Unintentional Pediatric Ingestion of Cannabis-Addressing a Growing Public Health Risk.

This Viewpoint discusses the growing unintentional ingestion of cannabis and copycat products by children and urges clinicians, legitimate cannabis companies, large consumer brands, state attorneys general, and national legislators to provide solutions and education to adult users.

Synthesis and characterization of d5 -barbarin for use in barbarin-related research.

Based on structural similarities and equine administration experiments, Barbarin, 5-phenyl-2-oxazolidinethione from Brassicaceae plants, is a possible source of equine urinary identifications of aminorex, (R,S)-5-phenyl-4,5-dihydro-1,3-oxazol-2-amine, an amphetamine-related US Drug Enforcement Administration (DEA) controlled substance considered illegal in sport horses. We now report the synthesis and certification of d5 -barbarin to facilitate research on the relationship between plant barbarin and such aminorex identifications. D5 -barbarin synthesis commenced with production of d5 -2-oxo-2-phenylacetaldehyde oxime (d5 -oxime) from d5 -acetophenone via butylnitrite in an ethoxide/ethanol solution. This d5 -oxime was then reduced with lithium aluminum hydride (LiAlH4 ) to produce the corresponding d5 -2-amino-1-phenylethan-1-ol (d5 -phenylethanolamine). Final ring closure of the d5 -phenylethanolamine was performed by the addition of carbon disulfide (CS2 ) with pyridine. The reaction product was purified by recrystallization and presented as a stable white crystalline powder. Proton NMR spectroscopy revealed a triplet at 5.88 ppm for one proton, a double doublet at 3.71 ppm for one proton, and double doublet at 4.11 ppm for one proton, confirming d5 -barbarin as the product. Further characterization by high resolution mass spectrometry supports the successful synthesis of d5 -barbarin. Purity of the recrystallized product was ascertained by High Performance Liquid Chromatography (HPLC) to be greater than 98%. Together, we have developed the synthesis and full characterization of d5 -barbarin for use as an internal standard in barbarin-related and equine forensic research.

Gabapentin, a human therapeutic medication and an environmental substance transferring at trace levels to horses: a case report.

Gabapentin, 1-(Aminomethyl)cyclohexaneacetic acid, MW 171.240, is a frequently prescribed high dose human medication that is also used recreationally. Gabapentin is orally absorbed; the dose can be 3,000 mg/day and it is excreted essentially unchanged in urine. Gabapentin is stable in the environment and routinely detected in urban wastewater. Gabapentin randomly transfers from humans to racing horses and is at times detected at pharmacologically ineffective / trace level concentrations in equine plasma and urine. In Ohio racing between January 2019 and July 2020,18 Gabapentin identifications, all less than 2 ng/ml in plasma, were reported. These identifications were ongoing because the horsemen involved were unable to pin down and therefore avoid the source of these identifications. Given that 44 ng/ml or less is an Irrelevant Plasma Concentration (IPC) of Gabapentin in horses, we proposed a 5 ng/ml plasma interim Screening Limit of Detection for Gabapentin identifications in Ohio racing, and an essentially similar 8 ng/ml plasma Screening Limit of Detection was suggested by a scientific advisor to the Ohio Horse Racing Commission. As such, an analytical Screening Limit of 8 ng /ml in plasma is an appropriate and pharmacologically conservative analytical "cut-off" or Screening Limit of Detection (SLOD) for Gabapentin in equine competitive events to avoid the calling of "positive" identifications on random unavoidable trace level identifications of this widely prescribed human therapeutic medication in equine forensic samples.

Sporadic worldwide "clusters" of feed driven Zilpaterol identifications in racing horses: a review and analysis.

Zilpaterol is a ß2-adrenergic agonist medication approved in certain countries as a cattle feed additive to improve carcass quality. Trace amounts of Zilpaterol can transfer to horse feed, yielding equine urinary "identifications" of Zilpaterol. These "identifications" occur because Zilpaterol is highly bioavailable in horses, resistant to biotransformation and excreted as unchanged Zilpaterol in urine, where it has a 5 day or so terminal half-life.In horses, urinary steady-state concentrations are reached 25 days (5 half-lives) after exposure to contaminated feed. Zilpaterol readily presents in horse urine, yielding clusters of feed related Zilpaterol identifications in racehorses. The first cluster, April 2013, involved 48 racehorses in California; the second cluster, July 2013, involved 15 to 80 racehorses in Hong Kong. The third cluster, March 2019, involved 24 racehorses in Mauritius; this cluster traced to South African feedstuffs, triggering an alert concerning possible Zilpaterol feed contamination in South African racing. The fourth cluster, September/October 2020 involved 18 or so identifications in French racing, reported by the French Laboratories des Courses Hippiques, (LCH), and in July 2021, a fifth cluster of 10 Zilpaterol identifications in South Africa.The regulatory approach to these identifications has been to alert horsemen and feed companies and penalties against horsemen are generally not implemented. Additionally, given their minimal exposure to Zilpaterol, there is little likelihood of Zilpaterol effects on racing performance or adverse health effects for exposed horses.The driving factor in these events is that Zilpaterol is dissolved in molasses for incorporation into cattle feed. Inadvertent incorporation of Zilpaterol containing molasses into horse feed was the source of the California and Hong Kong Zilpaterol identifications. A second factor in the 2019 Mauritius and 2020 French identifications was the sensitivity of testing for Zilpaterol in Mauritius and France, with the French laboratory reportedly testing at a "more sensitive level for Zilpaterol". As of January 1st, 2021, the new FEI Atypical Finding (ATF) policy specifies Zilpaterol as a substance to be treated as an Atypical Finding (ATF), allowing consideration of inadvertent feed contamination in the regulatory evaluation of Zilpaterol identifications.

Plasma concentrations of diclazuril following oral administration of diclazuril and diclazuril sodium salt to cattle.

Diclazuril is a triazine-based antiprotozoal agent widely used in veterinary practice that may have clinical application in the treatment of bovine protozoal diseases. The present study reports on the bioavailability, pharmacokinetics, and metabolism of diclazuril and diclazuril sodium salt in cattle following administration of diclazuril suspended in water and by direct application of diclazuril sodium salt to the oral mucosa. Compared with diclazuril itself, the sodium salt formulation of diclazuril applied to the oral mucosa was rapidly and reliably absorbed. Plasma concentrations of diclazuril peaked at around 8 h after oral-mucosal administration of diclazuril sodium salt. On the contrary, application of diclazuril itself orally resulted in delayed and variable absorption. The mean bioavailability of diclazuril as pure powder was 42.5% relative to diclazuril sodium salt indicating approximately 2.5-fold increase in bioavailability of diclazuril as a sodium salt relative to diclazuril as a pure compound in cattle. The present study also reports finding of a previously unreported diclazuril metabolite at high concentrations in plasma especially after oral administration of diclazuril. Further studies, including synthesis and characterization of the novel described metabolite, are required to accurately determine aspects of the metabolism of diclazuril in cattle.

Synthesis and characterization of barbarin, a possible source of unexplained aminorex identifications in forensic science.

Aminorex is a US DEA Schedule 1 controlled substance occasionally detected in racing horses. A number of aminorex identifications in sport horses were thought to have been caused by exposure to plant sources of aminorex. Glucobarbarin, found in plants of the Brassicaceae family, has been suggested as a potential proximate chemical source by being metabolized in the plant or the horse to aminorex. In Brassicaceae, glucobarbarin is hydrolyzed by myrosinase to yield barbarin, which serves as an insect repellant and/or attractant and is structurally related to aminorex. The synthesis, purification, and characterization of barbarin is now reported for use as a reference standard in aminorex related research concerning equine urinary identifications of aminorex and also for possible use in equine administration experiments. Synthesis of barbarin was performed via ring closure between phenylethanolamine and carbon disulfide in tetrahydrofuran with the catalyst pyridine under reflux. The reaction yielded a white crystalline substance that was purified and chemically characterized as barbarin for use as a Certified Reference Standard or for studies related to equine aminorex identification.

Unscheduled Procedural Sedation: A Multidisciplinary Consensus Practice Guideline.

The American College of Emergency Physicians (ACEP) organized a multidisciplinary effort to create a clinical practice guideline specific to unscheduled, time-sensitive procedural sedation, which differs in important ways from scheduled, elective procedural sedation. The purpose of this guideline is to serve as a resource for practitioners who perform unscheduled procedural sedation regardless of location or patient age. This document outlines the underlying background and rationale, and issues relating to staffing, practice, and quality improvement.

Aminorex identified in horse urine following consumption of Barbarea vulgaris; a preliminary report.

BACKGROUND: Aminorex, (RS)-5- Phenyl-4,5-dihydro-1,3-oxazol-2-amine, is an amphetamine-like anorectic and in the United States a Drug Enforcement Administration [DEA] Schedule 1 controlled substance. Aminorex in horse urine is usually present as a metabolite of Levamisole, an equine anthelmintic and immune stimulant. Recently, Aminorex identifications have been reported in horse urine with no history or evidence of Levamisole administration. Analysis of the urine samples suggested a botanical source, directing attention to the Brassicaceae plant family, with their contained GlucoBarbarin and Barbarin as possible sources of Aminorex. Since horsepersons face up to a 1 year suspension and a $10,000.00 fine for an Aminorex identification, the existence of natural sources of Aminorex precursors in equine feedstuffs is of importance to both individual horsepersons and the industry worldwide. RESULTS: Testing the hypothesis that Brassicaceae plants could give rise to Aminorex identifications in equine urine we botanically identified and harvested flowering Kentucky Barbarea vulgaris, ("Yellow Rocket") in May 2018 in Kentucky and administered the plant orally to two horses. Analysis of post-administration urine samples yielded Aminorex, showing that consumption of Kentucky Barbarea vulgaris can give rise to Aminorex identifications in equine urine. CONCLUSIONS: Aminorex has been identified in post administration urine samples from horses fed freshly harvested flowering Kentucky Barbarea vulgaris, colloquially "Yellow Rocket". These identifications are consistent with occasional low concentration identifications of Aminorex in equine samples submitted for drug testing. The source of these Aminorex identifications is believed to be the chemically related Barbarin, found as its precursor GlucoBarbarin in Kentucky Barbarea vulgaris and related Brassicaceae plants worldwide.

Clinical signs associated with a case of iatrogenic poisoning by a turpentine-based commercial product in a 3-day-old foal / Sinais clínicos associados a um caso de envenenamento iatrogênico de um equino com três dias de idade por um produto comercial baseado em terebintina

The aim of this study is to report a case of iatrogenic poisoning by a turpentine-based commercial product in a 3-day-old foal and the successful treatment of this condition. A 3-day-old male foal presented with acute cardio-respiratory collapse, anaphylactic shock, severe respiratory distress, dyspnea and pulmonary edema. The animal's history included previous administration of a commercial veterinary product (UNITIPAN). Clinical examination revealed: temperature: (39.9 °C), pulse: 135 bpm, respiration: 51 bpm, mucous membranes: moist and congested, capillary refill time: 3 sec or less. The foal was treated with emergency hydration, duphalyte, steroidal anti-inflammatory, atropine sulphate and antibiotic. After 6 h of treatment, the foal was stabilized and vital signs were normalized 8 h after treatment start.(AU)

O objetivo deste estudo é relatar um caso de intoxicação iatrogênica por um produto comercial a base de terebentina em um potro de três días de idade e o sucesso do tratamento dessa condição. Um potro de três dias de idade foi apresentou um colapso cardiorrespiratório agudo, choque anafilático, desconforto respiratório grave, dispnéia e edema pulmonar. A história incluiu a administração prévia de um produto veterinário comercial (UNITIPAN). Ao exame clínico: temperatura: (39,9 °C), pulso: 135 bpm, respiração 51 bpm, membranas mucosas, congestionamento úmido, tempo de enchimento capilar: três segundos ou menos. O potro foi tratado com hidratação de emergência, duphalyte, anti-inflamatório esteroidal, sulfato de atropina e antibiótico. Após seis horas de tratamento, o potro foi estabilizado e os sinais vitais foram normalizados depois de oito horas do inicio do tratamento. O presente trabalho relata um caso de intoxicação iatrogênica por um produto à base de terebintina comercial em um potro de três dias de idade com rápido desenvolvimento de sinais de toxicidade aguda e uma resposta muito favorável ao tratamento sintomático.(AU)

Recognition of a likely two phased extinction at the K-Pg boundary in Antarctica.

The southernmost Cretaceous - Paleogene (K-Pg) outcrop exposure is the well-studied exposure on Seymour Island, Antarctica. Deposition across the K-Pg boundary there is uninterrupted, and as a consequence the ammonite fossil record is commonly used to test statistical methods of evaluating mass extinctions to account for the incompleteness of the fossil record. Numerous detailed fossil data sets from Seymour Island, comprised dominantly of mollusks, have been published over the last 30 years, but in most cases have not received statistical treatment. Here a previously published statistical technique is modified, automated, and applied to all published macrofossil data sets available from Seymour Island. All data sets reveal likely evidence of two separate multi-species extinctions, one synchronous with bolide impact evidence at the K-Pg boundary, and another 45 ± 15 meters (~140-290 ky) below the boundary. The apparent earlier extinction primarily affects benthic mollusks, while the boundary extinction primarily affects ammonites. While there is no unique sedimentological change over the interval where the earlier extinction is identified, it is impossible to exclude the possibility that this pattern is stratigraphically controlled. The automation of this technique allows it to be applied easily to other large fossil data sets.

Staying Awake and Aware: The Importance of Sleep in Psychiatric Nursing Practice.

Given that approximately 70 million Americans suffer from sleep-wake disorders and their under-recognized role in practice, psychiatric nurses may see, or may be already seeing, patients with undiagnosed sleep disorders. Assessment of sleep-wake disorders can and should be a part of psychiatric nursing education and practice. Many practicing clinicians lack formal training regarding sleep-wake issues and treatment. Even as sleep disturbances are common concerns among psychiatric populations, sleep-wake issues may go unrecognized. The article presents a stylized progression of care to enable clinicians to identify, address, and treat underlying sleep-wake disorders in psychiatric settings. The article recommends instituting screening procedures for sleep-wake issues and follow-up assessments, particularly overnight pulse oximetry and polysomnograms. Just as clinicians already screen for physical conditions that would affect psychiatric care, practitioners can evaluate patients for potential sleep-wake disorders as part of their existing practice and intake procedures. Further, the piece details implications for psychopharmacology as well as evidence from clinical practice. Psychiatric nurses should stay awake to the importance of sleep medicine and aware of how sleep-wake disorders can affect psychiatric populations.

Therapeutics for Equine Protozoal Myeloencephalitis.

Equine protozoal myeloencephalitis is an infectious disease of the central nervous system caused by Sarcocystis neurona or Neospora hughesi. Affected horses routinely present with progressive and asymmetrical neurologic deficits. The diagnosis relies on the presence of neurologic signs, ruling out other neurologic disorders, and the detection of intrathecally derived antibodies to either S neurona and/or N hughesi. Recommended treatment is use of an FDA-approved anticoccidial drug formulation. Medical and supportive treatment is provided based on the severity of neurologic deficits and complications. This article focuses on recent data related to diagnosis, pharmacologic treatment, and prevention.

A cluster of trace-concentration methamphetamine identifications in racehorses associated with a methamphetamine-contaminated horse trailer: A report and analysis.

Three low concentration methamphetamine "positive" tests were linked to use of a methamphetamine-contaminated trailer to transport the affected horses. This incident establishes methamphetamine as a human-use substance that can inadvertently enter the environment of racing horses, resulting in urinary methamphetamine "positives;" an interim regulatory cut-off of 15 ng/mL for methamphetamine in post-race urine is proposed.

Identifications de concentrations de méthamphétamine à l'état de traces chez des chevaux de course associées à une remorque contaminée : rapport et analyse. Trois tests «positifs¼ de faibles concentrations de méthamphétamine ont été associés à l'utilisation d'une remorque contaminée par les méthamphétamines qui était utilisée pour transporter les chevaux affectés. Cet incident établit la méthamphétamine comme une substance à utilisation humaine qui peut pénétrer par inadvertance dans le milieu des chevaux de course, entainant ainsi des tests d'urine «positifs¼; un niveau intérimaire réglementaire de 15 ng/mL pour les méthamphétamines est proposé pour les tests d'urine après la course.(Traduit par Isabelle Vallières).

Clinical Psychopharmacology Update: What's in a Name? Confusion Prompts Change for Vortioxetine's Brand Name.

Similar names between two unrelated drugs have led the FDA to issue warnings about and now approve a name change for vortioxetine, which was branded as Brintellix® until recently. While the trade name had been screened prior to the product's launch, the FDA received numerous reports of prescribing and dispensing errors, specifically with regard to the anti-coagulant drug Brilinta® (ticagrelor). Starting 1 June 2016, vortioxetine will be marketed under the name Trintellix™ in an effort to reduce confusion. Clinicians are advised that while the name and National Drug Code number with this product will change, it will retain the same formulation, indication, and dosage information. To the extent possible, clinicians can and should take actions to identify and reduce potential medication errors in prescriptions, especially when using electronic records and e-prescription systems.

Clinical Psychopharmacology Update: Additional Safety Concerns for Using Varenicline (Chantix) for Smoking Cessation Treatment.

Smoking cessation remains a positive therapeutic goal and should be encouraged for the millions of individuals who continue to smoke and struggle to quit. While psychiatric nurses should encourage patients to start or continue smoking cessation therapies, they must be aware of the additional safety concerns relating to the use of varenicline (Chantix). Research published subsequent to the last clinical update in this journal (Tobin, 2007 ) has prompted additional warnings from the Food and Drug Administration concerning varenicline for smoking cessation therapy. In particular, clinicians need to be aware of increased concerns about varenicline's association with neuropsychiatric side effects, seizures, and alcohol interactions.

Sudden death, aortic rupture in horses, literature review, case studies reported and risk factors / Morte súbita por ruptura da aorta em cavalos, literatura, estudos de casos relatados e fatores de risco

Sudden deaths of horses in multiple equestrian disciplines have been attributed to acute and chronic respiratory and cardiovascular diseases. The aim of this study was to perform a review of aortic rupture in horses analyzing, case studies and assessing risk factors. The literature has reported a total of 137 cases of aortic rupture in horses for 28 years (1986-2014), with approximately five horses dying of aortic rupture per year. Histopathologically, there are observed discrete macroscopic degenerative changes in the intima layer only in the aorta. The histological evaluation in the beginning portion of the aorta of the heart evidenced degenerative changes with loss of continuity and distribution of elastic fibers. Risk factors for the rupture of the aorta are: spontaneous rupture associated with hypertension, preexisting vascular injury (aneurysm), dilated or hypertrophic cardiomyopathy, copper levels in the endothelium, genetic factors such as inbreeding, toxicology or pharmacological factors. Aortic rupture shows similarity with pulmonary hemorrhage induced by exercise especially under the locomotors induced trauma theory of exercise that can induce pulmonary hemorrhage. In conclusion, degenerative changes to discrete elastic fiber of the intima of the aorta in the emergence of the heart seem to predispose the aorta wall rupture at the time of maximum blood pressure during exercise and the consequent collapse and athletic horses death...

As mortes súbitas de cavalos em várias provas equestres têm sido atribuídas a doenças respiratórias e cardiovasculares agudas e crônicas. O objetivo deste estudo foi efetuar uma revisão de literatura da ruptura da aorta em cavalos analisando estudos de caso e estabelecendo os possíveis fatores de risco. Na revisão da literatura no período de 28 anos (1986-2014) foram localizados 137 casos de ruptura da aorta em cavalos com aproximadamente cinco cavalos morrendo por essa causa por ano. Histologicamente, são observadas alterações macroscópicas discretas degenerativas na camada íntima da aorta. A avaliação histológica na porção inicial da aorta do coração evidencia alterações degenerativas com perda de continuidade e distribuição das fibras elásticas. Fatores de risco para a ruptura da aorta dos cavalos são: ruptura espontânea associada com hipertensão, lesão vascular pré-existente (aneurisma), cardiomiopatia dilatada ou hipertrófica, níveis de cobre no endotélio, fatores genéticos, tais como a consanguinidade na criação, toxicologia e aspectos farmacológicos. A ruptura aórtica mostra semelhança com hemorragia pulmonar induzida pelo exercício. Em conclusão, alterações degenerativas discretas das fibras elásticas da íntima da aorta parecem predispor a ruptura da parede da aorta, no momento da pressão máxima de sangue durante o exercício determinando o consequente colapso e morte do cavalo atleta...

Diclazuril Protects against Maternal Gastrointestinal Syndrome and Congenital Toxoplasmosis.

BACKGROUND: Toxoplasmosis is a common cause of foodborne, gastrointestinal and congenital syndrome with particularly severe or unknown health consequences. There is no safe and effective preventive or therapeutic modality against congenital toxoplasmosis or to eliminate the persistent chronic infection. HYPOTHESIS: Diclazuril to be safe in pregnancy and effective against gastrointestinal toxoplasmosis. METHODS: CD1 programmed pregnant mice were divided into groups and administered a diet containing diclazuril, or sham control. Treatments were initiated on Day 5 of pregnancy and continued until Day 16 when dams were euthanatized. On Day 8 of pregnancy dams were infected intraperitoneally with escalating doses of tachyzoites (0, 100, 300, 600) from Type II strain. Dams were monitored daily for distress, pain, and abortion and samples collected at the end of the experiments. RESULTS: Infected dams developed moderate to severe Toxoplasma related complications in tachyzoites dose dependent manner. Animals became anemic and showed hydrothorax, and ascities. Diclazuril effectively protected dams from ascities and anemia (p < 0.05). Infected dams showed splenomegaly, with massive infiltration of epithelioid cells compared with the protective effect of diclazuril in treated animals. Infected dams exhibited severe hepatitis (score 0 to 4 scale = 3.5 ± 0.01) with influx of inflammatory and plasma cells, dysplastic hepatocytes, multinucleated giant cell transformation and hepatic cells necrosis. Diclazuril treatment significantly protected dams from hepatitis, also in tachyzoites dose (100, 300, 600) dependent manner (respectively infected-treated versus infected controls, p < 0.001, p < 0.01 and p < 0.05). Colonic tissues were significantly shortened in length, with infiltration of lymphocytes, and macrophages and microabscess formations in the cryptic structures, with significant improvement in diclazuril treated animals. Additionally, the number of fetuses, fetal length and fetal weight were preserved in diclazuril treated dams. CONCLUSIONS: This is the first report describing of diclazuril safety in pregnancy as well as efficacy against mild to moderate hepato-gastrointestinal syndrome in dams and fetal toxoplasmosis (Special issue, "Treatment of Liver Diseases").

Scopolamine in racing horses: trace identifications associated with dietary or environmental exposure.

Scopolamine (L-hyoscine) identifications, often in small-number clusters, have been reported worldwide in performance horses over the last 30 years. Scopolamine is an Association of Racing Commissioners International (ARCI) class 3, penalty class B, substance with potential to affect performance. As such, scopolamine identification(s) in race or performance horses can result in significant penalties for the connections of the horse(s). Reviewed here is the worldwide distribution of scopolamine containing plants (primarily Datura spp.), with estimates of their potential toxicity to horses through dietary and/or environmental exposure. Also reviewed are the basic pharmacology of scopolamine and its precursor, urinary concentrations following feedstuff exposure, and the probable pharmacological/forensic significance of such findings. Based on an overview of the world literature on scopolamine, the expected characteristics of inadvertent environmental exposure are also presented with a view to making clear the potential of scopolamine identifications, with or without atropine, as a direct and expected outcome of both the worldwide distribution of scopolamine-containing plants and the sensitivity of modern equine drug testing. It is of particular interest that only 2/30 reported post-event equine identifications of scopolamine have been associated with atropine, suggesting that failure to identify atropine is not a biomarker of pharmaceutical administration of scopolamine. Available quantitative information associated with scopolamine identifications is consistent with the 75 ng/mL regulatory threshold for scopolamine currently used in Louisiana racing in the USA and the 30 ng/mL reporting threshold in effect in European racing.