Single cell transcriptomics of bone marrow derived macrophages reveals Ccl5 as a biomarker of direct IFNAR-independent responses to DNA sensing.

Introduction: The type I interferon (IFN) response is an innate immune program that mediates anti-viral, anti-cancer, auto-immune, auto-inflammatory, and sterile injury responses. Bone marrow derived macrophages (BMDMs) are commonly used to model macrophage type I IFN responses, but the use of bulk measurement techniques obscures underlying cellular heterogeneity. This is particularly important for the IFN response to immune stimulatory double-stranded DNA (dsDNA) because it elicits overlapping direct and indirect responses, the latter of which depend on type I IFN cytokines signaling via the IFN alpha receptor (IFNAR) to upregulate expression of interferon stimulated genes (ISGs). Single cell transcriptomics has emerged as a powerful tool for revealing functional variability within cell populations. Methods: Here, we use single cell RNA-Seq to examine BMDM heterogeneity at steady state and after immune-stimulatory DNA stimulation, with or without IFNAR-dependent amplification. Results: We find that many macrophages express ISGs after DNA stimulation. We also find that a subset of macrophages express ISGs even if IFNAR is inhibited, suggesting that they are direct responders. Analysis of this subset reveals Ccl5 to be an IFNAR-independent marker gene of direct DNA sensing cells. Discussion: Our studies provide a method for studying direct responders to IFN-inducing stimuli and demonstrate the importance of characterizing BMDM models of innate immune responses with single cell resolution.

Healthcare quality during pediatric mental health boarding: A qualitative analysis.

BACKGROUND: Following initial evaluation and management, youth requiring inpatient psychiatric care often experience boarding, defined as being held in the emergency department or another location while awaiting inpatient care. Although mental health boarding is common, little research has examined the quality of healthcare delivery during the boarding period. OBJECTIVE: This study aimed to explore the perspectives and experiences of multidisciplinary clinicians and parents regarding mental health boarding and to develop a conceptual model to inform quality improvement efforts. DESIGN, SETTING, & PARTICIPANTS: We conducted semistructured interviews with clinicians and parents of youth experiencing boarding. Interviews focused on experiences of care and perceived opportunities for improvement were continued until thematic saturation was reached. Interviews were recorded, transcribed, and analyzed to identify emergent themes using a general inductive approach. Axial coding was used to inform conceptual framework development. RESULTS: Interviews were conducted with 19 clinicians and 11 parents. Building on the Donabedian structure-process-outcome model of quality evaluation, emergent domains, and associated themes included: (1) infrastructure for healthcare delivery, including clinician training, healthcare team composition, and the physical environment; (2) processes of healthcare delivery, including clinician roles and responsibilities, goals of care, communication with families, policies/procedures, and logistics of inter-facility transfer; and (3) measurable outcomes, including patient safety, family experience, mental health status, timeliness of care, and clinician moral distress. CONCLUSION: This qualitative study summarizes clinician and family perspectives about care for youth experiencing boarding. The conceptual model resulting from this analysis can be applied to implement and evaluate quality improvement endeavors to support this vulnerable population.

Reducing Outpatient Infant Blood Draws with Transcutaneous Measurement of Bilirubin.

INTRODUCTION: Newborn jaundice is a common outpatient problem. Transcutaneous bilirubin (TcB) measurements correlate well with total serum bilirubin (SB) measurements below 15 mg/dl and are efficient and noninvasive. Some concern exists that TcB measurement may subsequently lead to an increase in the number of SB measurements performed in the outpatient setting. We aimed to implement the use of a TcB device in an outpatient clinic. By doing so, we sought to increase the number of newborns screened solely by TcB as opposed to SB, by 30%, within 12 months. METHODS: We conducted plan-do-study-act cycles with targeted interventions to promote the use of TcB in an outpatient clinic for eligible newborns older than 35 weeks gestational age, aged 1-20 days, and without a history of transfusion, phototherapy, extensive bruising, or risk of hemolysis. We used statistical process control methods to measure proportions of newborns evaluated with TcB (run chart) and patients-between SB measurements (G-chart) over time in the outpatient clinic. RESULTS: We collected preintervention data for 18-months and intervention data for 12 months. For newborns attending the outpatient clinic, the proportion of TcB measurements increased after implementation of the use of TcB measurement. There was an increase in patients-between SB measurements. At project inception, SB was drawn for every 8 eligible patients. By the end of the project, there were 98 eligible newborns between instances of SB testing. CONCLUSION: Implementation of a quality-improvement initiative to measure TcB in the outpatient clinic was feasible and reduced the number of SB tests.