A predictive risk model for nonfatal opioid overdose in a statewide population of buprenorphine patients.

BACKGROUND: Predicting which individuals who are prescribed buprenorphine for opioid use disorder are most likely to experience an overdose can help target interventions to prevent relapse and subsequent consequences. METHODS: We used Maryland prescription drug monitoring data from 2015 to identify risk factors for nonfatal opioid overdoses that were identified in hospital discharge records in 2016. We developed a predictive risk model for prospective nonfatal opioid overdoses among buprenorphine patients (N = 25,487). We estimated a series of models that included demographics plus opioid, buprenorphine and benzodiazepine prescription variables. We applied logistic regression to generate performance measures. RESULTS: About 3.24% of the study cohort had ≥1 nonfatal opioid overdoses. In the model with all predictors, odds of nonfatal overdoses among buprenorphine patients were higher among males (OR = 1.39, 95% CI:1.21-1.62) and those with more buprenorphine pharmacies (OR = 1.19, 95% CI:1.11-1.28), 1+ buprenorphine prescription paid by Medicaid (OR = 1.21, 95% CI:1.02-1.48), Medicare (OR = 1.93, 95% CI:1.63-2.43), or a commercial plan (OR = 1.98, 95% CI:1.30-2.89), 1+ opioid prescription paid by Medicare (OR = 1.30, 95% CI:1.03-1.68), and more benzodiazepine prescriptions (OR = 1.04, 95% CI:1.02-1.05). The odds were lower among those with longer days of buprenorphine (OR = 0.64, 95% CI:0.60-0.69) or opioid (OR = 0.79, 95% CI:0.65-0.95) supply. The model had moderate predictive ability (c-statistic = 0.69). CONCLUSIONS: Several modifiable risk factors, such as length of buprenorphine treatment, may be targets for interventions to improve clinical care and reduce harms. This model could be practically implemented with common prescription-related information and allow payers and clinical systems to better target overdose risk reduction interventions, such as naloxone distribution.

Evaluation of an Opiate Overdose Educational Intervention and Naloxone Prescribing Program in Homeless Adults Who Use Opiates.

Opiate overdose deaths are considered an epidemic by the Centers for Disease Control and Prevention. Homeless adults are disproportionately affected by opioid overdoses. The purpose of this project was to implement an opiate overdose training and routine naloxone prescribing program for patients at a Health Care for the Homeless clinic. Education consisted of overdose risk factors, signs of overdose, how to respond to an opiate overdose, and how to administer naloxone. Knowledge was measured with a pretest and a posttest. Intranasal naloxone was prescribed for each person who received the education, and prescription fill rates were tracked 1 week after the clinic visit. Patients had a significant increase in knowledge, and the overall naloxone fill rate was 33%. Fill rates varied by housing, insurance, and other prescription status. Opiate overdose education can effectively be delivered in a homeless medical clinic, although more research is needed regarding barriers to naloxone fill rates.

Epidemiología de las intoxicaciones agudas por drogas de abuso en las urgencias de un hospital del Centro de España basada en datos de análisis toxicológico de orina / Epidemiology of acute poisonings for drugs of abuse in the emergency room of a hospital from the Center of Spain based on analysis data toxicological urine

Introducción: las intoxicaciones agudas son motivo de consulta cada vez más frecuente en los Servicios de Urgencia hospitalarios (SUH) debido a la mayor disponibilidad y acceso a productos químicos tóxicos. Se observan diferentes patrones en cada área sanitaria según el tipo de población, geografía y perfil epidemiológico de consumo. Material y métodos: el objetivo de nuestro estudio es realizar un perfil epidemiológico y describir el manejo del paciente que acude por clínica compatible con intoxicación aguda por drogas de abuso (IA) basado en la determinación de tóxicos en orina para seis sustancias (cannabis, opiáceos, cocaína, anfetaminas, benzodiazepinas y éxtasis) solicitados en el período de estudio 2010-2012. Resultados: se solicitaron 2755 peticiones, de las cuales fueron positivas 1429, y se estudiaron al azar 661 historias clínicas. El perfil de paciente intoxicado de nuestra área es el de varón de entre 30 y 40 años, consumidor preferentemente de cannabis y cocaína; las benzodiazepinas son el tóxico más frecuente en las mujeres, con clínica mayoritariamente neurológica, sin diferencias en cuanto a la franja horaria o el mes del año en que recibió el alta desde el propio SUH en casi el 60% de los casos. Discusión: las IA en los SUH representan casi el 1% de las consultas y tienen una escasa mortalidad. En algunos casos, el médico de urgencias comienza el tratamiento antes de conocer el resultado toxicológico, lo que nos hace plantearnos la utilidad real y el coste-efectividad de estas determinaciones en todos los pacientes con alteración del nivel de conciencia. (AU)

Introduction: acute intoxications are a rising and common query demand on the emergency rooms because of the easy access and disponibility to toxic substances, where we can observe different patterns attending to type of population, geography and epidemiologic consume profile. Material and methods: our objective is to analyze the epidemiology and patient handling coming to the Emergency Room (ER) with compatible symptoms of street drugs abuse, based on the determination of cannabis, cocaine, amphetamine, benzodiazepine, opiates and ectasy urine levels in the period 2010-2012. Results: the ER requested 2755 determinations being positive 1429 and randomly examined 661 clinical histories. The profile of intoxicated patient was male, 30 to 40 years old, preferently cannabis and cocaine consumer (benzodiazepine in women), mostly with neurological symptoms when arrive, without differences between months or day time and, almost 60% of them, discharged directly from the ER. Conclusions: acute intoxications barely represent 1% of ER demands and produce poor or scarce mortality. Sometimes, doctors in charge start with therapeutic measures before knowing the results of toxicology, what leads us to ask about actual usefulness and cost-efficiency of the toxicology assay to every patient with low conscious level. (AU)

Therapeutical Neurotargeting via Magnetic Nanocarrier: Implications to Opiate-Induced Neuropathogenesis and NeuroAIDS.

Magnetite (Fe3O4) is the most commonly and extensively explored magnetic nanoparticles (MNPs) for drug-targeting and imaging in the field of biomedicine. Nevertheless, its potential application as safe and effective drug-carrier for CNS (Central Nervous System) anomalies is very limited. Previous studies have shown an entangled epidemic of opioid use and HIV infection and increased neuropathogenesis. Opiate such as morphine, heroine, etc. are used frequently as recreational drugs. Existing treatments to alleviate the action of opioid are less effective at CNS level due to impermeability of therapeutic molecules across brain barriers. Thus, development of an advanced nanomedicine based approach may pave the way for better treatment strategies. We herein report magnetic nanoformulation of a highly selective and potent morphine antagonist, CTOP (D-Pen-Cys-Tyr-DTrp-Orn-Thr-Pen-Thr-NH2), which is impenetrable to the brain. MNPs, synthesized in size range from 25 to 40 nm, were characterized by Transmission electron microscopy and assembly of MNPs-CTOP nanoformulations were confirmed by FTIR spectroscopy and fluorescent detection. Flow-cytometry analysis showed that biological efficacy of this nanoformulation in prevention of morphine induced apoptosis in peripheral blood mononuclear cells remains equivalent to that of free CTOP. Similarly, confocal microscopy reveals comparable efficacy of free and MNPs bound CTOP in protecting modulation of neuronal dendrite and spine morphology during morphine exposure and morphine-treated HIV infection. Further, typical transmigration assay showed increased translocation of MNPs across in vitro blood-brain barrier upon exposure of external magnetic force where barrier integrity remains unaltered. Thus, the developed nanoformulation could be effective in targeting brain by application of external magnetic force to treat morphine addiction in HIV patients.

Causes of rhabdomyolysis in acute poisonings.

BACKGROUND/AIM: Rhabdomyolysis (RM) is potentially lethal syndrome, but there are no enough published data on its frequency and characteristics in acute poisonings. The aim of this study was to determine the causes and severity of RM in acute poisonings. METHODS: Patients hospital charts were retrospectively screened during a one-year period in order to identify patients with RM among 656 patients treated due to acute poisonings with different agents. All the patients with RM were selected. Entrance criterion was the value of creatine kinase (CK) over 250 U/L. The severity of RM was assessed according to the Poison Severity Score. The patients were divided into three groups: the first one with mild RM (CK from 250 to 1,500 U/L), the second with moderate RM (CK from 1,500 to 10,000 U/L) and the third with severe RM (CK greater than 10,000 U/L). RESULTS: RM occurred in 125 (19%) of the patients with acute poisonings. It was mainly mild (61%), or moderate (36%), and only in 3% of the patients was severe RM. The incidence of RM was the highest in poisonings with opiates (41%), pesticides (38%), neuroleptics (26%), anticonvulsants (26%), ethyl alcohol (20%), and gases (19%). Psychotropic agents were the most common causes of poisoning, and consequently of RM. Fatal outcomes were registered in 32 (25.60%) of all RM patients. The incidence of fatal outcomes in poisonings with mild, moderate and severe RM was 19.73%, 31.11% and 75%, respectively. CONCLUSION: RM syndrome occurs at a relatively high rate in acute poisonings. Although agent's toxicity is crucial for the outcome, severe RM and its complications may significantly influence the clinical course and prognosis of poisoning. Routine analysis of CK, as a relevant marker for RM may indicate the development of RM in acute poisoning and initiate prompt therapeutic measures in preventing acute renal failure as the most frequent consequence of extensive rhabdomyolysis.

Method for quantification of opioids and their metabolites in autopsy blood by liquid chromatography-tandem mass spectrometry.

A method using liquid chromatography-electrospray ionization-tandem mass spectrometry was developed and validated for the determination of morphine, codeine, hydromorphone, dihydrocodeine, oxycodone, buprenorphine, and naloxone with their metabolites morphine-3-glucuronide, morphine-6-glucuronide, normorphine, 6-acetylmorphine, 6-acetylcodeine, codeine-6-glucuronide, norcodeine, hydromorphine-3-glucuronide, dihydrocodeine-6-glucuronide, dihydromorphine, dihydromorphine-3-glucuronide, dihydromorphine-6-glucuronide, oxymorphone, norbuprenorphine, buprenorphine-3-glucuronide, norbuprenorphine-3-glucuronide, and naloxone-3-glucuronide in human whole blood. Polar metabolites (glucuronides) and other analytes were extracted by SPE using Bond Elut C18. Chromatographic separation was performed on a Phenomenex Synergi reversed-phase column with gradient elution based on a mobile phase consisting of 10mM ammonium formate adjusted to pH 3 and acetonitrile. Intraday and interday precision for all analytes were between 0.6% and 13.8%, and recoveries were between 80.3% and 101.4%. Calibration curves were linear for all analytes over the concentration range 5-400 ng/mL, and correlation coefficients (R(2)) were better than 0.999. Limits of detection and quantitation were 0.16-1.2 ng/mL and 0.5-4.09 ng/mL, respectively. The method described consolidates previous work on opioids and their metabolites published in the literature and is the first to include the detection of naloxone-3-glucuronide. The method has been applied in routine postmortem cases after opiate overdose with the threefold purpose of providing interpretive information on the cause and type of death (rapid, sub-acute, or delayed death) and to distinguish heroin, morphine, and codeine users.

Physicians' knowledge of and willingness to prescribe naloxone to reverse accidental opiate overdose: challenges and opportunities.

Naloxone, the standard treatment for heroin overdose, is a safe and effective prescription drug commonly administered by emergency room physicians or first responders acting under standing orders of physicians. High rates of overdose deaths and widely accepted evidence that witnesses of heroin overdose are often unwilling or unable to call 9-1-1 has led to interventions in several US cities and abroad in which drug users are instructed in overdose rescue techniques and provided a "take-home" dose of naloxone. Under current Food and Drug Administration (FDA) regulations, such interventions require physician involvement. As part of a larger study to evaluate the knowledge and attitudes of doctors towards providing drug treatment and harm reduction services to injection drug users (IDUs), we investigated physician knowledge and willingness to prescribe naloxone. Less than one in four of the respondents in our sample reported having heard of naloxone prescription as an intervention to prevent opiate overdose, and the majority reported that they would never consider prescribing the agent and explaining its application to a patient. Factors predicting a favorable attitude towards prescribing naloxone included fewer negative perceptions of IDUs, assigning less importance to peer and community pressure not to treat IDUs, and increased confidence in ability to provide meaningful treatment to IDUs. Our data suggest that steps to promote naloxone distribution programs should include physician education about evidence-based harm minimization schemes, broader support for such initiatives by professional organizations, and policy reform to alleviate medicolegal concerns associated with naloxone prescription. FDA re-classification of naloxone for over-the-counter sales and promotion of nasal-delivery mechanism for this agent should be explored.