Aminotransferases During Treatment Predict Long-Term Survival in Patients With Autoimmune Hepatitis Type 1: A Landmark Analysis

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Sex Disparities in Risk of Mortality Among Children With ESRD

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Extubación ultra fast-track vs. convencional tras cirugía cardiaca en un centro de referencia cardiovascular en Colombia. Estudio longitudinal

Introduction

The fast track / ultra-fast-track protocols are techniques used to optimise the patient care process and a quick recovery after cardiac surgery. They are one of the mainstays of efficient practice. With their use, the length of hospital and intensive care unit (ICU) stays are reduced, with a direct impact on costs and the quality of the health service.

2015—2017年解放军总医院抗震颤麻痹药物的使用情况分析

目的 了解解放军总医院抗震颤麻痹药物的应用情况与用药趋势。方法 采用世界卫生组织（WHO）推荐的以限定日剂量（DDD）为指标的分析方法，对2015-2017年解放军总医院抗震颤麻痹药物的销售金额、用药频度（DDDs）、日均费用（DDC）及排序比（B/A）等进行统计分析。结果 普拉克索、多巴丝肼和恩他卡朋的用药金额始终处于前3位，普拉克索的用药金额逐渐上升，卡比多巴/左旋多巴的用药金额逐渐下降；DDDs排序列前2位的是多巴丝肼和司来吉兰，多巴丝肼的DDDs逐年上升，一直处于第1位；2015-2016年各种抗震颤麻痹药物的DDC较为稳定，2016-2017年各种抗震颤麻痹药物的DDC开始略有下降；除普拉克索和恩他卡朋的B/A始终小于1.00，其他抗震颤麻痹药物的B/A均在1.00以上波动。结论 解放军总医院抗震颤麻痹药物的使用较为合理，其中多巴丝肼、普拉克索和司来吉兰具有很好的市场前景。     

多层螺旋CT定量评估慢性阻塞性肺疾病病情的价值

目的探讨多层螺旋CT(MSCT)定量评估慢性阻塞性肺疾病病情的价值。方法选取2017年8月～2018年7月在湖州市第一人民医院就诊的73例慢性阻塞性肺疾病(COPD)患者作为研究对象,按照病情轻重分为Ⅰ组(轻度患者17例)、Ⅱ组(中度患者32例)、Ⅲ组(重度患者24例),并选取同期于该院体检的健康者20例为对照组。所有研究对象均行MSCT低剂量扫描,观察比较各组管腔面积(Ai)、支气管壁面积百分比(WA%)、管壁厚度与体表面积比值(T/BSA)、壁厚度与直径比值(TDR),同时予以肺功能检查,采用定量CT气道分析软件分别测量气道相关参数,并用Siemens Pulmo软件Pearson定量分析其相关性。结果对照组、Ⅰ组、Ⅱ组、Ⅲ组的FEV1均呈逐渐下降趋势,FEV1/FVC呈逐渐上升趋势,差异均有统计学意义(P0.05)。对照组、Ⅰ组、Ⅱ组、Ⅲ组的WA%、T/BSA、TDR比较,均呈逐渐上升趋势,Ai呈下降趋势,差异均有统计学意义(P0.05)。FEV1与WA%、TDR之间呈负相关(r=-0.291,P=0.000;r=-0.473,P=0.000),FEV1/FVC与WA%、TDR之间呈正相关(r=0.285,P=0.000;r=0.472,P=0.000)。结论 MSCT扫描及定量分析可为COPD患者气道病变情况提供可靠的评估信息。     

Understanding the Influence of Nanocarrier-Mediated Brain Delivery on Therapeutic Performance Through Pharmacokinetic-Pharmacodynamic Modeling

This study aimed at evaluating how encapsulation in a regular nanocarrier (NC) (providing extended circulation time) or in a brain-targeting NC (providing prolonged circulation time and increased brain uptake) may influence the therapeutic index compared with the unformulated drug and to explore the key parameters affecting therapeutic performance using a model-based approach. Pharmacokinetic (PK) models were built with chosen PK parameters. For a scenario where central effect depends on area under the unbound brain concentration curve and peripheral toxicity relates to peak unbound plasma concentration, dose-effect and drug-side effect curves were constructed, and the therapeutic index was evaluated. Regular NC improved the therapeutic index compared with the unformulated drug due to reduced peripheral toxicity, while brain-targeting NC enhanced the therapeutic index by lowering peripheral toxicity and increasing central effect. Decreasing drug release rate or systemic clearance of NC with drug still encapsulated could increase the therapeutic index. Also, a drug with shorter half-life would therapeutically benefit more from a NC encapsulation. This work provides insights into how a NC for brain delivery should be optimized to maximize the therapeutic performance and is helpful to predict if and to what extent a drug with certain PK properties would obtain therapeutic benefit from nanoencapsulation.     

In Vitro-In Vivo Extrapolation and Hepatic Clearance-Dependent Underprediction

Accurately predicting the hepatic clearance of compounds using in vitro to in vivo extrapolation (IVIVE) is crucial within the pharmaceutical industry. However, several groups have recently highlighted the serious error in the process. Although empirical or regression-based scaling factors may be used to mitigate the common underprediction, they provide unsatisfying solutions because the reasoning behind the underlying error has yet to be determined. One previously noted trend was intrinsic clearance-dependent underprediction, highlighting the limitations of current in vitro systems. When applying these generated in vitro intrinsic clearance values during drug development and making first-in-human dose predictions for new chemical entities though, hepatic clearance is the parameter that must be estimated using a model of hepatic disposition, such as the well-stirred model. Here, we examine error across hepatic clearance ranges and find a similar hepatic clearance-dependent trend, with high clearance compounds not predicted to be so, demonstrating another gap in the field.