[An overview of natural entheogens]. / Un aperçu des enthéogènes naturels.

Entheogens are a group of little-known psychoactive substances which consumption is nevertheless frequently mentioned in outpatient care and which can have harmful effects. This raises the question of appropriate management of their effects, as well as the treatment of any overdose. In this article, we focus on five of these substances, which are rarely described in the medical literature. At present, few studies exist on their long-term effects on health, and this type of niche consumption does not seem problematic from the authorities' point of view. Rapid screening is unavailable because it has not been developed, and the management of overdoses is often limited to non-specific supportive treatment with benzodiazepines.

Les enthéogènes sont un groupe de substances psychoactives méconnues mais dont la consommation apparaît toutefois lors de consultations ambulatoires et qui peuvent engendrer des effets néfastes. Se pose alors la question de la prise en charge adaptée concernant leurs effets mais également le traitement d'un éventuel surdosage. Dans cet article, le focus a été mis sur cinq de ces substances peu décrites dans la littérature médicale. Actuellement, peu d'études existent sur leurs effets à long terme sur la santé et ce type de consommation de niche ne semble pas problématique du point de vue des autorités. Le dépistage rapide n'est pas disponible car pas développé et la prise en charge des surdosages se limite souvent à un traitement de soutien non spécifique par benzodiazépines.

County-level factors associated with a mismatch between opioid overdose mortality and availability of opioid treatment facilities.

BACKGROUND: Opioid overdose deaths in the United States remain a major public health crisis. Little is known about counties with high rates of opioid overdose mortality but low availability of opioid use disorder (OUD) treatment facilities. We sought to identify characteristics of United States (US) counties with high rates of opioid overdose mortality and low rates of opioid treatment facilities. METHODS: Rates of overdose mortality from 3,130 US counties were compared with availability of opioid treatment facilities that prescribed or allowed medications for OUD (MOUD), from 2018-2019. The outcome variable, "risk-availability mismatch" county, was a binary indicator of a high rate (above national average) of opioid overdose mortality with a low (below national average) rate of opioid treatment facilities. Covariates of interest included county-level sociodemographics and rates of insurance, unemployment, educational attainment, poverty, urbanicity, opioid prescribing, depression, heart disease, Gini index, and Theil index. Multilevel logistic regression, accounting for the clustering of counties within states, was used to determine associations with being a "risk-availability mismatch" county. RESULTS: Of 3,130 counties, 1,203 (38.4%) had high rates of opioid overdose mortality. A total of 1,098 counties (35.1%) lacked a publicly-available opioid treatment facility in 2019. In the adjusted model, counties with an additional 1% of: white residents (odds ratio, OR, 1.02; 95% CI, 1.01-1.03), unemployment (OR, 1.11; 95% CI, 1.05-1.19), and residents without insurance (OR, 1.04; 95% CI, 1.01-1.08) had increased odds of being a mismatch county. Counties that were metropolitan (versus non-metropolitan) had an increased odds of being a mismatch county (OR, 1.85; 95% CI, 1.45-2.38). CONCLUSION: Assessing mismatch between treatment availability and need provides useful information to characterize counties that require greater public health investment. Interventions to reduce overdose mortality are unlikely to be effective if they do not take into account diverse upstream factors, including sociodemographics, disease burden, and geographic context of communities.

Acute quadruple extremity compartment syndrome due to angio-oedema after polypharmacy overdose including olmesartan medoxomil, telmisartan and vildagliptin.

This case report describes a rare manifestation of acute compartment syndrome (ACS) involving all four extremities, precipitated by angio-oedema in a middle-aged woman who consumed an overdose of multiple medications: nifedipine, azelnidipine, amlodipine besylate, olmesartan medoxomil, telmisartan, esaxerenone and vildagliptin. She presented with haemodynamic instability, necessitating intubation. Despite stabilising haemodynamic parameters within 24 hours, she manifested escalating extremity oedema. At 52 hours after ingestion, mottled skin was observed, along with necrotic alterations in the swollen hands and compartment pressures exceeding 30 mm Hg in all extremities. ACS was diagnosed, leading to fasciotomies. The aetiology is postulated to be drug-induced angio-oedema, possibly intensified by the concurrent overdose of olmesartan medoxomil, telmisartan and vildagliptin, each of which has a risk of angio-oedema even at standard dosages. This scenario is a very rare case caused by drug-induced angio-oedema, which underscores the importance of vigilant monitoring to detect ACS in patients with progressing limb oedema.

Effect of intravenous lipid therapy in critically ill pediatric patients with calcium channel blocker toxicity.

BACKGROUND: Overdose with calcium-channel blockers (CCBs) still maintain their importance with a high lethality rate after exposure. We report the intravenous lipid emulsion therapy (ILE) therapy in our CCB overdose patients. METHODS: We retrospectively analyzed the records of 6 patients with CCB intoxication from Batman Training and Research Hospital PICU between March 2021 and September 2022. Patients aged 0-18 years who received ILE treatment for CCB poisoning were included. RESULTS: All six patients ingested CCB with the intention of committing suicide and were followed up in the pediatric intensive care unit (PICU). All patients received ILE therapy due to hemodynamic instability despite intravenous fluid boluses, calcium, glucagon, insulin-dextrose, and vasoactive agents. Vasoactive-Inotropic Score (VIS) decreased after ILE treatment. All patients were transferred from the PICU after recovery. CONCLUSIONS: ILE therapy should be kept in mind as a salvage therapy in hemodynamically unstable CCB poisoning cases that do not respond to initial and advanced options.

Developing medical simulations for opioid overdose response training: A qualitative analysis of narratives from responders to overdoses.

Medical simulation offers a controlled environment for studying challenging clinical care situations that are difficult to observe directly. Overdose education and naloxone distribution (OEND) programs aim to train potential rescuers in responding to opioid overdoses, but assessing rescuer performance in real-life situations before emergency medical services arrive is exceedingly complex. There is an opportunity to incorporate individuals with firsthand experience in treating out-of-hospital overdoses into the development of simulation scenarios. Realistic overdose simulations could provide OEND programs with valuable tools to effectively teach hands-on skills and support context-sensitive training regimens. In this research, semi-structured interviews were conducted with 17 individuals experienced in responding to opioid overdoses including emergency department physicians, first responders, OEND program instructors, and peer recovery specialists. Two coders conducted qualitative content analysis using open and axial thematic coding to identify nuances associated with illicit and prescription opioid overdoses. The results are presented as narrative findings complemented by summaries of the frequency of themes across the interviews. Over 20 hours of audio recording were transcribed verbatim and then coded. During the open and axial thematic coding process several primary themes, along with subthemes, were identified, highlighting the distinctions between illicit and prescription opioid overdoses. Distinct contextual details, such as locations, clinical presentations, the environment surrounding the patient, and bystanders' behavior, were used to create four example simulations of out-of-hospital overdoses. The narrative findings in this qualitative study offer context-sensitive information for developing out-of-hospital overdose scenarios applicable to simulation training. These insights can serve as a valuable resource, aiding instructors and researchers in systematically creating evidence-based scenarios for both training and research purposes.

Adverse Effects After Prehospital Administration of Naloxone by Bystanders: A Preliminary Study.

OBJECTIVE: Opioid use disorder is a cause of significant morbidity and mortality. In order to reverse opioid overdose as quickly as possible, many institutions and municipalities have encouraged people with no professional medical training to carry and administer naloxone. This study sought to provide preliminary data for research into the rates of adverse effects of naloxone when administered by bystanders compared to Emergency Medical Services (EMS) personnel, since this question has not been studied previously. METHODS: This was a retrospective cohort study performed at an urban, tertiary, academic medical center that operates its own EMS service. A consecutive sample of patients presenting to EMS with opioid overdose requiring naloxone was separated into two groups based on whether naloxone was administered by bystanders or by EMS personnel. Each group was analyzed to determine the incidence of four pre-specified adverse events. RESULTS: There was no significant difference in the rate of adverse events between the bystander (19%) and EMS (16%) groups (OR = 1.23; 95% CI, 0.63 - 2.32; P = .499) in this small sample. Based on these initial results, a study would need a sample size of 6,188 in order to reach this conclusion with 80% power. Similarly, there were no significant differences in the rates of any of the individual adverse events. Secondary analysis of patients' demographics showed differences between the two groups which generate hypotheses for further investigation of disparities in naloxone administration. CONCLUSIONS: This preliminary study provides foundational data for further investigation of naloxone administration by bystanders. Adverse events after the prehospital administration of naloxone are rare, and future studies will require large sample sizes. These preliminary data did not demonstrate a statistically significant difference in adverse event rates when comparing naloxone administration by bystanders and EMS clinicians. This study provides data that will be useful for conducting further research on multiple facets of this topic.

Emergency Department Take-Home Naloxone Improves Access Compared with Pharmacy-Dispensed Naloxone.

BACKGROUND: Opioid overdose is a major cause of mortality in the United States. In spite of efforts to increase naloxone availability, distribution to high-risk populations remains a challenge. OBJECTIVE: To assess the effects of multiple different naloxone distribution methods on patient obtainment of naloxone in the emergency department (ED) setting. METHODS: Naloxone was provided to patients in three 12-month phases between February 2020 and February 2023. In Phase 1, physicians could offer patients electronic prescriptions, which were filled in a nearby in-hospital discharge pharmacy. In Phase 2, physicians directly provided patients with take-home naloxone at discharge. In Phase 3, distribution was expanded to allow ED staff to hand patients take-home naloxone at time of discharge. The total number of prescriptions, rate of prescription filling, and amount of take-home naloxone kits provided to patients were then statistically analyzed using 95% confidence intervals (CI) and chi-squared testing. RESULTS: In Phase 1, 348 naloxone prescriptions were written, with 133 (95% CI 112.5-153.5) filled. In Phase 2, 327 (95% CI 245.5-408.5) take-home naloxone kits were given to patients by physicians. In Phase 3, 677 (95% CI 509.5-844.5) take-home naloxone kits were provided to patients by ED staff. There were statistically significant increases in naloxone distribution from Phase 1 to Phase 2, and Phase 2 to Phase 3. CONCLUSIONS: Take-home naloxone increases access when compared with naloxone prescriptions in the ED setting. A multidisciplinary approach combined with the removal of regulatory and administrative barriers allowed for further increased distribution of no-cost naloxone to patients.

Denial of prescription pain medication among people who use drugs in Vancouver, Canada.

BACKGROUND: People who use drugs experience pain at two to three times the rate of the general population and yet continue to face substantial barriers to accessing appropriate and adequate treatment for pain. In light of the overdose crisis and revised opioid prescribing guidelines, we sought to identify factors associated with being denied pain medication and longitudinally investigate denial rates among people who use drugs. METHODS: We used multivariable generalized estimating equations analyses to investigate factors associated with being denied pain medication among people who use drugs reporting pain in three prospective cohort studies in Vancouver, Canada. Analyses were restricted to study periods in which participants requested a prescription for pain from a healthcare provider. Descriptive statistics detail denial rates and actions taken by participants after being denied. RESULTS: Among 1168 participants who requested a prescription for pain between December 2012 and March 2020, the median age was 47 years and 63.0% were male. Among 4,179 six-month observation periods, 907 (21.7%) included a report of being denied requested pain medication. In multivariable analyses, age was negatively associated with prescription denial (adjusted odds ratio [AOR] = 0.98, 95% confidence interval [CI]:0.97-0.99), while self-managing pain (AOR = 2.48, 95%CI:2.04-3.00), experiencing a non-fatal overdose (AOR = 1.51, 95%CI:1.22-1.88), engagement in opioid agonist therapy (AOR = 1.32, 95%CI:1.09-1.61), and daily use of heroin or other unregulated opioids (AOR = 1.32, 95%CI:1.05-1.66) were positively associated with being denied. Common actions taken (n = 895) after denial were accessing the unregulated drug supply (53.5%), doing nothing (30.6%), and going to a different doctor/emergency room (6.1%). The period following the introduction of new prescribing guidelines was not associated with a change in denial rates. CONCLUSIONS: A substantial proportion of people who use drugs continue to be denied prescriptions for pain, with such denial associated with important substance use-related harms, including non-fatal overdose. Guidelines specific to the pharmaceutical management of pain among people who use drugs are needed.

Fact vs. fiction: naloxone in the treatment of opioid-induced respiratory depression in the current era of synthetic opioids.

Opioid-induced respiratory depression (OIRD) deaths are ~80,000 a year in the US and are a major public health issue. Approximately 90% of fatal opioid-related deaths are due to synthetic opioids such as fentanyl, most of which is illicitly manufactured and distributed either on its own or as an adulterant to other drugs of abuse such as cocaine or methamphetamine. Other potent opioids such as nitazenes are also increasingly present in the illicit drug supply, and xylazine, a veterinary tranquilizer, is a prevalent additive to opioids and other drugs of abuse. Naloxone is the main treatment used to reverse OIRD and is available as nasal sprays, prefilled naloxone injection devices, and generic naloxone for injection. An overdose needs to be treated as soon as possible to avoid death, and synthetic opioids such as fentanyl are up to 50 times more potent than heroin, so the availability of new, higher-dose, 5-mg prefilled injection or 8-mg intranasal spray naloxone preparations are important additions for emergency treatment of OIRDs, especially by lay people in the community. Higher naloxone doses are expected to reverse a synthetic overdose more rapidly and the current formulations are ideal for use by untrained lay people in the community. There are potential concerns about severe withdrawal symptoms, or pulmonary edema from treatment with high-dose naloxone. However, from the perspective of first responders, the balance of risks would point to administration of naloxone at the dose required to combat the overdose where the risk of death is very high. The presence of xylazines as an adulterant complicates the treatment of OIRDs, as naloxone is probably ineffective, although it will reverse the respiratory depression due to the opioid. For these patients, hospitalization is particularly vital. Education about the benefits of naloxone remains important not only in informing people about how to treat emergency OIRDs but also how to obtain naloxone. A call to emergency services is also essential after administering naloxone because, although the patient may revive, they may overdose again later because of the short half-life of naloxone and the long-lasting potency of fentanyl and its analogs.

Azathioprine and hydroxychloroquine overdose in Sjögren's syndrome patient with hypocalcemia: a case report.

INTRODUCTION: Hydroxychloroquine and azathioprine have been routinely used to control and treat primary and secondary Sjögren's syndrome, which potentially triggered some overdoses by these drugs. Toxicity from hydroxychloroquine and azathioprine manifests in the form of cardiac conduction abnormalities, nausea, vomiting, and muscle weakness. Recognizing these unique drug overdoses and management of these toxicities is important. This case report aims to expand our current understanding of these drug overdoses and their management and also underscores the importance of anticipating and identifying fewer common complications, such as hypocalcemia. CASE REPORT: A 34-year-old Persian woman with a history of Sjögren's syndrome presented to the emergency department 3.5-4 hours after an intentional overdose of hydroxychloroquine and azathioprine and severe hypotension and loss of consciousness. Although the patient was regularly taking other medications, such as fluoxetine, naproxen, and prednisolone, she explicitly clarified that these were not the substances involved in her overdose. Early investigations showed hypokalemia (2.4 mEq/L), hypocalcemia (7.5 mg/dL), and hypoglycemia (65 mg/dL). She was also diagnosed with metabolic acidosis and respiratory alkalosis. The electrocardiogram showed changes in favor of hypokalemia; other lab tests were run on the patient. Supportive treatments were applied, including rapid intravenous fluid dextrose 5%, normal saline, potassium chloride 30 mEq, and calcium gluconate 100 mg. The patient was managed and monitored overnight in the emergency room and recovered without residual side effects. CONCLUSION: Hydroxychloroquine and azathioprine toxicity are considered rare, but it is likely to increase in frequency given the prevalence and increase in autoimmune diseases and the increasing usage of these drugs in treating such diseases. We found hypocalcemia as the presentation to this patient, which needs further investigation into the probable mechanism. Clinicians need to consider the unique effects of hydroxychloroquine and azathioprine poisoning and initiate appropriate emergency interventions to improve the outcomes in similar patients.

Simulating the Simultaneous Impact of Medication for Opioid Use Disorder and Naloxone on Opioid Overdose Death in Eight New York Counties.

BACKGROUND: The United States is in the midst of an opioid overdose epidemic; 28.3 per 100,000 people died of opioid overdose in 2020. Simulation models can help understand and address this complex, dynamic, and nonlinear social phenomenon. Using the HEALing Communities Study, aimed at reducing opioid overdoses, and an agent-based model, Simulation of Community-Level Overdose Prevention Strategy, we simulated increases in buprenorphine initiation and retention and naloxone distribution aimed at reducing overdose deaths by 40% in New York Counties. METHODS: Our simulations covered 2020-2022. The eight counties contrasted urban or rural and high and low baseline rates of opioid use disorder treatment. The model calibrated agent characteristics for opioid use and use disorder, treatments and treatment access, and fatal and nonfatal overdose. Modeled interventions included increased buprenorphine initiation and retention, and naloxone distribution. We predicted a decrease in the rate of fatal opioid overdose 1 year after intervention, given various modeled intervention scenarios. RESULTS: Counties required unique combinations of modeled interventions to achieve a 40% reduction in overdose deaths. Assuming a 200% increase in naloxone from current levels, high baseline treatment counties achieved a 40% reduction in overdose deaths with a simultaneous 150% increase in buprenorphine initiation. In comparison, low baseline treatment counties required 250-300% increases in buprenorphine initiation coupled with 200-1000% increases in naloxone, depending on the county. CONCLUSIONS: Results demonstrate the need for tailored county-level interventions to increase service utilization and reduce overdose deaths, as the modeled impact of interventions depended on the county's experience with past and current interventions.

Opioid Misuse Harm Reduction.

BACKGROUND/AIMS: The misuse of opioids by the public is a major health issue. Prescription opioids and nonprescription opioids, such as heroin and opium, are misused in epidemic proportions. When opioids are used incorrectly or illegally, they can lead to drug dependence, addiction, morbidity, and mortality. This program is in collaboration with the Jolt Foundation that provides resources to prevent opioid overdose deaths. DESIGN/METHODS: This program involves community education on the dangers of opioid use and training on the use of naloxone rescue procedures to prevent overdose deaths. A pretest-posttest design was employed to determine if participants gained knowledge regarding the naloxone administration procedures. PARTICIPANTS: The researcher presented 10 community naloxone trainings that included staff from 20 different social service agencies, two schools, and three local churches. Each agency received at least one naloxone kit. FINDINGS: The outcomes were met and included educating 137 participants on the risk factors and signs and symptoms of opioid overdose and the proper procedure to administer naloxone. One hundred twenty-eight posttests were returned and showed that the objectives for the project were met. The overall mean score for the pretests was 65.00 ( n = 126) with a standard deviation of 19.01, and the overall mean for the posttests was 86.64 ( n = 128) with a standard deviation of 14.60. CONCLUSIONS: Community social service agency staff were successfully educated to respond appropriately to overdose situations in a group training setting as evidenced by significant posttest scores.

Factors associated with gaps in naloxone knowledge: evidence from a 2022 great plains survey.

BACKGROUND: The rising prevalence of fast-acting opioids in the USA suggests the increased need for non-professional first responder administration of naloxone. Effective administration of naloxone during an overdose requires that bystanders are familiar with, have access to, and know how to use naloxone. METHODS: Drawing on a statewide, address-based sample of Nebraskan adults, we used logistic regression to predict the likelihood of respondents' familiarity with, access to, and competency to administer naloxone. Our independent variables included measures indicating proximity to drug use, perceived community stigma toward people who use drugs, and demographic data. RESULTS: There were significant gaps in naloxone knowledge in Nebraska. Although 74.8% of respondents were familiar with naloxone, only 18.2% knew how to access it and 18.0% knew how to use it. Being close to an overdose experience, lifetime illicit opioid use, being close to a person who uses opioids, and having access to illicit opioids were not significantly associated with naloxone familiarity, access, or competency among respondents in Nebraska's two largest cities, Omaha and Lincoln. Outside of these cities, being close to a past overdose experience and access to illicit opioids was associated with higher odds of naloxone access and competency, but lifetime opioid use and being close to a person who uses opioids were not. Finally, among those familiar with naloxone, a higher perception of community stigma toward people who use opioids generally was associated with lower odds of naloxone access and competency. Higher perception of community stigma toward people who use heroin, methamphetamines, and cocaine, however, was associated with higher odds of naloxone access. CONCLUSIONS: Our findings highlight the continued need for education on naloxone with a specific focus on access and competency to further reduce opioid-related overdose deaths. Specific focus should be placed on promoting naloxone knowledge among people with a higher likelihood of needing to administer naloxone to reduce otherwise avoidable deaths. Further work is needed to understand differences in the relationship between substance-specific perceived stigma and its association with naloxone access.

Comparison of Administration of 8-Milligram and 4-Milligram Intranasal Naloxone by Law Enforcement During Response to Suspected Opioid Overdose - New York, March 2022-August 2023.

In 2021, an 8-mg intranasal naloxone product was approved by the Food and Drug Administration; however, no studies have examined outcomes among persons who receive the 8-mg naloxone product and those who receive the usual 4-mg product. During March 2022-August 2023, New York State Department of Health (NYSDOH) supplied some New York State Police (NYSP) troops with 8-mg intranasal naloxone; other troops continued to receive 4-mg intranasal naloxone to treat suspected opioid overdose. NYSP submitted detailed reports to NYSDOH when naloxone was administered. No significant differences were observed in survival, mean number of naloxone doses administered, prevalence of most postnaloxone signs and symptoms, postnaloxone anger or combativeness, or hospital transport refusal among 4-mg and 8-mg intranasal naloxone recipients; however, persons who received the 8-mg intranasal naloxone product had 2.51 times the risk for opioid withdrawal signs and symptoms, including vomiting, than did those who received the 4-mg intranasal naloxone product (95% CI = 1.51-4.18). This initial study suggests no benefits to law enforcement administration of higher-dose naloxone were identified; more research is needed to guide public health agencies in considering whether 8-mg intranasal naloxone confers additional benefits for community organizations.

Non-fatal overdose with a new synthetic opioid. / Ikke-fatal overdose med nytt syntetisk opioid.

A young man experienced respiratory arrest at home, and cardiopulmonary resuscitation was performed. The patient received naloxone with good effect and was admitted to hospital. He disclosed opioid use, but no substances were detected in routine drug screenings.

Organize and mobilize for implementation effectiveness to improve overdose education and naloxone distribution from syringe services programs: a randomized controlled trial.

BACKGROUND: The United States (US) continues to face decades-long increases in opioid overdose fatalities. As an opioid overdose reversal medication, naloxone can dramatically reduce opioid overdose mortality rates when distributed to people likely to experience or witness an opioid overdose and packaged with education on its use, known as overdose education and naloxone distribution (OEND). Syringe services programs (SSPs) are ideal venues for OEND with staff who are culturally competent in providing services for people who are at risk of experiencing or observing an opioid overdose. We carried out a randomized controlled trial of SSPs to understand the effectiveness of the organize and mobilize for implementation effectiveness (OMIE) approach at improving OEND implementation effectiveness within SSPs. METHODS: Using simple randomization, 105 SSPs were enrolled into the trial and assigned to one of two study arms - (1) dissemination of OEND best practice recommendations (Control SSPs) or the OMIE approach along with dissemination of the OEND best practice recommendations (i.e., OMIE SSPs). OMIE SSPs could participate in 60-min OMIE sessions once a month for up to 12 months. At 12-month post-baseline, 102 of 105 SSPs (97%) responded to the follow-up survey. RESULTS: The median number of sessions completed by OMIE SSPs was 10. Comparing OMIE SSPs to control SSPs, we observed significant increases in the number of participants receiving naloxone (incidence rate ratio: 2.15; 95% CI: 1.42, 3.25; p < 0.01) and the rate of naloxone doses distributed per SSP participant (adjusted incidence rate ratio: 1.97; 95% CI: 1.18, 3.30; p = 0.01). We observed no statistically significant difference in the number of adopted best practices between conditions (difference in means 0.2, 95% CI: - 0.7, 1.0; p = 0.68). We also observed a threshold effect where SSPs receiving a higher OMIE dose had greater effect sizes with regard to the number of people given naloxone and the number of naloxone doses distributed. CONCLUSIONS: In conclusion, the multifaceted OMIE approach was effective at increasing naloxone distribution from SSPs, despite substantial external shocks during the trial. These findings have major implications for addressing the overdose crisis, which has continued unabated for decades. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03924505 . Registered 19 April 2019.