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INTRODUCTION: Estimates of the prevalence of drug-related out of hospital cardiac arrest (OHCA) vary, ranging from 1.8% to 10.0% of medical OHCA. However, studies conducted prior to the recent wave of fentanyl deaths likely underestimate the current prevalence of drug-related OHCA. We evaluated recent trends in drug-related OHCA, hypothesizing that the proportion of presumed drug-related OHCA treated by emergency medical services (EMS) has increased since 2015. METHODS: We conducted a retrospective analysis of OHCA patients treated by EMS providers in San Francisco, California between 2015 and 2023. Participants included OHCA cases in which resuscitation was attempted by EMS. The study exposure was the year of arrest. Our primary outcome was the occurrence of drug-related OHCA, defined as the EMS impression of OHCA caused by a presumed or known overdose of medication(s) or drug(s). RESULTS: From 2015 to 2023, 5044 OHCA resuscitations attended by EMS (average 561 per year) met inclusion criteria. The median age was 65 (IQR 50-79); 3508 (69.6%) were male. The EMS impression of arrest etiology was drug-related in 446/5044 (8.8%) of OHCA. The prevalence of presumed drug-related OHCA increased significantly each year from 1% in 2015 to 17.6% in 2023 (p-value for trend = 0.0001). After adjustment, presumed drug-related OHCA increased by 30% each year from 2015-2023. CONCLUSION: Drug-related OHCA is an increasingly common etiology of OHCA. In 2023, one in six OHCA was presumed to be drug related. Among participants less than 60 years old, one in three OHCA was presumed to be drug related.

Fentanyl-mixed and substituted heroin is well-documented, but less is known about unintentional fentanyl use among people using stimulants. To determine the prevalence of and racial and ethnic disparities in unintentional fentanyl use among people experiencing a medically attended opioid overdose, we reviewed 448 suspected non-fatal overdose cases attended by a community paramedic overdose response team in San Francisco from June to September 2022. We applied a case definition for opioid overdose to paramedic records and abstracted data on intended substance use prior to overdose. Among events meeting case criteria with data on intended substance use, intentional opioid use was reported by 57.3%, 98.0% of whom intended to use fentanyl. No intentional opioid use was reported by 42.7%, with most intending to use stimulants (72.6%), including methamphetamine and cocaine. No intentional opioid use was reported by 58.5% of Black, 52.4% of Latinx, and 28.8% of White individuals (p = 0.021), and by 57.6% of women and 39.5% of men (p = 0.061). These findings suggest that unintentional fentanyl use among people without opioid tolerance may cause a significant proportion of opioid overdoses in San Francisco. While intentional fentanyl use might be underreported, the magnitude of self-reported unintentional use merits further investigation to confirm this phenomenon, explore mechanisms of use and disparities by race and ethnicity, and deploy targeted overdose prevention interventions.

Severe cases of hydrocarbon aspiration requiring Extracorporeal Membrane Oxygenation (ECMO) are rarely reported in pediatrics, and 90% of hospitalized patients have a relatively benign clinical course. We describe a 14 month-old female with accidental hydrocarbon ingestion and aspiration due to organic makeup brush cleaner that suffered severe ARDS and multiorgan failure, successfully managed with ECMO and surfactant. She was decannulated after a total of 72 hours on ECMO, extubated on hospital day 15 (HD 15), and discharged home in her normal state of health after one month in the hospital. ECMO and adjunctive therapies such as surfactant may be helpful in the management of severe hydrocarbon pneumonitis and there are limited reports of ECMO as a supportive method for these pediatric patients.

IntroductionDeaths from drug overdoses are rising dramatically in the United States. Treatment for opioid use disorders may include behavioral treatments as well as medications for opioid use disorders (MOUD). Buprenorphine can be prescribed by physicians, nurse practitioners (NPs), other advanced practice registered nurses (APRNs), and physician assistants (PAs) and required a training and a federal waiver until recently. The number of NP MOUD prescribers grew steadily over the past decade, but research has identified state-level scope of practice regulations as a barrier to NP MOUD prescribing. This article explores the contributions of, and remaining barriers faced by NP and other APRN MOUD prescribers. We describe qualitative findings from a study of NPs and other key stakeholders involved in MOUD treatment in four states with two differing levels of regulatory structure.MethodsIn this qualitative study, we conducted site visits and semi-structured interviews with NPs and other APRNs, physicians, clinic managers, and regulators in four states including New Mexico and West Virginia (full practice authority for NPs), and Ohio and Michigan (which require physician supervision). Interview notes were entered into a qualitative software package and coded and reviewed by two members of the research team. Data were grouped into key themes.ResultsA total of 76 participants participated in individual or small group interviews in the four states. We found key themes and several subthemes that describe NP practice in MOUD. Participants described key contributions of NP engagement in MOUD, including increasing access, serving rural areas, the unique role of psychiatric NPs, and the value of the nursing model of care in working with people with substance use disorders (SUD). Participants also identified barriers including scope of practice regulations, other regulatory barriers, stigma, and lack of supportive services to address psychosocial needs.ConclusionsThe waiver requirements were eliminated at the end of 2022 in federal budget legislation. Other barriers for NP and other APRN prescribers remain and should be addressed in practice, and in state and federal regulations. Research needs to explore the impact of the waiver elimination on MOUD prescribing and access to services.

BACKGROUND: Both increases and decreases in patients prescribed daily opioid dose have been linked to increased overdose risk, but associations between 30-day dose trajectories and subsequent overdose risk have not been systematically examined. OBJECTIVE: To examine the associations between 30-day prescribed opioid dose trajectories and fatal opioid overdose risk during the subsequent 15 days. DESIGN: Statewide cohort study using linked prescription drug monitoring program and death certificate data. We constructed a multivariable Cox proportional hazards model that accounted for time-varying prescription-, prescriber-, and pharmacy-level factors. PARTICIPANTS: All patients prescribed an opioid analgesic in California from March to December, 2013 (5,326,392 patients). MAIN MEASURES: Dependent variable: fatal drug overdose involving opioids. Primary independent variable: a 16-level variable denoting all possible opioid dose trajectories using the following categories for current and 30-day previously prescribed daily dose: 0-29, 30-59, 60-89, or ≥90 milligram morphine equivalents (MME). KEY RESULTS: Relative to patients prescribed a stable daily dose of 0-29 MME, large (≥2 categories) dose increases and having a previous or current dose ≥60 MME per day were associated with significantly greater 15-day overdose risk. Patients whose dose decreased from ≥90 to 0-29 MME per day had significantly greater overdose risk compared to both patients prescribed a stable daily dose of ≥90 MME (aHR 3.56, 95%CI 2.24-5.67) and to patients prescribed a stable daily dose of 0-29 MME (aHR 7.87, 95%CI 5.49-11.28). Patients prescribed benzodiazepines also had significantly greater overdose risk; being prescribed Z-drugs, carisoprodol, or psychostimulants was not associated with overdose risk. CONCLUSIONS: Large (≥2 categories) 30-day dose increases and decreases were both associated with increased risk of fatal opioid overdose, particularly for patients taking ≥90 MME whose opioids were abruptly stopped. Results align with 2022 CDC guidelines that urge caution when reducing opioid doses for patients taking long-term opioid for chronic pain.

BACKGROUND: The overdose crisis driven by synthetic opioids continues to escalate in the USA. We evaluated the efficacy of multiple manufacturing lots of a fentanyl test strip (FTS) to detect fentanyl and fentanyl analogs and assessed cross-reactivity with possible interferences. METHODS: Drug standards were dissolved in water in a laboratory setting and serially diluted. Drug dilutions were tested using five different manufacturing lots of BTNX Rapid Response (20 ng/mL cutoff) lateral flow chromatographic immunoassay strips to assess lot-to-lot variability for FTS sensitivity and cross-reactivity for the analytes of interest. RESULTS: All five manufacturing lots cross-reacted with fentanyl and eleven fentanyl analogs. Diphenhydramine, lidocaine, MDMA, and methamphetamine were found to cause false positives with the strips. There was notable lot-to-lot variability in the sensitivity of the strips for fentanyl, fentanyl analogs, and known interferences. DISCUSSION: FTS remains an important overdose prevention tool, but lot-to-lot variability in performance complicates robust instructions that balance the prevention of false positives and false negatives. Continued lot-to-lot performance assessment is recommended to ensure health education for FTS remains accurate. More sophisticated drug checking technologies and services are needed in the community landscape to augment personal FTS use to facilitate informed consumption and overdose risk mitigation.

BACKGROUND: Illicitly manufactured fentanyls and stimulants are implicated in the escalating US mortality from drug overdose. San Francisco, California (SF) has seen declining fentanyl injection while smoking has increased. Beliefs and behaviors surrounding this development are not well understood. METHODS: The study used rapid ethnography to explore fentanyl and methamphetamine use in SF. The team conducted semi-structured interviews (n = 34) with participants recruited from syringe service programs. Video-recorded smoking sequences (n = 12), photography and daily field notes supplemented interview data. RESULTS: Difficulty injecting and fear of overdose motivated transitions from injecting to smoking. Fentanyl was extremely cheap-$10/gram-with variability in quality. Foil was the most commonly used smoking material but glass bubbles, bongs and dabbing devices were also popular. No reliable visible methods for determining fentanyl quality existed, however, participants could gauge potency upon inhalation, and developed techniques to regulate dosage. Several participants reported at least hourly use, some reporting one or more grams of daily fentanyl consumption. Smoking was also very social, with people sharing equipment, drugs and information. Participants raised concerns about hygiene and overdose risk to others arising from shared equipment. Reportedly potent fentanyl residue accumulated on smoking materials and was commonly shared/traded/stolen or consumed accidentally with diverse preferences for its use. CONCLUSION: Our data highlight fentanyl residue as a new overdose risk with potential mismatch between the potency of the residual drug and the recipients tolerance. Further, large doses of fentanyl are being consumed (estimated at approximately 50 mg of pure fentanyl/day). Smoking fentanyl has potential health benefits over injecting and may be protective against overdose, but substantial uncertainty exists. However, SF overdose mortality hit a record high in 2023. Recommendations to reduce fentanyl smoking overdose risks through pacing, greater awareness of dosages consumed and checking tolerance of residue recipients are potentially viable interventions deserving further exploration.

BackgroundMortality related to opioid overdose in the U.S. has risen sharply in the past decade. In California, opioid overdose death rates more than tripled from 2018 to 2021, and deaths from synthetic opioids such as fentanyl increased more than seven times in those three years alone. Heightened attention to this crisis has attracted funding and programming opportunities for prevention and harm reduction interventions. Drug checking services offer people who use drugs the opportunity to test the chemical content of their own supply, but are not widely used in North America. We report on qualitative data from providers and clients of harm reduction and drug checking services, to explore how these services are used, experienced, and considered.MethodsWe conducted in-depth semi-structured key informant interviews across two samples of drug checking stakeholders: "clients" (individuals who use drugs and receive harm reduction services) and "providers" (subject matter experts and those providing clinical and harm reduction services to people who use drugs). Provider interviews were conducted via Zoom from June-November, 2022. Client interviews were conducted in person in San Francisco over a one-week period in November 2022. Data were analyzed following the tenets of thematic analysis.ResultsWe found that the value of drug checking includes but extends well beyond overdose prevention. Participants discussed ways that drug checking can fill a regulatory vacuum, serve as a tool of informal market regulation at the community level, and empower public health surveillance systems and clinical response. We present our findings within three key themes: (1) the role of drug checking in overdose prevention; (2) benefits to the overall agency, health, and wellbeing of people who use drugs; and (3) impacts of drug checking services at the community and systems levels.ConclusionThis study contributes to growing evidence of the effectiveness of drug checking services in mitigating risks associated with substance use, including overdose, through enabling people who use and sell drugs to test their own supply. It further contributes to discussions around the utility of drug checking and harm reduction, in order to inform legislation and funding allocation.

This protocol outlines a proposed scoping review to characterize evidence on implementation and quality improvement (QI) strategies that aim to improve equitable, evidence-informed care delivery for pregnant and birthing people with substance use disorder (SUD) in acute care. Untreated SUD during pregnancy is associated with an increased risk of overdose and severe maternal morbidity. Acute care settings are one important place to deliver equitable, evidence-informed clinical care. While clinical practice guidelines for substance use treatment and care of pregnant and birthing people with SUD exist, there are gaps in implementation. Our population of interest is pregnant and birthing people with SUD in an acute care setting. We will include US-based studies that describe or evaluate implementation or QI strategies, including experimental, observational, and descriptive studies published from 2016 to 2023. The proposed scoping review will be conducted in accordance with JBI methodology for scoping reviews and registered at OSF (registration number: BC4VZ). We will search MEDLINE (PubMed), CINAHL Complete (EBSCO), Scopus (Elsevier), and APA PsychInfo (Ovid) for published studies. Conference proceedings and Perinatal Quality Collaborative websites will be searched for grey literature. Two reviewers will independently screen then extract studies that meet inclusion criteria using a data extraction tool. The completion of this scoping review will help illuminate strengths and gaps in research and practice that aim to inform substance use treatment and care in acute care settings for pregnant and birthing people with SUD.

BackgroundAgainst the backdrop of North America's overdose crisis, most overdose deaths are occurring in housing environments, largely due to individuals using drugs alone. Overdose deaths in cities remain concentrated in marginal housing environments (e.g., single-room occupancy housing, shelters), which are often the only forms of housing available to urban poor and drug-using communities. This commentary aims to highlight current housing-based overdose prevention interventions and to situate them within the broader environmental contexts of marginal housing. In doing so, we call attention to the need to better understand marginal housing as sites of overdose vulnerability and public health intervention to optimize responses to the overdose crisis.Harm reduction and overdose prevention in housingIn response to high overdose rates in marginal housing environments several interventions (e.g., housing-based supervised consumption rooms, peer-witnessed injection) have recently been implemented in select jurisdictions. However, even with the growing recognition of marginal housing as a key intervention site, housing-based interventions have yet to be scaled up in a meaningful way. Further, there have been persistent challenges to tailoring these approaches to address dynamics within housing environments. Thus, while it is critical to expand coverage of housing-based interventions across marginal housing environments, these interventions must also attend to the contextual drivers of risks in these settings to best foster enabling environments for harm reduction and maximize impacts.ConclusionEmerging housing-focused interventions are designed to address key drivers of overdose risk (e.g., using alone, toxic drug supply). Yet, broader contextual factors (e.g., drug criminalization, housing quality, gender) are equally critical factors that shape how structurally vulnerable people who use drugs navigate and engage with harm reduction interventions. A more comprehensive understanding of these contextual factors within housing environments is needed to inform policy and programmatic interventions that are responsive to the needs of people who use drugs in these settings.

Objective Design Setting Animals Interventions Measurements and Main Results Conclusions To determine and compare the efficacy of intranasal (IN) atomization, IN drops, and IM injection of atipamezole for reversal of medetomidine‐induced sedation in healthy dogs.Prospective, randomized, blinded study.University teaching hospital.Forty mixed‐breed, shelter‐owned dogs with an average weight of 29.9 ± 5.6 kg (mean ± SD) that required sedation for minor diagnostic or therapeutic procedures.Atipamezole was administered by a dog handler at 200 µg/kg via IN atomization (ATI‐INA, n = 10), IN drops (ATI‐IND, n = 10), or IM injection (ATI‐IM, n = 10) 20 minutes following medetomidine administration (40 µg/kg). A control group (n = 10) received no atipamezole.Ease of atipamezole administration was evaluated. Sedation score, heart rate (HR), respiratory rate (RR), and blood pressure (BP) were recorded pre‐medetomidine administration (T0), pre‐atipamezole administration (T20), and at multiple intervals following atipamezole administration. ATI‐IM resulted in the fastest recovery, followed by ATI‐INA, with ATI‐IND being the slowest. The adverse cardiovascular impacts of medetomidine were not completely mitigated. ATI‐IM showed initial HR restoration followed by a decline. HR in both IN groups showed a slower increase compared to ATI‐IM, but no subsequent decline was observed. ATI‐IM resulted in a transient decrease in BP, though dogs remained normotensive. A gradual reduction in BP was noted in the IN groups. At T50, RR of all atipamezole groups differed from control, and a significant increase in RR was observed in ATI‐IM dogs compared to pre‐atipamezole value. No adverse effects were observed.All routes for atipamezole administration effectively reversed medetomidine‐induced sedation, with ATI‐IM being fastest. IN routes were easy for the dog handler to administer, making them viable alternatives in cases of accidental drug exposure, particularly outside a hospital setting. [ABSTRACT FROM AUTHOR]

Aims Design Setting Cases Measurements Findings Conclusion To determine the contribution that variation in the unregulated drug market has on the risk of heroin overdose across individuals with different levels of personal overdose risk.A retrospective cohort study of heroin injecting episodes and overdose cases were examined over a 12‐month period between 30 June 2022 and 30 June 2023.The Medically Supervised Injecting Room in Melbourne, Australia.1474 witnessed heroin overdose cases were examined amongst a cohort of 337 individuals who were predominantly male (n = 276, 81.7%) with a median age of 43.5 years (interquartile range 37.25–49.00 years, range 20–75 years).The daily overdose rate was used to differentiate High and Low daily overdose risk categories. The number of overdose events that an individual experienced during the study period was used to differentiate people into Standard, Moderate and High personal overdose risk categories. Each overdose case was differentiated by the personal overdose risk of the individual who experienced the overdose, as well as the overdose risk of the day that overdose occurred. A stratified overdose risk profile was then derived across the nine different daily overdose risk and personal overdose risk categories.The rate of overdose approximately doubled on High overdose risk days compared with Standard overdose risk days, increasing by a factor of 2.11, 2.41 and 2.03 times for individuals in the Standard, Moderate and High personal overdose risk groups. Conversely, the rate of overdose was also substantially reduced on Low overdose risk days to a factor of 0.17, 0.28 and 0.20, respectively.Among heroin users in Melbourne, Australia, there is an approximately 10‐times difference in the risk of overdose on some days compared with others, which appears to be attributable to the effects of the unregulated drug market and not the effects of variation in personal overdose risk of individuals. [ABSTRACT FROM AUTHOR]

The letter to the editor responds to a study by West et al. on counterfeit opioid analgesic products, highlighting the public health challenges posed by the rise in suspected counterfeit opioid exposures, particularly involving synthetic opioids like fentanyl. The study found that 23.7% of opioid analgesic abuse exposures in 2021 involved counterfeit opioids, with younger males disproportionately affected. The authors suggest further exploration and refinement of predictive models to improve public health interventions targeting the risks associated with counterfeit opioids. [Extracted from the article]

Introduction: Emergency medical services (EMS) systems are piloting interventions to respond to overdoses with additional services such as leave‐behind naloxone and medication for opioid use disorder, but little is known about the perspectives of people who use drugs (PWUD) on these interventions being delivered by EMS during an overdose response. Methods: The Consolidated Framework for Implementation Research guided the development of data collection tools, the analytic strategy and the organisation of results. A community engaged method was used which included both academically trained researchers and community trained researchers who are also PWUD. This study used semi‐structured interviews to gather data from 13 PWUD in King County, Washington in June 2022. Data were analysed using thematic analysis. Results: The people interviewed for this study viewed EMS distribution of leave‐behind naloxone and field‐based buprenorphine favourably. They viewed EMS facilitation of hepatitis C virus and HIV testing in the field less favourably and were concerned about stigmas associated with those results. Additional themes emerged regarding: the need for different approaches to post‐overdose care; the need for new services, including post‐overdose trauma counselling and an alternative destination to the emergency department; and the harms of law enforcement presence at overdose responses. Discussion and Conclusions: This study found strong support for leave‐behind naloxone and field‐initiated buprenorphine. Further training for EMS should include trauma‐informed care and strategies to address burnout and increase compassion. Alternatives to the emergency department as a post‐overdose destination are needed. These strategies should be considered by jurisdictions revising overdose response protocols. [ABSTRACT FROM AUTHOR]

Introduction: There has been a significant increase in methamphetamine/amphetamine use in North America, particularly among people who use opioids. Despite its association with several negative health consequences, the population of people who use methamphetamine/amphetamine with opioids is not well characterised. The aim of this study was to investigate correlates of methamphetamine/amphetamine use among adults with prescription‐type opioid use disorder (POUD) starting methadone or buprenorphine/naloxone as part of a pragmatic randomised treatment trial in Canada. Methods: Multivariable logistic regression analyses were used to determine factors associated with baseline methamphetamine/amphetamine use (measured by urine drug test [UDT]) among participants of a pan‐Canadian pragmatic trial conducted between 2017 and 2020 comparing supervised methadone versus flexible take‐home dosing buprenorphine/naloxone models of care in people with POUD (e.g., licit or illicit, including fentanyl, prescribed or not). Results: The sample included 269 participants, of which 142 (52.8%) had positive baseline methamphetamine/amphetamine UDT. In the multivariable model, positive fentanyl UDT (adjusted odds ratio [AOR] 13.21, 95% confidence interval [CI] 6.45, 28.30), non‐fatal overdose in the last 6 months (AOR 2.26, CI 1.01, 5.17) and a lifetime history of opioid agonist therapy exposure prior to study entry (AOR 2.30, CI 1.09, 4.87) remained positively associated with baseline methamphetamine/amphetamine use. Discussion and Conclusions: In this sample of people with POUD, methamphetamine/amphetamine use was associated with markers of complex and severe OUD, including overdose risk. This suggests the need for targeted interventions to optimise treatment outcomes and prevent future overdoses in this population. Clinical Trial Registration: Available at: ClinicalTrials.gov NCT03033732. [ABSTRACT FROM AUTHOR]

Suicide remains a leading cause of death in the United States, and recent data suggest suicide deaths involving opioids are increasing. Given unprecedented increases in drug-poisoning deaths, suicidality, and suicide deaths in recent years, an updated examination of the trends in suicide deaths involving opioids is warranted. In this descriptive epidemiologic analysis, we leverage final and provisional mortality data from the US Centers for Disease Control and Prevention's WONDER database to examine trends in suicide deaths involving opioid poisoning from 1999 to 2021 by biological sex. Results reveal complex changes over time: the number and age-adjusted rate of suicide deaths involving opioid poisoning among male and female residents tended to track together, and both increased through 2010, but then diverged, with the number and rate of suicide deaths involving opioid poisoning among female residents outpacing that of male residents. However, the number and rate of suicide deaths involving opioid poisoning among male residents then began to stabilize, while that of female residents declined, closing the sex-based gap. Across all years of data, the proportion of suicide deaths that involved opioid poisoning was consistently higher among female decedents (5.8%-11.0%) compared with male decedents (1.4%-2.8%). Findings have implications for improved suicide prevention and harm reduction efforts. This article is part of a Special Collection on Mental Health. [ABSTRACT FROM AUTHOR]

This is the first clinical practice guideline (CPG) from the American Academy of Pediatrics outlining evidence-based approaches to safely prescribing opioids for acute pain in outpatient settings. The central goal is to aid clinicians in understanding when opioids may be indicated to treat acute pain in children and adolescents and how to minimize risks (including opioid use disorder, poisoning, and overdose). The document also seeks to alleviate disparate pain treatment of Black, Hispanic, and American Indian/Alaska Native children and adolescents, who receive pain management that is less adequate and less timely than that provided to white individuals. There may also be disparities in pain treatment based on language, socioeconomic status, geographic location, and other factors, which are discussed. The document recommends that clinicians treat acute pain using a multimodal approach that includes the appropriate use of nonpharmacologic therapies, nonopioid medications, and, when needed, opioid medications. Opioids should not be prescribed as monotherapy for children or adolescents who have acute pain. When using opioids for acute pain management, clinicians should prescribe immediate-release opioid formulations, start with the lowest age- and weight-appropriate doses, and provide an initial supply of 5 or fewer days, unless the pain is related to trauma or surgery with expected duration of pain longer than 5 days. Clinicians should not prescribe codeine or tramadol for patients younger than 12 years; adolescents 12 to 18 years of age who have obesity, obstructive sleep apnea, or severe lung disease; to treat postsurgical pain after tonsillectomy or adenoidectomy in patients younger than 18 years; or for any breastfeeding patient. [ABSTRACT FROM AUTHOR]

Psychedelics have long been used by individuals seeking peace and a sense of wellness. This article examines widespread adoption of ketamine as a proxy for psychedelics. For ketamine, there is a need to protect vulnerable persons from exploitation that should be balanced against risks of hypermedicalization. This article suggests strategies for striking such a balance, including by carefully differentiating between persons with psychiatric illnesses, such as treatment-resistant depression, who could benefit from psychedelics, and persons using psychedelics for peace and wellness under careful guidance. [ABSTRACT FROM AUTHOR]

AbstractIntroductionMethodsResultsDiscussionConclusionWhile factors like high serum paracetamol (acetaminophen) concentration and delayed acetylcysteine treatment increase hepatotoxicity risk, existing predictive tools, such as the paracetamol concentration aminotransferase activity multiplication product and the psi (ψ) parameter, lack definitive accuracy. This study evaluated the paracetamol psi parameter multiplication product addition against the psi parameter and the paracetamol concentration aminotransferase activity multiplication product for predicting hepatotoxicity following an acute paracetamol overdose.A retrospective analysis of patients with acute paracetamol overdose from January 2007 to December 2016 was conducted. The paracetamol psi parameter multiplication product addition, calculated by summing the psi parameter (mmol/L × h) and the paracetamol concentration aminotransferase activity multiplication product (g U/L2), was used. Hepatotoxicity was defined as aspartate or alanine aminotransferase activities ≥1,000 U/L. Diagnostic accuracy was assessed through sensitivity, specificity, the area under the receiver operating characteristic curve, and their corresponding 95% CI, with the optimal cutoff determined using the maximum Youden index method.The study comprised 421 patients, mostly female (82.9%) with a median age of 23 years. Hepatotoxicity occurred in 13.5% (57 patients). The paracetamol psi parameter multiplication product addition showed an area under the receiver operating characteristic curve of 0.989 (95% CI: 0.974–0.997), with an optimal cutoff at 9.723, providing 96.5% sensitivity and 97.3% specificity. The paracetamol psi parameter multiplication product addition demonstrated superior performance in area under the receiver operating characteristic curve compared to the individual assessments of the psi parameter (0.916; 95% CI: 0.885–0.941) and the paracetamol concentration aminotransferase activity multiplication product (0.901; 95% CI: 0.868–0.928).The paracetamol psi parameter multiplication product addition appears to be a more effective diagnostic tool than the psi parameter or the paracetamol concentration aminotransferase activity multiplication product alone.Incorporating the paracetamol psi parameter multiplication product addition into clinical protocols could improve paracetamol overdose management by enabling precise identification of individuals at heightened risk for hepatotoxicity, thereby facilitating the customization of treatment approaches. [ABSTRACT FROM AUTHOR]