This article explores the implementation of a culturally relevant mathematics lesson in an Algebra, Functions, and Data Analysis (AFDA) classroom, where students analyzed Fentanyl overdose data using mathematical concepts such as rate of change, percent increase, and predictive modeling. Grounded in Culturally Relevant Pedagogy (CRP) and the Culturally Relevant Cognitively Demanding (CRCD) Mathematics Task Framework, this lesson engaged students in real-world problem-solving while fostering critical thinking about social inequities. The project culminated in a gallery walk where students presented their findings. Reflections on student engagement, mathematical reasoning, and recommendations for implementation highlight the impact of CR mathematics on student learning.

Few studies have quantified the effects of non-pharmacological interventions (e.g., rescue breathing) in the setting of community opioid overdose. We extended a previously validated model for opioid antagonists by incorporating the mechanism of rescue breathing, and quantified combinatorial effects between rescue breathing and various formulations of naloxone under different fentanyl overdose scenarios in a virtual patient population suffering from opioid-induced respiratory failure. We defined successful reversal of an overdose as fewer than 5% of the virtual population experiencing cardiac arrest after intervention. Our model showed that timely rescue breathing reduced the naloxone dose needed for successful overdose reversal from greater than 8 mg (intranasal) to less than 2 mg (intramuscular) and extended the naloxone rescue window to 10 minutes under a median fentanyl intravenous overdose scenario. Administration of 4 mg naloxone intranasally reduced the duration of rescue breathing needed from 11 hours to 5 minutes under a median fentanyl transmucosal overdose scenario. High-quality (as delivered by well-trained rescuers), but not low-quality (as delivered by laypersons), rescue breathing could successfully rescue severe opioid overdose scenarios. Even in cases where virtual subjects survived without naloxone, 4 mg intranasal naloxone provided benefit by shortening the time to recovery of spontaneous. Our results highlight the importance of utilizing both pharmacological and non-pharmacological interventions in reversal of overdose.

A two-wave death story: fentanyl overdoses in the US, bullets in Mexico

Fentanyl test strip use and homelessness among people who use drugs in Rhode Island.

Background Fentanyl overdose deaths rose precipitously in the United States from 2015 to 2022, dramatically outpacing all other drugs. Within Texas, Travis County (Austin, Texas) has the highest fentanyl overdose death rate across the state, surpassing larger metro areas such as Houston and Dallas. Local research indicates that many users are aware of fentanyl in the drug supply, but few utilize harm reduction behaviors, indicating the need locally for improved messaging and education among people who use drugs (PWUD). As such, the local health department approached our team to develop a culturally competent, evidenced based health communication campaign rooted in harm reduction principles intended for PWUD as part of a multi-pronged effort to reduce fentanyl-related overdose deaths locally. Objectives This paper describes the process of creating and disseminating the campaign entitled, “In Austin, We Keep Each Other Safe,” as well as a discussion of broader implications for future research and public health efforts. Results Utilizing previous research, an environmental scan, and a community-engaged approach, we developed and disseminated a mass media campaign focused for PWUD locally. Conclusions/Importance Findings of this work support previous research that harm reduction approaches are best poised to support PWUD by providing non-stigmatizing, fact-based information to make informed choices and practice safer substance consumption. Finally, we advocate that by centering both evidence-based strategies with a community-engaged approach, it is possible to create meaningful health communication campaigns that can impart important, time-sensitive health information effectively to marginalized and niche audiences.

We assessed the impact of the COVID-19 pandemic on the implementation of a peer-integrated enhancement of integrated clinical care intervention to address the mental health needs of 450 patients undergoing treatment for a physical injury. Qualitative data were collected by 7 clinician investigators of a randomized controlled trial acting as participant observers in a trauma care setting of a major U.S. metropolitan hospital and analyzed in collaboration with an external mixed methods specialist. The pandemic created or exacerbated several implementation barriers, including increased risk of infection, homelessness, hospitalizations and comorbid conditions such as fentanyl overdoses that increased demand on emergency department and Trauma Center services, imposition of safety measures to reduce risk of infection in clinical settings, transition from face-to-face to virtual interactions with study patients, shortages of specialty mental health providers, suspension of recruitment of patients into the study, scheduling calls with patients, and an increased workload for the study clinical interventionists. Peer specialists perceived the transition to virtual interactions with patients reduced their effectiveness; however, this was not reflected in assessments of patient satisfaction with services received and may have inadvertently increased adoption by Trauma Center staff. Reduction in reach of the intervention to target population was temporary. The COVID-19 pandemic exacerbated existing barriers and created new barriers to successfully implementing evidence-based practices in trauma care settings, resulting in an attenuation of their effectiveness. However, the shift from face-to-face to virtual services delivery may have actually led to improved implementation outcomes. ClinicalTrials.gov identifier: NCT03569878. Registered June 15, 2018.

Fentanyl leads to tens of thousands of overdose deaths every year despite widespread availability of naloxone. Like other opioids, fentanyl causes respiratory depression. Unlike morphine, high dose fentanyl rapidly produces airway obstruction, muscle rigidity, and cardiovascular failure. Using a rat model of opioid overdose, we compared the physiological effects of fentanyl and morphine and studied the efficacy of a novel rescue strategy. In contrast to morphine, we report that fentanyl more frequently causes respiratory failure secondary to vocal cord closure and leads to more severe cardiovascular disruption, including the blockade of baroreflex-like rebound in blood pressure. We also show that administration of intramuscular naloxone immediately after intravenous infusion of fentanyl did not improve survival. However, combining intramuscular naloxone with the alpha-2 adrenergic agonist clonidine rescued vocal cord function and stabilized cardiovascular and respiratory physiology from fentanyl-induced effects. Our findings demonstrate that fentanyl is associated with a unique and more severe toxidrome compared to morphine. Also, supplementing naloxone with drugs targeting the adrenergic system improves survival primarily by reopening the upper airway, implicating airway obstruction as a significant component of fentanyl-induced respiratory depression. Therefore, reversal of vocal cord closure appears to be the necessary precursor to the restoration of not only respiration, but also vascular autoregulation, a significant determinant of survival from fentanyl overdose.

The escalating synthetic opioid crisis necessitates noveltreatments,especially for fentanyl overdose. This study presents 84 ring-expandedfentanyl analogs, replacing its piperidine core with 4-azepane and5-azocane structures. In vivo antagonism studiesidentified 15 compounds that effectively blocked synthetic opioidantinociception. Further dose–response analysis identifiedfour potent antagonists (16, 46, 53, and 69) against both fentanyl and morphine. Notably,Compound 53 demonstrated the highest potency with AD50 of 2.02 mg/kg against morphine and 4.02 mg/kg against fentanyl.Compound 53 exhibits a favorable pharmacokinetic profile,including moderate human metabolic stability, low efflux, and efficient,sustained CNS penetration, making it a promising centrally actingMOR antagonist candidate. Significantly, whole-body plethysmographyconfirmed that compound 53 reversed fentanyl-inducedrespiratory depression. These results suggest that expanding the corering structure of fentanyl is a promising strategy to develop potentmu opioid receptor antagonists to inhibit both antinociception andrespiratory depression offering potential solutions to fentanyl overdose.

The incidence of fatal drug overdoses has increased dramatically over the past decade due to the widespread availability of fentanyl and its analogs. As a complementary strategy to current overdose reversal agents, monoclonal antibodies (mAbs) are in development as therapeutics for prevention and reversal of fentanyl overdose. In the present study, the anti-fentanyl mAb HY6-F9 was tested for reversal of fentanyl-induced respiratory arrest (apnea) in a porcine model. In a first study, following fentanyl-induced apnea, chimeric HY6-F9 and naloxone control were administered as an intravenous bolus. Both chimeric HY6-F9 and naloxone restored spontaneous breathing within 90 seconds. Treatment with mAb increased the concentration of fentanyl in serum by 10-fold within the first minute after mAb bolus administration. In a second study, after induction of apnea, humanized HY6-F9 and naloxone control were administered as a slow intravenous infusion over 10 minutes to determine the ED50 to restore baseline breathing. In this study, the mean ± SEM ED50 of humanized HY6-F9 and naloxone to restore baseline respiratory rate were 16.0 ± 1.3 mg/kg and 6.9 ± 1.8 μg/kg, respectively. During mAb infusion, the concentration of fentanyl in serum increased proportionally to the concentration of infused mAb. The anti-fentanyl mAb ablated fentanyl-dependent opioid receptor activation in an in vitro system with concentrations of fentanyl similar to those observed in pigs after mAb treatment. These results demonstrate the efficacy of an anti-fentanyl mAb as a treatment to reverse fentanyl overdose. SIGNIFICANCE STATEMENT: Treatments for opioid use disorder and overdose are urgently needed. Here, we show that an anti-fentanyl monoclonal antibody reversed fentanyl-induced apnea in pigs, and caused rapid (<1 minute) redistribution of fentanyl into serum. Fentanyl was 99% bound by monoclonal antibodies and showed no activity at the opioid receptor.

A 33-year-old man with altered mental status, generalized weakness, and paranoia following fentanyl overdose: A clinical vignette.

Background Structural barriers can pose challenges to retaining people who use drugs in longitudinal research. This study assessed baseline characteristics associated with retention in a year-long clinical trial addressing whether fentanyl test strip provision decreased rates of nonfatal overdose among people who use drugs. Methods From September 2020 to February 2023, 505 participants enrolled in the year-long RAPIDS clinical trial. Outcome visits were completed at 6 and 12 months following enrollment. Bivariable and multivariable analyses were conducted to assess baseline characteristics associated with the completion of none, one, or both study outcome assessments. We used multinomial logistic regression to identify statistically significant baseline predictors of retention in the RAPIDS trial. Results Among eligible participants, 41.6% (n = 210) only completed a baseline assessment, 23.4% (n = 118) completed one outcome visit, and 35.0% (n = 177) completed both. In the final multinomial logistic regression model, women were more likely to complete both outcome visits compared to men (adjusted odds ratio [AOR] = 1.69, 95% CI: 1.08–2.62), while participants with a history of drug selling were less likely to complete two visits (AOR = 0.62, 95% CI: 0.39–0.98). Conclusions Study results challenge stigmatizing beliefs about the impact of sociodemographic and drug use-related characteristics on retention in longitudinal research. Retention strategies that target men and people who sell drugs are needed. Investigators can collect multiple pieces of contact information, have monthly check-ins with participants, and partner with community organizations to make research more accessible and acceptable to structurally vulnerable populations.

Co-use of opioids (e.g., fentanyl) and stimulants (e.g., methamphetamine; METH) contributed to >30% of the almost 106,000 fatal overdoses in the United States in 2023. Although NarCan® (naloxone) is effective at reversing opioid-induced cardiorespiratory depression, larger and/or more frequent doses are often required for fentanyl and multi-drug overdoses involving fentanyl. Using collar-based pulse oximetry, this study characterized the effects of intravenous (IV) fentanyl (0.0056–0.56 mg/kg), heroin (0.32–5.6 mg/kg), and METH (0.1–1 mg/kg), as well as mixtures of 0.56 mg/kg fentanyl +1 mg/kg METH and 5.6 mg/kg heroin +1 mg/kg METH on blood oxygen saturation (SpO2), heart rate (HR), and breath rate (BR) in male and female Sprague-Dawley rats. To evaluate the potency and effectiveness of naloxone to reverse cardiorespiratory depression, naloxone (0.01–3.2 mg/kg; IV) or vehicle was administered 5 min after opioids or opioid + stimulant mixtures. Naloxone was fully effective at reversing the effects of fentanyl and heroin alone but was more potent for fentanyl. Naloxone was fully effective and equipotent at reversing the cardiorespiratory effects of heroin and heroin + METH but was less potent and less effective at reversing the cardiorespiratory effects of fentanyl + METH compared to fentanyl alone. When administered after fentanyl, heroin, or heroin + METH, naloxone recovered baseline SpO2 in all rats, however, SpO2 was only recovered in 75% of rats treated with fentanyl + METH. These findings suggest that naloxone may be less potent and effective at reversing fentanyl-induced cardiorespiratory depression when METH is co-administered.

Variability in trends of opioid-related hospital utilization among U.S. Adults, 2016-2021 check.

ABSTRACT This study explored whether law enforcement/first responder-reported fentanyl overdose response actions (such as administration of the opioid overdose reversal agent naloxone) differed between overdoses in which xylazine was, versus was not, suspected to be co-involved. Data were drawn from the Pennsylvania State Police’s Overdose Information Network (ODIN) for 11,478 suspected fentanyl-involved overdoses, 137 reportedly co-involving xylazine, recorded across Pennsylvania (January 2018–January 16, 2025), excluding Philadelphia. We used relative frequencies, Fisher’s exact tests, and binomial logistic regression to compare first responders’ overdose response actions in suspected fentanyl overdose cases in which xylazine was, versus was not, reportedly co-involved. Naloxone was administered at the scene of 46.0% of the overdoses reportedly involving fentanyl and xylazine, vs. 67.3% of the reported fentanyl-no-xylazine overdoses. Multivariable regression results (among the suspected fentanyl overdoses in ODIN, adjusting for age, sex, race/ethnicity, year, county rurality, and other drugs suspected to be involved) indicated that suspected xylazine co-involvement was associated with 60% lower odds of naloxone administration (adjusted odds ratio, 0.40; 95% confidence interval, 0.28–0.57). Observed differences in overdose response based on suspected xylazine co-involvement support the importance of equipping first responders with the tools and training to recognize/manage the distinct challenges of xylazine–fentanyl-involved overdose.

Abstract Introduction The American fentanyl epidemic has become the worst man-made epidemic the country has faced to date, claiming tens of thousands of lives each year. Methods Using population-based data provided by the Centers for Disease Control and Prevention, we examined the increase in unintentional, fatal fentanyl overdose since 2005 and analyzed the geographic variation in fentanyl mortality among census divisions, states, and counties. Results In 2022, 70 813 persons died of an unintentional fentanyl overdose, a 31-fold increase over the 2139 deaths that occurred in 2012; the age-adjusted mortality rate increased similarly. Fentanyl deaths resulted in ∼2.0-2.6 million estimated years of life lost. We estimated the economic loss to the nation resulting from premature mortality was on the order of $57-$67 billion. The impact of the fentanyl epidemic varied widely by geographic area. The mortality rate of West Virginia was 15 times greater than that of South Dakota. Conclusion Containing the fentanyl epidemic will require new, data-driven preventive and treatment approaches, coordinated across sectors, including public health, health care, law enforcement, education, and social services. Interventions should be based upon the risk profile of geographic areas and include harm reduction activities as well as social marketing campaigns to improve public awareness of fentanyl's health risks.

Background Fentanyl test strips may help People who inject drugs in detecting fentanyl in street drugs and thereby reduce the risk of overdose deaths. This study aims to determine the predictors of FTS awareness among PWID living in Northeast Georgia. Methods Adults (≥18 years) with a recent history of injection drug use (IDU) were surveyed between February and December 2023 (n = 179). FTS awareness was elicited by the question, “Have you ever heard of fentanyl test strips?”. Covariates include age, gender, race, education, syringe services program (SSP) attendance, needle-sharing behavior, IDU-related stigma, frequency of IDU, and primary drugs used. Descriptive, bivariate, and multivariable logistic regression analyses were performed. Results Less than half (45.3%) of the PWID were aware of FTS. In the multivariable model, the odds of FTS awareness were higher among PWID who attended SSP (adjusted Odds Ratio [aOR]: 2.30, 95% Confidence Interval [95%CI]: 1.10, 4.79) than those who did not. Awareness of FTS was also higher among individuals with high IDU-related stigma (aOR: 2.74, 95%CI: 1.34, 5.60) than those who had low stigma. African American PWID were less likely to be aware of FTS (aOR: 0.26, 95%CI: 0.11, 0.61) than White PWID. Conclusions FTS awareness is a critical first step for PWID to engage in harm reduction strategies for fentanyl overdose prevention. Findings highlight the need for innovative approaches to educate PWID who are not engaged in SSP services about the benefits of FTS. Tailored approaches for certain communities of people who use drugs are also urgently needed.

In 2022, 2.2 million adolescents were diagnosed with substance use disorders, including 265,000 with opioid use disorder. The National Survey on Drug Use and Health revealed that 130,000 adolescents misused prescription pain medications, often obtaining them from friends or relatives. This age group perceives weekly heroin use as less risky than those younger or older. A questionnaire was developed for 7th to 12th graders in a rural Texas school district as part of a fentanyl awareness curriculum. The questionnaire included Likert scale, multiple choice, and yes/no questions. The participants were categorized into younger (grades 7th and 8th) and older students (grades 9th through 12th), and associations were explored between demographic characteristics, responses, and grade groups using chi-square tests. To assess confidence, behavior, and the impact of education, we used chi-square and Fisher's exact tests. The participants (n = 94; 85.11%) identified as Hispanic or Latino, with a smaller percentage identifying as White or more than one race. An association was found between feeling more in control of actions related to substances and fentanyl (p-value = 0.04) after receiving education. No association was found between education and confidence in identifying fentanyl. This study aligns with a surge in fentanyl-related overdose deaths in a high-intensity drug trafficking region. Recent fentanyl overdoses among school-age children prompted legislative changes in 2023, making this study valuable for understanding the epidemic within the geographical context. These results suggest that school-based education may play a role in strengthening adolescents' behavioral intentions to fentanyl exposure, though additional efforts are needed to improve risk identification.

As the opioid epidemic continues to evolve in the U.S., so do the drug mixtures. For instance, the use of synthetic opioids in combination with other drugs, such as stimulants and other opioids, has taken off. This presentation will provide epidemiologic and toxicological data on new and evolving mixed-drug overdose trends, including cocaine and methamphetamine being mixed with fentanyl, and the emergence of nitazenes worldwide. In addition, we will discuss how investigators can use clinical data for surveillance of drug overdose trends with a specific focus on drug mixtures. Finally, we will discuss next steps and the need for a multi-disciplinary approach to tackle emerging trends in mixed-drug overdoses. On March 2, 2023, the CDC reported that cocaine was involved in 38.2% of overdose deaths and methamphetamine was involved in 24.8% of overdose deaths in the U.S. in 2021. In the western region of the U.S., 68.9% of methamphetamine-involved overdose deaths also involved cocaine combined with fentanyl. Here, we highlight public health surveillance efforts to quantify and characterize cocaine and methamphetamine mixed with fentanyl overdose deaths using death certificate and toxicologic data from Nevada. Among the 300 overdose deaths in 2021, the drugs involved in these deaths were cocaine alone, cocaine and methamphetamine, cocaine mixed with fentanyl, and cocaine and methamphetamine mixed with fentanyl. Toxicological data indicated that 87% of the decedents with cocaine mixed with fentanyl had a positive toxicology result for fentanyl.

The misuse of fentanyl and its analogs has significantly worsened the opioid crisis, leading to a sharp increase in overdose fatalities. Fentanyl overdose primarily causes severe respiratory depression, which can result in hypoxia, cardiac arrest, and death, often exacerbated by co-intoxication. Additionally, the opioid in question can induce chest wall rigidity, further complicating treatment procedures. Despite international control efforts, the drug’s high potency and low cost have fueled its widespread trafficking, including in counterfeit pills. While naloxone is the primary antidote, its effectiveness is limited, highlighting the need for stronger, long-acting treatments. Factors such as polypharmacy, prescription misuse, and environmental exposure – as well as the potential for fentanyl’s use as a chemical weapon – pose significant public safety risks. In conclusion, addressing the current wave of the opioid crisis requires a comprehensive approach, integrating treatment solutions, prevention, and harm reduction strategies.

Oral fluid is considered a favorable matrix for the identification of drug intake mainly because of its simple, observed, non-invasive collection. Fentanyl and fentanyl analog use, misuse, overdose, and deaths are currently occurring at an alarming rate in the USA. The law enforcement community, the Food and Drug Administration (FDA) and the Centers for Disease Control (CDC) are all keenly aware of the urgency in addressing an unmet public health need to identify opioid overdose in individuals as rapidly as possible. As part of a National Institute of Justice grant, the present study was intended to develop and validate an environmentally friendly, rapid, sensitive quantitative method using liquid chromatography coupled to tandem mass spectral detection (LC-MS/MS) for fentanyl and fentanyl analogs in oral fluid collected using the nform rapid test device. Oral fluid samples were subjected to liquid-liquid extraction incorporating bio-renewable solvents where possible, reducing the environmental footprint of the assay. A buffer/salt free mobile phase was employed consisting of 0.1% formic acid in water (95%): 0.1% formic acid in methanol (5%) at a flow rate of 0.8 mL/min; the run time was 4.5 minutes, again reducing environmental impact in terms of salt and solvent usage. The method included fentanyl, 4-anilino-N-phenethylpiperidine; (4-ANPP; desproprionyl fentanyl), acetyl fentanyl, carfentanil, p-fluorofentanyl, valeryl fentanyl, p-fluorobutyrylfentanyl, furanyl fentanyl and benzoyl fentanyl as well as xylazine, which is often detected with fentanyl. The method was validated according to ANSI/ASB 036 (2019) Standard Practices for Method Validation in Forensic Toxicology.