Genetics of substance use disorders in the era of big data.

Substance use disorders (SUDs) are conditions in which the use of legal or illegal substances, such as nicotine, alcohol or opioids, results in clinical and functional impairment. SUDs and, more generally, substance use are genetically complex traits that are enormously costly on an individual and societal basis. The past few years have seen remarkable progress in our understanding of the genetics, and therefore the biology, of substance use and abuse. Various studies - including of well-defined phenotypes in deeply phenotyped samples, as well as broadly defined phenotypes in meta-analysis and biobank samples - have revealed multiple risk loci for these common traits. A key emerging insight from this work establishes a biological and genetic distinction between quantity and/or frequency measures of substance use (which may involve low levels of use without dependence), versus symptoms related to physical dependence.

Can accurate demographic information about people who use prescription medications nonmedically be derived from Twitter?

Traditional substance use (SU) surveillance methods, such as surveys, incur substantial lags. Due to the continuously evolving trends in SU, insights obtained via such methods are often outdated. Social media-based sources have been proposed for obtaining timely insights, but methods leveraging such data cannot typically provide fine-grained statistics about subpopulations, unlike traditional approaches. We address this gap by developing methods for automatically characterizing a large Twitter nonmedical prescription medication use (NPMU) cohort (n = 288,562) in terms of age-group, race, and gender. Our natural language processing and machine learning methods for automated cohort characterization achieved 0.88 precision (95% CI:0.84 to 0.92) for age-group, 0.90 (95% CI: 0.85 to 0.95) for race, and 94% accuracy (95% CI: 92 to 97) for gender, when evaluated against manually annotated gold-standard data. We compared automatically derived statistics for NPMU of tranquilizers, stimulants, and opioids from Twitter with statistics reported in the National Survey on Drug Use and Health (NSDUH) and the National Emergency Department Sample (NEDS). Distributions automatically estimated from Twitter were mostly consistent with the NSDUH [Spearman r: race: 0.98 (P < 0.005); age-group: 0.67 (P < 0.005); gender: 0.66 (P = 0.27)] and NEDS, with 34/65 (52.3%) of the Twitter-based estimates lying within 95% CIs of estimates from the traditional sources. Explainable differences (e.g., overrepresentation of younger people) were found for age-group-related statistics. Our study demonstrates that accurate subpopulation-specific estimates about SU, particularly NPMU, may be automatically derived from Twitter to obtain earlier insights about targeted subpopulations compared to traditional surveillance approaches.

International evidence on lived experiences of trauma during homelessness and effects on mental health including substance use: a co-produced qualitative systematic review.

BACKGROUND: Trauma is an experience (physical or emotional) that is life-threatening, harmful, or out of the ordinary and has lasting effects on mental health and wellbeing. Much of the information about trauma within homeless populations focuses on events in childhood. Using coproduction principles, we aimed to synthesise qualitative evidence exploring the impact of trauma during adulthood homelessness on mental health, including substance use. METHODS: In this qualitative systematic review, we searched ASSIA, CINAHL, Cochrane, EMBASE, MEDLINE, Proquest theses and dissertations, PsychInfo, Scopus, and Web of Science for studies published from inception until Sept 6, 2022, alongside grey literature from relevant websites. Search terms were developed based on the PICO framework. No language, date, or geographical limits were applied. Any qualitative research reporting experiences of trauma and its impact on mental health during homelessness in adults was eligible. We extracted relevant data (eg, methodology, sample characteristics, homelessness, and findings). People with lived experience of homelessness were provided with bespoke training by the lead researcher. They contributed to refining the review aims, screening, coding, and theme development. Quality was assessed using the CASP Qualitative Studies Checklist. FINDINGS: We included 26 qualitative papers, including 876 adults experiencing homelessness between ages 18 and 70 years (448 [51%] women and 428 [49%] men). All papers focused on urban settings. Eight papers were from the USA, five from Canada, four from the UK and Australia, three from Brazil, and one from Ethiopia and Iran. A framework synthesis of these 26 papers identified three preliminary themes. People experiencing homelessness make sense of trauma in three ways: internalised understanding, relationality to others, and with a survival lens. Coping strategies for managing feelings of fear, anxiety, and depression included substance use, self-rationalisation, and strategies to feel safe. Finally, when people experienced repeated trauma, they became either dissociated, and accepted their situation, or resilient, wishing to change their circumstances. INTERPRETATION: Further evidence is needed in rural or coastal regions, where people experiencing homelessness may face greater isolation. Trauma rarely takes place in isolation, and often previous experiences of trauma shape how people experiencing homelessness make sense of trauma and cope with it. Support to address coping with the effects of trauma should focus on ensuring people do not become desensitised and prevent deterioration of mental health and substance use. The strength of this review is its coproduction with people with lived experience. Single person data extraction with secondary checks was a limitation. FUNDING: National Institute for Health and Care Research (NIHR) School for Primary Care Research as part of the Three NIHR Research Schools Mental Health Programme.

Hospital admissions for physical health and psychosocial adversity among people experiencing homelessness in England: a population-based retrospective cross-sectional study.

BACKGROUND: Homeless health care is often characterised by physical health, mental health, and substance use problems, resulting in high use of emergency care, poor outcomes, and extreme social inequities. We assessed health needs as prevention opportunities for hospitalised people experiencing homelessness (PEH) in England. METHODS: This population-based retrospective cross-sectional study used anonymised national Hospital Episodes Statistics Admitted Patient Care data. PEH were identified as having at least one homeless code ("no fixed abode", "registered with a homeless-exclusive GP practice", "clinical diagnosis of homelessness") from April 1, 2017, to March 31, 2018. We analysed admissions for PEH and for housed people. We estimated the prevalence of demographic and admission characteristics and diagnoses by 10th International Classification of Disease (ICD-10) chapter. We developed novel diagnostic phenotypes for physical health (internal disease processes) and psychosocial adversity (mental health, substance use, violence, and social factors). We compared admissions between PEH and housed people using sex-stratified logistic regression adjusted for age and ethnicity. FINDINGS: There were 15 566 010 admissions (51 643 PEH and 15 514 367 housed people). Compared with housed people, proportionately more PEH were younger (PEH aged 26-45 years, n=24 224 [46·9%], housed people n=3 323 951 [21·4%]), male (PEH n=37 662 [72·9%], housed people n=6 819 157 [44·0%]), and not White British (PEH n=14 605 [28·3%], housed people n=3 447 183 [22·2%]). Emergency admissions were more common among PEH (PEH male n=30 958 [82·2%], housed people male n=5 321 428 [34·3%], adjusted odds ratio [aOR] 8·76, 95% CI 8·53-9·00). The most common primary diagnoses by ICD-10 chapter for PEH were mental and behavioural conditions (PEH male n=7118 admissions [18·9%], housed people male n=155 144 [1·0%], 12·97, 12·61-13·34). Admissions for the psychosocial adversity phenotype were higher in PEH, particularly for women (PEH female n=3922 [28·1%], housed people female n=155 644 [1·79%], 18·18, 17·50-18·88). Physical health phenotype admissions were less common in PEH (PEH male n=7510 [19·9%], housed people male n=1 821 397 [26·7%], 0·91, 0·89-0·94), but specific infections, cancers, respiratory, and cardiovascular diseases were more common among PEH for both men and women. INTERPRETATION: These results support targeting of preventative interventions for PEH before, during and after admission to hospital, highlighting psychosocial needs. Future research should aim to produce reliable estimates of the size of the national homeless population to enable calculation of admission rates for psychosocial and physical health diagnoses. FUNDING: National Institute for Health and Care Research (NIHR).

Exploring substance misuse in a prison in Wales: a cross-sectional analysis.

BACKGROUND: Since 2015, the risks of dying due to drug-related causes are higher in prison than in the general population, with opiates and psychoactive substances being the most common substances recorded on death certificates in prison. Many individuals use drugs before entering the prison environment, it is not clear which individuals continue to use drugs while in prison. This study is a first step towards identifying characteristics of those who use drugs in prison, while exploring substances commonly used. METHODS: This retrospective cross-sectional analysis was performed on 299 men (mean age 38 years [SD 11]) in a long-stay UK prison in South Wales who participated in a research study exploring cardiometabolic risk in prison, in which substance misuse was included as a risk variable. All men aged 25 years or older with no previous diagnosis of cardiometabolic illness were eligible to participate. Data were collected between Oct 7 and Oct 23, 2019. Participants were asked details about their substance use before and since entering the prison. Mental wellbeing was assessed using the short Warwick Edinburgh Mental Wellbeing Score and low mental wellbeing calculated as 1 SD below the population mean score. To examine associations between characteristics (age groups, mental wellbeing, exposure to prison environment) and drug use, we used binary logistic regression (adjusted for characteristics such as age group, mental wellbeing, and exposure to prison environment ). FINDINGS: Overall, 195 (65%) of 299 participants reported a history of drug use before entering prison. Since entering prison 49 (16%) participants reported using drugs including methadone, and 24 (8%) reported using drugs excluding methadone. The next leading substances used in prison were spice (11 [4%] participants) and cannabis (six [2%] participants). All those who used drugs in prison had a history of drug use. Individuals more likely to continue using drugs in prison were aged 39 years and younger (adjusted odds ratio [aOR] 4·72, 95% CI 1·88-11·89; p=0·0009), with reported low mental wellbeing (3·38, 1·54-7·41; p=0·002), and had spent collectively more than 2·5 years in the prison environment (4·77, 2·09-10·91; p=0·0002). INTERPRETATION: This study, from a limited sample, describes the characteristics of those who use drugs in prison. Harm reduction interventions targeted to these individuals could reduce the risk of prison drug-related deaths. These findings should be interpreted with some caution, as this is a single site and may not reflect the wider UK prison environment. FUNDING: Public Health Wales.

Interventions to improve oral health and related health behaviours of substance use, smoking, and diet in people with severe and multiple disadvantage: a systematic review of effectiveness and cost-effectiveness.

BACKGROUND: Homelessness overlapping with substance use and offending is described as severe and multiple disadvantage (SMD). People experiencing SMD have poor oral health along with high levels of related behaviours such as substance use, smoking, and poor diet. Existing evidence largely describes the prevalence of oral health problems, substance use, and smoking in SMD groups. Little is known about interventions that can address these conditions in SMD groups. We aimed to review the effectiveness and cost-effectiveness of interventions on oral health and related health behaviours in adults experiencing SMD. METHODS: For this systematic review, we searched bibliographic databases (MEDLINE, EMBASE, PsycINFO, CINAHL, EBSCO, Scopus) and grey literature for papers published from inception to February 2023. Two researchers independently reviewed the searches. Randomised controlled trials (RCTs), comparative studies and economic evaluations were included. Risk of bias was assessed. Population included adults experiencing SMD (including homelessness and substance use or repeat offending). Outcomes included oral health, and related behaviours (substance use, smoking, poor diet). Results were narratively synthesised. This review was registered with PROSPERO, CRD42020202416. FINDINGS: The review included 38 studies (published between 1991 and 2023), with 34 reporting effectiveness. These studies comprised of 23 RCTs and 11 quasi-experimental studies conducted in the USA (25 studies), Canada (seven studies), France (one study), and Spain (one study). The interventions involving multiple components, such as housing services with substance use and mental health support, effectively reduced substance use in SMD groups; these were mostly individual-level interventions. However, these studies had short follow-up periods and high attrition rates. Only one study addressed oral health outcomes, none focused on diet, and three RCTs covered smoking, with one intervention showing smoking abstinence at 4 weeks. Some limited evidence suggested cost-effectiveness of substance use interventions. INTERPRETATION: This review found that integrating services such as housing with other health-care services together could be effective in improving health behaviours, especially substance use among SMD groups. More evidence is needed specifically on oral health, smoking, and diet-related interventions. The generalisability of findings of this review is limited to high-income countries and shorter-term outcomes. FUNDING: National Institute for Health and Care Research (NIHR) Policy Research Programme.

Associations between parental smoking and teenage alcohol and drug use in the Growing Up in Ireland cohort study: a longitudinal observational study.

BACKGROUND: Children with a parent who smokes are more likely to become substance users than those who do not have a parent who smokes. In this study, we examined whether childhood or early adolescent exposure to primary parent smoking increased the risk of subsequent teenage alcohol and drug use at ages 17-18 years. METHODS: For this longitudinal observational study, we analysed data from 6039 teenagers and their parents from the waves 1-3 of the Growing up in Ireland Cohort 98' Study. Parental smoking was assessed at baseline (9 years) and wave 2 (13 years) with responses coded as yes or no. The primary parent was defined as the person who provided most care and who knew most about the Study Child, usually the mother or mother figure for 98% of study participants. Teenage alcohol and drug use assessed at ages 17-18 years (wave 3) was determined by responses to the question "Have you ever consumed alcohol?" (answers yes or no), drug use was assessed by questions on ever trying aerosols/gas, cannabis, and non-prescribed drugs, with those answering yes being classified as other-drug ever users. We did a logistic regression analysis to examine the associations between parents' smoking on teenage alcohol and drug use, controlling for covariates: gender, education, income, education, region, and household type. Ethics approval for the GUI project was obtained from the Health Research Board. FINDINGS: Of the 6039 teenagers included in our study, 2968 (49%) were female, 3070 (51%) were male, 5351 (89%) ever used alcohol, 5065 (85%) were current users, and 2098 (35%) used other drugs. Rates of primary parent smoking were 31% (n=1883) in wave 1 and 30% (n=1829) in wave 2. After adjusting for other exposures known to be associated with teenage substance use, primary parent smoking at waves 1 and 2 was associated with higher odds of teenage alcohol ever use (adjusted odds ratios [aORs] 1·89 [95% CI 1·44--2·46] at wave 1 and 1·53 [1·20-1·98] at wave 2), current alcohol use (1·88 [1·50-2·36] and 1·59 [1·28-1·97]) and other-drug ever use (1·699 [1·45-1·95] and 1·71 [1·47-1·98]). INTERPRETATION: Teenagers aged 17-18 years exposed at ages 9 and 13 years to parental smoking were more likely to report significantly higher odds of alcohol and drug use at age 17-18 years. The finding that exposure to parent smoking in childhood increases the risk of teenage alcohol and other drug use suggests a need for interventions aimed at parents who smoke Limitations include potential unmeasured or residual confounders and reliance on self-reported teenage substance use behaviours. FUNDING: Royal City of Dublin Hospital Trust, Irish Research Council Government of Ireland Postgraduate Scholarship Programme.

Examining the impact of substance use on hospital length of stay in schizophrenia spectrum disorder: a retrospective analysis.

BACKGROUND: Among patients diagnosed with schizophrenia, the presence of substance use poses an aggravating comorbidity, exerting a negative impact on the course of the disease, adherence to therapeutic regimens, treatment outcomes, duration of hospital stays, and the frequency of hospitalizations. The primary objective of the present study is to investigate the relationship between comorbid substance use disorders, antipsychotic treatment, and the length of stay in individuals hospitalized for treatment of schizophrenia. METHODS: We conducted a retrospective analysis of electronic health records spanning a 12-month period, specifically focusing on adult patients diagnosed with schizophrenia who were discharged from the University Hospital of Psychiatry Zurich between January and December 2019. We documented the number and types of diagnosed substance use disorder, the antipsychotic treatment, the length of stay, and the number of previous hospitalizations for each patient. RESULTS: Over a third (n = 328; 37.1%) of patients with schizophrenia had comorbid substance use with cannabis being the most frequent consumed substance. Patients with substance use (either single or multiple) were more frequently hospitalized; those with multiple substance use more frequently than those with a single substance use (F(2, 882) = 69.06; p < 0.001). There were no differences regarding the rate of compulsory admission. Patients with no substance use had a lower HoNOS score at discharge (F(2, 882) = 4.06). Patients with multiple substance use had a shorter length of stay (F(2, 882) = 9.22; p < 0.001), even after adjusting for duration of illness, previous hospitalizations, diagnosis, and antipsychotic treatment. CONCLUSIONS: In patients with schizophrenia, comorbid single or multiple substance use has a relevant negative impact on treatment and thus on the course of disease. Substance use in patients with schizophrenia should therefore receive special attention in order to reduce re-hospitalization rates and improve the clinical outcome.

Racial and Ethnic Differences in Heroin, Methamphetamine, and Cocaine Use, Treatment, and Mortality Trends in 3 National Data Sources-United States, 2010-2019.

BACKGROUND: As overdose deaths continue to rise, public health officials need comprehensive surveillance data to design effective prevention, harm reduction, and treatment strategies. Disparities across race and ethnicity groups, as well as trends in substance use, treatment, or overdose deaths, have been examined individually, but reports rarely compare findings across multiple substances or data sources. OBJECTIVE: To provide a broad assessment of the overdose crisis, we describe trends in substance use, treatment, and overdose mortality across racial and ethnic groups for multiple substances. RESEARCH DESIGN: We conducted a longitudinal, cross-sectional analysis comparing trends. SUBJECTS: We identified self-reported use from the National Survey on Drug Use and Health, substance use treatment admissions from the Treatment Episode Data Set-Admissions, and overdose deaths from the CDC's Multiple Cause of Death files. MEASURES: We measured rates of substance use, treatment, and deaths involving heroin, methamphetamine, and cocaine among United States adults from 2010 to 2019. RESULTS: Heroin, methamphetamine, and cocaine use increased, though not all changes were statistically significant. Treatment admissions indicating heroin and methamphetamine increased while admissions indicating cocaine decreased. Overdose deaths increased among all groups: methamphetamine (257%-1,115%), heroin (211%-577%), and cocaine (88%-259%). Changes in rates of use, treatment, and death for specific substances varied by racial and ethnic group. CONCLUSIONS: Substance use, treatment, and overdose mortality changed considerably, though not always equivalently. Identifying diverging trends in substance-related measures for specific substances and racial and ethnic groups can inform targeted investment in treatment to reduce disparities and respond to emerging changes in the overdose crisis.

HIV Prevalence and HIV Screening History Among a Veterans Association Cohort of People with Opioid and Alcohol Use Disorders.

BACKGROUND: Veterans face high risk for HIV and substance use, and thus could be disproportionately impacted by the HIV and substance use disorder (SUD) "syndemic." HIV prevalence among veterans with SUD is unknown. OBJECTIVE: To project HIV prevalence and lifetime HIV screening history among US veterans with alcohol use disorder (AUD), opioid use disorder (OUD), or both. DESIGN: We conducted a retrospective cohort analysis using national Veterans Health Administration (VHA) data. PARTICIPANTS: We selected three cohorts of veterans with SUD: (1) AUD, (2) OUD, and (3) AUD/OUD. Included veterans had ICD codes for AUD/OUD from 2016 to 2022 recorded in VHA electronic medical records, sourced from the VA Corporate Data Warehouse (CDW). MAIN MEASURES: We estimated HIV prevalence by dividing the number of veterans who met two out of three criteria (codes for HIV diagnosis, antiretroviral therapy, or HIV screening/monitoring) by the total number of veterans in each cohort. We also estimated lifetime HIV screening history (as documented in VHA data) by cohort. We reported HIV prevalence and screening history by cohort and across demographic/clinical subgroups. KEY RESULTS: Our sample included 669,595 veterans with AUD, 63,787 with OUD, and 57,015 with AUD/OUD. HIV prevalence was highest in the AUD/OUD cohort (3.9%), followed by the OUD (2.1%) and AUD (1.1%) cohorts. Veterans of Black race and Hispanic/Latinx ethnicity, with HCV diagnoses, and aged 50-64 had the highest HIV prevalence in all cohorts. Overall, 12.8%, 29.1%, and 33.1% of the AUD/OUD, OUD, and AUD cohorts did not have history of HIV screening, respectively. CONCLUSIONS: HIV prevalence was high in all SUD cohorts, and was highest among veterans with AUD/OUD, with disparities by race/ethnicity and age. A substantial portion of veterans had not received HIV screening in the VHA. Findings highlight room for improvement in HIV prevention and screening services for veterans with SUD.

Cancer diagnosis after emergency presentations in people with mental health and substance use conditions: a national cohort study.

BACKGROUND: Cancer survival and mortality outcomes for people with mental health and substance use conditions (MHSUC) are worse than for people without MHSUC, which may be partly explained by poorer access to timely and appropriate healthcare, from screening and diagnosis through to treatment and follow-up. Access and quality of healthcare can be evaluated by comparing the proportion of people who receive a cancer diagnosis following an acute or emergency hospital admission (emergency presentation) across different population groups: those diagnosed with cancer following an emergency presentation have lower survival. METHODS: National mental health service use datasets (2002-2018) were linked to national cancer registry and hospitalisation data (2006-2018), to create a study population of people aged 15 years and older with one of four cancer diagnoses: lung, prostate, breast and colorectal. The exposure group included people with a history of mental health/addiction service contact within the five years before cancer diagnosis, with a subgroup of people with a diagnosis of bipolar disorder, schizophrenia or psychotic disorders. Marginal standardised rates were used to compare emergency presentations (hospital admission within 30 days of cancer diagnosis) in the exposure and comparison groups, adjusted for age, gender (for lung and colorectal cancers), ethnicity, area deprivation and stage at diagnosis. RESULTS: For all four cancers, the rates of emergency presentation in the fully adjusted models were significantly higher in people with a history of mental health/addiction service use than people without (lung cancer, RR 1.19, 95% CI 1.13, 1.24; prostate cancer RR 1.69, 95% CI 1.44, 1.93; breast cancer RR 1.42, 95% CI 1.14, 1.69; colorectal cancer 1.31, 95% CI 1.22, 1.39). Rates were substantially higher in those with a diagnosis of schizophrenia, bipolar disorder or psychotic disorders. CONCLUSIONS: Implementing pathways for earlier detection and diagnosis of cancers in people with MHSUC could reduce the rates of emergency presentation, with improved cancer survival outcomes. All health services, including cancer screening programmes, primary and secondary care, have a responsibility to ensure equitable access to healthcare for people with MHSUC.

Risk for psychiatric and substance use disorders as a function of transitions in Sweden's public educational system: a national study.

BACKGROUND: To clarify, in a national sample, associations between risk for seven psychiatric and substance use disorders and five key transitions in Sweden's public educational system. METHODS: Swedish-born individuals (1972-1995, N = 1 997 910) were followed through 12-31-2018, at mean age 34.9. We predicted, from these educational transitions, risk for major depression (MD), obsessive-compulsive disorder (OCD), bipolar disorder (BD), schizophrenia (SZ), anorexia nervosa (AN), alcohol use disorder (AUD), and drug use disorder (DUD), assessed from Swedish national registers, by Cox regression, censoring individuals with onsets ⩽17. We also predicted risk from the deviation of grades from family-genetic expectations (deviation 1) and from changes in grades from ages 16 to 19 (deviation 2). RESULTS: We observed four major risk patterns across transitions in our disorders: (i) MD and BD, (ii) OCD and SZ, (iii) AUD and DUD, and (iv) AN. Failing early educational transitions had the greatest impact on risk for OCD and SZ while for other disorders, not progressing from basic to upper high school had the largest effect. Completing vocational v. college-prep upper high school was strongly associated with risk for AUD and DUD, had little relation with MD, OCD, BD, and SZ risk, and was protective for AN. Deviation 1 predicted risk most strongly for SZ, AN, and MD. Deviation 2 predicted risk most strongly for SZ, AUD, and DUD. CONCLUSIONS: The pattern of educational transitions and within family and within person development deviations are strongly and relatively specifically associated with future risk for seven psychiatric and substance-use disorders.

The predictive effect of family genetic risk scores as an indirect measure of causal effects of one disorder on another.

BACKGROUND: One potential cause of comorbidity is the direct causal effect of one disorder - A - on risk for subsequent onset of disorder B. Could genetic risk scores be utilized to test for such an effect? If disorder A causally impacts on risk for disorder B, then genetic risk for disorder A should be lower in cases of disorder A with v. without a prior onset of B. METHODS: In all individuals (n = 905 736) born in Sweden from 1980 to 1990, from six psychiatric and drug use disorders (major depression, anxiety disorders, alcohol use disorder, drug use disorder, bipolar disorder, and schizophrenia), we formed 14 pairs of disorders A and B. In these pairs, we compared, using Cox proportional hazards models, the predictive effect of the familial-genetic risk score (FGRS) for disorder B in those who had v. had not had a prior onset of disorder A. RESULTS: In all pairs, the impact of the FGRS for disorder B was significantly stronger in cases without v. with a prior history of disorder A. These effects were similar across sex, stable across levels of FGRS and not likely due to clinician bias. In many of our disorder pairs, previous clinical studies suggest a mechanism for a causal effect of disorder A on B. CONCLUSIONS: Our findings provide indirect evidence that the occurrence of one psychiatric or substance use disorder often has a causal effect on risk for subsequent disorders. This mechanism may substantially contribute to the widespread comorbidity among psychiatric conditions.

Is age of onset and duration of stimulant therapy for ADHD associated with cocaine, methamphetamine, and prescription stimulant misuse?

BACKGROUND: To assess whether age of onset and duration of stimulant therapy for attention-deficit/hyperactivity disorder (ADHD) are associated with cocaine, methamphetamine, and prescription stimulant misuse during adolescence. METHODS: Nationally representative samples of US 10th and 12th grade students (N = 150,395) from the Monitoring the Future study were surveyed via self-administered questionnaires from 16 annual surveys (2005-2020). RESULTS: An estimated 8.2% of youth received stimulant therapy for ADHD during their lifetime (n = 10,937). More than one in 10 of all youth reported past-year prescription stimulant misuse (10.4%)-past-year cocaine (4.4%) and methamphetamine (2.0%) use were less prevalent. Youth who initiated early stimulant therapy for ADHD (≤9 years old) and for long duration (≥6 years) did not have significantly increased adjusted odds of cocaine or methamphetamine use relative to population controls (ie, non-ADHD and unmedicated ADHD youth). Youth who initiated late stimulant therapy for ADHD (≥10 years old) and for short duration (<1 year) had significantly higher odds of past-year cocaine or prescription stimulant misuse in adolescence than those initiating early stimulant therapy for ADHD (≤9 years old) and for long duration (≥6 years). Youth who initiated late stimulant therapy for ADHD (≥10 years) for short duration (<1 year) had significantly higher odds of past-year cocaine, methamphetamine, and prescription stimulant misuse versus population controls during adolescence. No differences in past-year cocaine, methamphetamine, and prescription stimulant misuse were found between individuals who only used non-stimulant therapy for ADHD relative to youth who initiated early stimulant therapy (≤9 years old) and for long duration (≥6 years). CONCLUSIONS: An inverse relationship was found between years of stimulant therapy and illicit and prescription stimulant misuse. Adolescents with later initiation and/or shorter duration of stimulant treatment for ADHD should be monitored for potential illicit and prescription stimulant misuse.

Substance use outcomes from the Child/Adolescent Anxiety Multimodal Extended Long-term Study (CAMELS).

BACKGROUND: Substance use problems and anxiety disorders are both highly prevalent and frequently cooccur in youth. The present study examined the benefits of successful anxiety treatment at 3-12 years after treatment completion on substance use outcomes (i.e. diagnoses and lifetime expected use). METHODS: The sample was from the Child/Adolescent Anxiety Multimodal Extended Long-term Study (CAMELS), a naturalistic follow-up study to the Child/Adolescent Anxiety Multimodal Study (CAMS) which randomized youth to cognitive behavioral therapy (CBT; Coping cat), medication (sertraline), their combination, or pill placebo. The first CAMELS visit occurred an average of 6.5 years following CAMS randomization. Participants were 319 youth (65.4% of the CAMS sample), aged 7-17 years at CAMS baseline assessment with a mean age of 17.6 years (range: 11-26 years) at the time of the first CAMELS follow-up. Substance use outcomes included diagnoses as well as lifetime substance use (i.e. alcohol and tobacco use). RESULTS: Eleven of 319 (3.4%) CAMELS participants were diagnosed with a substance use disorder at the initial follow-up visit. When compared to the population lifetime rate of 11.4%, the rate of diagnoses in the posttreated sample was significantly lower. Additionally, rates of lifetime alcohol use were lower than population rates at the initial and final follow-up visits. Rates of lifetime tobacco use were similarly lower than lifetime population rates at the initial visit (driven by significantly lower rates in the CBT treatment condition), but higher by the final visit. Furthermore, treatment remission (but not treatment response) was associated with a lower rate of substance use diagnoses at the initial follow-up visit, although rates of lifetime alcohol and tobacco use did not differ by treatment outcome. CONCLUSIONS: Anxiety treatments confer a beneficial impact on problematic substance use (i.e. diagnoses) as well as on expected substance use (i.e. alcohol and tobacco use) for on average, a period of 6.5 years.

Preexposure Prophylaxis (PrEP) for HIV Prevention at Outpatient Substance Use Treatment Facilities, United States, 2021.

Objectives. To determine the percentage of US outpatient substance use treatment facilities that offer HIV preexposure prophylaxis (PrEP). Methods. We used a retrospective cross-sectional design with data from the National Substance Use and Mental Health Services Survey, which was administered to directors of US outpatient substance use treatment facilities in 2021. We evaluated the percentage of outpatient substance use treatment facilities offering PrEP and factors associated with the likelihood of offering PrEP. Results. We included 12 182 outpatient substance use treatment facilities. Of these, 637 (5.2%) offered PrEP. Offering HIV treatment (adjusted odds ratio [AOR] = 45.3; 95% confidence interval [CI] = 36.0, 56.9) and offering programs for LGBTQ (lesbian, gay, bisexual, transgender, and queer or questioning) people (AOR = 1.3; 95% CI = 1.0, 1.6) were associated with higher likelihoods of offering PrEP. Conclusions. PrEP is highly effective and recommended for patients at risk for HIV from injection drug use. Nearly 95% of US outpatient substance use treatment facilities did not offer PrEP-a missed opportunity for harm reduction through primary HIV prevention. Public Health Implications. Diversification of the array of available HIV PrEP options and the ongoing HIV and opioid use epidemics require outpatient substance use treatment facilities to expand PrEP availability. (Am J Public Health. 2024;114(8):833-837. https://doi.org/10.2105/AJPH.2024.307699).

Excess Fatal Overdoses in the United States During the COVID-19 Pandemic by Geography and Substance Type: March 2020-August 2021.

Objectives. To assess heterogeneity in pandemic-period excess fatal overdoses in the United States, by location (state, county) and substance type. Methods. We used seasonal autoregressive integrated moving average (SARIMA) models to estimate counterfactual death counts in the scenario that no pandemic had occurred. Such estimates were subtracted from actual death counts to assess the magnitude of pandemic-period excess mortality between March 2020 and August 2021. Results. Nationwide, we estimated 25 668 (95% prediction interval [PI] = 2811, 48 524) excess overdose deaths. Specifically, 17 of 47 states and 197 of 592 counties analyzed had statistically significant excess overdose-related mortality. West Virginia, Louisiana, Tennessee, Kentucky, and New Mexico had the highest rates (20-37 per 100 000). Nationally, there were 5.7 (95% PI = 1.0, 10.4), 3.1 (95% PI = 2.1, 4.2), and 1.4 (95% PI = 0.5, 2.4) excess deaths per 100 000 involving synthetic opioids, psychostimulants, and alcohol, respectively. Conclusions. The steep increase in overdose-related mortality affected primarily the southern and western United States. We identified synthetic opioids and psychostimulants as the main contributors. Public Health Implications. Characterizing overdose-related excess mortality across locations and substance types is critical for optimal allocation of public health resources. (Am J Public Health. 2024;114(6):599-609. https://doi.org/10.2105/AJPH.2024.307618).

Characteristics of Alcohol, Marijuana, and Other Drug Use Among Persons Aged 13-18 Years Being Assessed for Substance Use Disorder Treatment - United States, 2014-2022.

Substance use often begins during adolescence, placing youths at risk for fatal overdose and substance use disorders (SUD) in adulthood. Understanding the motivations reported by adolescents for using alcohol, marijuana, and other drugs and the persons with whom they use these substances could guide strategies to prevent or reduce substance use and its related consequences among adolescents. A cross-sectional study was conducted among adolescents being assessed for SUD treatment in the United States during 2014-2022, to examine self-reported motivations for using substances and the persons with whom substances were used. The most commonly reported motivation for substance use was "to feel mellow, calm, or relaxed" (73%), with other stress-related motivations among the top reasons, including "to stop worrying about a problem or to forget bad memories" (44%) and "to help with depression or anxiety" (40%); one half (50%) reported using substances "to have fun or experiment." The majority of adolescents reported using substances with friends (81%) or using alone (50%). These findings suggest that interventions related to reducing stress and addressing mental health concerns might reduce these leading motivations for substance use among adolescents. Education for adolescents about harm reduction strategies, including the danger of using drugs while alone and how to recognize and respond to an overdose, can reduce the risk for fatal overdose.

Modelling the progression of illicit substance use patterns from real-world evidence.

AIMS: To investigate an innovative pharmacometrics approach that addresses the challenges of using real-world evidence to model the progression of illicit substance use. METHODS: The modelling strategy analysed real-world data from the National Longitudinal Study of Adolescent to Adult Health (AddHealth) survey using survival analyses and differential equations. Respondents were categorized into drug-naïve, active users and nonusers. The transitions between categories were modelled using interval-censored parametric survival analysis. The resulting hazard rate functions were used as time-dependent rate constants in a differential equation system. Covariate models for sex and depression status were assessed. RESULTS: AddHealth enrolled 6504 American teenagers (median age 16 years, range 11-21 years); this cohort was followed with five interviews over a 22-year period; the median age at the last interview was 38 years (range 34-45 years). The percentages of illicit drug users at Interviews 1-5 were 7.7%, 5.9%, 15.8%, 21.4% and 0.98%, respectively. The generalized gamma distribution emerged as the preferred model for the survival functions for transitions between categories. Age-dependent prevalence was obtained from the differential equation system. Active drug use was more prevalent in males, increased in adolescence and college years, peaked at 24 years, and decreased to low levels by 35 years. Depression, which was more frequent in females, increased the drug-naïve-active user transition rates but not the active user-nonuser and nonuser-active user transition rates. The evidence did not support an interaction between sex and depression. CONCLUSIONS: The model provided a satisfactory approximation for the age-dependent progression of illicit substance use from preadolescence to early middle age.

Predictors of Receiving Mental Health Services in Trauma Patients With Positive Drug Screen.

INTRODUCTION: Initial interaction with health care system presents an important opportunity to provide substance use disorder (SUD) rehabilitation in the form of mental health services (MHSs). This study aims to identify predictors of receipt of MHSs among adult trauma patients with SUD and positive drug screen. METHODS: In this analysis of 2017-2021 American College of Surgeons-Trauma Quality Improvement Program (ACS TQIP), adult(≥18 y) patients with SUD and positive drug screen who survived the hospital admission were included. Outcomes measure was the receipt of MHS. Poisson regression analysis with clustering by facility was performed to identify independent predictors of receipt of MHS. RESULTS: 128,831 patients were identified of which 3.4% received MHS. Mean age was 41 y, 76% were male, 63% were White, 25% were Black, 12% were Hispanic, and 82% were insured. Median injury severity score was 9, and 54% were managed at an ACS level I trauma center. On regression analysis, female gender (aOR = 1.17, 95% CI = 1.09-1.25), age ≥65 y (aOR = 0.98, 95% CI = 0.97-0.99), White race (aOR = 1.37, 95% CI = 1.28-1.47), Hispanic ethnicity (aOR = 0.84, 95% CI = 0.76-0.93), insured status (aOR = 1.22, 95% CI = 1.13-1.33), and management at ACS level I trauma centers (aOR = 1.47, 95% CI = 1.38-1.57) were independent predictors of receipt of MHS. CONCLUSIONS: Race, ethnicity, and socioeconomic factors predict the receipt of MHS in trauma patients with SUD and positive drug screens. It is unknown if these disparities affect the long-term outcomes of these vulnerable patients. Further research is warranted to expand on the contributing factors leading to these disparities and possible strategies to address them.