Role of l -arginine/nitric oxide/cyclic GMP/K ATP channel signaling pathway and opioid receptors in the antinociceptive effect of rutin in mice.

The l -arginine ( l -Arg)/nitric oxide/cyclic GMP/potassium channel (K ATP ) pathway and opioid receptors are known to play critical roles in pain perception and the antinociceptive effects of various compounds. While there is evidence suggesting that the analgesic effects of rutin may involve nitric oxide modulation, the direct link between rutin and the l -Arg/nitric oxide/cyclic GMP/K ATP pathway in the context of pain modulation requires further investigation. The antinociceptive effect of rutin was studied in male NMRI mice using the formalin test. To investigate the role of the l -Arg/nitric oxide/cyclic GMP/K ATP pathway and opioid receptors, the mice were pretreated intraperitoneally with different substances. These substances included l -Arg (a precursor of nitric oxide), S-nitroso- N -acetylpenicillamine (SNAP, a nitric oxide donor), N(gamma)-nitro- l -arginine methyl ester (L-NAME, an inhibitor of nitric oxide synthase), sildenafil (an inhibitor of phosphodiesterase enzyme), glibenclamide (a K ATP channel blocker), and naloxone (an opioid receptor antagonist). All pretreatments were administered 20 min before the administration of the most effective dose of rutin. Based on our investigation, it was found that rutin exhibited a dose-dependent antinociceptive effect. The administration of SNAP enhanced the analgesic effects of rutin during both the initial and secondary phases. Moreover, L-NAME, naloxone, and glibenclamide reduced the analgesic effects of rutin in both the primary and secondary phases. In conclusion, rutin holds significant value as a flavonoid with analgesic properties, and its analgesic effect is directly mediated through the nitric oxide/cyclic GMP/K ATP channel pathway.

Implementing a text-message-based intervention to increase access to naloxone for patients on chronic opioid therapy.

OBJECTIVE: To implement a text-message-based intervention for primary care patients taking chronic opioid therapy to increase access to naloxone. DESIGN: Retrospective analysis of a hospital quality improvement initiative. SETTING: This study was conducted with selected primary care practices affiliated with an academic medical center between March and July 2022. PARTICIPANTS: Patients were eligible for receiving the intervention if they had chronic (≥90 days) opioid use of ≥50 morphine milligram equivalents/day and had not previously opted out of receiving text messages. INTERVENTIONS: Text messages were sent to patients inquiring about interest in obtaining a naloxone kit, which prompted a pharmacist to contact the patient and provide the medication by mail. MAIN OUTCOME MEASURES: We examined response rates to text messages and numbers of naloxone kits dispensed. RESULTS: There were 243 patients identified who were sent the text message. Of these, 230 (94.7 percent) had a primary language of English, 150 (61.7 percent) were White, and 57 (23.5 percent) were Black/African American. The mean age was 57.3 years. After receiving the text messages, 64 (26.3 percent) of the 243 patients responded with "unsubscribe." Thirty-five (14.4 percent) patients responded to the message, and 18 patients (51.4 percent of those who responded or 7.4 percent of all included patients) wanted the medication and were contacted by a pharmacist who filled and mailed the prescription to them. CONCLUSIONS: A text-message-based program to provide naloxone to patients with chronic opioid use was feasible. However, fewer than 15 percent of patients responded to the message, and just half of those wanted the medicine.

Impact of an Education Module on the Knowledge and Attitudes of EM Physicians Towards Prescribing Buprenorphine/Naloxone for Opioid Use Disorder.

BACKGROUND: Opioid overdose continues to be a major cause of morbidity and mortality. Buprenorphine is an important treatment for patients with opioid-use disorder (OUD) and initiation in the emergency department (ED) has been shown to improve outcomes for these patients. PURPOSE/HYPOTHESIS: Our objective was to assess the impact of a three-pronged education package on the knowledge and attitudes of emergency physicians towards using buprenorphine for treatment of OUD. Procedures/data/observations: We developed a three-pronged educational package including back- ground rationale for OUD treatment with buprenorphine, an evidence-based ED buprenorphine induction pathway and electronic medical record tools. This package was deployed to providers in an urban academic ED. A voluntary confidential pre-post survey was administered. Using a 6-point Likert Scale, participants were asked about their understanding, experience, and confidence with prescribing. CONCLUSIONS/APPLICATIONS: A one-hour, three-pronged educational package changed the attitudes of emergency physicians towards buprenorphine treatment and demonstrated an increase in willingness and confidence to prescribe it for patients with OUD. Our findings suggest that healthcare entities that wish to boost buprenorphine prescribing can impact willingness and confidence to prescribe with a short education package.

[Opioid crisis in the USA: what are implications for Switzerland?] / Crise des opioïdes aux États-Unis : quelles implications pour la Suisse ?

Warnings in Europe signal a rise in illicitly-manufactured fentanyl and other high potency synthetic opioids which could destabilize drug markets, strain health systems, and escalate harms of substance use and death. Here, we provide an overview of fentanyl in North America, drawing implications for Switzerland. Fentanyl withdrawal starts sooner, is more severe, and has worse anxiety and pain. Clinical care includes aggressive use of full agonist opioids, opioid agonist therapies (OAT) and adjunctive medications for acute withdrawal, and a need for low-threshold, readily accessible OAT to engage patients and mitigate harms. The US experience suggests the importance of widespread naloxone distribution, peer-based initiatives, early warning systems, and partnerships across patient-groups, healthcare systems, and public health.

En Europe, des mises en garde signalent une augmentation du fentanyl et d'autres opioïdes de synthèse fabriqués illicitement, qui pourrait déstabiliser le marché des drogues, mettre à rude épreuve le système de santé et augmenter les dommages et le nombre de décès. Nous présentons ici la situation Nord-Américaine et ses implications pour la Suisse. Le sevrage du fentanyl survient tôt, est plus sévère et associé à une aggravation de l'anxiété et de la douleur. La prise en charge comprend l'utilisation agressive d'agonistes opioïdes complets, les traitements agonistes opiacés (TAO) et des médicaments d'appoint. L'expérience américaine montre l'importance d'une distribution généralisée de naloxone, de l'implication des pairs, des systèmes d'alerte précoce, et des partenariats entre les patients, les systèmes de soins et la santé publique.

Exploring the analgesic potential of isorhamnetin: insights from formalin-induced pain and diabetic neuropathy models.

OBJECTIVE: Isorhamnetin, a naturally occurring flavonoid compound, holds paramount importance as a primary constituent within several medicinal plants, exhibiting profound pharmacological significance. The aim of this study is to investigate the pain-relieving attributes of isorhamnetin in murine models through both formalin-induced pain and diabetic neuropathy scenarios. MATERIALS AND METHODS: To achieve our objective, isorhamnetin was orally administered to mice at varying dosage levels (10 to 100 mg/kg). Pain-related behaviors were assessed using the formalin test during its secondary phase. Additionally, the potential pain-alleviating effect of isorhamnetin was evaluated in a diabetic neuropathy model induced by streptozotocin. Additionally, we carried out advanced interventions using naloxone, which is a well-known antagonist of opioid receptors, yohimbine, which blocks α2-adrenergic receptors, and methysergide, which inhibits serotonergic receptors, during the formalin test. RESULTS: The oral intake of isorhamnetin showed a decrease in behaviors associated with pain that was proportional to the dose observed during the second phase of the formalin test when induced by formalin. In the diabetic neuropathy model, isorhamnetin administration effectively reversed the reduced pain threshold observed. Notably, naloxone, the opioid receptor antagonist, effectively counteracted the pain-relieving effect produced by isorhamnetin in the formalin test, whereas yohimbine and methysergide did not yield similar outcomes. Isorhamnetin also led to a reduction in elevated spinal cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) levels triggered by formalin, with this effect reversed by pre-treatment with naloxone. The compound also suppressed heightened spinal phosphorylated CREB (p-CREB) levels caused by diabetic neuropathy. CONCLUSIONS: This research determined that isorhamnetin has notable abilities to relieve pain in models of formalin-induced pain and diabetic neuropathy. The pain-relieving mechanism of isorhamnetin in the formalin-induced pain model seems to be connected to the activation of spinal opioid receptors and the adjustment of CREB protein amounts. This insight improves our knowledge of how isorhamnetin could be used therapeutically to treat pain conditions stemming from formalin-induced pain and diabetic neuropathy.

Evaluating fentanyl test strips as a harm reduction strategy in rural and urban counties: study protocol for a randomized controlled trial.

BACKGROUND: Opioid-related fatalities are a leading cause of death in Ohio and nationally, with an increasing number of overdoses attributable to fentanyl. Rapid fentanyl test strips can identify fentanyl and some fentanyl analogs in urine samples and are increasingly being used to check illicit drugs for fentanyl before they are used. Fentanyl test strips are a promising harm reduction strategy; however, little is known about the real-world acceptability and impact of fentanyl test strip use. This study investigates fentanyl test strip distribution and education as a harm reduction strategy to prevent overdoses among people who use drugs. METHODS: The research team will recruit 2400 individuals ≥ 18 years with self-reported use of illicit drugs or drugs purchased on the street within the past 6 months. Recruitment will occur at opioid overdose education and naloxone distribution programs in 16 urban and 12 rural Ohio counties. Participating sites will be randomized at the county level to the intervention or non-intervention study arm. A brief fentanyl test strip educational intervention and fentanyl test strips will be provided to participants recruited from sites in the intervention arm. These participants will be eligible to receive additional fentanyl test strips for 2 years post-enrollment. Participants recruited from sites in the non-intervention arm will not receive fentanyl test strip education or fentanyl test strips. All participants will be followed for 2 years post-enrollment using biweekly, quarterly, and 6-month surveys. Primary outcomes include (1) identification of perceived barriers and facilitating factors associated with incorporating fentanyl test strip education and distribution into opioid overdose education and naloxone distribution programs; (2) differences in knowledge and self-efficacy regarding how to test drugs for fentanyl and strategies for reducing overdose risk between the intervention and non-intervention groups; and (3) differences in non-fatal and fatal overdose rates between the intervention and non-intervention groups. DISCUSSION: Findings from this cluster randomized controlled trial will contribute valuable information about the feasibility, acceptability, and impact of integrating fentanyl test strip drug checking in rural and urban communities in Ohio and help guide future overdose prevention interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT05463341. Registered on July 19, 2022. https://clinicaltrials.gov/study/NCT05463341.

State Mandates On Naloxone Coprescribing Associated With Short-Term Increase In Naloxone Codispensing.

In the midst of the opioid crisis in the US, efforts to mitigate overdose risks have become paramount, leading some states to introduce mandates for coprescribing the life-saving overdose reversal drug naloxone. These mandates were designed to specifically address people receiving opioid analgesics who had an elevated risk for overdose. This included people receiving high opioid dosages, those concurrently using benzodiazepines, or those with a history of substance use disorder or overdose. Using a nationally representative, multipayer cohort of patients receiving prescription opioids, we investigated how naloxone codispensing rates changed at the state level from 2016 to 2021 among patients with an elevated risk for overdose. Then we used controlled interrupted time series analyses to assess mandates' longitudinal impact on naloxone codispensing in ten states that implemented mandates. We observed an immediate and significant increase in the naloxone codispensing rates in eight states after the implementation of mandates. Nevertheless, in five of these states, the codispensing rates exhibited a subsequent downward trend after the initial increase. State mandates show potential for improving naloxone codispensing; however, mandates alone might not be adequate for sustained change. Further research is needed to identify strategies complementing and enhancing the impact of mandates in combating the overdose crisis.

Morphine promotes non-small cell lung cancer progression by downregulating E-cadherin via the PI3K/AKT/mTOR pathway.

Morphine has been suggested to affect cancer cell dynamics and decrease survival rates in lung cancer patients at specific doses, but the precise mechanisms poorly understood. In this study, we aimed to investigate the molecular mechanisms by which morphine modulates the malignant characteristics of non-small cell lung cancer. Cell proliferation was assessed via the Cell Counting Kit-8 assay, and cell migration and invasion were examined via wound healing and Transwell assays. We employed immunofluorescence staining to evaluate E-cadherin expression in A549 and Lewis lung cancer (LLC) cell lines and immunohistochemistry to evaluate E-cadherin expression in nude mice tumours. Additionally, the in vivo effects of morphine on lung cancer progression were explored in a xenograft tumour experiments, in which naloxone was used as a morphine antagonist. Western blot analysis was performed to detect E-cadherin, phosphorylated mTOR (p-mTOR), mTOR, phosphorylated AKT (p-AKT), AKT, phosphorylated PI3K (p-PI3K), and PI3K protein levels in A549 and LLC cells as well as in tumour samples. Morphine (10 µM) significantly increased the proliferation of A549 and LLC cells in vitro (p < 0.05). It also enhanced the migratory and invasive capacities of these cell lines (p < 0.01). Mechanistically, morphine treatment (10 µM) led to a reduction in the expression of E-cadherin, and an increase in the phosphorylation of PI3K, AKT, and mTOR in A549 and LLC cells (p < 0.01). Morphine treatment (1.5 mg/kg) also reduced E-cadherin expression in xenograft tumours and promoted tumour growth in vivo (p < 0.05). This effect was reversed by naloxone (0.1 mg/kg). The results demonstrated that morphine stimulates the malignant proliferation of A549 and LLC cell lines and promotes xenograft tumour growth. Perhaps by specifically targeting MOR, morphine triggers a signalling cascade that activates the PI3K/AKT/mTOR pathway while inhibiting the EMT marker E-cadherin, which may consequently promote the progression of lung cancer.

Barriers to calling emergency services amongst people who use substances in the event of overdose: A scoping review.

BACKGROUND: North America is grappling with an ongoing drug overdose crisis. While harm reduction measures like take-home naloxone kits, and supervised consumption sites, have helped reduce mortality, other strategies to address this public health emergency are required. Good Samaritan Laws (GSLs) offer legal protection for individuals who report overdoses, yet people who use substances (PWUS) may still hesitate to seek help due to concerns about existing legislation. This scoping review explores barriers preventing PWUS from calling emergency services for overdoses, along with potential solutions and facilitators to address this challenge. METHODS: PRISMA-ScR was used as a guide to conduct this study. Health sciences librarians searched Medline, Embase, PsychINFO, CINAHL, and SCOPUS to identify relevant articles. Six reviewers contributed to screening and extracting the articles through Covidence. Two reviewers performed thematic analysis using NVivo software to identify key barriers and facilitators. RESULTS: An initial search found 6275 articles for title and abstract screening, resulting in 48 studies meeting the inclusion criteria. The primary barrier to calling 911 pertained to concerns about police arrivng with other first responders, especially regarding their presence and involvement at the scene of overdose. This was followed by legal repercussions, including fear of arrest, incarceration, and fear of eviction, amongst others. Some studies noted the lack of knowledge or trust in GSLs as a deterrent to seeking medical assistance. Additional barriers included concerns about privacy and confidentiality, preference to manage an overdose alone/receive help from another peer, confidence in naloxone effectiveness, limited access to cell phones, peer pressure to not call for help, and identifying as Black, Indigenous, or a Person of Colour (BIPOC). Facilitators include increased GSL awareness among PWUS and law enforcement, expanded legal safeguards for 911 callers, reduced police intervention in overdose cases, and enhanced naloxone availability at key access points. CONCLUSION: Despite the good intentions of GSLs, PWUS continue to experience significant barriers to calling emergency services in the event of an overdose. Understanding these barriers and key facilitators is necessary to inform future drug policy and advocacy efforts.

Take-home naloxone administered in emergency settings: feasibility of intervention implementation in a cluster randomized trial.

BACKGROUND: Opioids kill more people than any other class of drug. Naloxone is an opioid antagonist which can be distributed in kits for peer administration. We assessed the feasibility of implementing a Take-home Naloxone (THN) intervention in emergency settings, as part of designing a definitive randomised controlled trial (RCT). METHODS: We undertook a clustered RCT on sites pairing UK Emergency Departments (ED) and ambulance services. At intervention sites, we recruited emergency healthcare practitioners to supply THN to patients presenting with opioid overdose or related condition, with recruitment across 2019-2021. We assessed feasibility of intervention implementation against four predetermined progression criteria covering site sign up and staff training; identification of eligible patients; issue of THN kits and Serious Adverse Events. RESULTS: At two intervention sites, randomly selected from 4, 299/687 (43.5%) clinical staff were trained (ED1 = 107, AS1 = 121, ED2 = 25, AS2 = 46). Sixty THN kits were supplied to eligible patients (21.7%) (n: ED1 = 36, AS1 = 4, ED2 = 16, AS2 = 4). Across sites, kits were not issued to eligible patients on a further 164 occasions, with reasons reported including: staff forgot (n = 136), staff too busy (n = 15), and suspected intentional overdose (n = 3), no kit available (n = 2), already given by drugs nurse (n = 4), other (n = 4). Staff recorded 626 other patients as ineligible but considered for inclusion, with reasons listed as: patient admitted to hospital (n = 194), patient absconded (n = 161) already recruited (n = 64), uncooperative or abusive (n = 55), staff not trained (n = 43), reduced consciousness level (n = 41), lack of capacity (n = 35), patient in custody (n = 21), other (n = 12). No adverse events were reported. CONCLUSION: Staff and patient recruitment were low and varied widely by site. This feasibility study did not meet progression criteria; a fully powered RCT is not planned. TRIAL REGISTRATION: ISRCTN13232859 (Registered 16/02/2018).

Racialized environments and syringe services program implementation: County-level factors.

OBJECTIVE: Racialized health inequities in substance use-related harms might emerge from differential access to syringe service programs (SSPs). To explore this, we examined the association between county-level racialized environments, other factors, and (1) SSP presence, and (2) per capita syringe and (3) naloxone distribution. METHODS: 2021 US National Survey of SSP data (n=295/412;72 % response rate) was used to identify SSP presence and the sum of syringes and naloxone doses distributed in 2020 by county. Study measures included racial residential segregation (RRS; i.e., divergence and dissimilarity indexes for Black:Non-Hispanic White & Hispanic:Non-Hispanic White) and covariates (i.e., demographic proportions, urban/suburban/rural classifications, 2020 US presidential Republican vote share, and overdose mortality from 2019). We used logit Generalized Estimating Equations to determine factors associated with county-level SSP presence, and zero inflated negative binomial regression models to determine factors associated with per capita syringe and naloxone distribution. RESULTS: SSPs were reported in 9 % (283/3106) of US counties. SSP presence was associated with higher divergence and dissimilarity indexes, urban and suburban counties, higher opioid overdose mortality, and lower 2020 Republican presidential vote share. Per capita syringes distributed was associated with lower RRS (divergence and Hispanic:White dissimilarity), lower racially minoritized population proportions and rural counties, while per capita naloxone distribution was associated with lower Hispanic and "other" population proportions, and rural counties. CONCLUSIONS: Racialized environments are associated with SSP presence but not the scope of those programs. Preventing HIV and HCV outbreaks, and overdose deaths requires addressing community level factors that influence SSP implementation and accessibility.

Strategies used to reduce harms associated with fentanyl exposure among rural people who use drugs: multi-site qualitative findings from the rural opioid initiative.

AIM: Illicitly manufactured fentanyl and its analogs are the primary drivers of opioid overdose deaths in the United States (U.S.). People who use drugs may be exposed to fentanyl or its analogs intentionally or unintentionally. This study sought to identify strategies used by rural people who use drugs to reduce harms associated with unintentional fentanyl exposure. METHODS: This analysis focused on 349 semi-structured qualitative interviews across 10 states and 58 rural counties in the U.S conducted between 2018 and 2020. Interview guides were collaboratively standardized across sites and included questions about drug use history (including drugs currently used, frequency of use, mode of administration) and questions specific to fentanyl. Deductive coding was used to code all data, then inductive coding of overdose and fentanyl codes was conducted by an interdisciplinary writing team. RESULTS: Participants described being concerned that fentanyl had saturated the drug market, in both stimulant and opioid supplies. Participants utilized strategies including: (1) avoiding drugs that were perceived to contain fentanyl, (2) buying drugs from trusted sources, (3) using fentanyl test strips, 4) using small doses and non-injection routes, (5) using with other people, (6) tasting, smelling, and looking at drugs before use, and (7) carrying and using naloxone. Most people who used drugs used a combination of these strategies as there was an overwhelming fear of fatal overdose. CONCLUSION: People who use drugs living in rural areas of the U.S. are aware that fentanyl is in their drug supply and use several strategies to prevent associated harms, including fatal overdose. Increasing access to harm reduction tools (e.g., fentanyl test strips, naloxone) and services (e.g., community drug checking, syringe services programs, overdose prevention centers) should be prioritized to address the polysubstance-involved overdose crisis. These efforts should target persons who use opioids and other drugs that may contain fentanyl.

Harm Reduction and Treatment Among People at High Risk of Overdose.

Importance: Rates of overdose deaths involving synthetic opioids remain high, increasingly involve stimulants combined with opioids, and are increasing rapidly in racially and ethnically minoritized communities, yet little is known about access to harm reduction and treatment services in these groups. Objective: To characterize access and barriers to harm reduction and treatment in a racially and ethnically diverse population of people who use drugs. Design, Setting, and Participants: A cross-sectional telephone survey of people recruited from 39 treatment, harm reduction, and social service organizations in Milwaukee County, Wisconsin; Flint and Detroit, Michigan; and statewide in New Jersey was conducted from January 30 to July 28, 2023. Adults who used cocaine, methamphetamine, or opioids in the past 30 days called a study hotline and completed an interview in English or Spanish. Exposures: Overdose experience, drug types used (opioids only, stimulants only, and polysubstance), and social risk factors (eg, financial instability and criminal legal involvement). Main Outcomes and Measures: Recent use of any harm reduction services, fentanyl test strips, naloxone possession, treatment, and self-reported barriers to services. Results: Of the total sample of 1240 adults, 486 (39.2%) were Black non-Hispanic, 183 (14.8%) were Hispanic, and 464 (37.4%) were White non-Hispanic. In the past 30 days, 826 individuals (66.6%) were polysubstance users, 135 (10.9%) used only opioids, and 279 (22.5%) used only stimulants. A total of 349 respondents (28.1%) experienced a prior-year overdose. Compared with those without a prior-year overdose, people with overdose were more likely to possess naloxone (80.7% vs 68.2%; P < .001), possess fentanyl test strips (36.8% vs 23.5%; P < .001), and use harm reduction services (63.4% vs 53.0%; P = .003), while differences in treatment use were nonsignificant (52.0% vs 46.6%; P = .24). Among stimulant-only users, 51.4% possessed naloxone compared with 77.3% of opioid-only users (P < .001) and 77.6% of polysubstance users (P < .001), with similar disparities in fentanyl test strip possession. Conclusions and Relevance: In this cross-sectional study of people who used drugs in the past 30 days, findings highlighted low use of harm reduction and treatment services among people who use stimulants. Additional communication regarding their importance may help increase the use of the services amidst a rapidly changing drug supply.

Motor effects of fentanyl in isoflurane-anaesthetized pigs and the subsequent effect of ketanserin or naloxone.

OBJECTIVE: To examine the effect of ketanserin and naloxone on fentanyl-induced motor activity in isoflurane-anaesthetized pigs. STUDY DESIGN: Randomized, blinded, prospective two-group study. ANIMALS: A group of 12 crossbred pigs weighing 22-31 kg. METHODS: Fentanyl was administered to isoflurane-anaesthetized pigs at 7.5 µg kg-1 hour-1 for 40 minutes intravenously, followed by an intravenous injection of naloxone 0.1 mg kg-1 or ketanserin 1 mg kg-1. Electromyography (EMG) and accelerometry were used to record motor unit activity and tremors, respectively. To test the effect of drug administration on motor activity, data from a 5 minute period at baseline, immediately before and after antagonist injection were compared in a mixed model; p < 0.05. RESULTS: Results are reported with the median difference, 95% confidence intervals and corresponding p-values in brackets. Fentanyl significantly increased EMG activity [30.51 (1.84-81.02) µV, p = 0.004] and induced tremors [0.09 (0.02-0.18) m s-2, p < 0.001] in 10 of 12 pigs. Ketanserin significantly reduced EMG [32.22 (6.29-136.80) µV, p = 0.001] and tremor [0.10 (0.03-0.15) m s-2, p = 0.007] activity. No significant effect was found for naloxone on EMG [26.76 (-13.28-91.17) µV, p = 0.4] or tremors [0.08 (-0.01-0.19) m s-2, p = 0.08]. CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl can induce motor activity in anaesthetized pigs, with a suggested link to the serotonergic system. This study shows that ketanserin can antagonize this activity, which supports the role of serotonin. This knowledge contributes to the general understanding of the motor effects of fentanyl and especially the problem of tremors in anaesthetized pigs.

Naloxone and Patient Outcomes in Out-of-Hospital Cardiac Arrests in California.

Importance: The incidence of opioid-associated out-of-hospital cardiac arrest (OA-OHCA) has grown from less than 1% of OHCA in 2000 to between 7% and 14% of OHCA in recent years; American Heart Association (AHA) protocols suggest that emergency medical service (EMS) clinicians consider naloxone in OA-OHCA. However, it is unknown whether naloxone improves survival in these patients or in patients with undifferentiated OHCA. Objective: To evaluate the association of naloxone with clinical outcomes in patients with undifferentiated OHCA. Design, Setting, and Participants: Retrospective cohort study of EMS-treated patients aged 18 or older who received EMS treatment for nontraumatic OHCA in 3 Northern California counties between 2015 and 2023. Data were analyzed using propensity score-based models from February to April 2024. Exposure: EMS administration of naloxone. Main Outcomes and Measures: The primary outcome was survival to hospital discharge; the secondary outcome was sustained return of spontaneous circulation (ROSC). Covariates included patient and cardiac arrest characteristics (eg, age, sex, nonshockable rhythm, any comorbidity, unwitnessed arrest, and EMS agency) and EMS clinician determination of OHCA cause as presumed drug-related. Results: Among 8195 patients (median [IQR] age, 65 [51-78] years; 5540 male [67.6%]; 1304 Asian, Native Hawaiian, or Pacific Islander [15.9%]; 1119 Black [13.7%]; 2538 White [31.0%]) with OHCA treated by 5 EMS agencies from 2015 to 2023, 715 (8.7%) were believed by treating clinicians to have drug-related OHCA. Naloxone was administered to 1165 patients (14.2%) and was associated with increased ROSC using both nearest neighbor propensity matching (absolute risk difference [ARD], 15.2%; 95% CI, 9.9%-20.6%) and inverse propensity-weighted regression adjustment (ARD, 11.8%; 95% CI, 7.3%-16.4%). Naloxone was also associated with increased survival to hospital discharge using both nearest neighbor propensity matching (ARD, 6.2%; 95% CI, 2.3%-10.0%) and inverse propensity-weighted regression adjustment (ARD, 3.9%; 95% CI, 1.1%-6.7%). The number needed to treat with naloxone was 9 for ROSC and 26 for survival to hospital discharge. In a regression model that assessed effect modification between naloxone and presumed drug-related OHCA, naloxone was associated with improved survival to hospital discharge in both the presumed drug-related OHCA (odds ratio [OR], 2.48; 95% CI, 1.34-4.58) and non-drug-related OHCA groups (OR, 1.35; 95% CI, 1.04-1.77). Conclusions and Relevance: In this retrospective cohort study, naloxone administration as part of EMS management of OHCA was associated with increased rates of ROSC and increased survival to hospital discharge when evaluated using propensity score-based models. Given the lack of clinical practice data on the efficacy of naloxone in OA-OHCA and OHCA in general, these findings support further evaluation of naloxone as part of cardiac arrest care.

Dissemination of health content through social networks: YouTube and opioid use disorders.

INTRODUCTION: Most Americans now access social media platforms, including YouTube, to obtain health information. However, few studies have evaluated the quality of YouTube content related to opioid use disorder (OUD), including medications for OUD (MOUD; buprenorphine) and harm reduction resources (e.g., naloxone). The purpose of this cross-sectional analysis was to assess the quality, accuracy, and reliability of MOUD and harm reduction-related video content available on YouTube. METHODS: The study team conducted a YouTube search between June 2022 and July 2022 using key words related to MOUD and harm reduction content (e.g., "suboxone," "methadone," "Narcan"). The 5 most viewed videos from each search term were analyzed for quality (i.e., Global Quality Scale; GQS), accuracy (i.e., JAMA Benchmark Criteria), and reliability (i.e., DISCERN). Videos that were non-English, duplicate, or that did not directly mention OUD, MOUD, or harm reduction were excluded from the review (N = 6). RESULTS: YouTube videos (N = 70) were mostly produced by medical professionals (27.1 %), independent nonmedical users (21.4 %; e.g., vloggers, individuals documenting their experiences), medical organizations (17.1 %; e.g., hospitals, treatment programs), and/or media (14.3 %; e.g., news agencies). The target audience was primarily the general public (65.7 %), people who use opioids (20.0 %), and healthcare providers (10.0 %). Videos containing MOUD content (N = 64, 61.4 %) mostly focused on suboxone (25.0 %), methadone (23.4 %), Sublocade (14.1 %), and subutex/buprenorphine (14.1 %). The median quality score was 2 based on the GQS with 3 videos receiving the highest quality rating (5). Two videos were highly rated for accuracy per all three JAMA Benchmark criteria. Videos produced by nonmedical educational channels had the highest overall reliability scores on the DISCERN criteria (median 4), followed by medical professionals (median 3), and medical organizations (median 2.5). CONCLUSION: The overall quality, accuracy, and reliability of MOUD and harm reduction related content posted on YouTube is poor. The lack of evidence-based content posted on YouTube reinforces the need for public health expert involvement in disseminating guideline-based content on social media.

An individual-based dynamic model to assess interventions to mitigate opioid overdose risk.

BACKGROUND: Illicit opioid overdose continues to rise in North America and is a leading cause of death. Mathematical modeling is a valuable tool to investigate the epidemiology of this public health issue, as it can characterize key features of population outcomes and quantify the broader effect of structural and interventional changes on overdose mortality. The aim of this study is to quantify and predict the impact of key harm reduction strategies at differing levels of scale-up on fatal and nonfatal overdose among a population of people engaging in unregulated opioid use in Toronto. METHODS: An individual-based model for opioid overdose was built featuring demographic and behavioural variation among members of the population. Key individual attributes known to scale the risk of fatal and nonfatal overdose were identified and incorporated into a dynamic modeling framework, wherein every member of the simulated population encompasses a set of distinct characteristics that govern demographics, intervention usage, and overdose incidence. The model was parametrized to fatal and nonfatal overdose events reported in Toronto in 2019. The interventions considered were opioid agonist therapy (OAT), supervised consumption sites (SCS), take-home naloxone (THN), drug-checking, and reducing fentanyl in the drug supply. Harm reduction scenarios were explored relative to a baseline model to examine the impact of each intervention being scaled from 0% use to 100% use on overdose events. RESULTS: Model simulations resulted in 3690.6 nonfatal and 295.4 fatal overdoses, coinciding with 2019 data from Toronto. From this baseline, at full scale-up, 290 deaths were averted by THN, 248 from eliminating fentanyl from the drug supply, 124 from SCS use, 173 from OAT, and 100 by drug-checking services. Drug-checking and reducing fentanyl in the drug supply were the only harm reduction strategies that reduced the number of nonfatal overdoses. CONCLUSIONS: Within a multi-faceted harm reduction approach, scaling up take-home naloxone, and reducing fentanyl in the drug supply led to the largest reduction in opioid overdose fatality in Toronto. Detailed model simulation studies provide an additional tool to assess and inform public health policy on harm reduction.

Fentanyl harm reduction strategies among Latinx communities in the United States: a scoping review.

PURPOSE: Fueled by the prescription opioid overdose crisis and increased influx of illicitly manufactured fentanyl, fentanyl overdoses continue to be a public health crisis that has cost the US economy over $1 trillion in reduced productivity, health care, family assistance, criminal justice, and accounted for over 74,000 deaths in 2023. A recent demographic shift in the opioid crisis has led to a rise in overdose deaths among the Latinx population. Harm reduction interventions, including the use of naloxone and fentanyl test strips, have been shown to be effective measures at reducing the number of opioid overdose deaths. The aim of this scoping review is to summarize naloxone and fentanyl test strip interventions and public health policies targeted to Latinx communities. METHODS: PubMed, CINHAL, Web of Science, Embase, and PsycINFO research databases using the keywords "fentanyl," "Latinx," "Harm Reduction," "Naloxone," and "Fentanyl Test Strips'' to identify studies published between January 1, 2013 and December 31, 2023. Endnote and Covidence software were used to catalog and manage citations for review of studies. Subsequently, studies that met inclusion criteria were then summarized using resulting themes. RESULTS: Twenty-seven articles met the inclusion criteria and were further abstracted for the scoping review. Of these articles, 77.7% (n = 21) included a naloxone intervention, while only 11.1% (n = 3) included a fentanyl test strip intervention. Furthermore, 30.1% (n = 8) of these studies were Latinx targeted, and 7.7% (n = 2) of the studies were adapted for Latinx populations. Four themes, including an overall lack of knowledge and awareness, a lack of access to harm reduction or opioid overdose prevention resources, an overall lack of culturally adapted and/or targeted interventions, and restrictive and punitive policies that limit the effectiveness of protective factors were highlighted in this scoping review. CONCLUSION: Limited published research exists on the use of emerging harm reduction behaviors, such as the use of naloxone and fentanyl test strips as community intervention strategies to prevent opioid overdose deaths. Even fewer publications exist on the targeting and cultural adaptation of harm reduction interventions responsive to Latinx communities, especially those using theoretical approaches or frameworks to support these interventions. Future research is needed to assess the unique needs of Latinx populations and to develop culturally responsive programs to prevent opioid-related overdose deaths among this population.

Increases in housing rules and surveillance during COVID-19: impacts on overdose and overdose response in a community-based cohort of sex workers who use drugs in Vancouver, BC.

INTRODUCTION: Since the beginning of the COVID-19 pandemic, COVID-19 risk mitigation measures have expanded to include increased rules and surveillance in supportive housing. Yet, in the context of the dual public health emergencies of COVID-19 and the unregulated drug toxicity crisis, we have not evaluated the unintended health and social consequences of such measures, especially on criminalized women. In order to address this dearth of evidence, our aim was to assess the association between increased housing rules and surveillance during COVID-19 and (a) nonfatal overdose, and (b) administration of naloxone for overdose reversal among women sex workers who use drugs in Vancouver, BC. METHODS: This study is nested within An Evaluation of Sex Workers Health Access (AESHA), a community-based prospective cohort of women sex workers in Metro Vancouver (2010-present). Using cross-sectional data collected during the first year of COVID-19 (April 2020-2021), we developed separate multivariable logistic regression confounder models to examine the independent associations between experiencing increased housing rules and surveillance during COVID-19 on (a) nonfatal overdose, and (b) administration of naloxone for overdose reversal in the last 6 months. RESULTS: Amongst 166 participants, 10.8% reported experiencing a recent non-fatal overdose and 31.3% recently administered naloxone for overdose reversal. 56.6% reported experiencing increased rules and surveillance within their housing during COVID-19. The prevalence of non-fatal overdose and administering naloxone was significantly elevated among those exposed to increased housing rules and surveillance during COVID-19 versus those who were unexposed (83.3% vs. 52.1%; 75.0% vs. 48.2%, respectively). In separate multivariate confounder models, exposure to increased housing rules and surveillance during COVID-19 was independently associated with increased odds of administering naloxone [AOR: 3.66, CI: 1.63-8.21], and marginally associated with non-fatal overdose [AOR: 3.49, CI: 0.92-13.27]. CONCLUSION: Efforts to prioritize the right to safe, adequate and affordable housing must avoid reinforcing an overly coercive reliance on surveillance measures which, while often well-intended, can negatively shape residents' well-being. Furthermore, public health responses to pandemics must include criminalized populations so that measures do not exacerbate overdose risk. Implementation of a regulated drug supply is recommended, alongside housing policies that promote residents' rights, safety, and health.