RESUMO
BACKGROUND: Prothrombin/international normalized ratio and activated partial thromboplastin time (PT/INR and aPTT) are frequently ordered in emergency departments (EDs), but rarely affect management. They offer limited utility outside of select indications. Several quality improvement initiatives have shown reduction in ED use of PT/INR and aPTT using multifaceted interventions in well-resourced settings. Successful reduction of these low-value tests has not yet been shown using a single intervention across a large hospital system in a safety net setting. This study aims to determine if an intervention of two BPAs is associated with a reduction in PT/INR and aPTT usage across a large safety net system. METHODS: This initiative was set at a large safety net system in the United States with 11 acute care hospitals. Two Best Practice Advisories (BPAs) discouraging inappropriate PT/INR and aPTT use were implemented from March 16, 2022-August 30, 2022. Order rate per 100 ED patients during the pre-intervention period was compared to the post-intervention period on both the system and individual hospital level. Complete blood count (CBC) testing served as a control, and packed red blood cell transfusions served as a balancing measure. An interrupted time series regression analysis was performed to capture immediate and temporal changes in ordering for all tests in the pre and post-intervention periods. RESULTS: PT/INR tests exhibited an absolute decline of 4.11 tests per 100 ED encounters (95% confidence interval -5.17 to -3.05; relative reduction of 18.9%). aPTT tests exhibited absolute decline of 4.03 tests per 100 ED encounters (95% CI -5.10 to -2.97; relative reduction of 19.8%). The control measure, CBC, did not significantly change (-0.43, 95% CI -2.83 to 1.96). Individual hospitals showed variable response, with absolute reductions from 2.02 to 9.6 tests per 100 ED encounters for PT/INR (relative reduction 12.1%-30.5%) and 2.07 to 10.04 for aPTT (relative reduction 12.1%-31.4%). Regression analysis showed that the intervention caused an immediate 25.7% decline in PT/INR and 24.7% decline in aPTT tests compared to the control measure. The slope differences (rate of order increase pre vs post intervention) did not significantly decline compared to the control. CONCLUSIONS: This BPA intervention reduced PT/INR and aPTT use across 11 EDs in a large, urban, safety net system. Further study is needed in implementation to other non-safety net settings.
RESUMO
Brainstem gliomas (BSG) are a rare group of central nervous system tumors that arise mostly in children and usually portend a particularly poor prognosis. We report the development of a genetically engineered mouse model of BSG using the RCAS/tv-a system and its implementation in preclinical trials. Using immunohistochemistry, we found that platelet-derived growth factor (PDGF) receptor alpha is overexpressed in 67% of pediatric BSGs. Based on this observation, we induced low-grade BSGs by overexpressing PDGF-B in the posterior fossa of neonatal nestin tv-a mice. To generate high-grade BSGs, we overexpressed PDGF-B in combination with Ink4a-ARF loss, given that this locus is commonly lost in high-grade pediatric BSGs. We show that the likely cells of origin for these mouse BSGs exist on the floor of the fourth ventricle and cerebral aqueduct. Irradiation of these high-grade BSGs shows that although single doses of 2, 6, and 10 Gy significantly increased the percent of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive nuclei, only 6 and 10 Gy significantly induce cell cycle arrest. Perifosine, an inhibitor of AKT signaling, significantly induced TUNEL-positive nuclei in this high-grade BSG model, but in combination with 10 Gy, it did not significantly increase the percent of TUNEL-positive nuclei relative to 10 Gy alone at 6, 24, and 72 hours. Survival analysis showed that a single dose of 10 Gy significantly prolonged survival by 27% (P = 0.0002) but perifosine did not (P = 0.92). Perifosine + 10 Gy did not result in a significantly increased survival relative to 10 Gy alone (P = 0.23). This PDGF-induced BSG model can serve as a preclinical tool for the testing of novel agents.
