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.     

上海市黄浦区社会办医疗美容机构《医疗美容管理办法》知晓情况调查

目的了解上海市黄浦区社会办医疗美容机构的管理人员和医师对《医疗美容管理办法》相关内容的掌握情况,发现存在的问题并提出改善建议.方法采用现场调查与现场问卷调查相结合的方式,对在上海市黄浦区开展医疗美容科目的所有社会办医疗机构(共计38家)进行全覆盖现场调查,并对其中的管理人员41人、相关医师31人进行问卷调查.结果38家社会办医疗美容机构中,美容外科和美容皮肤科的开展率较高,分别为96.8%和97.2%,而美容牙科开展率为52.4%,美容中医科开展率最低(25.0%).管理人员关于非主诊医师可在主诊医师指导下工作的知晓率仅68.3%.关于美容外科、皮肤科、中医科、牙科主诊医师应具备的工作年限,管理人员答对率为90.2%,医师答对率为72.0%,二者有显著性差异(P<0.05).结论社会办医疗美容机构中的二级科目设置需进一步优化,以减少资源空置.应加强对医疗机构管理人员和医师的法律培训,改变经营模式,制定明确的准入与退出机制,从而减少违法违规行为的发生.     

Addressing Substance Use in Adolescents: Screening,Brief Intervention,and Referral to Treatment

Adolescent substance use is a national public health crisis. The most commonly used substances among adolescents are nicotine, alcohol, and marijuana. Use of these substances during adolescence has serious adverse effects on brain development, with impairments that can endure into adulthood. Advanced practice nurses in primary care can address substance use in the adolescent population with the use of evidence-based interventions, such as Screening, Brief Intervention, and Referral to Treatment (SBIRT). This article describes trends in adolescent substance use and use of the SBIRT intervention for low, medium, and high-risk use in this population.     

中性粒细胞与淋巴细胞比值对三阴性乳腺癌临床预后及与Ki - 67表达的影响

目的 探讨中性粒细胞与淋巴细胞比值（neutrophil to lymphocyte ratio，NLR）对三阴性乳腺癌的临床预后影响及与Ki - 67表达的关系。方法 回顾性分析2006年1月 - 2012年12月于我院乳腺外科住院治疗的134例三阴性乳腺癌患者。NLR最佳临床分界值采用ROC曲线确定，并依此分NLR＜2.64组和NLR≥2.64组。临床独立预后因素采用单因素和多因素Cox回归模型分析。术后生存时间和生存曲线比较采用Kaplan - Meier和log - rank方法。Ki - 67的表达采用免疫组织化学方法检测。结果 NLR是三阴性乳腺癌的独立预后因素，最佳临界值为2.64。NLR＜2.64组术后中位DFS为39.10月，中位OS为52.30月；NLR≥2.64组术后中位DFS为27.35月，中位OS为37.35月。2组术后DFS和OS比较，差异具有统计学意义（P＜0.05）。NLR低组伴Ki - 67表达阴性的三阴性患者术后中位DFS和OS生存时间显著高于其他情况。结论 NLR是三阴性乳腺癌的关键影响预后因素，具有重复性强、非侵袭性、方便实用等特性，可用于预测三阴性乳腺癌临床预后。