ABSTRACT
INTRODUCTION: Heated high-flow nasal cannula (HHFNC) therapy for bronchiolitis has become increasingly prevalent without evidence that this therapy impacts patient outcomes. Lack of criteria for appropriate use may lead to overutilization, resulting in increased costs without patient benefit. Our primary aim was to decrease use of HHFNC in patients with bronchiolitis over one season. METHODS: Patients with Bronchiolitis younger than 2 years of age admitted to the Hospital Medicine Service were included in this study. Using the model for improvement framework, we identified key drivers for HHFNC overuse and revised our bronchiolitis protocol to include low-flow nasal cannula trials before HHFNC initiation. We compared preintervention HHFNC utilization (December 2018-April 2019) with postintervention HFNC utilization (December 2019-March 2020). RESULTS: One hundred ninety patients met inclusion criteria, 98 of them in the preintervention cohort and 92 in the postintervention cohort. Overall, the median age was 9 months and 65% of patients were male. Our HHFNC utilization rate decreased from 62% (61/98) to 43% (40/92) in the postintervention period. Our SPC analysis suggested special cause variation based on 7 points below the preintervention mean. CONCLUSIONS: This QI intervention implementing a specified low-flow nasal cannula trial before the initiation of HHFNC shows promise in reducing overall HHFNC use. Future studies should focus on clear initiation and discontinuation criteria for HHFNC use in bronchiolitis.
ABSTRACT
Mounting evidence suggests that the circadian clock plays an integral role in the regulation of many physiological processes including blood pressure, renal function, and metabolism. The canonical molecular clock functions via activation of circadian target genes by Clock/Bmal1 and repression of Clock/Bmal1 activity by Per1-3 and Cry1/2. However, we have previously shown that Per1 activates genes important for renal sodium reabsorption, which contradicts the canonical role of Per1 as a repressor. Moreover, Per1 knockout (KO) mice exhibit a lowered blood pressure and heavier body weight phenotype similar to Clock KO mice, and opposite that of Cry1/2 KO mice. Recent work has highlighted the potential role of Per1 in repression of Cry2. Therefore, we postulated that Per1 potentially activates target genes through a Cry2-Clock/Bmal1-dependent mechanism, in which Per1 antagonizes Cry2, preventing its repression of Clock/Bmal1. This hypothesis was tested in vitro and in vivo. The Per1 target genes αENaC and Fxyd5 were identified as Clock targets in mpkCCDc14 cells, a model of the renal cortical collecting duct. We identified PPARα and DEC1 as novel Per1 targets in the mouse hepatocyte cell line, AML12, and in the liver in vivo. Per1 knockdown resulted in upregulation of Cry2 in vitro, and this result was confirmed in vivo in mice with reduced expression of Per1. Importantly, siRNA-mediated knockdown of Cry2 and Per1 demonstrated opposing actions for Cry2 and Per1 on Per1 target genes, supporting the potential Cry2-Clock/Bmal1-dependent mechanism underlying Per1 action in the liver and kidney.
