RESUMEN

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.

Asunto(s)

Fentanilo , Reducción del Daño , Ensayos Clínicos Controlados Aleatorios como Asunto , Tiras Reactivas , Fentanilo/orina , Fentanilo/efectos adversos , Humanos , Ohio , Naloxona/administración & dosificación , Sobredosis de Droga/prevención & control , Sobredosis de Droga/orina , Detección de Abuso de Sustancias/métodos , Trastornos Relacionados con Opioides/prevención & control , Trastornos Relacionados con Opioides/orina , Trastornos Relacionados con Opioides/diagnóstico , Analgésicos Opioides/orina , Analgésicos Opioides/efectos adversos , Antagonistas de Narcóticos , Sobredosis de Opiáceos/prevención & control , Sobredosis de Opiáceos/epidemiología , Estudios Multicéntricos como Asunto , Servicios Urbanos de Salud , Drogas Ilícitas/orina

RESUMEN

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.

Asunto(s)

Analgésicos Opioides , Sobredosis de Droga , Naloxona , Antagonistas de Narcóticos , Naloxona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Humanos , Sobredosis de Droga/prevención & control , Sobredosis de Droga/tratamiento farmacológico , Estados Unidos , Masculino , Femenino , Trastornos Relacionados con Opioides/tratamiento farmacológico , Adulto , Persona de Mediana Edad

RESUMEN

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.

Asunto(s)

Analgésicos , Arginina , GMP Cíclico , Canales KATP , NG-Nitroarginina Metil Éster , Óxido Nítrico , Receptores Opioides , Rutina , Transducción de Señal , Animales , Masculino , Ratones , Arginina/farmacología , Óxido Nítrico/metabolismo , Rutina/farmacología , Analgésicos/farmacología , Transducción de Señal/efectos de los fármacos , Receptores Opioides/metabolismo , Receptores Opioides/efectos de los fármacos , Canales KATP/metabolismo , GMP Cíclico/metabolismo , NG-Nitroarginina Metil Éster/farmacología , Gliburida/farmacología , Citrato de Sildenafil/farmacología , Dimensión del Dolor/efectos de los fármacos , Dimensión del Dolor/métodos , Naloxona/farmacología , Sulfonas/farmacología , Piperazinas/farmacología , Purinas/farmacología , S-Nitroso-N-Acetilpenicilamina/farmacología , Dolor/tratamiento farmacológico , Dolor/metabolismo , Antagonistas de Narcóticos/farmacología , Relación Dosis-Respuesta a Droga , Donantes de Óxido Nítrico/farmacología

RESUMEN

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.

Asunto(s)

Cadherinas , Carcinoma de Pulmón de Células no Pequeñas , Movimiento Celular , Proliferación Celular , Neoplasias Pulmonares , Morfina , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Serina-Treonina Quinasas TOR , Cadherinas/metabolismo , Humanos , Serina-Treonina Quinasas TOR/metabolismo , Animales , Morfina/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Transducción de Señal/efectos de los fármacos , Ratones , Proliferación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Ratones Desnudos , Células A549 , Progresión de la Enfermedad , Línea Celular Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , Regulación hacia Abajo/efectos de los fármacos , Naloxona/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Masculino

RESUMEN

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.

Asunto(s)

Analgésicos , Neuropatías Diabéticas , Formaldehído , Quercetina , Animales , Ratones , Neuropatías Diabéticas/tratamiento farmacológico , Neuropatías Diabéticas/inducido químicamente , Quercetina/análogos & derivados , Quercetina/farmacología , Quercetina/uso terapéutico , Analgésicos/farmacología , Analgésicos/uso terapéutico , Masculino , Modelos Animales de Enfermedad , Dolor/tratamiento farmacológico , Dolor/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/complicaciones , Yohimbina/farmacología , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Naloxona/farmacología , Naloxona/uso terapéutico , Estreptozocina , Dimensión del Dolor/efectos de los fármacos , Relación Dosis-Respuesta a Droga

RESUMEN

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.

Asunto(s)

Naloxona , Programas de Intercambio de Agujas , Humanos , Naloxona/uso terapéutico , Estados Unidos/epidemiología , Sobredosis de Droga/epidemiología , Antagonistas de Narcóticos/uso terapéutico , Accesibilidad a los Servicios de Salud , Hispánicos o Latinos , Población Blanca

RESUMEN

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.

Asunto(s)

Analgésicos Opioides , Fentanilo , Reducción del Daño , Población Rural , Humanos , Fentanilo/envenenamiento , Femenino , Estados Unidos/epidemiología , Adulto , Masculino , Analgésicos Opioides/envenenamiento , Analgésicos Opioides/efectos adversos , Persona de Mediana Edad , Trastornos Relacionados con Opioides/prevención & control , Sobredosis de Droga/prevención & control , Sobredosis de Droga/epidemiología , Sobredosis de Opiáceos/prevención & control , Sobredosis de Opiáceos/epidemiología , Adulto Joven , Investigación Cualitativa , Naloxona/uso terapéutico

RESUMEN

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.

Asunto(s)

Sobredosis de Droga , Reducción del Daño , Humanos , Femenino , Masculino , Adulto , Estudios Transversales , Sobredosis de Droga/prevención & control , Persona de Mediana Edad , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Adulto Joven , Naloxona/uso terapéutico , Trastornos Relacionados con Sustancias , Factores de Riesgo , Wisconsin , New Jersey , Michigan , Analgésicos Opioides/uso terapéutico

Asunto(s)

Naloxona , Antagonistas de Narcóticos , Epidemia de Opioides , Lugar de Trabajo , Humanos , Naloxona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Salud Laboral , Trastornos Relacionados con Opioides/prevención & control

RESUMEN

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.

Asunto(s)

Reducción del Daño , Difusión de la Información , Trastornos Relacionados con Opioides , Medios de Comunicación Sociales , Grabación en Video , Humanos , Medios de Comunicación Sociales/normas , Trastornos Relacionados con Opioides/epidemiología , Estudios Transversales , Difusión de la Información/métodos , Reproducibilidad de los Resultados , Naloxona/uso terapéutico , Buprenorfina/uso terapéutico

RESUMEN

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.

Asunto(s)

Reducción del Daño , Naloxona , Antagonistas de Narcóticos , Sobredosis de Opiáceos , Trastornos Relacionados con Opioides , Humanos , Sobredosis de Opiáceos/prevención & control , Sobredosis de Opiáceos/epidemiología , Sobredosis de Opiáceos/mortalidad , Naloxona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Trastornos Relacionados con Opioides/mortalidad , Trastornos Relacionados con Opioides/epidemiología , Trastornos Relacionados con Opioides/prevención & control , Femenino , Adulto , Masculino , Modelos Teóricos , Ontario/epidemiología , Analgésicos Opioides/envenenamiento , Adulto Joven , Persona de Mediana Edad , Adolescente , Fentanilo/envenenamiento , Sobredosis de Droga/prevención & control , Sobredosis de Droga/mortalidad , Sobredosis de Droga/epidemiología

RESUMEN

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.

Asunto(s)

Fentanilo , Reducción del Daño , Hispánicos o Latinos , Naloxona , Antagonistas de Narcóticos , Humanos , Fentanilo/envenenamiento , Naloxona/uso terapéutico , Estados Unidos/epidemiología , Antagonistas de Narcóticos/uso terapéutico , Hispánicos o Latinos/estadística & datos numéricos , Trastornos Relacionados con Opioides/prevención & control , Analgésicos Opioides/envenenamiento , Sobredosis de Droga/prevención & control , Sobredosis de Opiáceos/prevención & control

Asunto(s)

Paro Cardíaco , Naloxona , Antagonistas de Narcóticos , Humanos , Paro Cardíaco/tratamiento farmacológico , Paro Cardíaco/terapia , Naloxona/uso terapéutico , Naloxona/administración & dosificación , Antagonistas de Narcóticos/uso terapéutico , Reanimación Cardiopulmonar/métodos

Asunto(s)

Reducción del Daño , Naloxona , Antagonistas de Narcóticos , Rhode Island , Humanos , Naloxona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Femenino , Masculino , Adulto , Sobredosis de Droga/prevención & control , Disparidades en Atención de Salud , Trastornos Relacionados con Opioides/tratamiento farmacológico

RESUMEN

Importance: Despite the proliferation of pharmacy standing-order naloxone dispensing across many US states before the change to over-the-counter status, few policy analyses have evaluated the implementation of pharmacy naloxone standing orders in addressing opioid overdose fatality among communities. Objective: To determine whether the implementation of pharmacy standing-order naloxone was associated with lower opioid fatality rates compared with communities without pharmacies with standing-order naloxone. Design, Setting, and Participants: This retrospective multisite study was conducted with an interrupted time series analysis across 351 municipalities in Massachusetts over 24 quarters (from January 1, 2013, through December 31, 2018). Standing-order naloxone dispensing data were collected from 2 sources for all major chain pharmacies and many independent pharmacies, covering 70% of retail pharmacies in Massachusetts. Municipalities had various standing-order naloxone implementation inceptions during the study period. Data were analyzed from December 2021 to November 2023. Exposure: The main exposure was measured by the first quarter with standing-order naloxone dispensation as the actual implementation inception. Main Outcomes and Measures: The primary study outcome was municipal opioid fatality rate per 100 000 population obtained from the Massachusetts Registry of Vital Records and Statistics. Results: The median (IQR) population size across 351 municipalities was 10 314 (3635 to 21 781) people, with mean (SD) proportion of female individuals was 51.1% (2.8 percentage points). Pharmacies from 214 municipalities (60.9%) reported dispensing standing-order naloxone over the study period. At the baseline of the first quarter of 2013, municipalities that eventually had standing-order naloxone had greater quarterly opioid fatality rates compared with those that never implemented standing-order naloxone (3.51 vs 1.03 deaths per 100 000 population; P < .001). After adjusting for municipal-level sociodemographic and opioid prevention factors, there was significant slope decrease of opioid fatality rates (annualized rate ratio, 0.84; 95% CI, 0.78-0.91; P < .001) following standing-order naloxone dispensing, compared with the municipalities that did not implement standing-order naloxone. There were no significant level changes of opioid fatality rates in the adjusted models. Sensitivity analyses yielded similar and significant findings. Conclusions and Relevance: These findings suggest that community pharmacy dispensing of naloxone with standing orders was associated with a relative, gradual, and significant decrease in opioid fatality rates compared with communities that did not implement the standing-order naloxone program. These findings support the expansion of naloxone access, including over-the-counter naloxone as part of a multifaceted approach to address opioid overdose.

Asunto(s)

Naloxona , Antagonistas de Narcóticos , Naloxona/uso terapéutico , Humanos , Massachusetts/epidemiología , Estudios Retrospectivos , Antagonistas de Narcóticos/uso terapéutico , Femenino , Masculino , Sobredosis de Opiáceos/mortalidad , Sobredosis de Opiáceos/tratamiento farmacológico , Sobredosis de Opiáceos/epidemiología , Análisis de Series de Tiempo Interrumpido , Órdenes Permanentes , Adulto , Persona de Mediana Edad , Farmacias/estadística & datos numéricos , Analgésicos Opioides/uso terapéutico , Sobredosis de Droga/mortalidad , Sobredosis de Droga/tratamiento farmacológico , Trastornos Relacionados con Opioides/mortalidad , Trastornos Relacionados con Opioides/tratamiento farmacológico

RESUMEN

BACKGROUND: Despite the widespread use of the phrase "harm reduction" and the proliferation of programs based on its principles during the current opioid epidemic, what it means in practice is not universally agreed upon. Harm reduction strategies have expanded from syringe and needle exchange programs that emerged in the mid-1980s primarily in response to the HIV epidemic, to include medication for opioid use disorder, supervised consumption rooms, naloxone distribution, and drug checking technologies such as fentanyl test strips. Harm reduction can often be in tension with abstinence and recovery models to address substance use, and people who use drugs may also hold competing views of what harm reduction means in practice. Street-based outreach workers are increasingly incorporated into harm reduction programs as part of efforts to engage with people more fully in various stages of drug use and nonuse. METHOD: This paper explores how peer outreach workers, called "members," in a street-based naloxone distribution program define and practice harm reduction. We interviewed 15 members of a street-based harm reduction organization in an urban center characterized by an enduring opioid epidemic. Inductive data analysis explored harm reduction as both a set of principles and a set of practices to understand how frontline providers define and enact them. RESULTS: Analysis revealed that when members talked about their work, they often conceptualized harm reduction as a collection of ways members and others can "save lives" and support people who use drugs. They also framed harm reduction as part of a "path toward recovery." This path was complicated and nonlinear but pursued a common goal of life without drug use and its residual effects. These findings suggest the need to develop harm reduction programs that incorporate both harm reduction and recovery to best meet the needs of people who use drugs and align with the value systems of implementers.

Asunto(s)

Reducción del Daño , Naloxona , Antagonistas de Narcóticos , Grupo Paritario , Humanos , Naloxona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Femenino , Trastornos Relacionados con Opioides/prevención & control , Masculino , Adulto , Investigación Cualitativa , Relaciones Comunidad-Institución , Programas de Intercambio de Agujas

RESUMEN

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).

Asunto(s)

Servicio de Urgencia en Hospital , Estudios de Factibilidad , Naloxona , Antagonistas de Narcóticos , Humanos , Naloxona/administración & dosificación , Naloxona/uso terapéutico , Antagonistas de Narcóticos/administración & dosificación , Antagonistas de Narcóticos/uso terapéutico , Masculino , Femenino , Adulto , Reino Unido , Persona de Mediana Edad , Sobredosis de Droga/tratamiento farmacológico , Sobredosis de Opiáceos/tratamiento farmacológico

Asunto(s)

Naloxona , Antagonistas de Narcóticos , Paro Cardíaco Extrahospitalario , Humanos , Naloxona/uso terapéutico , Paro Cardíaco Extrahospitalario/tratamiento farmacológico , Antagonistas de Narcóticos/uso terapéutico , Analgésicos Opioides/uso terapéutico , Analgésicos Opioides/efectos adversos , Masculino , Femenino , Persona de Mediana Edad

RESUMEN

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.

Asunto(s)

COVID-19 , Sobredosis de Droga , Vivienda , Naloxona , Antagonistas de Narcóticos , Trabajadores Sexuales , Humanos , COVID-19/epidemiología , Femenino , Sobredosis de Droga/epidemiología , Adulto , Colombia Británica/epidemiología , Naloxona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Trabajadores Sexuales/estadística & datos numéricos , Estudios Prospectivos , Estudios Transversales , SARS-CoV-2 , Estudios de Cohortes , Adulto Joven

RESUMEN

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.

Asunto(s)

Anestésicos por Inhalación , Fentanilo , Isoflurano , Ketanserina , Naloxona , Animales , Fentanilo/farmacología , Fentanilo/administración & dosificación , Naloxona/farmacología , Porcinos , Ketanserina/farmacología , Isoflurano/farmacología , Anestésicos por Inhalación/farmacología , Femenino , Masculino , Actividad Motora/efectos de los fármacos , Anestésicos Intravenosos/farmacología , Antagonistas de Narcóticos/farmacología