Recent Advances in Peripheral Opioid Receptor Therapeutics.

PURPOSE OF REVIEW: Although opioids are excellent analgesics, they are associated with severe short- and long-term side effects that are especially concerning for the treatment of chronic pain. Peripherally acting opioid receptor agonists promise to mitigate the more serious centrally mediated side effects of opioids, and the goal of this paper is to identify and elaborate on recent advances in these peripheral opioid receptor therapeutics. RECENT FINDINGS: Peripheral opioid receptor agonists are effective analgesics that at the same time circumvent the problem of centrally mediated opioid side effects by (1) preferentially targeting peripheral opioid receptors that are often the source of the pain and (2) their markedly diminished permeability or activity across the blood-brain barrier. Recent novel bottom-up approaches have been notable for the design of therapeutics that are either active only at inflamed tissue, as in the case of fentanyl-derived pH-sensitive opioid ligands, or too bulky or hydrophilic to cross the blood-brain barrier, as in the case of morphine covalently bound to hyperbranched polyglycerols. Recent innovations in peripheral opioid receptor therapeutics of pH-sensitive opioid ligands and limiting opioid permeability across the blood-brain barrier have had promising results in animal models. While this is grounds for optimism that some of these therapeutics will be efficacious in human subjects at a future date, each drug must undergo individualized testing for specific chronic pain syndromes to establish not only the nuances of each drug's therapeutic effect but also a comprehensive safety profile.

Dual Enkephalinase Inhibitors and Their Role in Chronic Pain Management.

PURPOSE OF REVIEW: Dual enkephalinase inhibitors (DENKIs) are pain medications that indirectly activate opioid receptors and can be used as an alternative to traditional opioids. Understanding the physiology of enkephalins and their inhibitors and the pharmacology of these drugs will allow for proper clinical application for chronic pain patients in the future. RECENT FINDINGS: DENKIs can be used as an alternative mode of analgesia for patients suffering from chronic pain by preventing the degradation of endogenous opioid ligands. By inhibiting the two major enkephalin-degrading enzymes (neprilysin and aminopeptidase N), DENKIs can provide analgesia with less adverse effects than nonendogenous opioids. The purpose of this paper is to review the current literature investigating DENKIs and explore their contribution to chronic pain management.

Recent Advances in the Treatment of Opioid Use Disorder.

PURPOSE OF REVIEW: Opioid use disorder (OUD) remains a national epidemic with an immense consequence to the United States' healthcare system. Current therapeutic options are limited by adverse effects and limited efficacy. RECENT FINDINGS: Recent advances in therapeutic options for OUD have shown promise in the fight against this ongoing health crisis. Modifications to approved medication-assisted treatment (MAT) include office-based methadone maintenance, implantable and monthly injectable buprenorphine, and an extended-release injectable naltrexone. Therapies under investigation include various strategies such as heroin vaccines, gene-targeted therapy, and biased agonism at the G protein-coupled receptor (GPCR), but several pharmacologic, clinical, and practical barriers limit these treatments' market viability. This manuscript provides a comprehensive review of the current literature regarding recent innovations in OUD treatment.

Comprehensive Ultrasound Course for Special Operations Combat and Tactical Medics.

BACKGROUND: Advances in ultrasound technology with enhanced portability and high-quality imaging has led to a surge in its use on the battlefield by nonphysician providers. However, there is a consistent need for comprehensive and standardized ultrasound training to improve ultrasound knowledge, manual skills, and workflow understanding of nonphysician providers. MATERIALS AND METHODS: Our team designed a multimodal ultrasound course to improve ultrasound knowledge, manual skills, and workflow understanding of nine Special Operations combat medics and Special Operations tactical medics. The course was based on a flipped classroom model with a total time of 43 hours, consisting of an online component followed by live lectures and hands-on workshops. The effectiveness of the course was determined using a knowledge exam, expert ratings of manual skills using a global rating scale, and an objective structured clinical skills examination (OSCE). RESULTS: The average knowledge exam score of the medics increased from pre-course (56% ± 6.8%) to post-course (80% ± 5.0%, p < .001). Based on expert ratings, their manual skills improved from baseline to day 4 of the course for image finding (p = .007), image optimization (p = .008), image acquisition speed (p = .008), final image quality (p = .008), and global assessment (p = .008). Their average score at every OSCE station was > 91%. CONCLUSION: A comprehensive multimodal training program can be used to improve military medics' ultrasound knowledge, manual skills, and workflow understanding for various applications of ultrasound. Further research is required to develop a reliable, sustainable course.

Case Report: Drug-induced Leukocytoclastic Vasculitis in a Patient with Classic Ehlers-Danlos Syndrome.

Drug-induced skin reactions are common, but only a small portion (10%) are attributed to a vasculitic mechanism. Small-vessel vasculitis (SVV) with leukocytoclastic histopathology is usually described in drug-induced vasculitis; however, given the shared histopathologic features between drug-induced vasculitis and other SVV, it is crucial to rule out infectious or other autoimmune etiologies underlying the clinical presentation. We hereby sought to present a case of sulfonamide-induced leukocytoclastic vasculitis, limited to the skin, in a patient with Ehlers-Danlos syndrome in order to emphasize the need for a broad diagnostic and clinical exclusion workup.