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.

Paracetamol (acetaminophen) overdose and hepatotoxicity: mechanism, treatment, prevention measures, and estimates of burden of disease.

INTRODUCTION: Paracetamol is one of the most used medicines worldwide and is the most common important poisoning in high-income countries. In overdose, paracetamol causes dose-dependent hepatotoxicity. Acetylcysteine is an effective antidote, however despite its use hepatotoxicity and many deaths still occur. AREAS COVERED: This review summarizes paracetamol overdose and toxicity (including mechanisms, risk factors, risk assessment, and treatment). In addition, we summarize the epidemiology of paracetamol overdose worldwide. A literature search on PubMed for poisoning epidemiology and mortality from 1 January 2017 to 26 October 2022 was performed to estimate rates of paracetamol overdose, liver injury, and deaths worldwide. EXPERT OPINION: Paracetamol is widely available and yet is substantially more toxic than other analgesics available without prescription. Where data were available, we estimate that paracetamol is involved in 6% of poisonings, 56% of severe acute liver injury and acute liver failure, and 7% of drug-induced liver injury. These estimates are limited by lack of available data from many countries, particularly in Asia, South America, and Africa. Harm reduction from paracetamol is possible through better identification of high-risk overdoses, and better treatment regimens. Large overdoses and those involving modified-release paracetamol are high-risk and can be targeted through legislative change.