Drug supply measures and drug overdose mortality in the era of fentanyl and stimulants
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ABSTRACT:
SUBMITTER: Cano M
PROVIDER: S-EPMC10641574 | biostudies-literature | 2023 Oct
REPOSITORIES: biostudies-literature
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Project description:BackgroundAs of July 2018, 45 United States (US) states and the District of Columbia have enacted an overdose Good Samaritan law (GSL). These laws, which provide limited criminal immunity to individuals who request assistance during an overdose, may be of importance in the current wave of the overdose epidemic, which is driven primarily by illicit opioids including heroin and fentanyl. There are substantial differences in the structures of states' GSL laws which may impact their effectiveness. This study compared GSLs which have legal provisions protecting from arrest and laws which have more limited protections.MethodsUsing national county-level overdose mortality data from 3109 US counties, we examined the association of enactment of GSLs with protection from arrest and GSLs with more limited protections with subsequent overdose mortality between 2013 and 2018. Since GSLs are often enacted in conjunction with Naloxone Access Laws (NAL), we examined the effect of GSLs separately and in conjunction with NAL. We conducted these analyses using hierarchical Bayesian spatiotemporal Poisson models.ResultsGSLs with protections against arrest enactment in conjunction with a NAL were associated with 7% lower rates of all overdose deaths (rate ratio (RR): 0.93% Credible Interval (CI): 0.89-0.97), 10% lower rates in opioid overdose deaths (RR: 0.90; CI: 0.85-0.95) and 11% lower rates of heroin/synthetic overdose mortality (RR: 0.89; CI: 0.82-0.96) two years after enactment, compared to rates in states without these laws. Significant reductions in overdose mortality were not seen for GSLs with protections for charge or prosecution.ConclusionGSLs with more expansive legal protections combined with a NAL, were associated with lower rates of overdose deaths, although these risk reductions take time to manifest. Policy makers should consider enacting and implementing more expansive GSLs with arrest protections to increase the likelihood people will contact emergency services in the event of an overdose.
| S-EPMC9529169 | biostudies-literature
Project description:IntroductionIllicitly manufactured fentanyl (IMF) is responsible for a growing number of deaths. Some case series have suggested that IMF overdoses require significantly higher naloxone doses than heroin overdoses. Our objective was to determine if the naloxone dose required to treat an opioid overdose is associated with the finding of fentanyl, opiates, or both on urine drug screen (UDS).MethodsA retrospective chart review was conducted at a single emergency department and its affiliated emergency medical services (EMS) agency. The charts of all patients who received naloxone through this EMS from 1/1/2017 to 6/15/2018 were reviewed. The study included patients diagnosed with a non-suicidal opioid overdose whose UDS was positive for opiates, fentanyl, or both. Data collected included demographics, vital signs, initial GCS, EMS and ED naloxone administrations, response to treatment, laboratory findings, and ED disposition. The fentanyl-only and fentanyl + opiate groups were compared to the opiate-only group using the stratified (by ED provider) variant of the Mann-Whitney U test.ResultsEight hundred and thirty-seven charts were reviewed, and 121 subjects were included in the final analysis. The median age of included subjects was 38 years and 75% were male. In the naloxone dose analysis, neither the fentanyl-only (median 0.8 mg, IQR 0.4-1.6; p = 0.68) nor the fentanyl + opiate (median 0.8 mg, IQR 0.4-1.2; p = 0.56) groups differed from the opiate-only group (median 0.58 mg, IQR 0.4-1.6).ConclusionOur findings refute the notion that high potency synthetic opioids like illicitly manufactured fentanyl require increased doses of naloxone to successfully treat an overdose. There were no significant differences in the dose of naloxone required to treat opioid overdose patients with UDS evidence of exposure to fentanyl, opiates, or both. Further evaluation of naloxone stocking and dosing protocols is needed.
| S-EPMC6942078 | biostudies-literature
Project description:The recreational use of fentanyl in combination with xylazine (i.e., "tranq-dope") represents a rapidly emerging public health threat characterized by significant toxicity and mortality. This study quantified the interactions between these drugs on lethality and examined the effectiveness of potential rescue medications to prevent a lethal overdose. Male and female mice were administered acute doses of fentanyl, xylazine, or their combination via intraperitoneal injection, and lethality was determined 30, 60, 90, 120, and 1440 min (24 hr) after administration. Both fentanyl and xylazine produced dose-dependent increases in lethality when administered alone. A nonlethal dose of fentanyl (56 mg/kg) produced an approximately 5-fold decrease in the estimated LD50 for xylazine (i.e., the dose estimated to produce lethality in 50% of the population). Notably, a nonlethal dose of xylazine (100 mg/kg) produced an approximately 100-fold decrease in the estimated LD50 for fentanyl. The opioid receptor antagonist, naloxone (3 mg/kg), but not the alpha-2 adrenergic receptor antagonist, yohimbine (3 mg/kg), significantly decreased the lethality of a fentanyl-xylazine combination. Lethality was rapid, with death occurring within 10 min after a high dose combination and generally within 30 min at lower dose combinations. Males were more sensitive to the lethal effects of fentanyl-xylazine combinations under some conditions, suggesting biologically relevant sex differences in sensitivity to fentanyl-xylazine lethality. These data provide the first quantification of the lethal effects of "tranq-dope" and suggest that rapid administration of naloxone may be effective at preventing death following overdose.
| S-EPMC10557575 | biostudies-literature
Project description: Not available
| S-EPMC10637371 | biostudies-literature
Project description:ImportanceDrug overdoses from opioids like fentanyl and heroin and stimulant drugs such as methamphetamine and cocaine are a major cause of mortality in the United States, with potential sex differences across the lifespan.ObjectiveTo determine overdose mortality for specific drug categories across the lifespan of males and females, using a nationally representative state-level sample.DesignState-level analyses of nationally representative epidemiological data on overdose mortality for specific drug categories, across 10-year age bins (age range: 15-74).SettingPopulation-based study of Multiple Cause of Death 2020-2021 data from the Centers of Disease Control and Prevention (CDC WONDER platform).ParticipantsDecedents in the United States in 2020-2021.Main outcome measuresThe main outcome measure was sex-specific rates of overdose death (per 100,000) for: synthetic opioids excluding methadone (ICD-10 code: T40.4; predominantly fentanyl), heroin (T40.1), psychostimulants with potential for misuse, excluding cocaine (T43.6, predominantly methamphetamine; labeled "psychostimulants" hereafter), and cocaine (T40.5). Multiple regression analyses were used to control for ethnic-cultural background, household net worth, and sex-specific rate of misuse of the relevant substances (from the National Survey on Drug Use and Health, 2018-2019).ResultsFor each of the drug categories assessed, males had greater overall overdose mortality than females, after controlling for rates of drug misuse. The mean male/female sex ratio of mortality rate for the separate drug categories was relatively stable across jurisdictions: synthetic opioids (2.5 [95%CI, 2.4-2.7]), heroin, (2.9 [95%CI, 2.7-3.1], psychostimulants (2.4 [95%CI, 2.3-2.5]), and cocaine (2.8 [95%CI, 2.6-2.9]). With data stratified in 10-year age bins, the sex difference generally survived adjustment for state-level ethnic-cultural and economic variables, and for sex-specific misuse of each drug type (especially for bins in the 25-64 age range). For synthetic opioids, the sex difference survived adjustment across the lifespan (i.e., 10-year age bins ranging from 15-74), including adolescence, adulthood and late adulthood.Conclusions and relevanceThe robustly greater overdose mortality in males versus females for synthetic opioids (predominantly fentanyl), heroin, and stimulant drugs including methamphetamine and cocaine indicate that males who misuse these drugs are significantly more vulnerable to overdose deaths. These results call for research into diverse biological, behavioral, and social factors that underlie sex differences in human vulnerability to drug overdose.Key pointsQuestion: What are the current national trends in overdose mortality from opioids (synthetic opioids such as fentanyl, and heroin) and stimulant drugs (psychostimulants such as methamphetamine and cocaine) for males and females, over the lifespan (overall range 15-74 years)?Findings: State-level analyses of data from CDC for 2020-2021 indicate that after controlling for rates of drug misuse, males had significantly greater (2-3 fold) overdose mortality rates than females for synthetic opioids, heroin, psychostimulants and cocaine. These findings were generally consistent across the lifespan, studied as 10-year age bins (especially in the 25-64 age range).Meaning: These data indicate that males who misuse opioids and stimulant drugs are considerably more vulnerable to overdose mortality, compared to females. This finding calls for research on the underlying biological, behavioral, and social factors.
| S-EPMC9882660 | biostudies-literature
Project description:BackgroundU.S. research examining the illicit drug supply remains rare even though the information could help reduce overdoses. Relatively little is known regarding how often opioids are found in stimulants and whether temporal and geographic trends exist. We examined trends in fentanyl-cocaine and fentanyl-methamphetamine combinations in the national illicit drug supply.MethodsWe analysed serial cross-sectional data from the National Forensic Laboratory Information System (NFLIS) collected between January 2011 and December 2016. We restricted the analysis to cocaine (N = 1,389,968) and methamphetamine (n = 1,407,474) samples and calculated proportions containing fentanyl (including 23 related analogs) over time.ResultsThe combined presence of fentanyl and cocaine steadily increased nationally between 2012-2016 (p = 0.01), and the number of such samples tripled from 2015 to 2016 (n = 423 to n = 1,325). Similarly, the combined presence of fentanyl and methamphetamine increased 179 % from 2015 to 2016 (n = 82-n = 272). Patterns varied widely by state; in 2016, fentanyl-cocaine samples were most common in New Hampshire (7.2 %), Connecticut (5.4 %), Ohio (2.6 %) and Massachusetts (2.1 %), whereas fentanyl-methamphetamine samples were most often in New Hampshire (6.1 %), Massachusetts (5.6 %), Vermont (2.4 %) and Maine (1.2 %).ConclusionsAlthough relatively uncommon, the presence of fentanyl in the stimulant supply increased significantly between 2011 and 2016, with the greatest increases occuring between 2015-2016; the presence of these products was concentrated in the U.S. Northeast. Given these trends, strengthening community-based drug checking programs and surveillance within the public health infrastructure could help promote timely responses to novel threats posed by rapid shifts in the drug supply that may lead to inadvertent exposures.
| S-EPMC7751390 | biostudies-literature
Project description: Not available
| S-EPMC10388669 | biostudies-literature
Project description:ImportanceOpioid-involved overdose mortality has been on the rise for 2 decades in the US, exacerbated by an unregulated drug supply that is unpredictable and has increasingly contained highly potent fentanyl analogs starting a decade ago.ObjectiveTo determine whether there is a geospatial association between law enforcement drug seizures and opioid-involved overdose mortality in San Francisco.Design, setting, and participantsThis cross-sectional study used location- and time-stamped overdose mortality data from the Office of the Chief Medical Examiner and publicly available crime data from the San Francisco Police Department between 2020 and 2023 to assess whether location and time of law enforcement drug seizures were associated with subsequent opioid-involved overdose mortality. Data were analyzed from January 2020 to September 2023.ExposuresTime-stamped locations of law enforcement drug seizures involving a drug distribution charge.Main outcomes and measuresThe primary outcomes were the time and location of (1) overdose mortality involving any opioid and (2) overdose mortality involving fentanyl or any fentanyl analog. The relative risk (RR) and 95% CIs for endemic and epidemic factors were calculated.ResultsThere were 2653 drug seizure crime events that involved any drug distribution charge and 1833 overdose deaths that tested positive for any opioid or synthetic opioid, including heroin and fentanyl analogs. Within the surrounding 100 meters, law enforcement drug seizures were associated with increase risk of fatal opioid-involved overdoses the day following the drug seizure event (RR, 1.74; 95% CI, 1.06-2.83; P = .03) and elevated risk persisted for 7 days (2 days: RR, 1.55; 95% CI, 1.09-2.21; P = .02; 3 days: RR, 1.45; 95% CI, 1.08-1.93; P = .01; 7 days: RR, 1.27; 95% CI, 1.11-1.46; P = .001). Similar statistically significant spatiotemporal patterns were observed in the 250- and 500-meter spatial bandwidths. Within each space-time kernel, the strength of the association, all of which were statistically significant, dissipated the further away in time and distance from the law enforcement drug seizure event.Conclusions and relevanceThe findings of this cross-sectional study suggest that the enforcement of drug distribution laws to increase public safety for residents in San Francisco may be having an unintended negative consequence of increasing opioid overdose mortality. To reduce overdose mortality, it may be better to focus on evidence-based health policies and interventions.
| S-EPMC11923703 | biostudies-literature
Project description:IntroductionOpioid and sedative/hypnotic drug overdoses are major causes of morbidity in the U.S. This study compares 12-month incidence of fatal unintentional drug overdose, suicide, and other mortality among emergency department patients presenting with nonfatal opioid or sedative/hypnotic overdose.MethodsThis is a retrospective cohort study using statewide, longitudinally linked emergency department patient record and mortality data from California. Participants comprised all residents presenting to a licensed emergency department at least once in 2009-2011 with nonfatal unintentional opioid overdose, sedative/hypnotic overdose, or neither (a 5% random sample). Participants were followed for 1 year after index emergency department presentation to assess death from unintentional overdose, suicide, or other causes, ascertained using ICD-10 codes. Absolute death rates per 100,000 person years and standardized mortality ratios relative to the general population were calculated. Data were analyzed February-August 2019.ResultsFollowing the index emergency department visit, unintentional overdose death rates per 100,000 person years were 1,863 following opioid overdose, 342 following sedative/hypnotic overdose, and 31 for reference patients without an index overdose (respective standardized mortality ratios of 106.1, 95% CI=95.2, 116.9; 24.5, 95% CI=21.3, 27.6; and 2.6, 95% CI=2.2, 3.0). Suicide mortality rates per 100,000 were 319, 174, and 32 following opioid overdose, sedative/hypnotic overdose, and reference visits, respectively. Natural causes mortality rates per 100,000 were 8,058 (opioid overdose patients), 17,301 (sedative/hypnotic overdose patients), and 3,097 (reference patients).ConclusionsEmergency department patients with nonfatal opioid or sedative/hypnotic drug overdose have exceptionally high risks of death from unintentional overdose, suicide, and other causes. Emergency department-based interventions offer potential for reducing these patients' overdose and other mortality risks.
| S-EPMC7311279 | biostudies-literature
Project description:BackgroundUnited States drug overdose deaths are being driven by the increasing prevalence of fentanyl, but whether patients are knowingly using fentanyl is unclear. We examined the analytical confirmation of fentanyl in emergency department (ED) patients with documented heroin overdose.HypothesisWe hypothesized that the proportion of fentanyl and fentanyl analogs would be higher than that of confirmed heroin.MethodsThis is a subgroup analysis from a prospective multicenter consecutive cohort of ED patients age 18+ with opioid overdose presenting to 10 US sites within the Toxicology Investigators Consortium from 2020 to 2021. Toxicology analysis was performed using liquid chromatography quadrupole time-of-flight mass spectrometry. De-identified toxicology results were paired with the clinical database. The primary outcome was the proportion of patients with fentanyl analytes detected in their serum.ResultsOf 1006 patients screened, 406 were eligible, and of 168 patients who reported that they had taken heroin or had a documented heroin overdose, 88% (n = 147) were in fact found to have fentanyl and/or a fentanyl analog present on serum analysis (p < 0.0001). In contrast, only 46 of the 168 patients with reported or documented heroin overdose (27%) were found to have heroin biomarkers present.ConclusionThe prevalence of confirmed fentanyl in ED patients with suspected heroin overdose was extremely high, while the prevalence of heroin was very low. There was a high degree of mismatch between the opioids believed to be the overdose agent versus the actual opioids identified on serum toxicology. Clinicians in the United States should presume that fentanyl is involved in all illicit opioid overdoses and should counsel patients on harm reduction measures.
| S-EPMC11331419 | biostudies-literature