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Sven Gottschling,1 Oyedeji Ayonrinde,2 Arun Bhaskar,3 Marc Blockman,4 Oscar D’Agnone,5 Danial Schecter,6 Luis David Suárez Rodríguez,7 Sherry Yafai,8 Claude Cyr9 1Universitätsklinikum des Saarlandes, Homburg (Saar), Germany; 2Queen’s University, Kingston, Ontario, Canada; 3Imperial College Healthcare NHS Trust, London, UK; 4University of Cape Town and Groot Schuur Hospital, Cape Town, South Africa; 5The OAD Clinic, London, UK; 6Spectrum Therapeutics, Smiths Falls, Ontario, Canada; 7Centro de Medicina Integrativa Sanar, Playa del Carmen, Mexico; 8The Releaf Institute, Santa Monica, CA, USA; 9McGill University, Montreal, Quebec, CanadaCorrespondence: Claude CyrMcGill University, 3500 DeMaisonneuve Boulevard, Suite 1520, Montreal, Quebec H3Z3C1, CanadaTel +1-514-264-9657Email claudecyrmd@gmail.comAbstract: Cannabinoids are a diverse class of chemical compounds that are increasingly recognized as potential therapeutic options for a range of conditions. While many studies and reviews of cannabinoids focus on efficacy, safety is much less well reported. Overall assessment of the safety of cannabinoid-based medicines is confounded by confusion with recreational cannabis use as well as different study designs, indications, dosing, and administration methods. However, clinical studies in registered products are increasingly available, and this article aims to discuss and clarify what is known regarding the safety profiles of cannabinoid-based medicines, focusing on the medical and clinical safety evidence and identifying areas for future research. The two most well-studied cannabinoids are Δ9-tetrahydrocannabinol (THC), or its synthetic variants (dronabinol, nabilone), and cannabidiol (CBD). Across diverse indications, dizziness and fatigue are generally the most common adverse events experienced by patients receiving THC or combined THC and CBD. Patients receiving THC may experience adverse cognitive effects and impairment in psychomotor skills, with implications for driving and some occupations, while CBD may help to lower the psychotropic effects of THC when used in combination. Studies on dependency and addiction in a medical context are limited, but have shown inconsistent findings regarding misuse potential. Generally, the recommended route of administration is oral ingestion, as smoking medicinal cannabinoid products potentially releases mutagenic and carcinogenic by-products. There are several potential drug–drug interactions and contraindications for cannabinoid-based medicines, which physicians should account for when making prescribing decisions. The available evidence shows that, as with any other class of pharmaceuticals, cannabinoid-based medicines are associated with safety risks which should be assessed in the context of potential therapeutic benefits. Each patient should be assessed on an individual basis and physicians must rely on informed, evidence-based decision-making when determining whether a cannabinoid-based medicine could be an appropriate treatment option.Keywords: cannabis, cannabinoid, safety, cannabidiol, Δ9-tetrahydrocannabinol

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Background Direct factor Xa inhibitors (FXaIs) account for most oral anticoagulant use and FXaI-associated bleeding events are common. Clinicians have variable national and regional access to specific FXaI reversal agents such as andexanet alfa. Many centers have adopted the use of prothrombin complex concentrates (PCCs) as hemostatic therapy for FXaI-associated major bleeding events. PCC does not impact circulating FXaI levels and its mechanism of action to achieve hemostasis in FXaI-associated bleeding is uncertain. While PCC increases quantitative thrombin generation assay (TGA) parameters, it does not correct FXaI-altered thrombin generation kinetics, nor does it normalize thrombin generation. Clinical data supporting the use of PCC are based on cohort studies reporting clinical hemostatic efficacy, which is difficult to measure. The benefits of PCC for FXaI-associated bleeding beyond supportive care are uncertain.

BACKGROUND: The efficacy of seat belts in reducing deaths from motor vehicle crashes is well documented. A unique association of injuries has emerged in adults and children with the use of seat belts. The 'seat-belt syndrome' refers to the spectrum of injuries associated with lap-belt restraints, particularly flexion-distraction injuries to the spine (Chance fractures). METHODS: We describe the injuries sustained by 8 children, including 2 sets of twins, in 3 different motor vehicle crashes. RESULTS: All children were rear seat passengers wearing lap or 3-point restraints. All had abdominal lap-belt ecchymosis and multiple abdominal injuries due to the common mechanism of seat-belt compression with hyperflexion and distraction during deceleration. Five of the children had lumbar spine fractures and 4 remained permanently paraplegic. CONCLUSIONS: These incidents illustrate the need for acute awareness of the complete spectrum of intra-abdominal and spinal injuries in restrained pediatric passengers in motor vehicle crashes and for rear seat restraints that include shoulder belts with the ability to adjust them to fit smaller passengers, including older children. [ABSTRACT FROM AUTHOR]