A Phase I Dose Escalation Study of the Safety,Tolerability, and Pharmacokinetics of Ipilimumab in Chinese Patients with Select Advanced Solid Tumors

Lessons Learned

• The overall safety profiles of ipilimumab 3 mg/kg and 10 mg/kg administered every 3 weeks, were consistent between Chinese patients with solid tumors in the current study and patients from previous U.S. ipilimumab monotherapy studies. No new safety signals were identified.
• The mean systemic exposures to ipilimumab (assessed by first dose area under the curve during the dosing interval and maximum serum concentration) were numerically lower in the Chinese patient population than in U.S. patients for both 3 mg/kg and 10 mg/kg doses; however, the range of serum concentrations in the Chinese and U.S. populations overlapped (3 mg/kg and 10 mg/kg), suggesting that ipilimumab pharmacokinetics was ethnically insensitive in this study.

BackgroundThis phase I, open‐label study assessed ipilimumab safety, tolerability, pharmacokinetics (PK), immunogenicity, and antitumor activity in Chinese patients with unresectable, metastatic, recurrent malignant melanoma (MM) or nasopharyngeal carcinoma (NPC).MethodsOf 39 patients enrolled, 25 received ipilimumab (11 patients received 3 mg/kg, and 14 patients received 10 mg/kg). Reasons for not receiving treatment were withdrawal of consent (3 patients), no longer meeting the criteria (10 patients), and one recorded as “other.” During the induction phase, patients received ipilimumab (3 mg/kg, i.v.), on day 1 of a 3‐week cycle, to a maximum of four doses or progressive disease (PD). During the maintenance phase at week 24, patients received ipilimumab (3 mg/kg, i.v.) on day 1 of a 12‐week cycle, to a maximum of 3 years or PD. Considering the co‐primary safety and PK endpoints, the successive dosing required nine patients with two or fewer dose‐limiting toxicities during the 42‐day observation period to proceed with a new cohort of nine patients at 10 mg/kg.ResultsIpilimumab safety and PK profiles were similar in Chinese and predominantly White populations. Ipilimumab was well tolerated. Most adverse events (AEs) were grades 1–2 and experienced by 11 patients treated with 3 mg/kg and 14 patients treated with 10 mg/kg. There were no new safety concerns. Incidence of anti‐ipilimumab antibodies was low (1 of 10 in the 3 mg/kg patients and 2 of 13 in the 10 mg/kg patients) and without safety implications. In the 3 mg/kg group, 8 of 11 patients had PD. In the 10 mg/kg group (all NPC, 0 MM patients), 11 of 14 patients had PD. Three patients had stable disease (one at 3 mg/kg and two at 10 mg/kg).ConclusionIpilimumab was well tolerated in Chinese patients, showing similar safety and PK to previous studies in predominantly White populations.     

基于标准化患者法评价四川农村基层医生两种慢性病诊断准确性及其影响因素

目的 运用标准化患者法评估四川农村地区基层医生不稳定型心绞痛和2型糖尿病两种慢性病诊断准确性现状,探讨基层医生两种慢性病诊断准确性的主要影响因素,为提升基层医生两种慢性病诊断准确性提供科学依据。方法 采用多阶段随机整群抽样方法,抽取四川省自贡市5个区/县50个乡镇100个村为研究现场,以调查当日在岗的全科及内科医生作为研究对象。共进行两轮数据采集,第1轮采集样本乡镇卫生院和村卫生室医生的基本信息;第1轮调查完成1个月后,运用标准化患者法开展第2轮调查,收集农村基层医生对不稳定型心绞痛和2型糖尿病诊断结果信息。运用Logistic回归分析农村基层医生不稳定型心绞痛和2型糖尿病诊断准确性的影响因素。结果 共纳入172名农村基层医生,完成186次标准化患者访问,正确诊断率为48.39%。其中不稳定型心绞痛的正确诊断率为18.68%(17/91),2型糖尿病的正确诊断率为76.84%(73/95)。Logistic回归分析显示,具有执业医师资质的农村基层医生更有可能做出正确诊断(OR=4.857,95%CI=1.076~21.933,P=0.040)。农村基层医生在诊断过程中涉及的必要问诊和检查条目越多,做出正确诊断的概率越高(OR=1.627,95%CI=1.065~2.485,P=0.024)。与不稳定型心绞痛相比,农村基层医生对2型糖尿病做出正确诊断的可能性更高(OR=6.306,95%CI=3.611~11.013,P<0.001)。结论 四川农村基层医生不稳定型心绞痛和2型糖尿病诊断准确性整体较差,建议以基层医生慢性病诊断过程质量改善为突破口,提升基层医生执业水平,进而提高慢性病诊断准确性。     

中药生产过程质量控制关键技术研究进展

中医药发展已上升到国家战略层面,在医药行业贯彻实施"中国制造2025"战略的新形势下,中药生产过程质量控制是中药工业需要加快突破的关键领域之一。对中药生产过程质量控制领域在工艺设计、分析检测、过程建模、制造装备等方面的关键共性问题进行解析,综述了中药生产过程质量控制体系中工艺过程理解、生产过程实时分析方法开发、过程控制策略建立3个方面的研究进展;并结合企业研究实践,介绍了质量源于设计(quality by design,Qb D)、过程分析技术(process analytical technology,PAT)、实验设计(design of experiment,DOE)、多变量统计分析等关键技术在上述3个研究方向中的应用进展,分析了实际工业应用的难点问题并对其应用前景进行展望,旨在为中药企业应用和提升生产过程质量控制技术提供参考。     

经9次核酸检测终确诊的新型冠状病毒肺炎患者1例分析

目前新型冠状病毒肺炎(COVID-19)疫情在全球蔓延,形势严峻,并对全球公共卫生事业构成巨大挑战,快速准确的诊断COVID-19对疫情的防控有重要意义。本文报道1例COVID-19患者的调查和确诊过程,以对COVID-19确诊和疫情防控提供有价值的参考。患者为赴渝务工于2020年1月23日返乡人员,在渝期间,其同工地的一同事确诊为COVID-19,之后该工地接连有另外8位同事被确诊。患者返乡后2月2日被当地疫情防控单位采取医学隔离。患者于隔离后不久出现咳嗽,阵发性,干咳为主,偶可咳出黄色痰液等COVID-19相关临床症状,遂被当地新型冠状病毒肺炎定点医疗单位收治,后经市级新型冠状病毒肺炎诊治专家组远程视频会诊转入四川大学华西医院资阳医院。患者先后经历9次核酸检测,在前8次核酸检测均为阴性的情况下,于第9次核酸检测结果为阳性,2月21日最终确诊为新型冠状病毒肺炎。     

人格特质对二胎返岗护士产适应水平的影响

目的 了解二胎返岗护士适应水平现状,并探讨人格特质对其返岗适应水平的影响。方法 2018年1-12月,采用便利抽样法选取山东省3所三级甲等医院360名护士为研究对象,采用一般资料调查表、艾森克人格问卷、护士产后返岗适应问卷对其进行调查。结果 护士产二胎后返岗适应水平均分为(2.16±0.51)分;外向型人格特征与返岗适应水平呈正相关(r=0.540,P<0.001),精神质、神经质人格特征与返岗适应水平均呈负相关(r=-0.410,P<0.001;r=-0.350,P<0.001)。多元线性回归分析结果显示,年龄、返岗时间、工作负荷、返岗培训、内-外倾向、精神质、神经质是护士产二胎后返岗适应的独立影响因素。结论 护士产二胎后返岗适应处于中等偏下水平,人格特质、生育年龄、返岗时间、工作负荷、返岗培训为其影响因素,护理管理者可结合人格特质等特点采取管理策略,提高护士产二胎后返岗适应的水平。