Pharmacologic Pain Management Trends among Adults Hospitalized with Cellulitis: An Evidence-Based Practice Project.

BACKGROUND: Nurses commonly administer opioids, following "as needed" order sets, to patients hospitalized for acute pain conditions like cellulitis. Practice guidelines recommend limiting opioid administration for acute pain management. At two hospitals in the Pacific Northwest, an opioid stewardship committee was formed to align with best practice. AIMS: The main objective was to describe changes to inpatient rates of opioid and non-opioid administration following implementation of evidence-based opioid stewardship efforts. DESIGN: Observational, retrospective, evidence-based practice project. SETTINGS: One 200-bed and one 680-bed hospital in Washington State. PARTICIPANTS/SUBJECTS: Data were included from patients aged 18 years or older hospitalized for cellulitis. METHODS: Demographic and pain-related data were extracted from the electronic health record (n = 4,523 encounters) guided by the symptom management framework. The proportion of patients receiving opioid or non-opioid medications before and after implementation of evidence-based practice opioid stewardship interventions was calculated descriptively. A logistic regression tested factors related to administration of an opioid medication. RESULTS: The proportion of patients receiving an opioid decreased following opioid stewardship efforts while those receiving non-opioid analgesics remained stable. Factors significantly influencing inpatient opioid administration were: average inpatient pain score, pre-hospital opioid prescription, length of stay, and year of hospitalization. CONCLUSIONS: Analgesic administration treating painful, acute cellulitis at two hospitals in the Pacific Northwest included opioid and non-opioid medications. The proportion of patients receiving opioids decreased following best practice opioid stewardship actions. Opportunities may exist for nurses to collaborate with providers to improve inpatient analgesic administration practices.

Cell-penetrating peptides enhance peptide vaccine accumulation and persistence in lymph nodes to drive immunogenicity.

Peptide-based cancer vaccines are widely investigated in the clinic but exhibit modest immunogenicity. One approach that has been explored to enhance peptide vaccine potency is covalent conjugation of antigens with cell-penetrating peptides (CPPs), linear cationic and amphiphilic peptide sequences designed to promote intracellular delivery of associated cargos. Antigen-CPPs have been reported to exhibit enhanced immunogenicity compared to free peptides, but their mechanisms of action in vivo are poorly understood. We tested eight previously described CPPs conjugated to antigens from multiple syngeneic murine tumor models and found that linkage to CPPs enhanced peptide vaccine potency in vivo by as much as 25-fold. Linkage of antigens to CPPs did not impact dendritic cell activation but did promote uptake of linked antigens by dendritic cells both in vitro and in vivo. However, T cell priming in vivo required Batf3-dependent dendritic cells, suggesting that antigens delivered by CPP peptides were predominantly presented via the process of cross-presentation and not through CPP-mediated cytosolic delivery of peptide to the classical MHC class I antigen processing pathway. Unexpectedly, we observed that many CPPs significantly enhanced antigen accumulation in draining lymph nodes. This effect was associated with the ability of CPPs to bind to lymph-trafficking lipoproteins and protection of CPP-antigens from proteolytic degradation in serum. These two effects resulted in prolonged presentation of CPP-peptides in draining lymph nodes, leading to robust T cell priming and expansion. Thus, CPPs can act through multiple unappreciated mechanisms to enhance T cell priming that can be exploited for cancer vaccines with enhanced potency.

Nanoparticle permeation induces water penetration, ion transport, and lipid flip-flop.

Nanoparticles are generally considered excellent candidates for targeted drug delivery. However, ion leakage and cytotoxicity induced by nanoparticle permeation is a potential problem in such drug delivery schemes because of the toxic effect of many ions. In this study, we have carried out a series of coarse-grained molecular dynamics simulations to investigate the water penetration, ion transport, and lipid molecule flip-flop in a protein-free phospholipid bilayer membrane during nanoparticle permeation. The effect of ion concentration gradient, pressure differential across the membrane, nanoparticle size, and permeation velocity have been examined in this work. Some conclusions from our studies include (1) The number of water molecules in the interior of the membrane during the nanoparticle permeation increases with the nanoparticle size and the pressure differential across the membrane but is unaffected by the nanoparticle permeation velocity or the ion concentration gradient. (2) Ion transport is sensitive to the size of nanoparticle as well as the ion concentration gradient between two sides of the membrane; no anion/cation selectivity is observed for small nanoparticle permeation, while anions are preferentially translocated through the membrane when the size of nanoparticle is large enough. (3) Incidences of lipid molecule flip-flop increases with the size of nanoparticle and ion concentration gradient and decreases with the pressure differential and the nanoparticle permeation velocity.