Critical limits to define a lab adverse event during phase I studies: a study in 1134 subjects

Objective: The first goal of phase I drug development is the determination of maximal tolerated dose, which must be established by case-by-case analysis, sometimes using a laboratory adverse event. Since no accurate rule defining lab adverse events, has been validated yet, we propose a new “combined method” based on combination of two thresholds: inclusion values and magnitude of variation. Using this combined method, the label “lab adverse event” is applied if any lab value exceeds the inclusion threshold and is associated with a variation from baseline exceeding the variation threshold defined from reference change limit. Thus, this study aimed to test this combined method on a large healthy volunteer population, studied in 19 phase I centres worldwide, and on five lab parameters: alanine amino transferase, aspartate amino transferase, alkaline phosphatases, creatinine and polymorphonuclear leukocytes. Methods: The inclusion threshold from each center was used. Reference change limits were defined from volunteers previously included in comparable studies and were expressed as absolute values: increases of 10?IU?·?l^?1 for alanine amino transferase or aspartate amino transferase, 15?IU?·?l^?1 for alkaline phosphatases, 15?μmol?·?l^?1 for creatinine and a 0.34 10⁹?·?l^?1 decrease for polymorphonuclear leukocytes. Comparison between the “combined method” and a normal range method was made using positive predictive value and a ratio between relevant and irrelevant results. This application was implemented in all young healthy volunteers (1134) included in 38 phase I studies sponsored by Rhône Poulenc Rorer from 1991 to 1993. Results: Seventy seven subjects (6.7%) were indicated in final study reports as having a lab adverse event (reference group). Of 179 subjects with lab abnormalities defined by the normal range method, 77 belonged to the reference group, inducing a poor 0.43 positive predictive value. Of ninety subjects with lab adverse events defined by the “combined method”, seventy-five belonged to the reference group, inducing a two-fold higher 0.83 positive predictive value. The combined method produced a high ratio of relevant/irrelevant results ( ) compared with the low ratio ( ) achieved using the normal range method. Conclusion: This new “combined method”, leading to a better definition of lab adverse event, seems an accurate and useful tool for routine case-by-case analysis within phase I drug development studies.     

养阴类中药成分与药理研究现状

本文综述了近年来养阴药的化学成分及药理作用,发现多糖、氨基酸、微量元素是其发挥功效的重要成分。     

现代人下颌颏形的变异及与化石人类的比较

目的分析中国现代人群颏形的表现特点及时代变异。方法将颏形分为3种类型,方形、圆形、尖形,比较不同时代间(新石器时代54例,青铜铁器时代197例,近代113例)各个类型出现率的差异。结果新石器时代颏形主要为圆形和方形,青铜铁器时代圆形颏形占绝对优势,近代主要为圆形。中国晚期智人颏形为圆形和尖形。结论颏形不同时代间有差异,颏形的变化可能与下颌骨尺寸、下颌前部形态的时代变异有关。     

中国全新世人群下颌骨几项观察性状的变异

目的 探讨中国现代人群（新石器时代56例,青铜铁器时代210例,近代113例）下颌骨几项观察性状的表现及时代变异特点。方法 将下颌角外翻、咬肌粗隆、翼肌粗隆、颏棘等分为几个类型,统计各个类型在不同时代间的出现率并比较时代间的差异。结果 青铜铁器时代下颌角外翻程度最大;咬肌粗隆、翼肌粗隆表现为显著的比例,在所比较的3个时代间都为新石器>青铜铁器>近代;颏棘的在不同时代间差异不明显。结论 咬肌粗隆、翼肌粗隆在全新世随时代而变弱,可能反映了咬肌、翼肌在全新世期间减弱,支持“咀嚼压力在全新世期间减弱”的观点。     

Needs and use of drug information sources in community pharmacies: a questionnaire based survey in German-speaking Switzerland

OBJECTIVES: To explore the types of drug information used by pharmacists in daily practice, their needs and wishes concerning drug information and their opinions about future changes of pharmacy practice. METHODS: Postal survey to a random sample of 223 (26% out of 859) community pharmacies from the German-speaking part of Switzerland. The 48-item questionnaires were processed automatically with the Cardiff TELEform-Software. In addition, a telephone-survey to a random sample of 20 non-responders was performed in order to test for non-response bias. RESULTS: A total of 108 pharmacists (response rate 48%) reported that the official Swiss drug reference book is still the most popular source of drug information used to solve all kinds of drug related problems. The Internet as a source of drug information is of minor importance, even though 88% of the pharmacies have Internet access. Deficits in drug information were reported for paediatrics, phytotherapy, drugs during pregnancy/lactation and for therapy guidelines. According to 35% of the pharmacists, the importance of offering drug information to customers will increase in the future. Most of the pharmacists are not afraid that Internet pharmacies would replace them. CONCLUSIONS: The results show that the majority of the community pharmacists are only partially satisfied with the sources of drug information currently available. The Internet still plays a minor role for solving drug-related problems in daily practice, even though the available infrastructure makes the community pharmacies able to use the Internet more frequently. The pharmacists need more websites tailored to their needs. The pharmacists have clear visions about possible future developments. They do, however, have to adopt quickly to the changes ahead in order to remain competitive.     

遥感与地理信息系统技术在疟疾研究中的应用与发展

疟疾是一种由疟原虫引起的、经按蚊叮咬而传播的重要寄生虫病,按蚊是人类疟疾的惟一传播媒介.气候、地理、生态等环境因素直接影响人和按蚊的生存环境,对疟疾的分布起决定性作用,所以地理环境因素对疟疾流行与传播的影响受到关注.地理信息系统(GIS)具有空间数据管理、分析与显示功能,卫星遥感(RS)技术可以对地表环境进行动态观测,获取地理环境信息,且覆盖面广、信息量大、不受地理环境条件限制.近年来,GIS和遥感的结合已越来越广泛地应用到疟疾研究中,在疟疾控制监测及预测预警方面发挥了重要作用.     

水银血压计替代产品的最新进展

水银血压计是当今医院中使用极其广泛的无创测量血压的基本医疗器械之一。但是水银对自然环境及人类是有害的。随着全世界范围内对水银血压计的限制使用．水银血压计的淘汰将不可避免。从临床医护人员的需求以及在医学工程的技术角度上．提出水银血压计的替代产品也提出一些要求及其进展。     

Recent childbirth is an adverse prognostic factor in breast cancer and melanoma,but not in Hodgkin lymphoma

BackgroundThe relationship between gestation, childbirth and cancer prognosis is unknown for most cancers (e.g. Hodgkin lymphoma), whereas a body of evidence exists for melanoma and breast cancer.MethodsThe national cancer registration and hospital discharge data for women in England (1998–2007) were linked, and the records for Hodgkin lymphoma, melanoma and breast cancer were indexed as to whether women had delivered a child in separate time periods prior to their cancer diagnosis. Survival analyses were conducted in order to characterise prognosis in relation to childbirth, with statistical adjustment for age and (where possible) stage.FindingsFor melanoma and breast cancer, survival was strongly reduced in women who gave birth in the year prior to cancer diagnosis. The age-adjusted hazard ratios (HR) with 95% confidence intervals (CI) were 2.06 (1.42–3.01) for melanoma and 1.84 (1.64–2.06) for breast cancer. The associations were only slightly attenuated by further adjustment for tumour stage. For breast cancer, the excess death rate in women with a recent childbirth peaked at 2 years and remained elevated for 6 to 8 years. Previous childbirth had no overall effect on the outcome of Hodgkin lymphoma.InterpretationMelanoma and breast cancer prognosis are adversely affected by recent gestation and childbirth in a way that is not due to stage of the cancer, but rather to inherent biological properties of the tumours. Possible biological mechanisms include immunosuppression (melanoma), the hormonal milieu in gestation and a tumour promoting microenvironment post-partum (breast cancer).     

浅谈新形势下二级医院的管理

本文通过对二级医院现在的管理模式及管理方法调查,探讨新形势下怎样改变二级医院的经营观念和管理理念（人才培养及人事改革、优化二级医院机构格局）,来应对新形势,以便使二级医院更好顺应形势的发展,为大众提供更好的卫生医疗服务,加强二级医院在市场经济条件下的竞争力和服务能力,促进二级医院在新形势下更好更快的发展。现在二级医院存在四大问题（公益性质薄,弱资源配置和机构格局不合理,过度行政化,医患关系紧张）,只有改变二级医院原来的经营观念和管理观念,才能顺应新形势,才能在市场经济条件下更有竞争力。经营是龙头,管理是基础,创新是动力。     

陕西省新报告HIV阳性嫖客的新发感染及相关因素分析

目的 了解陕西省新报告HIV抗体阳性嫖客新发感染状况及相关因素。方法 选择2013年1月1日至2014年6月30日期间新发现报告的现住址为陕西省且经核查后明确感染途径为“商业异性性传播”的男性HIV/AIDS病例,收集其一般人口学资料、确证前高危异性性行为和样本来源等相关信息以及血液样本,应用HIV-1捕获酶联免疫法（BED-CEIA）进行检测,计算新发感染比例并研究新发感染的相关因素。结果 陕西省新报告212名HIV抗体阳性嫖客,新发感染比例为25.5%（42/165）,确诊前HIV抗体检测率为6.6%（14/212）。HIV抗体阳性嫖客中,初中以上文化程度者比初中以下文化程度者更可能是长期感染（aOR=0.28,95% CI：0.08～0.93）;与其他就诊者/性病门诊就诊者检测相比,术前/受血前检测（aOR=3.14,95% CI：1.06～9.30）和无偿献血人员检测（aOR=4.19,95% CI：1.01～17.42）更容易发现HIV新发感染者;与确证前仅在西安和/或外省发生商业异性性行为相比,在省内其他城市发生商业异性性行为的更可能是长期感染（aOR=0.19,95% CI：0.07～0.57）;与确证前有临时异性性伴的相比,无临时异性性伴的更可能是新发感染（aOR=9.03,95% CI：3.00～27.18）,P值均<0.05。结论 陕西省HIV抗体阳性嫖客新发感染比例处于较高水平,确诊前HIV抗体检测率低,文化程度、样本来源、确证前商业异性性行为发生地点、确证前有无临时性伴是HIV阳性嫖客新发感染的相关影响因素。提示陕西省嫖客尤其是初中以下文化程度者艾滋病疫情不容乐观,针对该人群特征应加大行为干预及检测发现力度。