Adulterants present in the San Diego county fentanyl supply: a laboratory analysis of seized law enforcement samples.

BACKGROUND: The opioid overdose crisis is one of the worst public health crises ever to face the US and emerging evidence suggests its effects are compounded by the presence of drug adulterants. Here we report our efforts to characterize the adulterants present within the local fentanyl supply of San Diego County, obtained from undifferentiated drug samples seized by local law enforcement over the calendar year 2021. METHODS: Thirty-two participating local law enforcement agencies across San Diego submitted 4838 unknown individual illicit drug samples (total of 312 kg) to the San Diego County Sheriff's Department Regional Crime Laboratory for identification. RESULTS: Qualitative analysis of these samples via FTIR and GC-MS identified methamphetamine (38.7%), fentanyl (20.8%), diacetylmorphine (heroin) (10.2%), codeine (5.8%) and alprazolam (4.3%) as the most common illicit substances and the presence of 52 unique adulterants. The most common adulterants included 4-methylaminoantipyrine (4-MAAP) (10.9%), mannitol (9%), acetaminophen (8.5%), methamphetamine (4.2%), diacetylmorphine (heroin) (3.6%), tramadol (1.9%), and xylazine (1.7%). Several additional pharmacologically active adulterants and contaminants of interest were also identified. CONCLUSION: This analysis is vital for public health use and harm reduction efforts at the level of the individual consumer. Continued direct surveillance of the drug supply is necessary for the detection of potentially harmful adulterants that may pose serious threats to the public.

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

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

"Campfire corrosive: Isolated gastrointestinal injury following ingestion of copper salts".

Human exposures to "fire color changing" agents containing copper salts (CS) are rare. We report the case of an intentional mixed CS ingestion with resulting corrosive gastrointestinal injury absent classic laboratory abnormalities. A 23-year-old male with a history of bipolar disorder presented to the emergency department two hours after intentional ingesting an unknown quantity of the fire colorant "Mystical Fire," which contains cupric sulfate (CuSO4) and cupric chloride (CuCl2). He subsequently developed nausea and abdominal pain and had several episodes of vomiting. Physical examination was notable for diffuse abdominal tenderness without peritoneal signs. Laboratory evaluation was without signs of hemolysis, metabolic derangements, or acute kidney or liver injury. He was noted to have a methemoglobin concentration of 2.2%, which did not require treatment. Serum copper testing was within normal limits. Abdominal CT imaging showed no significant findings. Endoscopy was performed and revealed diffuse esophagitis and gastritis. The patient was started on a proton pump inhibitor and discharged. In this case, the absence of classic laboratory findings of copper did not rule out the presence of gastrointestinal injury. Further investigation is needed to determine the most effective means of ruling out clinically significant CS ingestions.

Taking the bait: Strychnine poisoning.

A 48-year-old male intentionally ingested "gopher killer" containing strychnine as a, suicide attempt. He rapidly developed generalized muscle spasms with opisthotonos followed by cardiovascular collapse. He was resuscitated, treated with 24 h of, neuromuscular paralysis, and was discharged on hospital day 10 without sequelae. A blood strychnine concentration obtained five hours post ingestion was 2.2 mg/L. Strychnine poisoning is exceedingly rare in the modern United States and this report contains a video recording of the classic exam findings.

Reversible Neurotoxicity Due To Excessive Use of Ethyl Chloride.

BACKGROUND: Ethyl chloride is commercially available as a DVD/VCR cleaner, and can be found as a gasoline additive and topical anesthetic. There is an emerging trend of recreational huffing to enhance sexual relations. Neurotoxicity from repeated abuse is uncommon. CASE REPORT: A 36-year-old man with a history of intermittent ethyl chloride use for 15 years presented to the Emergency Department with an inability to walk for 4 days after frequent use for 1 week. The patient reported a rapid titration of inhalation from zero to eight cans of 4.6 oz ethyl chloride aerosol per day over a 1-week period. Initial vital signs were heart rate 88 beats/min, blood pressure 147/60 mm Hg, temperature 37.2°C (99°F), and respiratory rate 16 breaths/min. Physical examination was notable for slurred speech, ptosis, a wide-based and ataxic gait with short strides, inability to stand without support, loss of toe/finger proprioception, horizontal and vertical nystagmus, and dysmetria on coordination testing. Strength and sensation were preserved. His work-up included computed tomography and magnetic resonance imaging of the brain, cervical, thoracic, and lumbar spine that demonstrated no acute abnormalities. On hospital day 9, the patient was able to ambulate with mild difficulty. WHY SHOULD AN EMERGENY PHYSICIAN BE AWARE OF THIS?: Toxicity from excessive ethyl chloride huffing has been rarely reported. The toxicity was characterized with cerebellar findings, no attributable laboratory abnormalities, and no radiographic abnormalities on computed tomography/magnetic resonance imaging. The neurotoxicity resolved with supportive care. This case of excessive huffing of ethyl chloride presenting with neurotoxicity and ataxia further characterizes a rare complication of ethyl chloride toxicity that is gaining popularity.

Crouching Zookeeper, Hidden Dragon: A Case of a Komodo Dragon Bite.

BACKGROUND: The Komodo dragon (Varanus komodoensis) is the world's largest living lizard and exists in private captivity worldwide. Bites to humans are rare and have been proposed to be both infectious and venomous. CASE REPORT: A 43-year-old zookeeper was bitten on the leg by a Komodo dragon and suffered local tissue damage with no excessive bleeding or systemic symptoms to suggest envenomation. No specific therapy was administered other than local wound irrigation. The patient was placed on prophylactic antibiotics and on follow-up, which revealed no local or systemic infections, and no other systemic complaints. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although venomous lizard bites are uncommon, prompt recognition of possible envenomation and management of these bites is important. Komodo dragon bites may produce not only superficial lacerations but also deep tissue injury, but are unlikely to produce serious systemic effects; whereas Gila monster and beaded lizard bites may cause delayed angioedema, hypotension, and other systemic symptoms. Treatment in all cases is supportive.

Pediatric Rattlesnake Envenomations Treated With Crotalidae Equine Immune F(Ab') 2 Antivenom : A 3-Year Retrospective Observational Analysis.

OBJECTIVES: Rattlesnake envenomations are uncommon, and the majority occur in adults. Although Crotalidae equine immune F(ab') 2 antivenom (F(ab') 2 AV; trade name ANAVIP) was introduced in 2018, no pediatric specific studies of F(ab') 2 AV have been reported to date. The objective of this study was to evaluate the clinical performance and adverse effects of F(ab') 2 AV in children. METHODS: A single-center, retrospective chart review was performed on patients with rattlesnake envenomation presenting to a children's hospital between October 2018 and August 2022. Inclusion criteria were age younger than 18 years and F(ab') 2 AV use. Exclusion criteria were other antivenom use at any time and presentation beyond 24 hours postenvenomation.Demographic characteristics, hemoglobin, platelet count, fibrinogen, international normalized ratio, number of F(ab') 2 AV vials used, infusion-related complications, and clinical outcomes were collected. RESULTS: Twenty-six patients, 19 males and 7 females, with a mean age of 7.7 years (0.67 to 16 years) met inclusion criteria. Fourteen (54%) were treated with only the initial 10 vial F(ab') 2 AV doses. Twelve patients were given additional doses with a median additional vials of 10 (4-34 vials; interquartile range, 8.75-12 vials). The median total vials given for all patients was 10 (10-44 vials; interquartile range, 10-20 vials).Two patients developed acute infusion reactions. Both were treated by slowing the infusion rate and with medications (diphenhydramine, corticosteroids). No delayed reactions were noted. No patients required blood products or surgical interventions.After discharge, no complications, recurrent symptoms, return visits, or readmissions were reported. Follow-up by chart review or phone was obtained for 18 patients, and no postdischarge complications were noted. Seven patients had postdischarge hematologic laboratory evaluations and all were normal. CONCLUSIONS: Although limited by small sample size and postdischarge follow-up, F(ab') 2 AV was well tolerated in our series of pediatric patients, consistent with prior studies of all age groups.

Symptomatic Diethylene Glycol Ingestion Successfully Treated with Fomepizole Monotherapy.

BACKGROUND: Diethylene glycol (DEG) is an industrial solvent with many uses, including brake fluids. It has also caused mass poisonings after use as an inappropriate substitute for propylene glycol or glycerin, though individual ingestions are rare. Like other toxic alcohols, DEG is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase, with toxicity likely mediated by the resulting metabolites. Fomepizole, an alcohol dehydrogenase inhibitor, is used to prevent metabolite formation with other toxic alcohol exposures. Fomepizole is recommended for DEG poisoning, though supporting clinical evidence is limited. CASE REPORT: A 31-year-old man presented after ingestion of DEG-containing brake fluid and hydrocarbon-containing "octane booster." He was noted to be clinically intoxicated, with a mildly elevated anion gap metabolic acidosis and no osmolar gap. DEG level was later found to be elevated, consistent with his ingestion. He was treated with fomepizole alone, with resolution of metabolic acidosis and clinical findings over the next 2 days. No delayed neurologic sequelae were present at 52-day follow-up. Our case provides additional evidence supporting the use of fomepizole for DEG poisoning. Consistent with other toxic alcohols, DEG poisoning, especially early presentations, may benefit from empiric fomepizole administration. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: DEG poisoning is potentially life threatening, but treatable if identified early. An ingestion can be toxic despite a normal osmolar gap, leading to false reassurance. Finally, it is rare, so emergency physicians must be made aware of its potential dangers.

Discovery of spirohydantoins as selective, orally bioavailable inhibitors of p300/CBP histone acetyltransferases.

p300 and CREB-binding protein (CBP) are essential for a multitude of cellular processes. Dysregulation of p300/CBP histone acetyltransferase activity is linked to a broad spectrum of human diseases including cancers. A novel drug-like spirohydantoin (21) has been discovered as a selective orally bioavailable inhibitor of p300/CBP histone acetyltransferase. Lead compound 21 is more potent than the first-in-class lead A-485 in both enzymatic and cellular assays and lacks the off-target inhibition of dopamine and serotonin transporters, that was observed with A-485.

Polyethylene glycol electrolyte lavage solution increases tablet dissolution of acetaminophen in an in vitro model mimicking acute poisoning.

INTRODUCTION: Polyethylene glycol electrolyte lavage solution (PEG-ELS) is similar to pharmaceutical solvent propylene glycol and used following acute poisonings for whole bowel irrigation (e.g., "body stuffing"). This raises concern of PEG-ELS increasing solubility following acute ingestions of non-sustained release xenobiotics in the stomach. We theorized PEG-ELS increases solubility of acetaminophen in an in vitro stomach model. MATERIAL AND METHODS: An in vitro artificial stomach with 500 mL simulated gastric fluid and either 500 mL of sodium chloride 0.9% (group A) or 500 mL of PEG-ELS (group B). Ten non-sustained release acetaminophen tablets added with concentrations 0, 15, 45 and 90 min in triplicate. Mean concentrations and mean area under the curve (AUC) (mg-min/L to 90 min). RESULTS: In control group A (normal saline + simulated gastric fluid) mean acetaminophen concentrations 0, 3, 13 and 36 mg/L at 0, 15, 45 and 90 min, respectively. In group B (PEG-ELS + simulated gastric fluid) mean acetaminophen concentrations 0, 34, 109 and 136 mg/L at 0, 15, 45 and 90 min, respectively (p < 0.05). Mean AUC 0-90 1385 [95% C.I. 990.5-1779] mg-min/L in control group A compared to mean AUC 0-90 in group B (PEG-ELS) 7673 mg-min/L [95% C.I. 4832-10513] (p < 0.05). DISCUSSION: Group B (PEG-ELS) with significantly higher mean acetaminophen concentrations and greater mean AUC compared to control group A (normal saline). CONCLUSION: We demonstrated increased mean acetaminophen concentrations and increased mean AUC of following exposure of PEG-ELS in an artificial stomach model.

Methohexital-Induced Seizure in a Patient Undergoing Conscious Sedation.

BACKGROUND: Methohexital is a short-acting barbiturate used for procedural sedation in the emergency department (ED). As with other sedatives, adverse effects with methohexital include excess sedation and hypotension, but this agent can also lower the seizure threshold. We report a patient who developed a generalized seizure after administration of methohexital. CASE REPORT: A 60-year-old man presented to the ED by ambulance with chest pain and shortness of breath. Paramedics had administered adenosine for supraventricular tachycardia without conversion before arrival to the ED. He had no history of seizures. His initial vital signs in the ED included heart rate of 189 beats/min with a supraventricular rhythm, blood pressure 137/108 mm Hg, respiration 22 breaths/min, and oxygen saturation of 98% on room air. It was decided to attempt synchronized electrical cardioversion, and methohexital 1 mg/kg (120 mg) was administered over 2 min for moderate sedation. Within 15 s of methohexital administration, the patient developed a generalized seizure that lasted for 90 s. After seizure termination, he was successfully cardioverted, returned to his previous baseline level of consciousness within 20 min, and discharged without further problems with a follow-up referral to neurology. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Methohexital is a short-acting barbiturate used for moderate sedation. Its adverse effects are unique in that it can lower the seizure threshold in some patients. Alternative agents for sedation should be considered in individuals with possible seizure disorders.

Fragment-based discovery of a potent NAMPT inhibitor.

NAMPT expression is elevated in many cancers, making this protein a potential target for anticancer therapy. We have carried out both NMR based and TR-FRET based fragment screens against human NAMPT and identified six novel binders with a range of potencies. Co-crystal structures were obtained for two of the fragments bound to NAMPT while for the other four fragments force-field driven docking was employed to generate a bound pose. Based on structural insights arising from comparison of the bound fragment poses to that of bound FK866 we were able to synthetically elaborate one of the fragments into a potent NAMPT inhibitor.

Ketamine exposure demographics and outcomes over 16 years as reported to US poison centers.

BACKGROUND: This study sought to examine ketamine exposures reported to US poison centers over the past 16 years and identify trends in exposures and outcomes. METHODS: A retrospective review was performed of all cases involving ketamine exposures reported to US poison centers and entered into the National Poison Data System from 2000 to 2015. Cases were divided into those involving ketamine alone and those involving ketamine and other agents. Data collected included: age, sex, form of ketamine used, reason for exposure, and outcome. RESULTS: A total of 3109 cases were evaluated. 1595 (51%) reported ketamine to be the only substance exposure, while 1514 (49%) involved multiple substances with ketamine. For single agent exposures, more involved males (67%) between the ages of 16-25 years (49%). Single agent ketamine exposures peaked between 2000 and 2002, fell consistently until 2008; then rebounded to previous peak levels through 2015. Intentional exposures (65% of all cases) were the most common reason for single agent ketamine exposures. 53% of ketamine-only cases resulted in minor effects, with two deaths. In contrast, ketamine exposures with multiple agents resulted in outcomes judged as moderate or worse in 62% of cases, including 20 deaths. CONCLUSION: Single-agent ketamine exposures reported to US poison centers have rebounded to historical peaks in recent years. More deaths and serious outcomes were reported in ketamine exposures involving multiple substances.

Recurrent Diffuse Large B-Cell Lymphoma Presenting with Pancoast Syndrome: A Rare Cause of Radicular Neck Pain in the Emergency Department.

BACKGROUND: Pancoast syndrome is an uncommon complication of apical lung tumors. Symptoms include pain, brachial plexopathy, and Horner's syndrome, and are the result of extrinsic compression of tissues within the thoracic inlet. Lymphoma is a very rare etiology. CASE REPORT: We describe the presentation of a 59-year-old male with recurrent diffuse large B-cell lymphoma presenting with Pancoast syndrome. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Cancer is an uncommon cause of radicular neck pain but should be considered in the differential, particularly when constitutional complaints are also present. Symptoms and physical examination findings associated with Pancoast syndrome are the consequence of compression of the C7-T2 vertebral roots and sympathetic chain. Computed tomography is usually required to definitively visualize the mass.

Brugada-Type Pattern on Electrocardiogram Associated with High-Dose Loperamide Abuse.

BACKGROUND: Loperamide has been increasing in popularity recently for its effects separate from treatment of diarrhea. In large doses or in combination with other agents, it can lead to desirable effects in the central nervous system. However, cardiotoxicity has been reported with its abuse. CASE REPORT: A 49-year-old male who had been chronically abusing loperamide was found to have Brugada-like changes on his electrocardiogram (ECG). He had no other clinical symptoms associated with Brugada syndrome and did not have similar findings on previous ECGs. After abstaining from further loperamide use during hospitalization, this pattern slowly resolved without clinically significant dysrthymias. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: A patient with a history of loperamide abuse is at risk for cardiotoxicity. While other dysrhythmias are reported more commonly with loperamide abuse, Brugada-like ECG changes can occur and warrant appropriate consultation and prompt follow-up.

A Prospective Study of Stingray Injury and Envenomation Outcomes.

BACKGROUND: Stingray injuries result in thousands of emergency department visits annually. OBJECTIVES: This study aimed to assess the complication rate and outcome of field treatment with hot water immersion. METHODS: This was an on-site, prospective, observational study. Subjects were enrolled after having been stung by a stingray. A trained researcher obtained the following information: age, sex, health conditions and medications, and wound description. The efficacy of hot water immersion on pain was recorded. Patients were contacted on postinjury days 3, 7, and 14 for follow up. RESULTS: Twenty-two subjects were included. No obvious foreign bodies were observed in wounds. Ten subjects were treated with hot water immersion and povidone-iodine, 12 with hot water immersion alone. Ongoing symptoms or complications were noted at the 3-day follow-up in 6 of 22 subjects (27.3%). One subject was diagnosed with cellulitis on post-sting day 8 and was treated with antibiotics. Ongoing symptoms or complications were reported more commonly in patients treated with hot water and povidone-iodine compared with those treated with hot water alone (p = 0.056). There was a significant difference in wound size between those with and without ongoing symptoms at the 3-day follow-up (p = 0.0102). No wounds <1 cm developed any complications. Average duration of water immersion was 73.6 min (range 35-145 min). The mean pain score pretreatment was 7.36 and posttreatment was 2.18, with an average decrease of 5.18 (95% confidence interval 4.22-6.15). CONCLUSION: Stingray injuries responded well to hot water immersion for pain control. Skin and soft tissue infection was diagnosed in 1 of 22 patients (4.55%).

SAR of amino pyrrolidines as potent and novel protein-protein interaction inhibitors of the PRC2 complex through EED binding.

Herein we disclose SAR studies of a series of dimethylamino pyrrolidines which we recently reported as novel inhibitors of the PRC2 complex through disruption of EED/H3K27me3 binding. Modification of the indole and benzyl moieties of screening hit 1 provided analogs with substantially improved binding and cellular activities. This work culminated in the identification of compound 2, our nanomolar proof-of-concept (PoC) inhibitor which provided on-target tumor growth inhibition in a mouse xenograft model. X-ray crystal structures of several inhibitors bound in the EED active-site are also discussed.

SAR and characterization of non-substrate isoindoline urea inhibitors of nicotinamide phosphoribosyltransferase (NAMPT).

Herein we disclose SAR studies that led to a series of isoindoline ureas which we recently reported were first-in-class, non-substrate nicotinamide phosphoribosyltransferase (NAMPT) inhibitors. Modification of the isoindoline and/or the terminal functionality of screening hit 5 provided inhibitors such as 52 and 58 with nanomolar antiproliferative activity and preclinical pharmacokinetics properties which enabled potent antitumor activity when dosed orally in mouse xenograft models. X-ray crystal structures of two inhibitors bound in the NAMPT active-site are discussed.

A Retrospective Review of the Presentation and Treatment of Stingray Stings Reported to a Poison Control System.

We studied stingray stings reported to our poison system to identify associated complications and treatments. We undertook a 14-year retrospective observational analysis of stingray stings reported to our poison system. Extracted data included caller age and gender, outcome, management site, symptoms, treatments, and geographical location of the sting. We examined suspected infection rate, hot water treatment efficacy, and possible presence of foreign bodies in the wound. Suspected infection rate was defined as "possible infection" or "likely infection." Hot water treatment efficacy was defined as cases that encoded hot water as a treatment and noted pain relief within 1 hour of treatment in the free-text record, before documentation of other analgesic administration. A total of 576 envenomations were reported. The majority were men (76%), with an average age of 24 years (range, 6-78 years). Symptoms were reported in 485 cases. A total of 9% recorded a foreign body or debris at the wound site. Symptoms included pain (79%), puncture wound (65%), and edema (25%). Infections were reported in 9% of cases. Hot/warm water immersion appeared effective for pain relief in 69% of cases where outcome was documented. The most common geographical location of stingray envenomations was Southern California. Stingray stings are common in California. Hot/warm water seemed to be effective in pain management in our series, whereas foreign bodies or retained spines and infections were other identified complications.