SummaryThe transcriptional activator PrfA, a member of the Crp/Fnr family, controls the expression of some key virulence factors necessary for infection by the human bacterial pathogen Listeria monocytogenes. Phenotypic screening identified ring-fused 2-pyridone molecules that at low micromolar concentrations attenuate L. monocytogenes cellular uptake by reducing the expression of virulence genes. These inhibitors bind the transcriptional regulator PrfA and decrease its affinity for the consensus DNA-binding site. Structural characterization of this interaction revealed that one of the ring-fused 2-pyridones, compound 1, binds at two separate sites on the protein: one within a hydrophobic pocket or tunnel, located between the C- and N-terminal domains of PrfA, and the second in the vicinity of the DNA-binding helix-turn-helix motif. At both sites the compound interacts with residues important for PrfA activation and helix-turn-helix formation. Ring-fused 2-pyridones represent a new class of chemical probes for studying virulence in L. monocytogenes.
Note: This is a revision of the previous joint policy statement titled "Guidelines for Care of Children in the Emergency Department." Children have unique physical and psychosocial needs that are heightened in the setting of serious or life-threatening emergencies. The majority of ill and injured children are brought to community hospital emergency departments (EDs) by virtue of proximity. It is, therefore, imperative that all EDs have the appropriate resources (medications, equipment, policies, and education) and capable staff to provide effective emergency care for children. This policy statement outlines resources necessary for EDs to stand ready to care for children of all ages. These recommendations are consistent with the recommendations of the Institute of Medicine (now called the National Academy of Medicine) in its report "The Future of Emergency Care in the United States Health System." Although resources within emergency and trauma care systems vary locally, regionally, and nationally, it is essential that ED staff, administrators, and medical directors seek to meet or exceed these recommendations to ensure high-quality emergency care is available for all children. These updated recommendations are intended to serve as a resource for clinical and administrative leadership of EDs as they strive to improve their readiness for children of all ages. BACKGROUNDThe National Hospital Ambulatory Medical Care Survey reported that in 2014 there were approximately 5,000 EDs in the United States. Of the more than 141
IntroductionWe conducted an epidemiologic evaluation of advance directives and do-not-resuscitate (DNR) prevalence among residents of extended care facilities (ECF) presenting to the emergency department (ED).MethodsWe performed a retrospective medical record review on ED patients originating from an ECF. Data were collected on age, sex, race, triage acuity, ED disposition, DNR status, power-of attorney (POA) status, and living will (LW) status. We generated descriptive statistics, and used logistic regression to evaluate predictors of DNR status.ResultsA total of 754 patients over 20 months met inclusion criteria; 533 (70.7%) were white, 351 (46.6%) were male, and the median age was 66 years (IQR 54–78). DNR orders were found in 124 (16.4%, 95% CI [13.9–19.1%]) patients. In univariate analysis, there was a significant difference in DNR by gender (10.5% female vs. 6.0% male with DNR, p=0.013), race (13.4% white vs. 3.1% non-white with DNR, p=0.005), and age (4.0% <65 years; 2.9% 65–74 years, p=0.101; 3.3% 75–84 years, p=0.001; 6.2% >84 years, p<0.001). Using multivariate logistic regression, we found that factors associated with DNR status were gender (OR 1.477, p=0.358, note interaction term), POA status (OR 6.612, p<0.001), LW (18.032, p<0.001), age (65–74 years OR 1.261, p=0.478; 75–84 years OR 1.737, p=0.091, >84 years OR 5.258, P<0.001), with interactions between POA and gender (OR 0.294, P=0.016) and between POA and LW (OR 0.227, p<0.005). Secondary analysis demonstrated that DNR orders were not significantly associated with death during admission (p=0.084).ConclusionAge, gender, POA, and LW use are predictors of ECF patient DNR use. Further, DNR presence is not a predictor of death in the hospital.
Objectives: Pediatric training is an essential component of emergency medicine (EM) residency. The heterogeneity of pediatric experiences poses a significant challenge to training programs. A national simulation curriculum can assist in providing a standardized foundation of pediatric training experience to all EM trainees. Previously, a consensus-derived set of content for a pediatric curriculum for EM was published. This study aimed to prioritize that content to establish a pediatric simulation-based curriculum for all EM residency programs. Methods: Seventy-three participants were recruited to participate in a three-round modified Delphi project from 10 stakeholder organizations. In round 1, participants ranked 275 content items from a published set of pediatric curricular items for EM residents into one of four categories: definitely must, probably should, possibly could, or should not be taught using simulation in all residency programs. Additionally, in round 1 participants were asked to contribute additional items. These items were then added to the survey in round 2. In round 2, participants were provided the ratings of the entire panel and asked to rerank the items. Round 3 involved participants dichotomously rating the items. Results: A total of 73 participants participated and 98% completed all three rounds. Round 1 resulted in 61 items rated as definitely must, 72 as probably should, 56 as possibly could, 17 as should not, and 99 new items were suggested. Round 2 resulted in 52 items rated as definitely must, 91 as probably should, 120 as possibly could, and 42 as should not. Round 3 resulted in 56 items rated as definitely must be taught using simulation in all programs.
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