Interferon regulatory factor-5 (IRF-5) is a mediator of virus-induced immune activation and type I interferon (IFN) gene regulation. In human primary plasmacytoid dendritic cells (PDC), IRF-5 is transcribed into four distinct alternatively spliced isoforms (V1, V2, V3, and V4), whereas in human primary peripheral blood mononuclear cells two additional new isoforms (V5 and V6) were identified. The IRF-5 V1, V2, and V3 transcripts have different noncoding first exons and distinct insertion/ deletion patterns in exon 6. Here we showed that V1 and V3 have distinct transcription start sites and are regulated by two discrete promoters. The V1 promoter (P-V1) is constitutively active, contains an IRF-E consensusbinding site, and is further stimulated in virus-infected cells by IRF family members. In contrast, endogenous V3 transcripts were up-regulated by type I IFNs, and the V3 promoter (P-V3) contains an IFN-stimulated responsive element-binding site that confers responsiveness to IFN through binding of the ISGF3 complex. In addition to V5 and V6, we have identified three more alternatively spliced IRF-5 isoforms (V7, V8, and V9); V5 and V6 were expressed in peripheral blood mononuclear cells from healthy donors and in immortalized B and T cell malignancies, whereas expression of V7, V8, and V9 transcripts were detected only in human cancers. The results of this study demonstrated the existence of multiple IRF-5 spliced isoforms with distinct cell typespecific expression, cellular localization, differential regulation, and dissimilar functions in virus-mediated type I IFN gene induction.

This study characterizes the current firearm-related anticipatory guidance practices of pediatricians-in-training and the factors affecting those practices. In this study of Pediatric residents in the Mid-Atlantic region, surveys were distributed to 189 trainees at three hospitals. Eighty-one responses were collected between June 2017 and March 2018. The survey gathered information about the residents' values related to firearms, firearm-specific counseling practices, barriers to providing counseling, and educational needs related to firearms. The residents surveyed overwhelmingly agreed (96%) that physicians have a responsibility to counsel patients on the risks posed by firearms. However, most (63%) never provide firearm-related counseling or do so in only 1-5% of well-child visits. Their unfamiliarity with safe storage devices contributes to a lack of comfort providing counseling. For pediatricians to provide potentially lifesaving counseling on firearm safety, they must be well-versed in the subject and feel comfortable and confident in doing so. Educational interventions addressing physician self-efficacy are necessary to accomplish this. There is an urgent need to develop a comprehensive firearm safety education program for physicians and trainees to improve firearm counseling.

BACKGROUND: Clinicians commonly obtain endotracheal aspirate cultures (EACs) in the evaluation of suspected ventilator-associated infections. However, bacterial growth in EACs does not distinguish bacterial colonization from infection and may lead to overtreatment with antibiotics. We describe the development and impact of a clinical decision support algorithm to standardize the use of EACs from ventilated PICU patients. METHODS: We monitored EAC use using a statistical process control chart. We compared the rate of EACs using Poisson regression and a quasi-experimental interrupted time series model and assessed clinical outcomes 1 year before and after introduction of the algorithm. RESULTS: In the preintervention year, there were 557 EACs over 5092 ventilator days; after introduction of the algorithm, there were 234 EACs over 3654 ventilator days (an incident rate of 10.9 vs 6.5 per 100 ventilator days). There was a 41% decrease in the monthly rate of EACs (incidence rate ratio [IRR]: 0.59; 95% confidence interval [CI] 0.51–0.67; P < .001). The interrupted time series model revealed a preexisting 2% decline in the monthly culture rate (IRR: 0.98; 95% CI 0.97–1.0; P = .01), immediate 44% drop (IRR: 0.56; 95% CI 0.45–0.70; P = .02), and stable rate in the postintervention year (IRR: 1.03; 95% CI 0.99–1.07; P = .09). In-hospital mortality, hospital length of stay, 7-day readmissions, and All Patients Refined Diagnosis Related Group severity and mortality scores were stable. The estimated direct cost savings was $26 000 per year. CONCLUSIONS: A clinical decision support algorithm standardizing EAC obtainment from ventilated PICU patients was associated with a sustained decline in the rate of EACs, without changes in mortality, readmissions, or length of stay.