Buprenorphine deaths confirmed by toxicology reveal a low proportion of opioid agonist treatment before death in Finland.

We studied opioid agonist treatment (OAT) status before buprenorphine-related death in Finland, where buprenorphine is the principal OAT medicine and also the most misused opioid, through a retrospective population-based study using medico-legal cause-of-death investigation and OAT patient records. The study included all death cases (N = 570) between 2018 and 2020 with a buprenorphine or norbuprenorphine finding in post-mortem toxicology and with known drug misuse history or concomitant findings of illicit drugs. Of the deceased, 10% had received OAT in the year before death. Less than 1% of individuals < 25 years had received OAT, whereas the proportion in individuals ≥ 25 years was 13% (p < 0.001). There were significantly more females and more fatal poisonings (p < 0.001) among those < 25 years than among those ≥ 25 years. OAT medication at the time of death was sublingual buprenorphine-naloxone in 74% and subcutaneous buprenorphine in 23%. Except for significantly fewer benzodiazepine findings among those receiving OAT, minimal differences were found in terms of age, gender, cause and manner of death, or concomitant substance use between the deceased in and outside of OAT. Concomitant misuse of benzodiazepines, psychostimulants, alcohol, and gabapentinoids was frequent both in and outside of OAT and likely contributed to the death. These results suggest that access to OAT especially for young people and treatment of multiple addictions should be improved. Comprehensive information from medico-legal cause-of-death investigation as a starting point, combined with subsequent ante-mortem patient records, proved to be a successful approach to shed light on the Finnish scene of buprenorphine mortality.

Pride-based violence, intoxicated sex and poly-drug use: a vocational school-based study of heterosexual and LGBT students in Bangkok.

BACKGROUND: In Thailand, drug use is widely observed, especially among vocational-school students, who are more inclined to use various types of drugs and to experience pride-based violence (violence based on institutional pride, honor, or on seniority status) than any other groups of students. Drug use contexts differ based on sexual orientation and gender identity (e.g., clubs). This study aims to examine the prevalence and correlates of poly-drug use (the use of at least three types of drugs) among vocational-school students, with a focus on sexual orientation and gender identity. METHODS: In this study, 638 vocational school students living in Bangkok metropolitan area participated in a three-year longitudinal survey of four vocational schools. Experiences of violence, sexual behaviours, and poly-drug use were assessed and analyzed using multivariable logistic regression. RESULTS: About one tenth of all students (11.3%) reported poly-drug use, a fifth among Lesbian, Gay, Bisexual and Transgender (LGBT) students (20.2%) and almost a tenth of heterosexual students (9.8%). In the multivariable logistic model of LGBT students, GPA, pride-based violence, intoxicated sex, and counseling needs were significantly associated with poly-drug use (AOR = 4.62; 95% CI 1.17-18.29, AOR = 6.01; 95% CI 1.31-27.32, AOR = 5.17; 95% CI 1.10-24.28, AOR = 4.64; 95% CI 1.16-18.54, respectively). Likewise, among heterosexual students, GPA and intoxicated sex were significantly associated with poly-drug use (AOR = 2.02; 95% CI 1.09-3.75, AOR = 5.31; 95% CI 2.81-10.04, respectively). CONCLUSIONS: LGBT vocational-school students have significantly higher prevalence of poly-drug use than their heterosexual peers. Correlates include lower GPA, having experienced pride-based violence and intoxicated sex. School-based intervention programs should also address pride-based violence and intoxicated sex in their harm reduction programs.

Role of mPFC and nucleus accumbens circuitry in modulation of a nicotine plus alcohol compound drug state.

Combined use of nicotine and alcohol constitute a significant public health risk. An important aspect of drug use and dependence are the various cues, both external (contextual) and internal (interoceptive) that influence drug-seeking and drug-taking behavior. The present experiments employed the use of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) and complementary Pavlovian drug discrimination procedures (feature-positive and feature-negative training conditions) in order to examine whether medial prefrontal cortex (prelimbic; mPFC-PL) projections to the nucleus accumbens core (AcbC) modulate sensitivity to a nicotine + alcohol (N + A) interoceptive cue. First, we show neuronal activation in mPFC-PL and AcbC following treatment with N + A. Next, we demonstrate that chemogenetic silencing of projections from mPFC-PL to nucleus accumbens core decrease sensitivity to the N + A interoceptive cue, while enhancing sensitivity to the individual components, suggesting an important role for this specific projection. Furthermore, we demonstrate that clozapine-N-oxide (CNO), the ligand used to activate the DREADDs, had no effect in parallel mCherry controls. These findings contribute important information regarding our understanding of the cortical-striatal circuitry that regulates sensitivity to the interoceptive effects of a compound N + A cue.

Factors Associated with Poly Drug Use in Adolescents.

Poly drug use in adolescents represents a significant public health issue, heightening risk for abuse, dependency, and a variety of short- and long-term psychological, psychosocial, and health consequences. However, past studies have typically examined just one or two substances in isolation and there is a lack of research that has comprehensively examined possible predictors of poly drug use in adolescents. To inform the development of comprehensive prevention programs that can simultaneously target multiple substances, the present study sought to identify psychological, environmental, and demographic factors that are most strongly associated with alcohol, tobacco, and cannabis poly drug use. Adolescents aged 15 to 17 years (n = 1661; 50.9% male) completed a survey on their use of alcohol, tobacco, and cannabis over the last 30 days. Various psychological, environmental, and demographic factors were also assessed. Weighted multiple-level logistic regression was conducted to assess the factors associated with poly drug use. In total, 20.3% of respondents had used at least one substance, 6.7% reported using two substances, and 3.3% reported using all three substances. The most common combined pattern of use was alcohol and tobacco, followed by alcohol and cannabis. Several factors emerged as significant, with conduct problems, depression, and the school environment accounting for the most variance. Specific psychological and environmental factors appear to be particularly important domains to target in adolescent substance use prevention programs. Early identification of adolescent depression and conduct problems and the development of programs that address these symptoms in youth may be effective approaches to delaying or preventing poly drug use in this population.

Changes in recreational drug use, drug use associated with chemsex, and HIV-related behaviours, among HIV-negative men who have sex with men in London and Brighton, 2013-2016.

OBJECTIVES: The objective of this study was to compare the prevalence of polydrug use, use of drugs associated with chemsex, specific drug use, and HIV-related behaviours, between two time periods, using two groups of HIV-negative men who have sex with men (MSM) attending the same sexual health clinics in London and Brighton, in two consecutive periods of time from 2013 to 2016. METHODS: Data from MSM in the cross-sectional Attitudes to and Understanding Risk of Acquisition of HIV (AURAH) study (June 2013 to September 2014) were compared with baseline data from different MSM in the prospective cohort study Attitudes to and Understanding Risk of Acquisition of HIV over Time (AURAH2) (November 2014 to April 2016). Prevalence of polydrug use, drug use associated with chemsex and specific drug use, and 10 measures of HIV-related behaviours including condomless sex, post-exposure prophylaxis (PEP) use, pre-exposure prophylaxis (PrEP) use, and HIV testing, were compared. Prevalence ratios (PRs) for the association of the study (time period) with drug use and HIV-related behaviour measures were estimated using modified Poisson regression analysis, unadjusted and adjusted for sociodemographic factors. RESULTS: In total, 991 MSM were included from AURAH and 1031 MSM from AURAH2. After adjustment for sociodemographic factors, use of drugs associated with chemsex had increased (adjusted PR (aPR) 1.30, 95% CI 1.11 to 1.53) and there were prominent increases in specific drug use; in particular, mephedrone (aPR 1.32, 95% CI 1.10 to 1.57), γ-hydroxybutyric/γ-butryolactone (aPR 1.47, 95% CI 1.15 to 1.87) and methamphetamine (aPR 1.42, 95% CI 1.01 to 2.01). Use of ketamine had decreased (aPR 0.54, 95% CI 0.38 to 0.78). Certain measures of HIV-related behaviours had also increased, most notably PEP use (aPR 1.50, 95% CI 1.21 to 1.88) and number of self-reported bacterial STI diagnoses (aPR 1.24, 95% CI 1.08 to 1.43). CONCLUSIONS: There have been significant increases in drug use associated with chemsex and some measures of HIV-related behaviours among HIV-negative MSM in the last few years. Changing patterns of drug use and associated behaviours should be monitored to enable sexual health services to plan for the increasingly complex needs of some clients.

Predictors of Aggressive Behavior While under the Influence of Illicit Drugs among Young Adult Methamphetamine Users.

BACKGROUND: Prior research indicates that patterns of combined alcohol and methamphetamine use may be associated with experiencing subjective feelings of aggression or hostility during methamphetamine use episodes. OBJECTIVES: This study examines whether subjective effects of methamphetamine use (i.e., aggression or hostility and paranoia) are associated with aggressive behavior while under the influence of any illicit drugs, controlling for combined alcohol and methamphetamine use and a number of other potential predictors. METHODS: Data from a population-based sample of Australian young adult methamphetamine users (n = 101) collected in 2010 was analyzed. A prediction model of aggressive behavior under the influence of illicit drugs was developed using penalized maximum likelihood logistic regression. RESULTS: Over one-third (34.7%) of methamphetamine users had engaged in verbal and/or physical aggression under the influence of illicit drugs in the last 12 months. In the prediction model, recurrent feelings of aggression or hostility attributed to methamphetamine use (≥3 times in the last 12 months) were associated with aggressive behavior (adjusted odds ratio 4.95, 95% confidence interval 1.67, 14.69). This association was independent of methamphetamine-attributed paranoia, combined alcohol and methamphetamine use, methamphetamine, ecstasy, cocaine, and cannabis use patterns, heavy episodic drinking, gender, and age. No association was found for combined alcohol and methamphetamine use. CONCLUSIONS: These findings indicate a link between methamphetamine-related subjective feelings of aggression or hostility and self-reported aggressive behavior while under the influence of illicit drugs. This suggests that subjective feelings of aggression or hostility may distinguish those who are involved in aggression from other methamphetamine users.

Poly-Drug Use of Prescription Medicine among People with Opioid Use Disorder in China: A Systematic Review and Meta-Analysis.

BACKGROUND: Opioid use disorder (OUD) causes substantial public health and social problems worldwide. Poly-drug use is common in people with OUD and increases morbidity and mortality. Investigation of the patterns and characteristics of poly-drug use of prescription medicine among opioid users is needed to develop appropriate prevention and intervention strategies. OBJECTIVES: To estimate the prevalence of poly-drug use of prescription medicine among people with OUD in China using meta-analysis. METHODS: We searched relevant epidemiological studies published before February 2017 in English and Chinese databases. The quality of included studies was assessed using the Agency for Healthcare Research and Quality scale. The pooled prevalences of prescription medicine use among people with OUD were estimated. RESULTS: We included 80 eligible studies in the meta-analysis. The main prescription medicines were benzodiazepines (BZDs) and prescription opioid analgesics. The pooled prevalence of unclassified BZDs and prescription opioids was 40.6% and 23.2%, respectively. Diazepam was the most frequently co-used BZD (32.6%), followed by triazolam (32.1%), and estazolam (9.2%). Tramadol was the most commonly used prescription opioid (27.3%), followed by methadone (16.8%), buprenorphine (12.6%), pethidine (8.9%), morphine (6.5%), dihydroetorphine (3.9%), and codeine-containing cough syrup (3.7%). BZDs were mainly used for self-medication (56.1%), whereas prescription opioids were primarily coused for nonmedical purposes (69.4%). CONCLUSIONS: The results demonstrate that prescription medicine use is widespread among opioid users in China. There needs to be more consideration of poly-drug use, and early interventions and management strategies are needed to prevent poly-drug use among opioid users in China.

Religious Involvement, Financial Strain, and Poly-Drug Use: Exploring the Moderating Role of Meaning in Life.

BACKGROUND: Research indicates that greater involvement in religion is associated with lower rates of substance use and misuse. However, religion is a complex construct that can be assessed in many ways. The purpose of this study is to explore a dimension of religion that has not been evaluated in previous research on poly-drug use: a religious sense of meaning in life. OBJECTIVES: It is hypothesized that a religious sense of meaning in life will offset (i.e., moderate) the effects of chronic financial strain on poly-drug use. In order to instill greater confidence in the findings, the moderating role of a religious sense of meaning in life is compared and contrasted with a general sense of meaning in life. METHODS: The data are provided by a recent nationwide survey of adults of all ages in the United States (N = 2,622). The relationships among the core study constructs are evaluated with ordinary least squares multiple regression. RESULTS: The results indicate that a greater religious sense of meaning in life buffers the effects of financial strain on poly-drug use. In contrast, a general sense of meaning in life does not appear to perform a similar stress-buffering function. Conclusions/Importance: The findings from this study are important because they provide greater insight into the potentially important ways in which involvement in religion may be associated with poly-drug use.

Lifetime influences for cannabis cessation in male incarcerated indigenous australians.

INTRODUCTION: Urban non-indigenous populations report life events (marriages, employment) as influences for self-initiated cannabis cessation. However, this hasn't been investigated in remote indigenous populations with different social paradigms. METHODS: We investigate cannabis use, harms, and poly-substance misuse in 101 consenting male incarcerated indigenous Australians. Interviews applied quantitative and qualitative questions assessing demographic characteristics, criminal history, drug use, the Marijuana Problems Inventory (MPI), and cannabis-cessation influences. Comparisons used Chi Square, Analysis of Variance, and Nvivo software. RESULTS: Cannabis use groups (current users, ex-users, and never users) were demographically similar except that current users reported more juvenile legal problems, younger school departure, and lower school achievement (p < 0.05). Mean cannabis consumption was 12.3 cones/day. Incarceration and family responsibilities were the strongest cessation influences. Employment responsibilities and negative self-image were rarely cited as influences. DISCUSSION: High cannabis use, with its associated problems, is concerning. These identified influences indicate incarceration should be used for substance reduction programs, plus post-release follow-up. Community-based programs focusing on positive influences, such as family responsibilities and social cohesion, may be successful within indigenous populations with strong kinship responsibilities, rather than programs that focus solely on substance harms.

Benzodiazepine Boom: Tracking Etizolam, Pyrazolam, and Flubromazepam from Pre-UK Psychoactive Act 2016 to Present Using Analytical and Social Listening Techniques.

INTRODUCTION: The designer benzodiazepine (DBZD) market continues to expand whilst evading regulatory controls. The widespread adoption of social media by pro-drug use communities encourages positive discussions around DBZD use/misuse, driving demand. This research addresses the evolution of three popular DBZDs, etizolam (E), flubromazepam (F), and pyrazolam (P), available on the drug market for over a decade, comparing the quantitative chemical analyses of tablet samples, purchased from the internet prior to the implementation of the Psychoactive Substances Act UK 2016, with the thematic netnographic analyses of social media content. METHOD: Drug samples were purchased from the internet in early 2016. The characterisation of all drug batches were performed using UHPLC-MS and supported with 1H NMR. In addition, netnographic studies across the platforms X (formerly Twitter) and Reddit, between 2016-2023, were conducted. The latter was supported by both manual and artificial intelligence (AI)-driven thematic analyses, using numerous.ai and ChatGPT, of social media threads and discussions. RESULTS: UHPLC-MS confirmed the expected drug in every sample, showing remarkable inter/intra batch variability across all batches (E = 13.8 ± 0.6 to 24.7 ± 0.9 mg; F = 4.0 ± 0.2 to 23.5 ± 0.8 mg; P = 5.2 ± 0.2 to 11.5 ± 0.4 mg). 1H NMR could not confirm etizolam as a lone compound in any etizolam batch. Thematic analyses showed etizolam dominated social media discussions (59% of all posts), with 24.2% of posts involving sale/purchase and 17.8% detailing new administration trends/poly-drug use scenarios. Artificial intelligence confirmed three of the top five trends identified manually. CONCLUSIONS: Purity variability identified across all tested samples emphasises the increased potential health risks associated with DBZD consumption. We propose the global DBZD market is exacerbated by surface web social media discussions, recorded across X and Reddit. Despite the appearance of newer analogues, these three DBZDs remain prevalent and popularised. Reporting themes on harm/effects and new developments in poly-drug use trends, demand for DBZDs continues to grow, despite their potent nature and potential risk to life. It is proposed that greater controls and constant live monitoring of social media user content is warranted to drive active regulation strategies and targeted, effective, harm reduction strategies.

Post mortem blood bromazolam concentrations and co-findings in 96 coronial cases within England and Wales.

Bromazolam is a newly emerging benzodiazepine drug which is not licensed for medicinal use. It may be sourced as a New Psychoactive Substance (NPS) for its desired effects or be consumed unknowingly via counterfeit Xanax® or Valium® preparations. As part of our Coronial workload, we observed an increase in the detection of bromazolam from September 2021 to November 2022. We report a series of 96 cases in which bromazolam was quantitated by high resolution accurate mass - mass spectrometry (HRAM - MS) in post-mortem blood. The mean (SD) post-mortem blood bromazolam concentration from our case series was 64.6 ( ± 79.4) µg/L (range <1-425 µg/L). Routine toxicological screening results have also been reported; the most commonly encountered drugs taken in combination with bromazolam were cocaine, gabapentinoids and diazepam. In 48% of cases at least one further designer benzodiazepine drug was also present (etizolam, flualprazolam, flubromazolam, flubromazepam). It is essential that laboratories providing toxicological investigations are aware of the limitations of their assays; and inclusion of bromazolam within targeted screening panels using LC-MS/MS is encouraged. Bromazolam has not been associated with death in isolation from resulting toxic concentrations; however, it is likely to enhance adverse clinical effects when taken in combination with stimulant and/or centrally-acting depressant drugs (poly-drug deaths). Bromazolam, similar to other benzodiazepines, may also impair cognition and decision making skills.

A novel alcohol+nicotine co-use self-administration procedure reveals sex differences and differential alteration of mesocorticolimbic TLR- and cholinergic-related neuroimmune gene expression in rats.

Although alcohol and nicotine are two of the most commonly co-used drugs with upwards of 90% of adults with an alcohol use disorder (AUD) in the US also smoking, we don't tend to study alcohol and nicotine use this way. The current studies sought to develop and assess a novel alcohol + nicotine co-access self-administration (SA) model in adult male and female Long-Evans rats. Further, both drugs are implicated in neuroimmune function, albeit in largely opposing ways. Chronic alcohol use increases neuroinflammation via toll-like receptors (TLRs) which in turn increases alcohol intake. By contrast, nicotine produces anti-inflammatory effects, in part, through the monomeric alpha7 receptor (ChRNa7). Following long-term co-access (6 months), rats reliably administered both drugs during daily sessions, however males generally responded for more alcohol and females for nicotine. This was reflected in plasma analysis with translationally relevant intake levels of both alcohol and nicotine, making it invaluable in studying the effects of co-use on behavior and CNS function. Moreover, male rats show sensitivity to alterations in alcohol concentration whereas females show sensitivity to alterations in nicotine concentration. Rats trained on this procedure also developed an anxiogenic phenotype. Finally, we assessed alterations in neuroimmune-related gene expression in the medial prefrontal cortex - prelimbic, (mPFC-PL), nucleus accumbens core (AcbC), and ventral tegmental area (VTA). In the AcbC, where α7 expression was increased and ß2 was decreased, markers of pro-inflammatory activity were decreased, despite increases in TLR gene expression suggesting that co-use with nicotine modulates inflammatory state downstream from the receptor level. By contrast, in mPFC-PL where α7 was not increased, both TLRs and downstream proinflammatory markers were increased. Taken together, these findings support that there are brain regional and sex differences with co-use of alcohol + nicotine SA and suggest that targeting nicotinic α7 may represent a novel strategy for treating alcohol + nicotine co-dependence.

Detection of anabolic-androgenic steroids in e-cigarettes seized from prisons: A case study.

The administration of new psychoactive substances (NPS), in particular synthetic cannabinoid receptor agonists (SCRAs), via e-cigarettes, within prison settings has been well publicized. This study provides an overview of five e-cigarette case samples seized from Scottish prisons between May 2022 and July 2023 where the anabolic-androgenic steroids (AASs) mestanolone and oxandrolone were identified following gas chromatography-mass spectrometry (GC-MS) analysis. These e-cigarette samples represented 2.9% of all samples containing e-cigarette cartridges (n = 170) and 9.4% of all samples found to contain AASs (n = 53) seized during the same time period. The AASs were detected in combination with other drugs, including cocaine, Δ9-tetrahydrocannabinol (Δ9-THC), SCRAs and nicotine. This represents a new and novel route of administration for AASs.

No decline in drug overdose deaths in Norway: An ecological approach to understanding at-risk groups and the impact of interventions.

Aim: This Norwegian case study examines groups at risk of drug overdose deaths, evidence-based harm reduction interventions, low-threshold services and treatment implemented, as well as trends in drug overdose deaths between 2010 and 2021. We aimed to explore the relevance of interventions for at-risk groups and discuss their potential impact on drug overdose trends. Method/data: Using an ecological approach, we analysed the following: (1) groups identified through latent profile analysis (LPA) among a sample of 413 high-risk drug users collected in 2010-2012, supplemented with other relevant studies up to 2021; (2) published information on harm-reduction interventions, low-threshold services and treatment in Norway; and (3) nationwide drug overdose mortality figures supplemented with published articles on the topic. Results: High-risk drug users in 2010-2012 commonly engaged in frequent illegal drug use, injecting and poly-drug use (including pharmaceutical opioids), which continued into following decade. The interventions implemented between 2010 and 2021 were relevant for at-risk groups identified in the surveys. However, there was no decrease in the trend of drug overdose deaths up to 2021. While relevant interventions may have mitigated a theoretical increase in mortality, new at-risk groups may have contributed to fatal outcomes associated with pharmaceutical opioids. Conclusion: The interventions were relevant to the risk groups identified among high-risk drug users and potentially effective in preventing an increase in drug overdose trends. However, tailored interventions are needed for individuals at risk of death from prescribed opioids. Comprehensive studies encompassing all at-risk populations, including both legal and non-medical users of prescription opioids, are needed.

Differential Effects of Nicotine, Alcohol, and Coexposure on Neuroimmune-Related Protein and Gene Expression in Corticolimbic Brain Regions of Rats.

Nicotine and alcohol co-use is extremely common and their use constitutes two of the most common causes of preventable death, yet the underlying biological mechanisms are largely understudied. Activation of neuroimmune toll-like receptors (TLRs) promotes the induction of proinflammatory cascades and increases alcohol intake in rodents, which further promotes TLRs in the brain; nicotine may decrease central proinflammatory signaling. The current studies sought to determine the effects of nicotine ± alcohol (alone or in combination) on circulating blood plasma and TLR protein/gene expression in addiction-associated corticolimbic brain regions, including the prefrontal cortex-prelimbic (mPFC-PL) and nucleus accumbens core (AcbC). Adult rats were treated with alcohol (0 or 2 g/kg, IG) and exposed to nicotine vapor (0 or 30 mg/mL solution) daily for 2, 14, or 28 days. Plasma studies indicated no effects of independent exposure or coexposure in males. Coexposure decreased plasma nicotine levels versus nicotine-only treated females, yet alcohol and cotinine concentrations were unchanged. By 28 days, the anti-inflammatory cytokine IL-13 was decreased in alcohol-only females. Divergent changes in TLR3 (but not TLR4) protein occurred for independent-drug exposed males (but not coexposure), with reductions in the mPFC-PL after 14 days and increases in the AcbC by 28 days. Gene expression following chronic coexposure suggests nicotine may regionally counteract alcohol-induced inflammation, including increased AcbC-TLR3/4/7 and several downstream markers in females and increased mPFC-PL-TLR3 and -STAT3 (but not IRF3) evident in males with exposure to either drug alone. These findings give further insight into the role of sex and the neuroimmune system in independent exposure and coexposure to nicotine ± alcohol.

Pathway of effects of adverse childhood experiences on the poly-drug use pattern among adults using drugs: A structural equation modeling.

Introduction: Adverse childhood experiences (ACEs) are associated with an increased risk of poly-substance use among drug-using adults. However, there is a paucity of literature on a direct or indirect relationship between ACEs and drug use patterns. We thus aimed to identify the pathway of effects of ACEs on drug use patterns in adults by the structural equation model (SEM). Methods: A cross-sectional study was conducted by respondent-driving sampling and consecutive sampling among adult drug users in Southwest China in 2021. Descriptive, univariate, and SEM analyses were performed by R software 4.2.1. Results: Of 406 participants recruited from a drug abuse clinic, the average age was 34 years. The majority of the participants were male patients (98.3%) from ethnic minorities (79.6%), who were unmarried (71.6%) and employed (81.2%). Nearly 95.5% experienced ACEs with 46.6% of them reporting four or more ACEs. The median value of self-perception of drug abuse score, friend drug use score, and drug use score was 8.0 (3.0, 11.0), 1.0 (0.0, 1.0), and 1.0 (1.0, 2.0) respectively. In the confirmatory analysis part of SEM, the construct of latent variables fitted well with the data. Poly-drug use was significantly and directly affected by three predictors including monthly incomes (ß = 0.09), friend drug use (ß = 0.50), and ACEs (ß = 0.11). The indirect effect of ACEs passing through self-perception of drugs (ß = 0.09) was not significant. Discussion: ACEs have an independent and direct effect on the drug user for poly-drug use apart from the effect of drug-using friends and family income.

Quantitative Assessment of High School Students' Poly-drug Use: Related Social Aspects and School Dropout.

INTRODUCTION: Poly-drug use has increased in recent decades, especially in young drugusing groups. Classic epidemiological indicators of drug use, such as prevalence and incidence of users of specific substances, are not adequate as measures of the possible harms of poly-drug use. We applied poly-drug use indicators, based on substance-specific harm scores reported by van Amsterdam and Nutt in 2015, to data from high school student surveys, showing their usefulness in identifying high-risk drug consumption. Analysing the 'correlation' between high-risk drug use of high school students and school dropout allows the evaluation of adopted prevention policies and may suggest more suitable approaches. METHODS: Each drug user is characterized by two specific scores: overall frequency of use of substances during the period of interest (FUS) and poly-drug use score (PDS). The poly-drug use score is a weighted average of the harm scores of the individual substances used multiplied by their respective frequencies of use. The PDS increases with the frequency of use, with the number of substances used, and with the specific harm scores of each substance. This indicator consists of two components, one representing the health harm score toward self and the other the social harm score toward others. RESULTS: The indicators have been applied to sample data involving youth population, specifically the ESPAD®Italia survey data on high school students conducted annually in Italy. The trends of poly-drug use at different ages of students, 15-19 years, over time, and gender have been studied. The results have been linked to educational outcomes, early school leaving and social aspects, making it possible to assess present prevention interventions and suggest appropriate planning of future prevention interventions. CONCLUSION: Poly-drug use indicators allow a comprehensive quantitative evaluation of the risks of drug use. The analysis of the links between heavy use of drugs, school performance and dropout, and the social variables that influence them, shown in this work, suggests how best to plan secondary or indicated prevention interventions at school. The problem of including "new" NPS in analyses is also briefly discussed.

Nail analysis for the assessment of caffeine abuse in Northwest China: A population-based study.

Caffeine is the most widely consumed psychoactive agent worldwide and has the potential for abuse, but studies monitoring caffeine abuse in China are scarce. This study aims to estimate the prevalence of caffeine abuse in northwest China and investigate the correlation between caffeine and other drugs in hair and nails using an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Fingernail clippings were collected from 376 participants in northwest China to detect caffeine and 13 other illicit psychoactive drugs and their metabolites. Paired hair and nail samples were collected from 39 participants to investigate the correlation between caffeine and other drugs in hair and nails. The samples were decontaminated, pulverized, and extracted by a high-throughput nail sample preparation method and analyzed by UPLC-MS/MS. The results showed a risk of caffeine abuse in northwest China, with concentrations ranging from 0.43 to 10.6 ng/mg for healthy volunteers, 0.49-246 ng/mg for caffeine abusers, and 0.25-363 ng/mg for drug addicts in community rehabilitation centers. Caffeine was detected together with other illicit psychoactive drugs and their metabolites. Furthermore, positive detection correlations were found between hair and nail samples. This study provides a current perspective on caffeine abuse in northwest China and demonstrates the practical use of UPLC-MS/MS for the simultaneous detection of caffeine and 13 illicit psychoactive drugs and their metabolites in hair and nails. The results highlight the potential of nails as a supplementary matrix when hair samples are unavailable and emphasize the need for handling caffeine carefully given its potential for abuse.

Prevalence of Multidrug-Resistant TB Among Smear-Positive Pulmonary TB Patients in Banadir, Somalia: A Multicenter Study.

Background: Tuberculosis (TB) is an infectious disease that is the second most common cause of death from a single infectious agent. TB infection affects anyone, regardless of age, gender, and ethnicity. Drug-resistant TB is a serious public health problem, which needs treatment with a second-line anti-TB drug and it includes poly-drug resistance (PDR), multi-drug resistance (MDR), and extensive drug resistance (XDR). The goal of this research is to find out the prevalence of MDR TB among pulmonary TB patients in Banadir, Somalia. Methods: This was a multicenter retrospective review of data involving 1732 smear-positive pulmonary TB patients visiting Banadir TB centers between July 1, 2019 and June 30, 2020. Demographic, clinical, and drug susceptibility data were retrieved from TB treatment cards. The data were analyzed using Statistical Package for Social Sciences (SPSS) software (IBM SPSS Statistics version 26). Results: All 1732 pulmonary TB cases were previously diagnosed by the Gene Xpert MTB/RIF test. Among them, 70.4% (1219/1732) were males. The mean age was 31.77 years. Overall, the prevalence of drug resistance TB was 10.56% (183/1732). The MDR TB was 1.96%, poly-drug resistance (PDR) was 0.12%, and extensive drug resistance was 0.06%. Conclusion: This study showed a prevalence of MDR-TB among pulmonary TB patients, which is similar to some of the eastern African countries.

U.S. older adults' heroin and psychostimulant use treatment admissions, 2012-2019: Sociodemographic and clinical characteristics.

BACKGROUND: Increases in U.S. older adults' nonprescription opioid and psychostimulant use call for examining their treatment admissions for these substances. METHODS: Using admissions age 55 + involving heroin (N = 299,073) from the 2012-2019 Treatment Episode Data Set-Admissions, we examined trends and sociodemographic and clinical characteristics of three groups: (1) heroin-only admissions (i.e., not involving cocaine or methamphetamine), (2) heroin-cocaine admissions, and (3) heroin-methamphetamine admissions. Bivariable and multivariable logistic regression analyses were conducted to examine the research questions. RESULTS: Between 2012 and 2019, the numbers of both heroin-only and heroin-cocaine admissions increased 2.3-fold and heroin-methamphetamine admissions increased seven-fold. First time heroin-methamphetamine admissions increased 18-fold. Heroin-methamphetamine admissions were concentrated in the Western region and heroin-cocaine admissions in the Northeastern region. Multivariable analyses showed a nearly 6 times higher relative risk ratio (RRR; 95% CI=5.24-6.74) for heroin-methamphetamine vs. heroin-only admissions in 2019 compared to 2012. Being non-Hispanic Black, compared to non-Hispanic White, was associated with a RRR of 2.4 (95% CI=2.34-2.46) for heroin-cocaine admissions and a RRR of 0.14 (95% CI=0.12-0.15) for heroin-methamphetamine admissions. Late-onset heroin use, experience of homelessness and other psychiatric problems, and past 30-day arrest episodes were associated with a higher likelihood of heroin-cocaine and heroin-methamphetamine admissions, while injection drug use (IDU) was associated with a higher likelihood of heroin-methamphetamine admissions only. CONCLUSIONS: Healthcare providers should assess and monitor psychostimulant, methamphetamine in particular, use among older adults. Those who use heroin and psychostimulants should receive substance use treatment and help to secure stable housing and meet other living needs.