Patient Pain Experiences and the Emergency Department Encounter: A Qualitative Analysis.

BACKGROUND: Legislation, practice recommendations, and the likely link between therapeutic opioid exposure and iatrogenic opioid use disorder (OUD) have led to reduced opioid prescribing. The effects of this change on unrelieved pain and the overdose crisis are not well-characterized. AIM: We explored emergency department (ED) patients' beliefs and experiences involving pain and emergency care to inform the development of future psychosocial interventions that balance the need for acute pain management with risks from opioid exposure. METHODS: Qualitative, semi-structured interviews were conducted after discharge from an urban, academic Level 1 trauma center ED from September 2020 to May 2021 with 18 adult patients presenting with acute pain. After transcription of audio recording, common themes were identified using framework analysis. Thematic hierarchy was validated with Pearson correlation coefficients for cluster analysis of word similarity. RESULTS: Of the 18 participants, most were Black (n = 11, 61%) and male (n = 12, 66.7%). Analysis identified one overarching theme: locus of control with an emergency pain encounter. Four themes were identified surrounding internal and external influences on pain management: (1) accessing healthcare for acute pain; (2) managing the pain after discharge; (3) seeking opioids: self-medicating and misuse; and (4) opioid crisis makes people in pain suffer. CONCLUSIONS: Patients discharged from the ED reported unrelieved pain, factors that influence their pain management, and an ability to seek opioids from non-medical sources. There is a significant disconnect between patients and providers in terms of priorities in pain management and the importance of individualized care.

Emergency Nurse Perceptions of Pain and Opioids in the Emergency Department.

The opioid crisis is a national health emergency with immense morbidity, mortality, and socioeconomic cost. Emergency department (ED) pain management is tightly linked to the issue of opioid use disorder (OUD), because opioid exposure is necessary for development of OUD. Emergency nurses are on the frontlines of this complex problem, yet little, if any, attention has been paid to the role they play in the prevention and management of either pain or OUD in this unique and important setting. A framework that conceptualizes and optimizes emergency nurses as change agents in the opioid epidemic is urgently needed. While ED pain management and OUD prevention is dependent on the entire care team, this innovative study qualitatively characterizes emergency nurse perceptions of pain management, OUD prevention, and their potential role in each. Content analysis produced 14 categories that were clustered into two themes, "nurses influence ED pain management" and "adjustments in ED pain management", and an overarching message that "pain management depends on the care team." By generating a more comprehensive and nuanced understanding of the role played by emergency nurses, our findings provide essential insights into potential interventions and frameworks.

Absence of VLDL secretion does not affect alpha-tocopherol content in peripheral tissues.

alpha-Tocopherol is a lipid-soluble antioxidant that helps to prevent oxidative damage to cellular lipids. alpha-Tocopherol is absorbed by the intestine and is taken up and retained by the liver; it is widely presumed that alpha-tocopherol is then delivered to peripheral tissues by the secretion of VLDL. To determine whether VLDL secretion is truly important for the delivery of alpha-tocopherol to peripheral tissues, we examined alpha-tocopherol metabolism in mice that lack microsomal triglyceride transfer protein (Mttp) expression in the liver and therefore cannot secrete VLDL (Mttp(Delta/Delta) mice). Mttp(Delta/Delta) mice have low plasma lipid levels and increased stores of lipids in the liver. Similarly, alpha-tocopherol levels in the plasma were lower in Mttp(Delta/Delta) mice than in controls, whereas hepatic alpha-tocopherol stores were higher. However, alpha-tocopherol levels in the peripheral tissues of Mttp(Delta/Delta) mice were nearly identical to those of control mice, suggesting that VLDL secretion is not critical for the delivery of alpha-tocopherol to peripheral tissues. When fed a diet containing deuterated alpha-tocopherol, Mttp(Delta/Delta) and control mice had similar incorporation of deuterated alpha-tocopherol into plasma and various peripheral tissues. We conclude that the absence of VLDL secretion has little effect on the stores of alpha-tocopherol in peripheral tissues, at least in the mouse.

On the physiological importance of endoproteolysis of CAAX proteins: heart-specific RCE1 knockout mice develop a lethal cardiomyopathy.

Proteins terminating with a CAAX motif, such as the Ras proteins and the nuclear lamins, undergo post-translational modification of a C-terminal cysteine with an isoprenyl lipid via a process called protein prenylation. After prenylation, the last three residues of CAAX proteins are clipped off by Rce1, an integral membrane endoprotease of the endoplasmic reticulum. Prenylation is crucial to the function of many CAAX proteins, but the physiologic significance of endoproteolytic processing has remained obscure. To address this issue, we used Cre/loxP recombination techniques to create mice lacking Rce1 in the heart, an organ where Rce1 is expressed at particularly high levels. The hearts from heart-specific Rce1 knockout mice manifested reduced levels of both the Rce1 mRNA and CAAX endoprotease activity, and the hearts manifested an accumulation of CAAX protein substrates. The heart-specific Rce1 knockout mice initially appeared healthy but died starting at 3-5 months of age. By 10 months of age, approximately 70% of the mice had died. Pathological studies revealed that the heart-specific Rce1 knockout mice had a dilated cardiomyopathy. By contrast, liver-specific Rce1 knockout mice appeared healthy, had normal transaminase levels, and had normal liver histology. These studies indicate that the endoproteolytic processing of CAAX proteins is essential for cardiac function but is less important for the liver.

Eliminating atherogenesis in mice by switching off hepatic lipoprotein secretion.

BACKGROUND: LDL receptor-deficient "apolipoprotein (apo)-B100-only" mice (Ldlr-/-Apob100/100 have elevated LDL cholesterol levels on a chow diet and develop severe aortic atherosclerosis. We hypothesized that both the hypercholesterolemia and the susceptibility to atherosclerosis could be eliminated by switching off hepatic lipoprotein production. METHODS AND RESULTS: We bred Ldlr-/-Apob100/100 mice that were homozygous for a conditional allele for Mttp (the gene for microsomal triglyceride transfer protein) and the inducible Mx1-Cre transgene. In these animals, which we called "Reversa mice," the hypercholesterolemia could be reversed, without modifying the diet or initiating a hypolipidemic drug, by the transient induction of Cre expression in the liver. After Cre induction, hepatic Mttp expression was virtually eliminated (as judged by quantitative real-time PCR), hepatic lipoprotein secretion was abolished (as judged by electron microscopy), and LDLs were virtually eliminated from the plasma. Intestinal lipoprotein production was unaffected. In mice fed a chow diet, Cre induction reduced plasma cholesterol levels from 233.9+/-46.0 to 37.2+/-6.5 mg/dL. In mice fed a high-fat diet, cholesterol levels fell from 525.7+/-32.2 to 100.6+/-14.3 mg/dL. The elimination of hepatic lipoprotein production completely prevented both the development of atherosclerosis and the changes in gene expression that accompany atherogenesis. CONCLUSIONS: We developed mice in which hypercholesterolemia can be reversed with a genetic switch. These mice will be useful for understanding gene-expression changes that accompany the reversal of hypercholesterolemia and atherosclerosis.