The Impact of a Comprehensive Simulation-Based Training and Certification Program on Resident Central Venous Catheter Complication Rates.

INTRODUCTION: Millions of central venous catheters (CVCs) are placed annually in the United States, many by resident physicians. Simulation training has been proposed as a means to increase resident physician competence with CVC placement and decrease the incidence of line-associated mechanical complications. We aimed to evaluate the impact of a novel simulation-based CVC training program for resident physicians on CVC-associated mechanical complication rates. We hypothesized that the CVC-related mechanical complication rates would be lower among simulation-trained residents (STRs) compared with nonsimulation, traditionally trained residents (TTRs). METHODS: A retrospective chart review was performed of patients with a CVC placed by a resident physician between October 2014 and January 2017 at MedStar Georgetown University Hospital in Washington, DC. Incidence of CVC mechanical complications, including pneumothorax, hemothorax, arterial injury, or retained guidewire, were extracted from the electronic medical record and compared between STR and TTR cohorts. In contrast to TTRs who were trained to place CVCs in a supervised clinical setting, STRs underwent a CVC training program using online modules, a hands-on simulation training and testing checklist, and a series of successful supervised insertions before being credentialed to place lines independently. RESULTS: Nine hundred twenty-four CVCs placed by resident physicians during the study period were analyzed. There was no statistically significant difference in total mechanical complication rates between the STRs and TTRs in this study period (2.4% vs. 2.2%, P = 1). Simulation-trained residents were more likely to use ultrasound guidance when indicated during CVC insertion compared with TTRs (94.8% vs. 70.5%, P < 0.001). CONCLUSIONS: Mechanical complication rates associated with CVC insertion were similar between the simulation and TTRs and were consistent with previously published literature. These findings suggest that residents who underwent simulation training and certification demonstrated performance on par with more experienced TTRs. In addition, they were more likely to use best practices including ultrasound guidance in line placement.

Multiple functional therapeutic effects of the estrogen receptor ß agonist indazole-Cl in a mouse model of multiple sclerosis.

Currently available immunomodulatory therapies do not stop the pathogenesis underlying multiple sclerosis (MS) and are only partially effective in preventing the onset of permanent disability in patients with MS. Identifying a drug that stimulates endogenous remyelination and/or minimizes axonal degeneration would reduce the rate and degree of disease progression. Here, the effects of the highly selective estrogen receptor (ER) ß agonist indazole chloride (Ind-Cl) on functional remyelination in chronic experimental autoimmune encephalomyelitis (EAE) mice were investigated by assessing pathologic, functional, and behavioral consequences of both prophylactic and therapeutic (peak EAE) treatment with Ind-Cl. Peripheral cytokines from autoantigen-stimulated splenocytes were measured, and central nervous system infiltration by immune cells, axon health, and myelination were assessed by immunohistochemistry and electron microscopy. Therapeutic Ind-Cl improved clinical disease and rotorod performance and also decreased peripheral Th1 cytokines and reactive astrocytes, activated microglia, and T cells in brains of EAE mice. Increased callosal myelination and mature oligodendrocytes correlated with improved callosal conduction and refractoriness. Therapeutic Ind-Cl-induced remyelination was independent of its effects on the immune system, as Ind-Cl increased remyelination within the cuprizone diet-induced demyelinating model. We conclude that Ind-Cl is a refined pharmacologic agent capable of stimulating functionally relevant endogenous myelination, with important implications for progressive MS treatment.

Estrogen receptor (ER) ß expression in oligodendrocytes is required for attenuation of clinical disease by an ERß ligand.

Treatment of experimental autoimmune encephalomyelitis (EAE) mice with the estrogen receptor (ER) ß ligand diarylpropionitrile (DPN) has been shown to have neuroprotective effects via stimulation of endogenous myelination. The direct cellular mechanisms underlying the effects of this ERß ligand on the central nervous system are uncertain because different cell types in both the peripheral immune system and central nervous system express ERs. ERß is the target molecule of DPN because DPN treatment fails to decrease EAE clinical symptoms in global ERß-null mice. Here we investigated the potential role of ERß expression in cells of oligodendrocyte (OL) lineage in ERß ligand-mediated neuroprotection. To this end, we selectively deleted ERß in OLs using the well-characterized Cre-loxP system for conditional gene knockout (CKO) in mice. The effects of this ERß CKO on ERß ligand-mediated neuroprotective effects in chronic EAE mice were investigated. ERß CKO in OLs prevented DPN-induced decrease in EAE clinical disease. DPN treatment during EAE did not attenuate demyelination, only partially improved axon conduction, and did not activate the phosphatidylinositol 3-kinase/serine-threonine-specific protein kinase/mammalian target of rapamycin signaling pathway in ERß CKO mice. However, DPN treatment significantly increased brain-derived neurotrophic factor levels in ERß CKO mice. These findings demonstrate that signaling through ERß in OLs is essential for the beneficial myelination effects of the ERß ligand DPN in chronic EAE mice. Further, these findings have important implications for neuroprotective therapies that directly target OL survival and myelination.