RESUMEN

Objective: Access to naloxone is a priority for reducing opioid overdose deaths. Although participants who receive naloxone training are able to successfully administer it, the impact of training on community member knowledge and attitudes has not been explored. Participants: A total of 105 participants 18 years and older at a medium-sized university completed assessments between August and December 2019. Methods: Participants were scheduled to complete a standardized 30-minute naloxone training as developed by the research team. Assessments were taken at baseline, immediately following, and three-months following education using the Opioid Overdose Knowledge Scale (OOKS) and Opioid Overdose Attitudes Scale (OOAS). Results: The primary endpoint of change from baseline to immediate post-education for total OOKS and OOAS median scores significantly improved (p < 0.001) by 31 and 34 points, respectively. Conclusions: Naloxone education provides an opportunity to improve community attitudes and reduce stigma over time.

Asunto(s)

RESUMEN

Who: This position statement is a collaborative effort by the American Academy of Clinical Toxicology (AACT) and the American Association of Poison Control Centers (AAPCC) and has been endorsed by the American College of Medical Toxicology (ACMT). The position statement describes loperamide misuse, proposed mechanisms of toxicity, adverse clinical effects, and recommendations for the acute monitoring and management of patients with loperamide toxicity.Why: Use of high-dose loperamide for its euphoric effects and to self-treat opioid use disorder (in place of evidence-based therapies, like buprenorphine or methadone), is increasing. Despite reports in the medical literature and lay press, many remain unaware of high-dose loperamide use and how to manage patients with loperamide-associated toxicities.Target audience: Providers in Emergency Medicine; Prehospital; Intensive Care; Internal Medicine; Primary Care; Gastroenterology; Addiction Medicine; Pharmacy.

Asunto(s)

RESUMEN

STUDY OBJECTIVE: Access to naloxone is a priority for reducing opioid deaths. Although community members who complete naloxone training are able to administer nasal naloxone successfully and rapidly, little is known about the ability of community members to administer naloxone without training. The objective of this study was to assess the ability of untrained individuals to administer naloxone successfully in a simulated opioid overdose setting. DESIGN: Prospective single-site open-label randomized usability assessment. SETTING: Scenario station at a large state fair during August and September 2017. PARTICIPANTS: A total of 207 healthy adults who were randomly assigned to administer naloxone using a nasal spray (NS) device (69 participants), an intramuscular (IM) kit (68 participants), or an improvised nasal atomizer (AT) kit (70 participants). INTERVENTION: Participants were instructed to administer the device to a high-fidelity mannequin in a public environment with distractions to mimic those that might be present in an actual overdose. No device instructions or administration materials were provided. MEASUREMENTS AND MAIN RESULTS: Participants were assessed by trained study team members who directly observed all naloxone administrations using the predetermined end-point criteria. Individual participant perceptions were evaluated immediately following the naloxone administration using a standardized questionnaire form. The primary outcome was successful administration, defined as administration within 7 minutes and without critical errors. Secondary outcomes were time to successful naloxone administration and ease of use of the device. The NS (66.7%, p<0.001) and IM (51.5%, p<0.001) devices had higher rates of successful administration than the improvised nasal AT device (2.9%). The NS device was administered more rapidly (median 16 sec) than the IM device (median 58 sec, p<0.001) or improvised nasal AT device (median 113 sec, p=0.012) devices, and it was the easiest to use. CONCLUSION: In this study of naloxone administration, participants administered the NS and IM devices more successfully than the AT device. The NS device was administered most rapidly and was easiest to use.

Asunto(s)

RESUMEN

Introduction: Limitations of urine drug-screening (UDS) by immunoassay include false-positive results. Pantoprazole, a proton-pump inhibitor (PPI), is reported to cause false-positive results for THC on UDS. The objective of this study was to determine if oral PPIs cause false-positive THC results using the THC One Step Marijuana Test Strip®.Methods: Eligible healthy volunteers completed a 5-day course of a PPI followed by urine testing using the THC One Step Marijuana Test Strip®. Phase one included 3 subjects taking pantoprazole 40 mg once daily for 5 days. On day 5, urine specimens underwent THC screening. Phase two included 9 subjects randomized to 5-day supply of once-daily oral esomeprazole 20 mg, lansoprazole 15 mg, or omeprazole 20 mg. All study methods and testing mirrored those in phase one.Results: All 12 subjects completed the study protocol. All urine samples collected on day 5 were negative for THC in all subjects.Discussion: Our results demonstrate that oral PPIs did not cause a false-positive THC using the THC One Step Marijuana Test Strip®. Limitations include small sample size, use of a single commercial immunoassay, and inability to confirm medication compliance. Further, large-scale research using other commercial urine immunoassays is warranted.

Asunto(s)

Asunto(s)

RESUMEN

BACKGROUND: Kratom is an herbal supplement containing alkaloids with opioid properties. This review was conducted to determine toxicities associated with kratom use in the United States in order to provide insight into its safety as a dietary supplement. METHODS: We conducted a retrospective review of kratom exposures reported to the National Poison Data System to determine the toxicities associated with kratom use. We also reviewed records from a county medical examiner's office in New York State to identify kratom-associated fatalities. RESULTS: A total of 2312 kratom exposures were reported, with 935 cases involving kratom as the only substance. Kratom most commonly caused agitation (18.6%), tachycardia (16.9%), drowsiness (13.6%), vomiting (11.2%), and confusion (8.1%). Serious effects of seizure (6.1%), withdrawal (6.1%), hallucinations (4.8%), respiratory depression (2.8%), coma (2.3%), and cardiac or respiratory arrest (0.6%) were also reported. Kratom was listed as a cause or contributing factor in the death of four decedents identified by the county medical examiner's office. CONCLUSIONS: Kratom use is increasing and is associated with significant toxicities. Our findings suggest kratom is not reasonably expected to be safe and poses a public health threat due to its availability as an herbal supplement.

Asunto(s)

Asunto(s)

Asunto(s)

RESUMEN

OBJECTIVE: St. Paul's Early Discharge Rule was derived to determine which patients could be safely discharged from the emergency department after a 1-hour observation period following naloxone administration for opiate overdose. The rule suggested that patients could be safely discharged if they could mobilize as usual and had a normal oxygen saturation, respiratory rate, temperature, heart rate, and Glasgow Coma Scale score. Validation of the St. Paul's Early Discharge Rule is necessary to ensure that these criteria are appropriate to apply to patients presenting after an unintentional presumed opioid overdose in the context of emerging synthetic opioids and expanded naloxone access. METHODS: In this prospective, observational validation study, emergency medicine providers assessed patients 1 hour after administration of prehospital naloxone. Unlike in the derivation study the threshold for normal oxygen saturation was set at 95% and patients were not immediately discharged after a normal 1-hour evaluation. Patients were judged to have a normal 1-hour evaluation if all six criteria of the rule were met. Patients were judged to have an adverse event (AE) if they had one or more of the preestablished AEs. RESULTS: A total of 538 patients received at least one administration of prehospital naloxone, were transported to the study hospital, and had a 1-hour evaluation performed by a provider. AEs occurred in 82 (15.4%) patients. The rule exhibited a sensitivity of 84.1% (95% confidence interval [CI] = 76.2%-92.1%), a specificity of 62.1% (95% CI = 57.6%-66.5%), and a negative predictive value of 95.6% (95% CI = 93.3%-97.9%). Only one patient with a normal 1-hour evaluation subsequently received additional naloxone following a presumed heroin overdose. CONCLUSION: This rule may be used to risk stratify patients for early discharge following naloxone administration for suspected opioid overdose.

Asunto(s)

Asunto(s)

RESUMEN

Until the mid-1950s, it was believed that genetic crossovers did not occur within genes. Crossovers occurred between genes, the "beads on a string" model. Then in 1956, Seymour Benzer published his classic paper describing crossing over within a gene, intragenic recombination. This result from a bacteriophage gene prompted Oliver Nelson to study intragenic recombination in the maize Waxy locus. His studies along with subsequent work by others working with maize and other organisms described the outcomes of intragenic recombination and provided some of the earliest evidence that genes, not intergenic regions, were recombination hotspots. High-throughput genotyping approaches have since replaced single gene intragenic studies for characterizing the outcomes of recombination. These large-scale studies confirm that genes, or more generally genic regions, are the most active recombinogenic regions, and suggested a pattern of crossovers similar to the budding yeast Saccharomyces cerevisiae. In S. cerevisiae recombination is initiated by double-strand breaks (DSBs) near transcription start sites (TSSs) of genes producing a polarity gradient where crossovers preferentially resolve at the 5' end of genes. Intragenic studies in maize yielded less evidence for either polarity or for DSBs near TSSs initiating recombination and in certain respects resembled Schizosaccharomyces pombe or mouse. These different perspectives highlight the need to draw upon the strengths of different approaches and caution against relying on a single model system or approach for understanding recombination.

RESUMEN

BACKGROUND AND AIMS: Expanded access to naloxone has been identified as a key intervention for reducing opioid-related morbidity and mortality. It is not known which naloxone device will result in rapid, successful administration when administered by community members. The aims of this study were to estimate and compare (1) the rate of successful administration and (2) time to successful administration for single-step nasal spray, multi-step atomized nasal spray and intramuscular simulated naloxone by community members. DESIGN: A prospective, single-site, open-label, randomized usability assessment of simulated naloxone administration in a convenience sample of community members. Participants were randomized to single-step nasal spray (SP), multi-step atomized nasal spray (AT) or intramuscular simulated (IM) naloxone and asked to administer the simulated medication to a mannequin after completing a 2-minute training video. SETTING: New York, USA at a state fair that attracts between 60 000 and 120 000 individuals daily. PARTICIPANTS: A total of 138 participants completed the study over a 2-day period in September 2016. All participants were at least 18 years of age and had no prior naloxone training. MEASUREMENTS: The rate of successful administration and time to successful administration were recorded for each device. FINDINGS: The SP device (100%; P < 0.001) had a higher rate of success compared with the IM device (69.6%). Although success differed between the AT (89.1%) device and IM device, as well as the AT device and SP device, these differences were not significant. The SP device also had a shorter median time to successful administration (34.3 sec) compared with the IM (99.9 sec; P < 0.001) and AT (110.3; P < 0.001) devices. CONCLUSIONS: After video training, community members are able to (1) administer single-step nasal spray naloxone with a higher rate of success than intramuscular naloxone in a simulated overdose setting and (2) administer single-step nasal spray naloxone more rapidly than both intramuscular and multi-step atomized nasal spray naloxone.

Asunto(s)

RESUMEN

BACKGROUND: Use of the QT interval corrected for heart rate (QTc) on the electrocardiogram (ECG) to predict torsades de pointes (TdP) risk from culprit drugs is neither sensitive nor specific. The ratio of the half-maximum inhibitory concentration of the hERG channel (hERG IC50) to the peak serum concentration of unbound drug (Cmax ) is used during drug development to screen out chemical entities likely to cause TdP. PURPOSE: To validate the use of the hERG IC50:Cmax ratio to predict TdP risk from a culprit drug by its correlation with TdP incidence. DATA SOURCES: Medline (between 1966 and March 2017) was accessed for hERG IC50 and Cmax values from the antihistamine, fluoroquinolone, and antipsychotic classes to identify cases of drug-induced TdP. Exposure to a culprit drug was estimated from annual revenues reported by the manufacturer. STUDY SELECTION: Inclusion criteria for TdP cases were provision of an ECG tracing that demonstrated QTc prolongation with TdP and normal serum values of potassium, calcium, and magnesium. Cases reported in patients with a prior rhythm disturbance and those involving a drug interaction were excluded. DATA EXTRACTION AND SYNTHESIS: The Meta-Analysis of Observational Studies in Epidemiology checklist was used for epidemiological data extraction by two authors. MAIN OUTCOME AND MEASURE: Negligible risk drugs were defined by an hERG IC50:Cmax ratio that correlated with less than a 5% chance of one TdP event for every 100 million exposures (relative risk [RR] 1.0). RESULTS: The hERG IC50:Cmax ratio correlated with TdP risk (0.312; 95% confidence interval 0.205-0.476, p<0.0001), a ratio of 80 (RR 1.0). The RR from olanzapine is on par with loratadine; ziprasidone is comparable with ciprofloxacin. Drugs with an RR greater than 50 include astemizole, risperidone, haloperidol, and thioridazine. CONCLUSIONS: The hERG IC50:Cmax ratio was correlated with TdP incidence for culprit drugs. This validation provides support for the potential use of the hERG IC50:Cmax ratio for clinical decision making in instances of drug selection where TdP risk is a concern.

Asunto(s)

Asunto(s)

RESUMEN

Loperamide is an over-the-counter antidiarrheal with µ-opioid agonist activity. Central nervous system opioid effects are not observed after therapeutic oral dosing because of poor bioavailability and minimal central nervous system penetration. However, central nervous system opioid effects do occur after supratherapeutic oral doses. Recently, oral loperamide abuse as an opioid substitute has been increasing among patients attempting to self-treat their opioid addiction. Ventricular dysrhythmias and prolongation of the QRS duration and QTc interval have been reported after oral loperamide abuse. We describe 2 fatalities in the setting of significantly elevated loperamide concentrations.

Asunto(s)

RESUMEN

Loperamide is an over-the-counter antidiarrheal with opioid-receptor agonist properties. Recommended over-the-counter doses (range = 2-8 mg daily) do not produce opioid effects in the central nervous system because of poor oral bioavailability and P-glycoprotein efflux* of the medication (1); recent reports suggest that large doses (50-300 mg) of loperamide produce euphoria, central nervous system depression, and cardiotoxicity (2-4). Abuse of loperamide for its euphoric effect or for self-treatment of opioid withdrawal is increasing (5). Cases of loperamide abuse reported to the Upstate New York Poison Center and New York City Poison Control Center were analyzed for demographic, exposure, clinical, and laboratory characteristics. Cases of intentional loperamide abuse reported to the National Poison Database System (NPDS) also were analyzed for demographic, dose, formulation, and outcome information.

Asunto(s)

Asunto(s)

Asunto(s)

RESUMEN

NMDA receptor antagonists include the prescription medication ketamine, the illicit xenobiotics PCP, MXE, and other novel PCP analogs, and the OTC medication DXM. The NMDA receptor antagonist most commonly abused by adolescents in the United States is DXM. These xenobiotics cause dissociative effects by non-competitively inhibiting the action of glutamate at the NMDA receptor. Additionally, these agents modulate the actions of monoamine neurotransmitters, agonize opioid receptors, and inhibit nitric oxide synthase. Patients typically present with sympathomimetic and neuropsychiatric clinical manifestations after abuse of NMDA receptor antagonists. Treatment is generally symptomatic and supportive. Interventions include benzodiazepines, propofol, fluids, antiemetics, aggressive cooling, and respiratory support.

Asunto(s)