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Study Objective To compare the effects of empiric vancomycin dosing regimens on attainment of optimal target trough concentrations in obese (body mass index [BMI] 30–40 kg/m2) and extremely obese (BMI ≥ 40 kg/m2) patients. Design Retrospective cohort study. Data Source National Veterans Affairs standardized databases. Patients A total of 263 obese and 71 extremely obese (actual body weight range 72–244 kg in both groups) inpatients from all Veterans Affairs facilities nationally who had suspected methicillin‐resistant Staphylococcus aureus pneumonia and were treated with vancomycin between 2002 and 2012. Measurements and Main Results Patients with steady‐state trough concentrations (measured ≤ 2 hours before the next vancomycin dose) and no evidence of acute kidney injury before vancomycin initiation were included. Logistic regression models were used to measure the effect of various vancomycin dosing regimens on attainment of optimal target trough concentrations (15–20 mg/L). The mean total daily vancomycin dose was lower in obese versus extremely obese patients (2005 ± 736 vs 2306 ± 934 mg, p<0.05). The mean weight‐based daily dose was higher in obese patients (20 ± 7 vs 17 ± 7 mg/kg/day, p<0.05). In each group, ~ 20% of patients achieved optimal target trough concentrations. In obese patients, the standard dose of ~ 30 mg/kg/day was appropriate for target trough concentration attainment (odds ratio 5.15, 95% confidence interval 1.69–15.64). In extremely obese patients, a lower dosage of 20 to 25 mg/kg/day was appropriate for target trough concentration attainment (odds ratio 6.07, 95% confidence interval 1.01–36.51). Conclusion In this real‐world study, we offer additional consideration of vancomycin dosing in obese and extremely obese patients. Extremely obese patients may require a lower weight‐based daily dose than obese patients to reach target vancomycin trough concentrations.
Study Objective To compare the effects of empiric vancomycin dosing regimens on attainment of optimal target trough concentrations in obese (body mass index [BMI] 30–40 kg/m2) and extremely obese (BMI ≥ 40 kg/m2) patients. Design Retrospective cohort study. Data Source National Veterans Affairs standardized databases. Patients A total of 263 obese and 71 extremely obese (actual body weight range 72–244 kg in both groups) inpatients from all Veterans Affairs facilities nationally who had suspected methicillin‐resistant Staphylococcus aureus pneumonia and were treated with vancomycin between 2002 and 2012. Measurements and Main Results Patients with steady‐state trough concentrations (measured ≤ 2 hours before the next vancomycin dose) and no evidence of acute kidney injury before vancomycin initiation were included. Logistic regression models were used to measure the effect of various vancomycin dosing regimens on attainment of optimal target trough concentrations (15–20 mg/L). The mean total daily vancomycin dose was lower in obese versus extremely obese patients (2005 ± 736 vs 2306 ± 934 mg, p<0.05). The mean weight‐based daily dose was higher in obese patients (20 ± 7 vs 17 ± 7 mg/kg/day, p<0.05). In each group, ~ 20% of patients achieved optimal target trough concentrations. In obese patients, the standard dose of ~ 30 mg/kg/day was appropriate for target trough concentration attainment (odds ratio 5.15, 95% confidence interval 1.69–15.64). In extremely obese patients, a lower dosage of 20 to 25 mg/kg/day was appropriate for target trough concentration attainment (odds ratio 6.07, 95% confidence interval 1.01–36.51). Conclusion In this real‐world study, we offer additional consideration of vancomycin dosing in obese and extremely obese patients. Extremely obese patients may require a lower weight‐based daily dose than obese patients to reach target vancomycin trough concentrations.
BackgroundWith concerns about the disastrous health and economic consequences caused by the influenza pandemic, comprehensively understanding the global host response to influenza virus infection is urgent. The role of microRNA (miRNA) has recently been highlighted in pathogen-host interactions. However, the precise role of miRNAs in the pathogenesis of influenza virus infection in humans, especially in critically ill patients is still unclear.MethodsWe identified cellular miRNAs involved in the host response to influenza virus infection by performing comprehensive miRNA profiling in peripheral blood mononuclear cells (PBMCs) from critically ill patients with swine-origin influenza pandemic H1N1 (2009) virus infection via miRNA microarray and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) assays. Receiver operator characteristic (ROC) curve analysis was conducted and area under the ROC curve (AUC) was calculated to evaluate the diagnostic accuracy of severe H1N1 influenza virus infection. Furthermore, an integrative network of miRNA-mediated host-influenza virus protein interactions was constructed by integrating the predicted and validated miRNA-gene interaction data with influenza virus and host-protein-protein interaction information using Cytoscape software. Moreover, several hub genes in the network were selected and validated by qRT-PCR.ResultsForty-one significantly differentially expressed miRNAs were found by miRNA microarray; nine were selected and validated by qRT-PCR. QRT-PCR assay and ROC curve analyses revealed that miR-31, miR-29a and miR-148a all had significant potential diagnostic value for critically ill patients infected with H1N1 influenza virus, which yielded AUC of 0.9510, 0.8951 and 0.8811, respectively. We subsequently constructed an integrative network of miRNA-mediated host-influenza virus protein interactions, wherein we found that miRNAs are involved in regulating important pathways, such as mitogen-activated protein kinase signaling pathway, epidermal growth factor receptor signaling pathway, and Toll-like receptor signaling pathway, during influenza virus infection. Some of differentially expressed miRNAs via in silico analysis targeted mRNAs of several key genes in these pathways. The mRNA expression level of tumor protein T53 and transforming growth factor beta receptor 1 were found significantly reduced in critically ill patients, whereas the expression of Janus kinase 2, caspase 3 apoptosis-related cysteine peptidase, interleukin 10, and myxovirus resistance 1 were extremely increased in critically ill patients.ConclusionsOur data suggest that the dysregulation of miRNAs in the PBMCs of H1N1 critically ill patients can regulate a number of key genes in the major signaling pathways associated with influenza virus infection. These differentially expressed miRNAs could be potential therapeutic targets or biomarkers for severe influenza virus infection.
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