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Introduction: The increasing presence of counterfeit opioid drugs in the United States can contaminate data collection systems and confound estimates derived from surveillance of the opioid epidemic. Data sources and analyses that can quantify the contribution of counterfeit opioid products are needed to provide accurate and timely data to inform public health responses. We describe a novel approach to identify and quantify intentional abuse and misuse exposures involving suspected counterfeit opioid products in United States poison center data. Methods: An ecological study was performed using data, including narrative case notes, reported to participating United States Poison Centers of the Researched Abuse, Diversion and Addiction Related Surveillance System between 2009-Quarter 1 and 2021-Quarter 4. A machine learning natural language processing approach was used to develop a predictive model. Results: Sensitivity for detecting suspected non-counterfeit-involved exposures by the predictive model was 92%, specificity was 73%, and the area under the receiver operating characteristic curve was 92%. Overall, only 2.1% of intentional abuse and misuse exposure calls were predicted to be suspected counterfeit-involved during 2009–2021; however, we observed an exponential increase in suspected counterfeit exposures over this time period. There was a 7-fold increase in the estimated number of suspected counterfeit exposures from 2009 to 2021, and 23.7% of all opioid analgesic intentional abuse and misuse exposures were suspected counterfeit-involved in 2021. Discussion: We demonstrate the feasibility and reliability of using machine learning natural language processing to identify exposures involving suspected counterfeit opioid products in United States poison center data. Results suggest that suspected counterfeits have had a meaningful influence on rates of intentional abuse exposures to opioid analgesics in more recent years. Conclusions: The increasing presence of counterfeit opioid drugs can contaminate data collection systems and compromise the reliability of the data. [ABSTRACT FROM AUTHOR]

Introduction: Recent decades have witnessed an extraordinary global crisis of drug misuse. Although opioid analgesics receive the most attention, numerous other drugs have increased rates of misuse. Ketamine and esketamine: Ketamine and esketamine offer a unique natural experiment to explore two medications that are similar pharmacologically but differ in their availability to users and in their regulation by government agencies. Misuse and abuse of ketamine and esketamine: Multisystem "mosaic" surveillance of many drugs using real-world data has emerged in recent years. Ketamine and esketamine have been monitored concurrently. Ketamine is much more widely available than esketamine and shows clear signs of increasing misuse and abuse. In contrast, esketamine is difficult to detect in postmarket surveillance even though availability is increasing. Discussion: Ketamine and esketamine offer insights regarding the safety of prescription medications with the potential for misuse. Since the pharmacology of ketamine and esketamine are similar, the regulatory apparatus may be the primary difference that limits misuse. Ketamine has few restrictions and can be prescribed or administered by many healthcare providers, and is available as an illicit drug. In contrast, the product labeling for esketamine has rigorous restrictions on its use. Many important issues remain to be addressed. We need a more rigorous evaluation of the natural experiment of ketamine and esketamine. How does this experience relate to the introduction of new psychedelics? Conclusions: Ketamine misuse use and misuse are increasing while esketamine use in increasing, but misuse is not increasing. It is reasonable to reevaluate the regulatory controls on ketamine to reduce its misuse and abuse. [ABSTRACT FROM AUTHOR]

BackgroundEnvenomation by crotaline snakes (rattlesnake, cottonmouth, copperhead) is a complex, potentially lethal condition affecting thousands of people in the United States each year. Treatment of crotaline envenomation is not standardized, and significant variation in practice exists.MethodsA geographically diverse panel of experts was convened for the purpose of deriving an evidence-informed unified treatment algorithm. Research staff analyzed the extant medical literature and performed targeted analyses of existing databases to inform specific clinical decisions. A trained external facilitator used modified Delphi and structured consensus methodology to achieve consensus on the final treatment algorithm.ResultsA unified treatment algorithm was produced and endorsed by all nine expert panel members. This algorithm provides guidance about clinical and laboratory observations, indications for and dosing of antivenom, adjunctive therapies, post-stabilization care, and management of complications from envenomation and therapy.ConclusionsClinical manifestations and ideal treatment of crotaline snakebite differ greatly, and can result in severe complications. Using a modified Delphi method, we provide evidence-informed treatment guidelines in an attempt to reduce variation in care and possibly improve clinical outcomes.

BackgroundBetween 2016 and 2017, the national mortality rate involving opioids continued its escalation; opioid deaths rose from 42,249 to 47,600, bringing the public health crisis to a new height. Considering that 69% of adults in the United States use online social media sites, a resource that builds a more complete understanding of prescription drug misuse and abuse could supplement traditional surveillance instruments. The Food and Drug Administration has identified 5 key risks and consequences of opioid drugs—misuse, abuse, addiction, overdose, and death. Identifying posts that discuss these key risks could lead to novel information that is not typically captured by traditional surveillance systems. ObjectiveThe goal of this study was to describe the trends of online posts (frequency over time) involving abuse, misuse, addiction, overdose, and death in the United States and to describe the types of websites that host these discussions. Internet posts that mentioned fentanyl, hydrocodone, oxycodone, or oxymorphone were examined. MethodsPosts that did not refer to personal experiences were removed, after which 3.1 million posts remained. A stratified sample of 61,000 was selected. Unstructured data were classified into 5 key risks by manually coding for key outcomes of misuse, abuse, addiction, overdose, and death. Sampling probabilities of the coded posts were used to estimate the total post volume for each key risk. ResultsAddiction and misuse were the two most commonly discussed key risks for hydrocodone, oxycodone, and oxymorphone. For fentanyl, overdose and death were the most discussed key risks. Fentanyl had the highest estimated number of misuse-, overdose-, and death-related mentions (41,808, 42,659, and 94,169, respectively). Oxycodone had the highest estimated number of abuse- and addiction-related mentions (3548 and 12,679, respectively). The estimated volume of online posts for fentanyl increased by more than 10-fold in late 2017 and 2018. The odds of discussing fentanyl overdose (odds ratios [OR] 4.32, 95% CI 2.43-7.66) and death (OR 5.05, 95% CI 3.10-8.21) were higher for social media, while the odds of discussing fentanyl abuse (OR 0.10, 95% CI 0.04-0.22) and addiction (OR 0.24, 95% CI 0.15-0.38) were higher for blogs and forums. ConclusionsOf the 5 FDA-defined key risks, fentanyl overdose and death has dominated discussion in recent years, while discussion of oxycodone, hydrocodone, and oxymorphone has decreased. As drug-related deaths continue to increase, an understanding of the motivations, circumstances, and consequences of drug abuse would assist in developing policy responses. Furthermore, content was notably different based on media origin, and studies that exclusively use either social media sites (such as Twitter) or blogs and forums could miss important content. This study sets out sustainable, ongoing methodology for surveilling internet postings regarding these drugs.

BackgroundIn rapidly changing fields such as the study of drug use, the need for accurate and timely data is paramount to properly inform policy and intervention decisions. Trends in drug use can change rapidly by month, and using study designs with flexible modules could present advantages. Timely data from online panels can inform proactive interventions against emerging trends, leading to a faster public response. However, threats to validity from using online panels must be addressed to create accurate estimates. ObjectiveThe objective of this study was to demonstrate a comprehensive methodological approach that optimizes a nonprobability, online opt-in sample to provide timely, accurate national estimates on prevalence of drug use. MethodsThe Survey of Non-Medical Use of Prescription Drugs Program from the Researched Abuse, Diversion and Addiction Related Surveillance (RADARS) System is an online, cross-sectional survey on drug use in the United States, and several best practices were implemented. To optimize final estimates, two best practices were investigated in detail: exclusion of respondents showing careless or improbable responding patterns and calibration of weights. The approach in this work was to cumulatively implement each method, which improved key estimates during the third quarter 2018 survey launch. Cutoffs for five exclusion criteria were tested. Using a series of benchmarks, average relative bias and changes in bias were calculated for 33 different weighting variable combinations. ResultsThere were 148,274 invitations sent to panelists, with 40,021 who initiated the survey (26.99%). After eligibility assessment, 20.23% (29,998/148,274) of the completed questionnaires were available for analysis. A total of 0.52% (157/29,998) of respondents were excluded based on careless or improbable responses; however, these exclusions had larger impacts on lower volume drugs. Number of exclusions applied were negatively correlated to total dispensing volume by drug (Spearman ρ=–.88, P

Fifty years ago, basic scientific studies and the availability of assay methods made the assessment of risk in paracetamol (acetaminophen) poisoning possible. The use of the antidote acetylcysteine linked to new methods of risk assessment transformed the treatment of this poisoning. This review will describe the way in which risk assessment and treatments have developed over the last 50 years and highlight the remaining areas of uncertainty. A search of PubMed and its subsidiary databases revealed 1,166 references published in the period 1963–2023 using the combined terms "paracetamol", "poisoning", and "acetylcysteine". Focused searches then identified 170 papers dealing with risk assessment of paracetamol poisoning, 141 with adverse reactions to acetylcysteine and 114 describing different acetylcysteine regimens. To manage the extensive literature, we focused mainly on contributions made by the authors during their time in Edinburgh and Denver. The key relationship between paracetamol dose and toxicity risk was established in 1971 and led to the development of the Rumack-Matthew nomogram from data collected in Edinburgh. A series of papers on the mechanisms of toxicity were published in 1973, and these showed that paracetamol hepatotoxicity was caused by the formation of a toxic intermediate epoxide metabolite normally detoxified by glutathione but which, in excess, was bound covalently to hepatic enzymes and proteins. An understanding of the relationship between the rate of paracetamol metabolism, paracetamol concentration, and toxic hazard in humans soon followed. These discoveries were followed by the testing of a range of sulfhydryl-donors in animals and "at risk" patients. Acetylcysteine was developed as the lead intravenous antidote in the United Kingdom. The license holder in the United States refused to make an intravenous formulation. Thus, oral acetylcysteine became the antidote trialed in the United States National Multicenter Study. Intravenous acetylcysteine regimens used initially in the United Kingdom and subsequently in the United States used loading doses of 150 mg/kg over 15 minutes or one hour, 50 mg/kg over four hours, and 100 mg/kg over 16 hours. These regimens were associated with adverse drug reactions (nausea, vomiting and anaphylactoid reactions) and hence, treatment interruption. Newer dosing regimens now give loading doses more slowly. One, the Scottish and Newcastle Anti-emetic Pretreatment protocol, using an acetylcysteine regimen of 100 mg/kg over two hours followed by 200 mg/kg over 10 hours, has been widely adopted in the United Kingdom. A cohort comparison study suggests this regimen has comparable efficacy to standard regimens and offers opportunities for selective higher acetylcysteine dosing. No dose-ranging studies with acetylcysteine were done, and no placebo-controlled studies were performed. Thus, there is uncertainty regarding the optimal dose of acetylcysteine, particularly in patients ingesting very large overdoses of paracetamol. The choice of intervention concentration on the Rumack-Matthew nomogram has important consequences for the proportion of patients treated. The United States National Multicenter Study used a "treatment" line starting at 150 mg/L (992 µmol/L) at 4 hours post overdose, extending to 24 hours with a half-life of 4 hours, now standard there, and subsequently adopted in Australia and New Zealand. In the United Kingdom, the treatment line was initially 200 mg/L (1,323 µmol/L) at 4 hours (the Rumack-Matthew "risk" line). In 2012, the United Kingdom Medicines and Healthcare products Regulatory Agency lowered the treatment line to 100 mg/L (662 µmol/L) at 4 hours for all patients, increasing the number of patients admitted and treated at a high cost. Risk assessment is a key issue for ongoing study, particularly following the development of potential new antidotes that may act in those at greatest risk. The development of biomarkers to assess risk is ongoing but has yet to reach clinical trials. Even after 50 years, there are still areas of uncertainty. These include appropriate acetylcysteine doses in patients who ingest different paracetamol doses or multiple (staggered) ingestions, early identification of at-risk patients, and optimal treatment of late presenters. [ABSTRACT FROM AUTHOR]