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The opioid overdose epidemic has rapidly expanded in North America, with rates accelerating during the COVID-19 pandemic. No existing study has demonstrated prospective opioid overdose at a population level. This study aimed to develop and validate a population-level individualized prospective prediction model of opioid overdose (OpOD) using machine learning (ML) and de-identified provincial administrative health data. The OpOD prediction model was based on a cohort of approximately 4 million people in 2017 to predict OpOD cases in 2018 and was subsequently tested on cohort data from 2018, 2019, and 2020 to predict OpOD cases in 2019, 2020, and 2021, respectively. The model's predictive performance, including balanced accuracy, sensitivity, specificity, and area under the Receiver Operating Characteristics Curve (AUC), was evaluated, achieving a balanced accuracy of 83.7, 81.6, and 85.0% in each respective year. The leading predictors for OpOD, which were derived from health care utilization variables documented by the Canadian Institute for Health Information (CIHI) and physician billing claims, were treatment encounters for drug or alcohol use, depression, neurotic/anxiety/obsessive-compulsive disorder, and superficial skin injury. The main contribution of our study is to demonstrate that ML-based individualized OpOD prediction using existing population-level data can provide accurate prediction of future OpOD cases in the whole population and may have the potential to inform targeted interventions and policy planning.
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http://dx.doi.org/10.1038/s41380-025-02992-4 | DOI Listing |
J Sch Health
September 2025
Brigham and Women's Hospital, Boston, Massachusetts, USA.
Background: The opioid crisis continues to claim lives across the United States, which has led to increased attention toward harm reduction strategies as methods for addressing this public health issue. Specifically, naloxone, an opioid overdose reversal drug, became available over-the-counter in 2023, greatly improving its accessibility. However, despite this progress, general awareness about how to use naloxone remains limited, especially among youth who are being increasingly impacted by the opioid epidemic.
View Article and Find Full Text PDFJ Opioid Manag
September 2025
Retired Addiction Physician and Psychiatrist, London SE1, United Kingdom. ORCID: https://orcid.org/0000-0002-5035-5833.
Despite the contribution of the µ-agonist fentanyl to the United States's opiate overdose epidemic, no human studies specifically address the ability of extended-release preparations of the opiate antagonist naltrexone (NTX) to block fentanyl's life-threatening µ-agonist-mediated respiratory depression. This paper presents three case histories of clinically necessary opiate challenges in opiate-abusing patients implanted with extended-release NTX (ER-NTX). It also reviews the sparse literature and is the first evidence that antagonist blood levels from ER-NTX preparations can completely block the lethal µ-agonist effects of at least 1,000 mcg of intravenous fentanyl.
View Article and Find Full Text PDFJ Opioid Manag
September 2025
HCA Florida Westside Hospital, Davie, Florida. ORCID: https://orcid.org/0009-0006-5906-983X.
Opioids are known to come with some relatively benign side effects, not including their addictive potential. This review will look at some of the side effects that occur when patients, especially chronic pain patients, take opioids chronically. These side effects include both hyperalgesia and allodynia caused by opioids.
View Article and Find Full Text PDFBackground Fentanyl is a potent synthetic opioid widely used for pain management and anesthesia, but the high prevalence of its misuse and its key contribution to overdose fatalities in the United States have made it a major drug of concern. Although fentanyl's onset, duration, and toxicity depend on its pharmacokinetics and specific tissue distribution, most studies have focused primarily on plasma concentrations, leaving its distribution in critical tissues largely unexplored (this knowledge gap limits our understanding of fentanyl's clinical effects, tissue accumulation, and the factors influencing its efficacy and safety). Here, we report the radiosynthesis of [ C]fentanyl for PET imaging and present a preliminary whole-body pharmacokinetic study in rodents.
View Article and Find Full Text PDFAm J Epidemiol
September 2025
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Non-dihydropyridine calcium channel blockers (CCBs), including diltiazem and verapamil, inhibit cytochrome P450 3A4 (CYP3A4), an enzyme involved in the metabolism of hydrocodone, the most commonly used opioid in the United States (US). This study evaluated whether concomitant use of hydrocodone with CYP3A4-inhibiting CCBs increases the risk of opioid overdose compared to use of hydrocodone with amlodipine, a CCB that does not inhibit CYP3A4. Using three US databases (2000-2021), two cohorts were identified: (1) hydrocodone initiation while on CCB; and (2) CCB initiation while on hydrocodone.
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