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Procedural sedation and analgesia (PSAA) is integral to facilitating painful and anxiety-inducing medical procedures in the emergency department (ED). Optimal PSAA enhances procedural success and improves both patient and provider satisfaction. The selection of appropriate sedative and analgesic agents, routes, and dosages, which depend on various patient- and procedure-specific factors is a complex process. Alternative routes of administration, such as intranasal, intramuscular, and oral, are all options, each with their own inherent benefits and limitations. It is important for providers to take into account patient-specific considerations, including age, medical history, body weight composition, and pregnancy, which can significantly impact PSAA effectiveness and safety. Implementation strategies targeted to minimize medication errors and optimize workflow are also important considerations in PSAA. By adopting a comprehensive and evidence-based approach, health care providers can navigate the intricacies of PSAA and ensure the best possible care for patients in the ED., Competing Interests: Disclosure: The authors have no conflict of interests to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Multiple agents exist for the reversal of oral Factor Xa inhibitor (FXa) associated bleeding, including Coagulation FXa Recombinant, Inactivated zhzo (andexanet alfa) and 4-factor prothrombin complex concentrate (4F-PCC). While classified as a 3F-PCC product, Profilnine contains up to 35 IU of Factor VII (per 100 IU of Factor IX) in addition to therapeutic levels of Factors II, IX, and X, and has demonstrated a similar impact on prothrombin time and blood product usage in non-warfarin related bleeding. This was a retrospective, multicenter study at four medical centers of adult patients who presented with major bleeding associated with oral FXa inhibitors and received either 4F-PCC (n = 64) or 3F-PCC (n = 61). The primary outcome was hemostatic effectiveness. Secondary outcomes included the incidence of thromboembolism, in-hospital mortality, and length of stay. The most common indication for reversal was intracranial bleeding. For the primary outcome, 84% of all patients were rated as effective with no difference noted between the groups (p = 0.81). No significant difference between groups was found in the multivariable analysis adjusting for baseline differences between groups including race, total body weight, type of bleeding, and the use of antiplatelet therapy. There was no difference in the length of stay, in-hospital mortality, or the incidence of thromboembolism between the groups. Overall, no significant differences were found in the effectiveness or safety of 4F-PCC and 3F-PCC use in the management of oral FXa inhibitor-associated bleeding. Further investigations are warranted to explore the use of 3F-PCC for this indication and its safety and effectiveness., (© 2024. The Author(s).)

Duchenne muscular dystrophy (DMD) is the most common X-linked disease. DMD is caused by a lack of dystrophin, a critical structural protein in striated muscle. Dystrophin deficiency leads to inflammation, fibrosis, and muscle atrophy. Boys with DMD have progressive muscle weakness within the diaphragm that results in respiratory failure in the 2nd or 3rd decade of life. The most common DMD mouse model - the mdx mouse - is not sufficient for evaluating genetic medicines that specifically target the human DMD (hDMD) gene sequence. Therefore, a novel transgenic mouse carrying the hDMD gene with an exon 52 deletion was created (hDMDΔ52;mdx). We characterized the respiratory function and pathology in this model using whole body plethysmography, histology, and immunohistochemistry. At 6-months-old, hDMDΔ52;mdx mice have reduced maximal respiration, neuromuscular junction pathology, and fibrosis throughout the diaphragm, which worsens at 12-months-old. In conclusion, the hDMDΔ52;mdx exhibits moderate respiratory pathology, and serves as a relevant animal model to study the impact of novel genetic therapies, including gene editing, on respiratory function., Competing Interests: Declaration of Competing Interest CAG is an advisor to Sarepta Therapeutics and an advisor and co-founder of Tune Therapeutics. CAG and JRH are inventors on patents and patent applications related to genome editing. AMB is an employee and stakeholder of Fulcrum Therapuetics., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Procedural sedation and analgesia is an essential activity in the emergency department for managing pain and anxiety during a variety of medical procedures. Various pharmacotherapy options, including opioid analgesics, antiemetics, anticholinergics, sedatives, and ketamine have been utilized, all with their unique efficacy and safety profiles. This review highlights the challenges associated with using certain agents and discusses emerging trends such as the use of newer synthetic opioids and the expanding use of dexmedetomidine. Overall, the selection of the optimal agents for procedural sedation and analgesia should be guided based on the unique characteristics of each agent tailored to the needs of the specific procedure, along with consideration for individual patient characteristics., Competing Interests: The authors have no conflict of interests to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To describe a population health-based program to support employee and dependent mental health and learn from engagement trends., Methods: Retrospective analysis of a program utilizing an assessment of mental health risk. For scoring "at risk," a Care Concierge is offered to connect users with resources., Results: Participation was offered to 56,442 employees and dependents. Eight thousand seven hundred thirty-one completed the assessment (15%). Of those, 4,644 (53%) scored moderate or higher. A total of 418 (9%) engaged the Care Concierge. Factors that negatively influenced the decision to engage care included bodily pain, financial concerns. Positive influences were younger age, high stress, anxiety, PTSD and low social support., Conclusion: Proactive assessment plus access to a Care Concierge facilitates mental healthcare utilization. Several factors influence likelihood to engage in care. A better understanding of these factors may allow for more targeted outreach and improved engagement., Competing Interests: MF was employed by Quest Diagnostics. JoH was employed by BHS. JeH was employed by emVitals. SC was employed by Johns Hopkins Healthcare. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Woodard, Bailey, Esagoff, Fragala, Hayward, Hunter, Hsu, Kim, Peters and Carr.)

Patients who develop an intracerebral hemorrhage (ICH) following thrombolysis in acute ischemic stroke (AIS) have a mortality rate as high as 50%. Treatment options include blood products, such as cryoprecipitate, or antifibrinolytics, such as tranexamic acid (TXA) or ε-aminocaproic acid (EACA). Current guidelines recommend cryoprecipitate first-line despite limited data to support one agent over another. In addition, compared to antifibrinolytics, cryoprecipitate is higher in cost and requires thawing before use. This case series seeks to characterize the management of thrombolytic reversal at a single institution as well as provide additional evidence for antifibrinolytics in this setting. Patients were included for a retrospective review if they met the following criteria: presented between January 2011-January 2017, were >18 years of age, were admitted for AIS, received a thrombolytic, and received TXA EACA, or cryoprecipitate. Twelve patients met the inclusion criteria. Ten (83.3%) developed an ICH, one (8.3%) experienced gastrointestinal bleeding, and one (8.3%) had bleeding at the site of knee arthroscopy. Eleven patients received cryoprecipitate (median dose: 10 units), three received TXA (median dose: 1,000 mg), and one patient received EACA (13 g). TXA was administered faster than the first blood product at a mean time of 19 min and 137 min, respectively. Hemorrhagic expansion (N = 8, 66.67%) and inhospital mortality (N = 7, 58.3%) were high. While limited by its small sample size, this case series demonstrates significant variability in reversal strategies for thrombolysis-associated bleeding. It also provides additional evidence for the role of antifibrinolytics in this setting., Competing Interests: Disclosure: The authors have no financial disclosures or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This article summarizes emerging nontraditional therapies administered via the nebulization route for use in the emergency department (ED)., Summary: Although traditional routes of medication administration (eg, intravenous) have been the mainstay of administration modalities for decades, these routes may not be appropriate for all patients. Nowhere is this more readily apparent than in the ED setting, where patients with a variety of presentations receive care. One unique route for medication administration that has increasingly gained popularity in the ED is that of aerosolized drug delivery. This route holds promise as direct delivery of medications to the site of action could yield a more rapid and effective therapeutic response while also minimizing systemic adverse effects by utilizing a fraction of the systemic dose. Medication administration via nebulization also provides an alternative that is conducive to rapid, less invasive access, which is advantageous in the emergent setting of the ED. This review is intended to analyze the existing literature regarding this route of administration, including the nuances that can impact drug efficacy, as well as the available literature regarding novel, noncommercial nebulized medication therapy given in the ED., Conclusion: Multiple medications have been investigated for administration via this route, and when implementing any of these therapies several practical considerations must be taken into account, from medication preparation to administration, to ensure optimal efficacy while minimizing adverse effects. The pharmacist is an essential bedside team member in these scenarios to assist with navigating unique and complex nuances of this therapy as they develop., (© American Society of Health-System Pharmacists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)