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Implementation of earlier antibiotic administration in patients with severe sepsis and septic shock in Japan: a descriptive analysis of a prospective observational study.
BACKGROUND: Time to antibiotic administration is a key element in sepsis care; however, it is difficult to implement sepsis care bundles. Additionally, sepsis is different from other emergent conditions including acute coronary syndrome, stroke, or trauma. We aimed to describe the association between time to antibiotic administration and outcomes in patients with severe sepsis and septic shock in Japan. METHODS: This prospective observational study enrolled 1184 adult patients diagnosed with severe sepsis based on the Sepsis-2 criteria and admitted to 59 intensive care units (ICUs) in Japan between January 1, 2016, and March 31, 2017, as the sepsis cohort of the Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) study. We compared the characteristics and in-hospital mortality of patients administered with antibiotics at varying durations after sepsis recognition, i.e., 0-60, 61-120, 121-180, 181-240, 241-360, and 361-1440 min, and estimated the impact of antibiotic timing on risk-adjusted in-hospital mortality using the generalized estimating equation model (GEE) with an exchangeable, within-group correlation matrix, with "hospital" as the grouping variable. RESULTS: Data from 1124 patients in 54 hospitals were used for analyses. Of these, 30.5% and 73.9% received antibiotics within 1 h and 3 h, respectively. Overall, the median time to antibiotic administration was 102 min [interquartile range (IQR), 55-189]. Compared with patients diagnosed in the emergency department [90 min (IQR, 48-164 min)], time to antibiotic administration was shortest in patients diagnosed in ICUs [60 min (39-180 min)] and longest in patients transferred from wards [120 min (62-226)]. Overall crude mortality was 23.4%, where patients in the 0-60 min group had the highest mortality (28.0%) and a risk-adjusted mortality rate [28.7% (95% CI 23.3-34.1%)], whereas those in the 61-120 min group had the lowest mortality (20.2%) and risk-adjusted mortality rates [21.6% (95% CI 16.5-26.6%)]. Differences in mortality were noted only between the 0-60 min and 61-120 min groups. CONCLUSIONS: We could not find any association between earlier antibiotic administration and reduction in in-hospital mortality in patients with severe sepsis
The Simian Virus 40 Large T Antigen Does Not Inhibit Translation of the 14-kDa Myelin Basic Protein mRNA in Reticulocyte Lysates or in Transfected Cells
Viral T antigens are transcription factors that have been suspected of inhibiting expression of the myelin basic protein (MBP) mRNA at the translational level in vitro and in vivo. The effect of simian virus 40 (SV40) large T antigen (T-ag) was examined on the translation of the 14-kDa MBP mRNA in reticulocyte lysates and on MBP expression after transfection into cells that express SV40 T-ag. SV40 T-ag did not inhibit translation of 14-kDa MBP cRNAs in cell-free translations even at 30 µ M (∼600 µg/ml) T-ag. Permanent transfection of COS-1 cells (which endogenously express SV40 T-ag) with the 14-kDa MBP cDNA resulted in the expression of the 14-kDa MBP as determined by western blot analysis. Permanent transfection of N20.1 cells, an oligodendrocyte line immortalized with a temperature-sensitive SV40 T-ag, with the 14-kDa MBP cDNA construct also resulted in the expression of the 14-kDa MBP under conditions in which the cells expressed functional SV40 T-ag. These results indicate that SV40 T-ag does not prevent expression of the MBP gene at the translational level and that in those immortalized oligodendrocyte lines that express MBP mRNA, but not MBP protein, some factor other than the SV40 large T-ag is responsible for the posttranscriptional regulation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65286/1/j.1471-4159.1995.64020928.x.pd
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