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ABSTRACT: The number of people facing mental health issues continues to grow in the aftermath of COVID-19. Nurses are challenged with providing care for an increasing number of patients, including veterans, with complex mental health needs across healthcare settings. Of concern, many students transitioning into practice feel they lack the necessary confidence, education, and skills to competently care for patients with mental health illness. This article discusses an innovative mental health immersion experience strategically integrated within a new-nurse residency program.
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COVID-19 , Humanos , COVID-19/enfermería , Enfermería Psiquiátrica/educación , SARS-CoV-2 , Estudiantes de Enfermería/psicología , Competencia Clínica , Bachillerato en Enfermería/organización & administración , Trastornos Mentales/enfermeríaRESUMEN
BACKGROUND: Gray horses are predisposed to equine malignant melanoma (EMM) with advancing age. Depending on the tumor's location and size, they can cause severe problems (e.g., defaecation, urination, feeding). A feasible therapy for EMM has not yet been established and surgical excision can be difficult depending on the location of the melanoma. Thus, an effective and safe therapy is needed. Naturally occurring betulinic acid (BA), a pentacyclic triterpene and its synthetic derivate, NVX-207 (3-acetyl-betulinic acid-2-amino-3-hydroxy-2-hydroxymethyl-propanoate) are known for their cytotoxic properties against melanomas and other tumors and have already shown good safety and tolerability in vivo. In this study, BA and NVX-207 were tested for their permeation potential into equine skin in vitro in Franz-type diffusion cell (FDC) experiments after incubation of 5 min, 30 min and 24 h, aiming to use these formulations for prospective in vivo studies as a treatment for early melanoma stages. Potent permeation was defined as reaching or exceeding the half maximal inhibitory concentrations (IC50) of BA or NVX-207 for equine melanoma cells in equine skin samples. The active ingredients were either dissolved in a microemulsion (ME) or in a microemulsion gel (MEG). All of the formulations were transdermally applied but the oil-in-water microemulsion was administered with a novel oxygen flow-assisted (OFA) applicator (DERMADROP TDA). RESULTS: All tested formulations exceeded the IC50 values for equine melanoma cells for BA and NVX-207 in equine skin samples, independently of the incubation time NVX-207 applied with the OFA applicator showed a significant time-dependent accumulation and depot-effect in the skin after 30 min and 24 h (P < 0.05). CONCLUSIONS: All tested substances showed promising results. Additionally, OFA administration showed a significant accumulation of NVX-207 after 30 min and 24 h of incubation. Further in vivo trials with OFA application are recommended.
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Administración Cutánea , Ácido Betulínico , Sistemas de Liberación de Medicamentos , Emulsiones , Triterpenos Pentacíclicos , Piel , Triterpenos , Animales , Caballos , Triterpenos/administración & dosificación , Piel/metabolismo , Piel/efectos de los fármacos , Sistemas de Liberación de Medicamentos/veterinaria , Geles , Melanoma/tratamiento farmacológico , Melanoma/veterinaria , Oxígeno/metabolismo , Absorción Cutánea , Enfermedades de los Caballos/tratamiento farmacológico , PropanolaminasRESUMEN
The naturally occurring betulinic acid (BA) and its derivative NVX-207 induce apoptosis in equine melanoma cells in vitro. After topical application, high concentrations of the substances can be reached in healthy equine skin. With the aim to investigate the effect and safety of topically applied BA and NVX-207 in horses with melanocytic tumors, the longitudinal, prospective, randomized, double-blind, placebo-controlled study protocol included eighteen Lipizzaner mares with early-stage cutaneous melanoma assigned to three groups. Melanocytic lesions were topically treated either with a placebo, 1% BA or 1% NVX-207 twice a day for 91 days. Caliper measurements, clinical examinations and blood tests were performed to assess the effects and safety of the medication. The topical treatment was convenient and safe. The volumes of tumors treated with BA were significantly reduced over time as compared to tumors treated with the placebo from day 80 of the study. Although treatment with NVX-207 seemed to decrease tumor volume, these results did not reach statistical significance. The findings must be regarded as preliminary due to the limited group size and need to be replicated in a larger cohort with modified pharmaceutical test formulations. Accordingly, the treatment protocol cannot yet be recommended in its current form.
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BACKGROUND: By inhibiting the adsorption of protein and platelets, surface-modifying macromolecules (SMMs) may improve the hemocompatibility of hemodialyzers. This trial aims to assess the performance and safety of a novel dialyzer with a fluorinated polyurethane SMM, Endexo™. METHODS: This prospective, sequential, multicenter, open-label study (NCT03536663) was designed to meet regulatory requirements for clinical testing of new hemodialyzers, including assessment of the in vivo ultrafiltration coefficient (Kuf). Adults prescribed thrice-weekly hemodialysis were eligible for enrollment. After completing 12 hemodialysis sessions with an Optiflux® F160NR dialyzer, patients received 38 sessions with the dialyzer with Endexo. Evaluated parameters included the in vivo Kuf of the dialyzer with Endexo extent of removal of urea, albumin, and ß2-microglobulin (ß2M), as well as complement activation. RESULTS: Twenty-three patients received 268 hemodialysis treatments during the Optiflux period, and 18 patients received 664 hemodialysis treatments during the Endexo period. Three serious adverse events were reported, and none of them were considered device related. No overt complement activation was observed with either dialyzer. Both dialyzers were associated with comparable mean increases in serum albumin levels from pre- to posthemodialysis (Optiflux: 7.9%; Endexo: 8.0%). These increases can be viewed in the context of a mean increase in hemoglobin of approximately 5% and a mean ultrafiltration volume removed of approximately 2.2 L. The corrected mean ß2M removal rate was 47% higher during the Endexo period (67.73%). Mean treatment times (208 vs. 205 min), blood flow rates (447.7 vs. 447.5 mL/min), dialysate flow rates (698.5 vs. 698.0 mL/min), urea reduction ratio (82 vs. 81%), and spKt/V (2.1 vs. 1.9) were comparable for the Endexo and Optiflux periods, respectively. The mean (SD) Kuf was 15.85 (10.33) mL/h/mm Hg during the first use of the dialyzer with Endexo (primary endpoint) and 16.36 (9.92) mL/h/mm Hg across the Endexo period. CONCLUSIONS: The safety of the novel dialyzer with Endexo was generally comparable to the Optiflux dialyzer, while exhibiting a higher ß2M removal rate.
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Materiales Biocompatibles/química , Fallo Renal Crónico/terapia , Poliuretanos/química , Diálisis Renal/instrumentación , Adulto , Anciano , Anciano de 80 o más Años , Materiales Biocompatibles/efectos adversos , Femenino , Halogenación , Humanos , Fallo Renal Crónico/sangre , Masculino , Membranas Artificiales , Persona de Mediana Edad , Poliuretanos/efectos adversos , Estudios Prospectivos , Diálisis Renal/efectos adversos , Albúmina Sérica/análisis , Albúmina Sérica/aislamiento & purificación , Urea/sangre , Urea/aislamiento & purificación , Microglobulina beta-2/sangre , Microglobulina beta-2/aislamiento & purificaciónRESUMEN
The naturally occurring betulinic acid (BA) and its derivative NVX-207 show anticancer effects against equine malignant melanoma (EMM) cells and a potent permeation in isolated equine skin in vitro. The aim of the study was to determine the in vivo concentration profiles of BA and NVX-207 in equine skin and assess the compounds' local and systemic tolerability with the intent of developing a topical therapy against EMM. Eight horses were treated percutaneously in a crossover design with 1% BA, 1% NVX-207 or a placebo in a respective vehicle twice a day for seven consecutive days with a seven-day washout period between each formulation. Horses were treated at the neck and underneath the tail. Concentration profiles of the compounds were assessed by high-performance liquid chromatography in the cervical skin. Clinical and histopathological examinations and blood analyses were performed. Higher concentrations of NVX-207 were found in the skin compared to BA. Good systemic tolerability and only mild local adverse effects were observed in all three groups. This study substantiates the topical application of BA and NVX-207 in further clinical trials with horses suffering from EMM; however, penetration and permeation of the compounds may be altered in skin affected by tumors.
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Antineoplásicos/farmacocinética , Caballos/metabolismo , Triterpenos Pentacíclicos/farmacocinética , Propanolaminas/farmacocinética , Triterpenos/farmacocinética , Administración Tópica , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Estudios Cruzados , Femenino , Masculino , Triterpenos Pentacíclicos/administración & dosificación , Triterpenos Pentacíclicos/efectos adversos , Permeabilidad , Proyectos Piloto , Propanolaminas/administración & dosificación , Propanolaminas/efectos adversos , Triterpenos/administración & dosificación , Triterpenos/efectos adversos , Ácido BetulínicoRESUMEN
BACKGROUND: Equine malignant melanoma (EMM) is a frequently occurring dermoepidermal tumor in grey horses. Currently available therapies are either challenging or inefficient. Betulinic acid (BA), a naturally occurring triterpenoid, is a promising compound for cancer treatment. To evaluate the potential of BA as a topical therapy for EMM, its anticancer effects on primary equine melanoma cells and dermal fibroblasts and its percutaneous permeation through isolated equine skin were assessed in vitro. RESULTS: BA showed antiproliferative and cytotoxic effects on both primary equine melanoma cells and fibroblasts in a time- and dose-dependent manner. The lowest half-maximal inhibitory concentrations were obtained 96 h after the beginning of drug exposure (12.7 µmol/L and 23.6 µmol/L for melanoma cells eRGO1 and MelDuWi, respectively, in cytotoxicity assay). High concentrations of the compound were reached in the required skin layers in vitro. CONCLUSION: BA is a promising substance for topical EMM treatment. Further clinical studies in horses are necessary to assess safety and antitumoral effects in vivo.