Naloxone Use in Novel Potent Opioid and Fentanyl Overdoses in Emergency Department Patients

Journal: JAMA Network Open, 2023, doi:10.1001/jamanetworkopen.2023.31264

Authors: Alexandra Amaducci; Kim Aldy, Sharan L. Campleman, Shao Li, Alison Meyn, Stephanie Abston, … Alex F. Manini


Importance: Synthetic opioids, such as the fentanyl analogue and nitazene drug class, are among the fastest growing types of opioids being detected in patients in the emergency department (ED) with illicit opioid overdose (OD). However, clinical outcomes from OD of novel potent opioids (NPOs), specifically nitazenes, are unknown aside from small case series.

Objective: To determine naloxone administration and clinical sequelae of patients who were in the ED with NPO overdose compared with fentanyl OD.

Design, Setting, and Participants: This is a cohort study subgroup analysis of adults admitted to the ED and tested positive for NPOs among in the ongoing nationwide ToxIC Fentalog cohort study from 2020 to 2022. Patients who were in the ED with a presumed acute opioid OD and residual blood samples were included, and those testing positive for NPOs were analyzed. Patients were included in this analysis if their confirmatory testing was positive for an NPO analyte, such as brorphine, isotonitazene, metonitazene, and/or N-piperidinyl etonitazene. A comparison group included patients that were positive for fentanyl and devoid of any other analytes on toxicologic analysis.

Exposures: Patients were exposed to NPOs, including brorphine, isotonitazene, metonitazene and/or N-piperidinyl etonitazene.

Main Outcomes and Measures: The primary outcome was the total number of naloxone doses and total cumulative naloxone dose administered as part of routine clinical care following the OD. Naloxone requirements and clinical sequelae of NPO-positive patients were compared with those testing positive for fentanyl only.

Results: During the study period, 2298 patients were screened, of whom 717 met inclusion criteria, 537 had complete laboratory testing data, with 11 (2.0%) positive for only fentanyl and 9 (1.7%) positive for NPOs (brorphine, isotonitazene, metonitazene, or N-piperidinyl etonitazene). The age range of patients was aged 20 to 57 years (4 males [44.4%] and 5 females [55.6%]). The NPO group received a statistically significantly higher mean (SD) number of naloxone boluses in-hospital (1.33 [1.50]) compared with the fentanyl group (0.36 [0.92]) (P = .02), which corresponded to a moderately large effect size (Cohen d = 0.78). Metonitazene overdose was associated with cardiac arrest and more naloxone doses overall. Metonitazene cases had a mean (SD) number of 3.0 (0) naloxone doses, and 2 of 2 patients (100%) with metonitazene overdoses were administered cardiopulmonary resuscitation.

Conclusions and Relevance: In this cohort study of patients admitted to the ED with confirmed opioid overdose testing positive for NPOs, in-hospital naloxone dosing was high compared with patients who tested positive for fentanyl alone. Further study is warranted to confirm these preliminary associations.

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Testing the Influence of Harm Reduction Messages on Health Risk Attitudes, Injunctive Norms and Perceived Behavioral Control

Journal: Harm Reduction Journal, 2023, doi: 10.1186/s12954-023-00846-2

Authors: Sherri Jean Katz, Elisia Cohen, & Dorothy Hatsukami


Background: E-cigarettes can potentially be a harm reduction pathway for adults who smoke and who are seeking to make the complete switch from cigarettes. However, often people who smoke believe that e-cigarettes are just as damaging as cigarettes to their health. From a harm reduction perspective, the key question is whether providing information about the reduced toxicant intake of e-cigarettes, compared to cigarettes, could influence their perceptions and whether there are certain message features that might further support this transition.

Methods: In this experiment (n = 305), we test whether a harm reduction (reduced toxicant intake, complete switch) message will influence the health risk attitudes, injunctive norms and perceived behavioral control of people who smoke, compared to those who do not view a message and whether including a “smoking cue” within the message influences their response.

Results: Results indicate that those who viewed the harm reduction message with a smoking cue had lower health risk attitudes than those who did not view a message (p = 0.025) and higher injunctive norms than those who viewed the message without a smoking cue (p = 0.006).

Conclusions: These findings demonstrate that a harm reduction message with a smoking cue can influence the perceptions of adults who smoke, lowering health risk attitudes and increasing injunctive norms.

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Onset of the Non-Medical Use of Prescription and Over-the-Counter Medications during Early Adolescence: Comparison with Alcohol, Tobacco, and Marijuana

Journal: Children, 2023, doi: 10.3390/children10081298

Authors: Sarosh Khan, Kenneth W. Griffin, & Gilbert J. Botvin


This study examined the prevalence and psychosocial predictors of the non-medical use of prescription and over-the-counter (OTC) medications and compared these to cigarette, marijuana, and alcohol use in a cohort of early adolescents (N = 1887) aged 11 to 13, a critical risk period for the initiation of substance use. Participants were students attending 22 middle schools in the northeastern United States. Participants completed surveys in the classroom, the first in the sixth grade and a second in the seventh grade, and the rate of overall substance use more than doubled from 5.5% to 11.9% over this period. Predictors of the onset of non-medical prescription and over-the-counter drug misuse overlapped substantially with those for marijuana and other substances. The perception of friends’ substance use and the belief that substance use can help you deal with problems predicted the onset of marijuana use, OTC medication misuse, and prescription drug misuse. Decision-making skills were protective for the onset of all substance use outcomes. The findings of this study have important implications for prevention and suggest that a single comprehensive approach may be sufficient for preventing multiple forms of substance use onset during early adolescence.

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Association of Loneliness and Mindfulness in Substance Use Treatment Retention

Journal: International Journal of Environmental Research & Public Health, 2023, doi: 10.3390/ijerph20166571

Authors: Johnathan M. Herczyk, Keith J. Zullig, Stephen M. Davis, Jennifer Mallow, Gerald R. Hobbs, Danielle M. Davidov, … Laurie Theeke


Elevated mental illness prevalence complicates efforts designed to address the opioid crisis in Appalachia. The recovery community acknowledges that loneliness impacts mood and engagement in care factors; however, the predictive relationship between loneliness and retention in medication-assisted outpatient treatment programs has not been explored. Our objectives were to identify associations between mental health factors and retention in treatment and elucidate treatment retention odds. Data were collected from eighty participants (n = 57 retained, n = 23 not retained) of a mindfulness-based relapse prevention (MBRP) intervention for individuals receiving medication for opioid use disorder (MOUD) in Appalachia. Loneliness, depression, and anxiety did not differ between the retained and not retained, nor did they predict not being retained; however, mindfulness was significantly lower among those not retained in treatment compared to those retained (OR = 0.956, 95% CI (0.912-1.00), and p < 0.05). Preliminary findings provide evidence for mindfulness training integration as part of effective treatment, with aims to further elucidate the effectiveness of mindfulness therapies on symptom reduction in co-occurring mental health disorders, loneliness, and MOUD treatment retention.

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Early Life Stress, Prenatal Secondhand Smoke Exposure, and the Development of Internalizing Symptoms across Childhood

Journal: Environmental Health, 2023, doi: 10.1186/s12940-023-01012-8

Authors: Mariah DeSerisy, Jacob W. Cohen, Jordan D. Dworkin, Jeanette A. Stingone, Bruce Ramphal, Julie B. Herbstman, … Amy E. Margolis


Background: Prior findings relating secondhand tobacco smoke (SHS) exposure and internalizing problems, characterized by heightened anxiety and depression symptoms, have been equivocal; effects of SHS on neurodevelopment may depend on the presence of other neurotoxicants. Early life stress (ELS) is a known risk factor for internalizing symptoms and is also often concurrent with SHS exposure. To date the interactive effects of ELS and SHS on children’s internalizing symptoms are unknown. We hypothesize that children with higher exposure to both prenatal SHS and ELS will have the most internalizing symptoms during the preschool period and the slowest reductions in symptoms over time.

Methods: The present study leveraged a prospective, longitudinal birth cohort of 564 Black and Latinx mothers and their children, recruited between 1998 and 2006. Cotinine extracted from cord and maternal blood at birth served as a biomarker of prenatal SHS exposure. Parent-reported Child Behavior Checklist (CBCL) scores were examined at four timepoints between preschool and eleven years-old. ELS exposure was measured as a composite of six domains of maternal stress reported at child age five. Latent growth models examined associations between SHS, ELS, and their interaction term with trajectories of children’s internalizing symptoms. In follow-up analyses, weighted quintile sum regression examined contributions of components of the ELS mixture to children’s internalizing symptoms at each time point.

Results: ELS interacted with SHS exposure such that higher levels of ELS and SHS exposure were associated with more internalizing symptoms during the preschool period (β = 0.14, p = 0.03). The interaction between ELS and SHS was also associated with a less negative rate of change in internalizing symptoms over time (β=-0.02, p = 0.01). Weighted quintile sum regression revealed significant contributions of maternal demoralization and other components of the stress mixture to children’s internalizing problems at each age point (e.g., age 11 WQS β = 0.26, p < 0.01).

Conclusions: Our results suggest that prior inconsistencies in studies of SHS on behavior may derive from unmeasured factors that also influence behavior and co-occur with exposure, specifically maternal stress during children’s early life. Findings point to modifiable targets for personalized prevention.

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