Activity

Opportunity for appropriate research supervision varied considerably by training region. Where research was being conducted, it was often conducted in trainees’ personal time due to the wide regional variation in dedicated research time.

Despite significant interest in clinical research and support by TPDs and clinical supervisors, access to experienced researchers and equitable protected research time by region needs urgent attention to enhance progress in evidence-based palliative medicine.

Despite significant interest in clinical research and support by TPDs and clinical supervisors, access to experienced researchers and equitable protected research time by region needs urgent attention to enhance progress in evidence-based palliative medicine.Although it is self-evident that education in neurology is important and necessary, how to fund the educational mission is a frequent challenge for neurology departments and clinicians. Department chairs often resort to a piecemeal approach, cobbling together funding for educators from various sources, but frequently falling short. Here, we review the various sources available to fund the educational mission in neurology, understanding that not every department will have access to every source. We describe the multiple different teaching models and formats used by the modern student and educator and their associated costs, some of which are exorbitant. We discuss possible nonfinancial incentives, including pathways to promotion, educational research, and other awards and recognition. Neurological education is commonly underfunded, and departments and institutions must be nimble and creative in finding ways to fund the time and effort of educators.The impact of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, is global and unprecedented. Although remdesivir has recently been approved by the FDA to treat SARS-CoV-2 infection, no oral antiviral is available for outpatient treatment. AT-527, an orally administered double prodrug of a guanosine nucleotide analog, was previously shown to be highly efficacious and well tolerated in hepatitis C virus (HCV)-infected subjects. Here, we report the potent in vitro activity of AT-511, the free base of AT-527, against several coronaviruses, including SARS-CoV-2. In normal human airway epithelial cells, the concentration of AT-511 required to inhibit replication of SARS-CoV-2 by 90% (EC90) was 0.47 μM, very similar to its EC90 against human coronavirus (HCoV)-229E, HCoV-OC43, and SARS-CoV in Huh-7 cells. Little to no cytotoxicity was observed for AT-511 at concentrations up to 100 μM. Substantial levels of the active triphosphate metabolite AT-9010 were formed in normal human bronchial and nasal epithelial cells incubated with 10 μM AT-511 (698 ± 15 and 236 ± 14 μM, respectively), with a half-life of at least 38 h. Results from steady-state pharmacokinetic and tissue distribution studies of nonhuman primates administered oral doses of AT-527, as well as pharmacokinetic data from subjects given daily oral doses of AT-527, predict that twice daily oral doses of 550 mg AT-527 will produce AT-9010 trough concentrations in human lung that exceed the EC90 observed for the prodrug against SARS-CoV-2 replication. This suggests that AT-527 may be an effective treatment option for COVID-19.Linezolid is an oxazolidinone antibiotic exhibiting efficacy against multidrug-resistant (MDR) Gram-positive-related infections. However, its population pharmacokinetic (PopPK) profile in Chinese critically ill children has not been characterized. Optimal dosing regimens should be established according to the PopPK/pharmacodynamic(PD) properties of linezolid in the specific population. This work aims to describe the pharmacokinetic (PK) properties of linezolid, assess the factors affecting interpatient variability, and establish an optimized regimen for children in pediatric intensive care unit (PICU). Selleckchem PD0166285 A single-center, prospective, open-labeled PK study was performed. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was applied to measure the plasma levels during linezolid treatment. PopPK analysis was conducted using Phoenix NLME software. Sixty-three critically ill pediatric patients were included. The data showed good fit for a two-compartment model with linear elimination. Bodl children were evaluated, and an optimal dosage regimen was constructed based on developmental PopPK/PD model and simulation. (This study has been registered in the Chinese Clinical Trial Registry under no. ChiCTR1900021386.).BACKGROUND.Candida auris has demonstrated the ability to colonize the skin of hospitalized patients, possibly contributing to nosocomial spread. OBJECTIVE. The objective was to determine whether two novel transdermal agents could clear skin colonization established by C. aurisMETHODS. A murine skin colonization model was first optimized and then used to test fungal burden reduction following treatment with 1% terbinafine or 1% clotrimazole in a proprietary Advanced Penetration Technology formulation (APT™). RESULTS. Both treatments significantly reduced fungal burden compared to control groups. CONCLUSION. These novel agents show promise as a topical means of preventing skin colonization by C. auris.Finding antivirals to reduce coronavirus disease 2019 (COVID-19) morbidity and mortality has been challenging. Large randomized clinical trials that aimed to test four repurposed drugs, hydroxychloroquine, lopinavir-ritonavir, interferon beta 1a, and remdesivir, have shown that these compounds lack an impact on the COVID-19 course. Although the phase III COVID-19 vaccine trial results are encouraging, the search for effective COVID-19 therapeutics should not stop. Recently, plitidepsin (aplidin) demonstrated highly effective preclinical activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its antiviral activity was 27.5-fold more potent than that of remdesivir (K. M. White, R. Rosales, S. Yildiz, T. Kehrer, et al., Science, 2021, https//science.sciencemag.org/content/early/2021/01/22/science.abf4058). Plitidepsin, a repurposed drug developed for the treatment of multiple myeloma, targets the host translation cofactor eEF1A. Plitidepsin has shown efficacy in animal models and phase I/II human trials.