and (2) how far the aforementioned predictors and baseline vaping frequency predict current vaping among those who reported ever vaped. Design Analysis of data from six waves of a longitudinal survey over 8 years. Longitudinal associations between predictors and outcomes were examined using multi‐level models. Setting: United Kingdom, United States, Canada and Australia. Participants: A total of 6296 daily smokers (53% females) who contributed data to at least two consecutive survey waves. Measurements The outcome variables were vaping uptake, vaping frequency and current vaping at follow‐up. The key predictor variables, measured in previous waves, were time to first cigarette, cigarettes smoked per day, depressive symptoms, intention to quit smoking, quitting self‐efficacy and worry about adverse health effects of smoking. Findings Number of cigarettes smoked daily was associated with (1) subsequent vaping uptake [odds ratio (OR) = 1.69, 95% confidence interval (CI) = 1.19, 2.39 for 30+ cigarette per day; reference category: 0–10 cigarettes] and (2) a higher frequency of current vaping (OR = 1.97, 95% CI = 1.36, 2.85 for 30+ cigarettes). Intention to quit was associated with a higher frequency of current vaping (OR = 1.48, 95% CI = 1.21, 1.82). Among those who reported ever vaped, higher baseline vaping frequency (OR = 11.98, 95% CI = 6.00, 23.93 for daily vaping at baseline; reference category: vaped less than monthly) predicted current vaping. Conclusion: Among daily smokers, amount smoked and intention to quit smoking appear to predict subsequent vaping uptake. Vaping frequency at baseline appears to predict current vaping at follow‐up. [ABSTRACT FROM AUTHOR]

Aims: In Australia, sales of nicotine containing electronic cigarettes (also known as e-cigarette) are banned unless approved as a therapeutic good. The aims of this study were to estimate the prevalence of e-cigarette use and its correlates in Australia using a nationally representative survey.Method: We analysed data from the largest drug use survey in Australia (the National Drug Strategy Household Survey [NDSHS]; N = 22,354).Results: We estimated that 227,000 Australians (1.2% of the population) were current e-cigarettes users, and 97,000 (0.5%) used them daily. Individuals who were male, younger, had higher level of psychological distress, and smoked were more likely to use electronic cigarettes. Among smokers, an intention to quit and reduction in smoking was associated with experimentation and daily use of e-cigarette, but not with occasional use. Recent quitting was associated with daily use.Conclusion: Overall, the prevalence of e-cigarette use was low in 2016 in Australia. Smoking status was the strongest correlates of e-cigarette use. Patterns of vaping were differentialy associated with an intention to quit smoking, smoking reduction and recent quitting. Some smokers may attempt to use e-cigarettes to cut-down their tobacco use, and those who vaped daily were mostly likely to be recent quitters. [ABSTRACT FROM AUTHOR]

Background: Online gaming or video game play can result in a persistent pattern of addictive behaviour associated with negative psychological consequences. Less studied are the physical aspects, so we examined negative physical problems associated with video gaming behaviours. Method: Data were from the 2022 International Gaming Study (IGS22) - a cross-sectional survey of individuals who play video games for 3 hours or more per week. This study included 955 participants who were aged 18-94 (M=46.10 [16.19]) and 45% were male. We examined socio-demographic and gaming behavioural factors associated with past 12 months experiences of physical problems. Respondents also completed the 10-item Internet Gaming Disorder Test (IGDT-10). Results: Preliminary results showed that playing video games for more than 12 hours per week (n = 327) was associated with hand pain (RR=1.39, p = .016), wrist pain (RR = 1.68, p<.001), and back pain or neck pain (RR = 1.21, p < 0.001). Playing for 3 or more hours in one session was associated with negative physical problems and pain (RR = 1.65-3.92, p < 0.01). Those who reported intentions to play video games professionally (n = 94) were more likely to report physical problems (59% vs 26%; p < .001). Those who met the positive cut-off according to the IGDT-10 (n = 139) were significantly more likely to report physical problems (66% vs 25%; p<0.001). Conclusions: In addition to negative psychological consequences, physical problems and pain should be considered in persons who engage in high frequency gaming behaviours, including those who aim to become professional video game players. [ABSTRACT FROM AUTHOR]

Background: In the newly published ICD-11, Gaming Disorder (GD) is included as a new behavioural addiction. In contrast to the spectrum of substance use disorders, no disorder comprising impairment (harm) from videogaming in the absence of addiction is identified. As part of the IGS22 four-country study, we examined whether there is evidence for a subaddiction entity of Harmful Gaming. Method: A sample of 796 adults who played online games for at least three hours per week was recruited from Australia, Canada, the US and the UK. They completed a survey of features of Gaming Disorder. Results: At least one feature of impaired control over gaming was present in 33.7%, increasing priority of gaming in 29.7%, and continued gaming despite harm in 28.0%. The diagnosis of GD requires all three, together with evidence of impairment and a pattern of repeated gaming over 12 months; 11.2% (n=89) fulfilled these requirements. Overall, 48.0% (n=382) experienced impairment and 34.9% (n=278) also had a 12 months+ pattern of gaming. Thus, 189 had evidence of impairment but did not fulfil the diagnostic requirements for GD, and can be considered to have Harmful Gaming. Conclusions: Impairment from gaming is common in participants who do not fulfill the diagnosis of Gaming Disorder and could be described as having "Harmful Gaming". This diagnosis was more than twice as common as GD. This provides support for Harmful Gaming to be included in ICD-11, and supports broadening the scope for prevention and intervention to minimise gaming-related harm. [ABSTRACT FROM AUTHOR]

Background: Gaming disorder is a condition described in both the International Classification of Diseases (ICD-11) and the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Most research on gaming disorder has occurred in males. The prevalence and associated symptoms of gaming disorder among female video game players is largely unexplored. Method: The 2022 International Gaming Study (IGS22) is a cross-sectional survey of 955 participants, who play video games for 3 hours or more per week. Respondents are from Australia, Canada, USA, and UK (age range=18-94; M=46.10 [16.19]; n=431 female). The participants answered items related to their video game playing behaviour and completed the 10-item Internet Gaming Disorder Test (IGDT-10) to assess their symptoms of gaming disorder. Results: Proportions who met IGDT-10 cut-off in females (16%) were not significantly different to males (20%) who spent similar amounts of time playing. Frequency and intensity of use was linearly related to the meeting IGDT-10 cut-off. For females who played several times a day, 22% met GDT-10 cut-off. This increased to 32% for 4 hours a day on a typical weekday, 35% for three or more hours in one session daily, and 42% for 6 hours or more in one session daily. Over half (51%) of females who reported that they plan to become a professional video game player excessed the IGDT-10 cut-off. Conclusions: Women engaging in high frequency video game playing met similar thresholds of gaming disorder. Analyses are underway to examine differences between specific symptoms reported between men and women. [ABSTRACT FROM AUTHOR]

Introduction and Aims: To estimate the prevalence of non-medical use of pharmaceutical opioids and examine the socio-demographic, psychological, health and behavioural correlates and type of opioids used.Design and Methods: Data from the Australian National Drug Strategy Household Survey 2016 was used. The sample consisted of. 23 448 participants aged over 14 years (54% female). The key measure was opioid use status in the past year. Based on participants' responses to questions about their substance use in the past 12 months, they were grouped into four opioid use status: (i) No illicit substance use (ISU) and no non-medical use of pharmaceutical opioids (NMUPO); (ii) ISU but no NMUPO; (iii) NMUPO but no ISU; and (iv) NMUPO and ISU.Results: The prevalence non-medical pharmaceutical opioid use was 3.56%. Two-thirds of them engaged in NMUPO but no ISU; one-third engaged in NMUPO and ISU. Younger people were more likely to use pharmaceutical opioids in addition to other illicit drugs, while older people were more likely to only use pharmaceutical opioids. Alcohol risk and daily smoking were associated with using pharmaceutical opioids and other illicit drugs, but not with pharmaceutical opioids only. Those who reported only using pharmaceutical opioids were more likely to use over-the-counter codeine products.Discussion and Conclusions: Over 700 000 Australian used pharmaceutical opioids for non-medical purpose. Among users, two-thirds used only opioids and one-third used opioids in addition to other illicit drugs. Profile of these two types of users were substantially different. Future prevention efforts targeting different type of opioids users may need to be optimised based on their profiles. [ABSTRACT FROM AUTHOR]

Background: To examine the longitudinal patterns of amphetamine use over twenty years from adolescence to the mid-thirties; and identify adolescent antecedents of future problematic patterns of use.Design: Ten-wave longitudinal study following participants from age 15 to age 35 in Victoria, Australia. Participants (N = 1755; 47% males) first enrolled in the Victoria Adolescent Health Cohort Study in 1992.Measurements: Outcome: Self-reported frequency of amphetamine use.Predictors: Gender, depression and anxiety, peer alcohol and tobacco use; self-reported alcohol, tobacco and cannabis use, self-reported adolescent antisocial behavior.Findings: Three different longitudinal patterns were identified: Non-user (83.7%); Occasional user (14.5%); Regular user (1.8%). Among the two user patterns, amphetamine use was commonly initiated in late teenage years or early 20s, peaked at mid-20s, and declined substantially by mid-30s. Participants who used cannabis and had smoking peers during adolescence were at significantly more likely to become an occasional or regular user (p <  .05).Conclusion: Regular cannabis use and peer tobacco use during adolescence were the two strongest predictors of a longitudinal pattern of regular amphetamine use in the mid-30s. This suggests that prevention programs could be implemented around or before mid-adolescence and interventions to reduce amphetamine harms focus on high-risk individuals in their 20s when amphetamine use was at its peak. [ABSTRACT FROM AUTHOR]

Aims: This study estimated the extent of familial alcohol supply in 45 low and middle income countries (LMIC), and examined the country-level effects of familial alcohol supply on adolescents' alcohol use.Method: We used data from 45 LMICs that participated in the Global School-Based Student Health Survey (GSHS) between 2003 and 2013 (n = 139,840). The weighted prevalence of familial alcohol supply in each country was estimated. Multilevel binary and ordinal logistic regression analyses were used to examine the country-level effect of familial alcohol supply on early onset of alcohol use (first alcohol before 12), past 30-day alcohol use, lifetime drunkenness and alcohol-related social problems.Results: There were large variations between LMICs in the prevalence of familial alcohol supply and pattern of adolescent alcohol use. The prevalence of familial supply ranged from 0.1% in Tajikistan to 23.8% in St Lucia. It was estimated that a one percentage change in prevalence of familial alcohol supply was associated with 10%, 12% and 12% change in the odds of lifetime drunkenness (OR = 1.10, 95% CI = [1.04, 1.16]), early onset of alcohol use (OR = 1.12, 95% CI = [1.07, 1.08]) and more frequent drinking in the past month (OR = 1.12, 95% CI = [1.04, 1.20]).Conclusion: There were large variations in the prevalence of familial alcohol supply and adolescent alcohol use among LMICs. Adolescents in countries with higher prevalence of familial alcohol supply were more likely to start using alcohol at an earlier age, to have used alcohol in the past 30 days and experience intoxication. [ABSTRACT FROM AUTHOR]

Apolipoprotein A-I (apoA-I) shares with other exchangeable apolipoproteins a high level of structural plasticity. In the lipid-free state, the apolipoprotein amphipathic α-helices interact intra- and intermolecularly, providing structural stabilization by self-association. We have reported that lipid-free apoA-I becomes amyloidogenic upon physiologically relevant (myeloperoxidase-mediated) Met oxidation. In this study, we established that Met oxidation promotes amyloidogenesis by reducing the stability of apoA-I monomers and irreversibly disrupting self-association. The oxidized apoA-I monomers also exhibited increased cellular cholesterol release capacity and stronger association with macrophages, compared to nonoxidized apoA-I. Of physiologic relevance, preformed oxidized apoA-I amyloid fibrils induced amyloid formation in nonoxidized apoA-I. This process was enhanced when self-association of nonoxidized apoA-I was disrupted by thermal treatment. Solid state NMR analysis revealed that aggregates formed by seeded nonoxidized apoA-I were structurally similar to those formed by the oxidized protein, featuring a ß-structure-rich amyloid fold alongside α-helices retained from the native state. In atherosclerotic lesions, the conditions that promote apoA-I amyloid formation are readily available: myeloperoxidase, active oxygen species, low pH, and high concentration of lipid-free apoA-I. Our results suggest that even partial Met oxidation of apoA-I can nucleate amyloidogenesis, thus sequestering and inactivating otherwise antiatherogenic and HDL-forming apoA-I. [ABSTRACT FROM AUTHOR]

The blood-brain barrier is a microvascular network that (1) provides neuroprotection from metabolic and environmental toxins and (2) limits the delivery of therapeutics to the central nervous system (CNS). The ATP-binding cassette transporter P-glycoprotein contributes to the latter by actively pumping clinical substrates back into circulation before they can reach the brain parenchyma. Targeting P-glycoprotein has proven effective in increasing the delivery of therapeutics to their cerebral targets. We provide a novel mechanism to achieve this end in functioning, intact rat brain capillaries, whereby the bioactive phospholipid lysophosphatidic acid (LPA) and tricyclic antidepressant (TCA) amitriptyline reduce basal P-glycoprotein transport activity through a distinct lysophosphatidic acid 1 receptor-mediated signaling cascade that requires G-protein coupling, Src kinase, and ERK 1/2. Furthermore, we demonstrate the ability of LPA and TCA amitriptyline to decrease induced P-glycoprotein transport activity in a human SOD1 transgenic rat model of amyotrophic lateral sclerosis. This work may translate to new clinical strategies for increasing the cerebral penetration of therapeutics in patients suffering from CNS diseases marked by exacerbated pharmacoresistance. [ABSTRACT FROM AUTHOR]

Angiotensin-converting enzyme inhibitors (ACEi) are widely employed to deter the progression of chronic kidney disease (CKD). Besides controlling hypertension and reduction of intra-glomerular pressure, ACEi appear to have anti-fibrotic effects in the renal cortex. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), an endogenous tetrapeptide that is degraded by ACE, has also been shown to ameliorate the pro-fibrotic phenotype displayed in CKD in our recent study. Whether the anti-fibrotic properties of ACEi are mediated by Ac- SDKP has not been fully investigated. To delineate the role of Ac-SDKP in ACE blockade, 12-week-old male BALB/c mice underwent sham operation or unilateral ureteric obstruction (UUO). UUO mice were subjected to: i) vehicle; ii) captopril or iii) captopril in conjunction with S17092, a prolyl oligopeptidase inhibitor. After 7 days, mice were sacrificed and kidneys harvested for analyses. After UUO, there were heightened expressions of collagen I, collagen III, fibronectin and a-SMA associated with significant levels of tubulointerstitial injury on histological examination. Furthermore, p44/42 Mitogen-Activated Protein Kinase (MAPK) and Transforming Growth Factor Beta 1(TGF-ß1) signaling were up-regulated. These were significantly ameliorated by captopril treatment alone but unaffected by co-administration of captopril with S17092. Captopril treatment had resulted in elevated urinary Ac-SDKP levels, an effect which was eliminated by the co-administration with S17092. This study allowed the investigation of the renoprotective property of ACEi in the absence of Ac-SDKP and proved conclusively that Ac-SDKP is the prime anti-fibrotic mediator of captopril, acting via p44/42 MAPK and TGF-ß1 signaling pathways. Future research to expand CKD armamentarium should explore the utility of augmenting Ac-SDKP levels. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To test if the degree of change in cannabis use between 2001 and 2013 differed according to socio‐economic status. Design: Repeated cross‐sectional household surveys that were nationally representative. Setting: Australia. Participants: Adult samples from the 2001 and 2013 National Drug Strategy Household Surveys (n = 23 642 in 2001 and n = 21 353 in 2013), the largest nationally representative survey on drug use in Australia. Measurements: Frequency of cannabis use coded as daily use, weekly use, less than weekly use and non‐current use; socio‐economic status (SES) as measured by personal income and educational level. Finding: There were significant differences in changes to levels of cannabis use between SES groups. Among participants who completed high school, the probability of daily use decreased from 0.014 to 0.009 (P < 0.001), and the probability of weekly use decreased from 0.025 to 0.017 (P < 0.001). These probabilities remained stable for participants who did not complete high school. The probability of weekly cannabis use decreased from 0.032 to 0.023 among participants with middle level income (P = 0.004), and from 0.021 to 0.013 among those with high income (P = 0.005). There were no significant changes in these probabilities among those with low income (0.026 in 2001 and 0.032 in 2013; P = 0.203). Conclusion: The decline in cannabis use in Australia from 2001 to 2013 occurred largely among higher socio‐economic status groups. For people with lower income and/or lower education, rates of frequent cannabis use remained unchanged. [ABSTRACT FROM AUTHOR]

Changes in select adipose tissue volumes may differentially impact bone mineral density. This study was performed to assess cross-sectional and longitudinal relationships between computed tomography-determined visceral (VAT), subcutaneous (SAT), inter-muscular (IMAT), and pericardial adipose tissue (PAT) volumes with respective changes in thoracic vertebral and lumbar vertebral volumetric trabecular bone mineral density (vBMD) in African Americans with type 2 diabetes. Generalized linear models were fitted to test relationships between baseline and change in adipose volumes with change in vBMD in 300 African American-Diabetes Heart Study participants; adjustment was performed for age, sex, diabetes duration, study interval, smoking, hypertension, BMI, kidney function, and medications. Participants were 50% female with mean ± SD age 55.1±9.0 years, diabetes duration 10.2±7.2 years, and BMI 34.7±7.7 kg/m2. Over 5.3 ± 1.4 years, mean vBMD decreased in thoracic/lumbar spine, while mean adipose tissue volumes increased in SAT, IMAT, and PAT, but not VAT depots. In fully-adjusted models, changes in lumbar and thoracic vBMD were positively associated with change in SAT (β[SE] 0.045[0.011], p<0.0001; 0.40[0.013], p = 0.002, respectively). Change in thoracic vBMD was positively associated with change in IMAT (p = 0.029) and VAT (p = 0.016); and change in lumbar vBMD positively associated with baseline IMAT (p<0.0001). In contrast, vBMD was not associated with change in PAT. After adjusting for BMI, baseline and change in volumes of select adipose depots were associated with increases in thoracic and lumbar trabecular vBMD in African Americans. Effects of adiposity on trabecular bone appear to be site-specific and related to factors beyond mechanical load. [ABSTRACT FROM AUTHOR]

Objective: Cardiovascular and renal complications contribute to higher mortality in patients with diabetes. We assessed novel and conventional predictors of mortality in African American-Diabetes Heart Study (AA-DHS) participants.Research Design and Methods: Associations between mortality and subclinical atherosclerosis, urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), plasma fibroblast growth factor 23 (FGF23) concentration, African ancestry proportion, and apolipoprotein L1 genotypes (APOL1) were assessed in 513 African Americans with type 2 diabetes; analyses were performed using Cox proportional hazards models.Results: At baseline, participants were 55.6% female with median (25th, 75th percentile) age 55 years (49.0, 62.0), diabetes duration 8 years (5.0, 13.0), glycosylated hemoglobin 60.7 mmol/mol (48.6, 76.0), eGFR 91.3 mL/min/1.73 m2 (76.4, 111.3), UACR 12.5 mg/mmol (4.2, 51.2), and coronary artery calcium 28.5 mg Ca2+ (1.0, 348.6); 11.5% had two APOL1 renal-risk variants. After 6.6-year follow-up (5.8, 7.5), 54 deaths were recorded. Higher levels of coronary artery calcified plaque, carotid artery calcified plaque, albuminuria, and FGF23 were associated with higher mortality after adjustment for age, sex, and African ancestry proportion. A penalized Cox regression that included all covariates and predictors associated with mortality identified male sex (hazard ratio [HR] 4.17 [95% CI 1.96-9.09]), higher FGF23 (HR 2.10 [95% CI 1.59-2.78]), and absence of APOL1 renal-risk genotypes (HR 0.07 [95% CI 0.01-0.69]) as the strongest predictors of mortality.Conclusions: Accounting for conventional risk factors, higher FGF23 concentrations and APOL1 non-renal-risk genotypes associated with higher mortality in African Americans with diabetes. These data add to growing evidence supporting FGF23 association with mortality; mechanisms whereby these novel predictors impact survival remain to be determined. [ABSTRACT FROM AUTHOR]

Background: Recent reports suggest an increase in use of extremely potent cannabis concentrates such as Butane Hash Oil (BHO) in some developed countries. The aims of this study were to examine the characteristics of BHO users and the effect profiles of BHO.Design: Anonymous online survey in over 20 countries in 2014 and 2015. Participants aged 18 years or older were recruited through onward promotion and online social networks. The overall sample size was 181,870. In this sample, 46% (N=83,867) reported using some form of cannabis in the past year, and 3% reported BHO use (n=5922).Measurements: Participants reported their use of 7 types of cannabis in the past 12 months, the source of their cannabis, reasons for use, use of other illegal substances, and lifetime diagnosis for depression, anxiety and psychosis. Participants were asked to rate subjective effects of BHO and high potency herbal cannabis.Findings: Participants who reported a lifetime diagnosis of depression (OR=1.15, p=0.003), anxiety (OR=1.72, p<0.001), and a larger number of substance use (OR=1.29, p<0.001) were more likely to use BHO than only using high potency herbal cannabis. BHO users also reported stronger negative effects and less positive effects when using BHO than high potency herbal cannabis (p<0.001) CONCLUSION: Mental health problems and other illicit drug use were associated with use of BHO. BHO was reported to have stronger negative and weaker positive effects than high potency herbal cannabis. [ABSTRACT FROM AUTHOR]

Background: Existing research on parental supply of alcohol analyses the effects of self-reported parental supply on adolescent drinking using individual level data. This study examined the contextual effect of parental supply of alcohol on adolescent alcohol use by examining the association between the prevalence of parental supply in each Australian state and adolescent alcohol use using a multilevel analytic framework.Methods: Adolescent samples (Age: 12-17) were drawn from the four National Drug Strategy Household Surveys (2004, 2007, 2010 and 2013; N = 6803). The prevalence of parental supply of alcohol, defined as the weighted percentage of sample who reported obtaining alcohol from their parents, was estimated in each state and territory across the four surveys. Three multilevel logistic regressions were used to examine the contextual effects of parental supply prevalence on adolescents' alcohol use in the past 12 months, weekly drinking and heavy drinking.Results: Overall, adolescents' rates of past 12 months alcohol use, heavy drinking and weekly drinking between 2004 and 2013 were 40.1, 14.4 and 6.4% respectively. The prevalence of parental supply was significantly associated with past 12 months alcohol use (OR = 1.06, p < .001) and heavy drinking (OR = 1.04, p < .001) but not with weekly drinking (OR = 1.03, p = .189). The results were adjusted for gender, age, socio-economic index for area, place of birth, survey year and prevalence of peer supply.Conclusion: A high prevalence of parental supply in a region was associated with heavier adolescent drinking, regardless of whether adolescents primarily obtained their alcohol from their own parents. [ABSTRACT FROM AUTHOR]

P -glycoprotein ( P -gp), Breast cancer resistance protein (BCRP) and Multidrug resistance-associated protein 2 (MRP2) residing at the blood-brain barrier (BBB) and the blood-spinal cord barrier (BSCB) are major obstacles for drug delivery to the Central Nervous System (CNS). Disease-induced changes of these xenobiotic transporters at the CNS barriers have been previously documented. Changes in the functional expression of these transporters at the CNS barriers would limit the clinical efficacy of therapeutic agents targeting the CNS. In this study, we characterized the changes in expression and efflux activity of P -gp, BCRP and MRP2 at the BBB and BSCB of an amyotrophic lateral sclerosis (ALS) SOD1-G93A transgenic rat model across the three stages of disease progression: pre-onset, onset and symptomatic. Up-regulation of P -gp and BCRP at the BBB and BSCB during disease progression of ALS would reduce drug entry to the CNS, while any decreases in transport activity would increase drug entry. In SOD rats at the ALS symptomatic stage, we observed increases in both P -gp transport activity and expression compared to age-matched wildtypes. BCRP and MRP2 levels were unchanged in these animals. Immunohistochemical analysis in brain and spinal cord capillaries of SOD rats from all three ALS stages and age-matched wildtypes showed no differences in nuclear localization of a known P -gp regulator, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB). It suggests that NFκB may have a limited role during P -gp induction observed in our study and additional signaling pathways could be responsible for this response. Our observations imply that novel pharmacological approaches for treating ALS require selecting drugs that are not P -gp substrates in order to improve therapeutic efficacy in the CNS during ALS progression. [ABSTRACT FROM AUTHOR]

Aims: This study examined the association between peer drug use and adolescent polysubstance use, and investigated if this association was moderated by parenting and/or school factors.Methods: The sample consisted of 9966 participants (mean age=14.3; 49.34% males) randomly selected from secondary schools in Victoria, Australia. Three 30-day polysubstance use profiles were derived from latent class analysis - no drug use (47.7%), mainly alcohol use (44.1%) and polysubstance use (8.2%). These profiles were then regressed on peer's drug use, family conflict, parental monitoring, parental disapproval of drug use, school commitment, reward for prosocial involvement in school and academic failure, and the interactions between peer's drug use and each of the parenting and school variables.Results: Relative to non-users, peer's drug use was strongly associated with polysubstance use (OR=30.91, p<0.001), and this association was moderated by parental disapproval of drug use (OR=0.46, p<0.001). This indicated that high level of parental disapproval may mitigate the negative influence of drug using peers. School commitment and parental monitoring were significantly associated with reduced likelihood of polysubstance use (p<0.05), but they did not moderate the relationship between peer drug use and adolescent polysubstance use. All analyses were adjusted for key demographic factors such as age, gender, areas of residence, birth place and family affluence.Conclusion: Reinforcing parent disapproval of drug use may be an important strategy in reducing adolescent substance use. Parents may need to be more integrated into mainstream prevention programs. [ABSTRACT FROM AUTHOR]

Introduction and Aims: This study examines the association of alcohol and polydrug use with risky sexual behaviour in adolescents under 16 years of age and if this association differs by gender.Design and Methods: The sample consisted of 5412 secondary school students under 16 years of age from Victoria, Australia. Participants completed an anonymous and confidential survey during class time. The key measures were having had sex before legal age of consent (16 years), unprotected sex before 16 (no condom) and latent-class derived alcohol and polydrug use variables based on alcohol, tobacco, cannabis, inhalants and other illegal drug use in the past month.Results: There were 7.52% and 2.55% of adolescents who reported having sex and having unprotected sex before 16 years of age, respectively. After adjusting for antisocial behaviours, peers' drug use and family and school risk factors, girls were less likely to have unprotected sex (odds ratio = 0.31, P = 0.003). However, the interaction of being female and polydrug use (odds ratio = 4.52, P = 0.004) was significant, indicating that girls who engaged in polydrug use were at higher risk of having unprotected sex. For boys, the effect of polydrug use was non-significant (odds ratio = 1.44, P = 0.310). Discussion and Conclusions For girls, polydrug use was significantly associated with unprotected sex after adjusting for a range of risk factors, and this relationship was non-significant for boys. Future prevention programs for adolescent risky sexual behaviour and polydrug use might benefit from a tailored approach to gender differences. [Chan GCK, Kelly AB, Hides L, Quinn C, Williams JW. Does gender moderate the relationship between polydrug use and sexual risk-taking among Australian secondary school students under 16 years of age? Drug Alcohol Rev 2016;35:750-754]. [ABSTRACT FROM AUTHOR]

Introduction and Aims: This study investigated the extent to which parental monitoring and parental disapproval of alcohol use account for the association between country of birth and adolescent alcohol use.Design and Methods: The sample consisted of 10 273 adolescents from grades 7 (Mean age = 12.5 years), 9 (14.5 years) and 11 (16.4 years) in Victoria, Australia. Participants completed a questionnaire during class time. Mediation analyses were performed to examine the extent to which parental monitoring and parental disapproval of alcohol use accounted for variations in past 30 day alcohol use between Australian-born and immigrant adolescents.Results: Alcohol use in the past 30 days ranged from 8.0% to 44.4% for participants from different countries/regions of birth. Those born in Asia (odds ratio 0.20-0.51, P < 0.05) and Africa (odds ratio 0.45, P < 0.01) were much less likely to have consumed alcohol compared to those born in Australia. Adolescents from these two regions (except for Western Asia) reported higher levels of parental monitoring and parental disapproval of alcohol use (P < 0.05). Higher levels of parental monitoring and parental disapproval of alcohol use partially mediated the association between birth place and alcohol use (P < 0.05).Discussion and Conclusions: There were large variations in alcohol use between Australian-born and immigrant adolescents from different countries/regions. Adolescents from Asia or Africa were much less likely to consume alcohol, and this protective effect was partially accounted for by parental monitoring and disapproval of alcohol use.[Chan GCK, Kelly AB, Connor JP, Hall WD, Young RM, Williams JW. Does parental monitoring and disapproval explain variations in alcohol use among adolescents from different countries of birth? Drug Alcohol Rev 2016;35:741-749]. [ABSTRACT FROM AUTHOR]

Background: Skog's collectivity theory of alcohol consumption predicted that changes in alcohol consumption would synchronize across all types of drinkers in a population. The aim of this paper is examine this theory in the Australian context. We examined whether there was a collective change in alcohol use in Australia from 2001 to 2013, estimated alcohol consumption in non-high risk and high risk drinkers, and examined the trends in alcohol treatment episodes. Methods: Data from the 2001-2013 National Drug Strategy Household Surveys (N =127,916) was used to estimate the prevalence and alcohol consumption of abstainers, high risk drinkers and frequent heavy episodic drinkers. Closed treatment episodes recorded in the Alcohol and Other Drug Treatment Services National Minimum Dataset (N= 608,367) from 2001 to 2013 were used to examine the trends of closed alcohol treatment episodes. Results: The prevalence of non-drinkers (abstainers) decreased to the lowest level in 2004 (15.3%) and rebounded steadily thereafter (20.4% in 2013; p < .001). Correspondingly, the per capita consumption of high risk drinkers (2 standard drinks or more on average per day) increased from 20.7 L in 2001 to peak in 2010 (21.5 L; p = .020). Non-high risk drinkers' consumption peaked in 2004 (2.9 L) and decreased to 2.8 L in 2013 (p < .05). There were decreases in alcohol treatment episodes across nearly all birth cohorts in recent years. Conclusion: These findings are partially consistent with and support Skog's collectivity theory. There has been a turnaround in alcohol consumption after a decade-long uptrend, as evident in the collective decreases in alcohol consumption among nearly all types of drinkers. There was also a turnaround in rate of treatment seeking, which peaked at 2007 and then decreased steadily. The timing of this turnaround differs with level of drinking, with non-high risk drinkers reaching its peak consumption in 2004 and high risk drinkers reaching its peak consumption in 2010. [ABSTRACT FROM AUTHOR]