Sample size re‐estimation in clinical trials

Adaptive clinical trials are becoming very popular because of their flexibility in allowing mid‐stream changes of sample size, endpoints, populations, etc. At the same time, they have been regarded with mistrust because they can produce bizarre results in very extreme settings. Understanding the advantages and disadvantages of these rapidly developing methods is a must. This paper reviews flexible methods for sample size re‐estimation when the outcome is continuous.     

慢性乙型肝炎舌红苔黄和舌淡苔白不同舌象的尿代谢组研究

目的：探索慢性乙型肝炎舌红苔黄和舌淡苔白不同舌象者的尿代谢差异指标,为中医舌象生物学物质基础微观辨证提供证据。方法：采用气相色谱／质谱联用（GC／MS ）技术方法获取慢性乙型肝炎舌红苔黄和舌淡苔白不同舌象者的尿液样本代谢指纹谱,用无监督的学习模式进行多变量统计分析,观察不同组别的人群之间是否存在“自然”的分类结构。利用有监督的学习模式进行数据分类模型的建立和检验,寻找造成样本聚集和离散的主要差异变量。利用商业化的代谢物谱库以及标准品数据库,进行物质鉴定。结果：慢性乙型肝炎舌红苔黄和舌淡苔白者在有监督的学习模式下具有良好的分开趋势,慢乙肝不同舌象者较健康者的差异代谢物谱主要与能量代谢、氨基酸代谢、核苷酸代谢以及肠道菌群代谢相关。结论：舌象是机体变化的重要窗口,不同舌象的外在表观潜在体内的代谢差异。     

Clinical considerations for the development of biosimilars in oncology

Despite availability of biologic therapies, limited patient access to many of the most-effective cancer treatments affects overall health outcomes. To address this issue, many governments have enacted legislation for the approval of biosimilars. The term “biosimilar” refers to a biologic product that is developed to be highly similar, as opposed to identical, to a licensed biologic product (the reference or innovator product), such that, per US Food and Drug administration draft guidelines, “no clinically meaningful differences [exist] between the biological product and the reference product in terms of safety, purity, and potency.” This article presents some considerations about the development of biosimilars in cancer treatment through an overview of biosimilars from a clinical perspective. Topics covered include the development requirements and unique regulatory requirements for biosimilars, labeling considerations, potential limitations to the uptake of biosimilars, and review of some biosimilars in development for oncology indications.     

Ligand binding strategies of human serum albumin: How can the cargo be utilized?

Human serum albumin (HSA), being the most abundant carrier protein in blood and a modern day clinical tool for drug delivery, attracts high attention among biologists. Hence, its unfolding/refolding strategies and exogenous/endogenous ligand binding preference are of immense use in therapeutics and clinical biochemistry. Among its fellow proteins albumin is known to carry almost every small molecule. Thus, it is a potential contender for being a molecular cargo/or nanovehicle for clinical, biophysical and industrial purposes. Nonetheless, its structure and function are largely regulated by various chemical and physical factors to accommodate HSA to its functional purpose. This multifunctional protein also possesses enzymatic properties which may be used to convert prodrugs to active therapeutics. This review aims to highlight current overview on the binding strategies of protein to various ligands that may be expected to lead to significant clinical applications. Chirality, 2010. © 2009 Wiley‐Liss, Inc.     

A link between the accumulation of DNA damage and loss of multi‐potency of human mesenchymal stromal cells

Human mesenchymal stromal cells (hMSCs) represent an attractive cell source for clinic applications. Besides being multi‐potent, recent clinical trials suggest that they secrete both trophic and immunomodulatory factors, allowing allogenic MSCs to be used in a wider variety of clinical situations. The yield of prospective isolation is however very low, making expansion a required step toward clinical applications. Unfortunately, this leads to a significant decrease in their stemness. To identify the mechanism behind loss of multi‐potency, hMSCs were expanded until replicative senescence and the concomitant molecular changes were characterized at regular intervals. We observed that, with time of culture, loss of multi‐potency was associated with both the accumulation of DNA damage and the respective activation of the DNA damage response pathway, suggesting a correlation between both phenomena. Indeed, exposing hMSCs to DNA damage agents led to a significant decrease in the differentiation potential. We also showed that hMSCs are susceptible to accumulate DNA damage upon in vitro expansion, and that although hMSCs maintained an effective nucleotide excision repair activity, there was a progressive accumulation of DNA damage. We propose a model in which DNA damage accumulation contributes to the loss of differentiation potential of hMSCs, which might not only compromise their potential for clinical applications but also contribute to the characteristics of tissue ageing.     

Haplorchis taichui as a Possible Etiologic Agent of Irritable Bowel Syndrome-Like Symptoms

The aim of this study is to clarify the clinical features of Haplorchis taichui infection in humans in Nan Province, Thailand, and to correlate the clinical features with irritable bowel syndrome (IBS)-like symptoms. In this study area, only H. taichui, but neither other minute intestinal flukes nor small liver flukes were endemic. The degree of infection was determined by fecal egg counts and also by collecting adult worms after deworming. The signs and symptoms of individual patients together with their hematological and biochemical laboratory data were gathered to evaluate the relationship between the clinical features and the severity of infection. Special emphasis was made to elucidate the possible similarities of the clinical features of H. taichui infection and IBS-like symptoms. The results showed useful clinical information and the significant (> 50%) proportion of haplorchiasis patients complained of abdominal pain, lassitude, and flatulence, which were the important diagnostic symptoms of IBS. This study has reported a possible link between H. taichui and IBS, and H. taichui might probably play a role in the etiology of these IBS-like symptoms.     

实施临床路径的医院概况及其成因分析

目的 通过对我国实施临床路径的医院的情况进行描述、分析,发现其中存在的问题,提出建议。方法 文献研究法,即分析以“临床路径”为关键词,在维普中文科技期刊数据库中搜索到的1 051篇相关文献,同时结合查阅互联网上的相关信息以及电话回访核对信息的方法。结果 我国实施临床路径的医院有162家,占全国医院总数的0.82%;162家医院在全国的分布情况为：华东、华中、华北、华南、东北、西南和西北分别占37.7%、17.9%、14.8%、13.0%、7.4%、4.9%和4.3%;实施临床路径的医院在级别和隶属关系上存在不同,三级医院实施的数量要多于其他级别的医院;82.7%的医院实施临床路径的病种数量少于10个,4.8%的医院实施的病种数量在50个以上;临床路径实施的持续时间平均为2.02年。结论 我国实施临床路径的医院数量少,区域分布不平衡,进入临床路径的病种数量相对较少,病种较单一;临床路径实施的持续时间较短。我国临床路径的实施与推广,需要政府政策、医院、患者多方面的努力,为临床路径的实施与推广奠定更好的基础。     

临床路径在神经根型颈椎病保守治疗中的应用与变异管理

目的 评价临床路径在神经根型颈椎病保守治疗中的应用效果。方法 通过制订临床路径,将实施临床路径前后病人的住院天数、医疗费用、健康知识评分、满意度进行比较并对出现的变异进行管理。结果 实施临床路径提高了医务人员工作的主动性,加强了医患沟通,使患者住院天数、医疗费用有所下降,健康知识掌握情况、满意度有所提高。统计学分析差异有显著性。结论 临床路径作为一种新型的医疗质量管理模式,值得在临床推广应用。临床执行过程中应注意对变异的管理。     

临床新技术评价指标体系的建立及应用研究

目的 建立科学的临床新技术评价指标体系,为临床新技术管理提供依据。方法 结合管理实践,通过文献及政策调研、专家咨询、实践验证等方法进行研究。结果 建立了临床新技术定性与定量相结合的评价指标体系,采取同行函审和集中评定相结合的办法进行了实证研究,探索了临床新技术管理的有效方法。结论 评价体系的建立和应用为临床新技术的科学管理提供了依据,推动医疗技术的进步和医院的发展。