ON USING PEOPLE MERELY AS A MEANS IN CLINICAL RESEARCH

It is often argued that clinical research should not violate the Kantian principle that people must not be used merely as a means for the purposes of others. At first sight, the practice of clinical research itself, however, seems to violate precisely this principle: clinical research is often beneficial to future people rather than to participants; even if participants benefit, all things considered, they are exposed to discomforts which are absent both in regular care for their diseases and in other areas of daily life. Therefore, in this paper we will consider whether people are used merely as a means by being enrolled in clinical research. On the basis of recent studies of Kantian scholars we will argue that clinical research is compatible with the Kantian principle if the conditions of possible consent and end‐sharing have been met. Participants are not used merely as a means if they have sufficient reasons to consent to being enrolled in clinical research and can share the ends of the researchers who use them. Moreover, we will claim that even if people are used merely as a means by participating in clinical research, it may not always be morally wrong to use them in this way.     

Application of stains in clinical microbiology

Stains have been used for diagnosing infectious diseases since the late 1800s. The Gram stain remains the most commonly used stain because it detects and differentiates a wide range of pathogens. The next most commonly used diagnostic technique is acid-fast staining that is used primarily to detect Mycobacterium tuberculosis and other severe infections. Many infectious agents grow slowly on culture media or may not grow at all; stains may be the only method to detect these organisms in clinical specimens. In the hands of experienced clinical microscopists, stains provide rapid and cost-effective information for preliminary diagnosis of infectious diseases. A review of the most common staining methods used in the clinical microbiology laboratory is presented here.     

Application of stains in clinical microbiology

Stains have been used for diagnosing infectious diseases since the late 1800s. The Gram stain remains the most commonly used stain because it detects and differentiates a wide range of pathogens. The next most commonly used diagnostic technique is acid-fast staining that is used primarily to detect Mycobacterium tuberculosis and other severe infections. Many infectious agents grow slowly on culture media or may not grow at all; stains may be the only method to detect these organisms in clinical specimens. In the hands of experienced clinical microscopists, stains provide rapid and cost-effective information for preliminary diagnosis of infectious diseases. A review of the most common staining methods used in the clinical microbiology laboratory is presented here.     

右美托咪定在临床麻醉中的应用进展

右美托咪定(Dexmedetomidine,Dex)是一种高度选择性α2肾上腺素受体激动剂,自1999年被FDA批准作为一种短期的镇静-镇痛药在重症监护室使用以来,Dex广泛应用于整个围术期的镇静和镇痛,即可作为术前用药,又可作为一种兼用于一般性和区域性的麻醉药,或是作为术后镇静和镇痛药。目前研究表明,Dex是许多临床应用的一种有效药物,该药已在减少阿片样药物、苯二酚和异丙酚的需求中显示出其功效。在广泛的临床条件中,Dex即被认为是一种有效的、安全的辅药,又已成为一种有效的治疗剂,其在临床麻醉应用中具有广泛的前景。本文从Dex的作用机制、围术期使用、术后使用、ICU镇静、清醒光纤插管、心脏外科手术及肥胖患者外科手术中应用等方面对其在临床麻醉中的应用现状作一综述,为Dex的临床应用及基础研究提供理论依据。     

iPS cells: a game changer for future medicine

The induced pluripotent stem cell (iPSC) technology is instrumental in advancing the fields of disease modeling and cell transplantation. We herein discuss the various issues regarding disease modeling and cell transplantation presented in previous reports, and also describe new iPSC‐based medicine including iPSC clinical trials. In such trials, iPSCs from patients can be used to predict drug responders/non‐responders by analyzing the efficacy of the drug on iPSC‐derived cells. They could also be used to stratify patients after actual clinical trials, including those with sporadic diseases, based on the drug responsiveness of each patient in the clinical trials. iPSC‐derived cells can be used for the identification of response markers, leading to increased success rates in such trials. Since iPSCs can be used in micromedicine for drug discovery, and in macromedicine for actual clinical trials, their use would tightly connect both micro‐ and macromedicine. The use of iPSCs in disease modeling, cell transplantation, and clinical trials could therefore lead to significant changes in the future of medicine.     

脊索瘤的临床治疗进展

脊索瘤是一种罕见的低度恶性肿瘤,临床治愈率低,复发率较高。手术切除是治疗脊索瘤的首选方法,目前公认的脊索瘤治疗方法是完整(或大块)切除。术后辅助放射治疗越来越多的应用于临床,而新药物的研发、术前动脉栓塞的应用,以及射频消融等都被用于脊索瘤的临床治疗。本文综述了目前临床上应用的诊疗进展,包括手术治疗、放射治疗、药物治疗及射频消融治疗等方法。     

脊索瘤的临床治疗进展

脊索瘤是一种罕见的低度恶性肿瘤,临床治愈率低,复发率较高。手术切除是治疗脊索瘤的首选方法,目前公认的脊索瘤治疗方法是完整（或大块）切除。术后辅助放射治疗越来越多的应用于临床,而新药物的研发、术前动脉栓塞的应用,以及射频消融等都被用于脊索瘤的临床治疗。本文综述了目前临床上应用的诊疗进展,包括手术治疗、放射治疗、药物治疗及射频消融治疗等方法。     

DNA microarrays in the clinic: how soon,how extensively?

Although DNA microarrays are now widely used in research settings, they have been slow to penetrate clinical practice in spite of their apparent advantages. This is due to the very different requirements for a clinical test in contrast to a research tool, and to a strict necessity for demonstrated clinical utility. There is a clear differentiation between two types of DNA array tests: "genomic" diagnostics, developed to ascertain the presence or absence of mutations, deletions or duplications, and for which clinical evidence is already established, and tests using expression profiling for prognosis or predictive purposes, in which case the clinical correlate must be proven. Most array diagnostics currently used belong, understandably, to the "genomic" variety. It is to be expected that future improvements in tailored technology, as well as a logical trend towards measuring an ever-increasing number of parameters, will ensure an important diagnostic role for DNA arrays in the coming decade.     

Biasogram: Visualization of Confounding Technical Bias in Gene Expression Data

Gene expression profiles of clinical cohorts can be used to identify genes that are correlated with a clinical variable of interest such as patient outcome or response to a particular drug. However, expression measurements are susceptible to technical bias caused by variation in extraneous factors such as RNA quality and array hybridization conditions. If such technical bias is correlated with the clinical variable of interest, the likelihood of identifying false positive genes is increased. Here we describe a method to visualize an expression matrix as a projection of all genes onto a plane defined by a clinical variable and a technical nuisance variable. The resulting plot indicates the extent to which each gene is correlated with the clinical variable or the technical variable. We demonstrate this method by applying it to three clinical trial microarray data sets, one of which identified genes that may have been driven by a confounding technical variable. This approach can be used as a quality control step to identify data sets that are likely to yield false positive results.     

The number needed to treat: a clinically useful measure of treatment effect.

The relative benefit of an active treatment over a control is usually expressed as the relative risk, the relative risk reduction, or the odds ratio. These measures are used extensively in both clinical and epidemiological investigations. For clinical decision making, however, it is more meaningful to use the measure "number needed to treat." This measure is calculated on the inverse of the absolute risk reduction. It has the advantage that it conveys both statistical and clinical significance to the doctor. Furthermore, it can be used to extrapolate published findings to a patient at an arbitrary specified baseline risk when the relative risk reduction associated with treatment is constant for all levels of risk.     

301株铜绿假单胞菌的分布及耐药性分析

目的 通过对临床中分离的铜绿假单胞菌的分布及对临床常用13种抗生素的耐药性进行分析指导临床合理用药.方法 收集大连医科大学附属第二医院2010年1月至12月临床送检的标本,采用全自动细菌和药敏分析仪分离铜绿假单胞菌同时进行药敏试验.结果 铜绿假单胞菌在痰液标本中分离率高达79.06％;对头孢噻肟、头孢西丁、头孢唑啉3种药物的耐药率均大于50％;对头孢他啶,哌拉西林/他唑巴坦耐药率低于20％.结论 铜绿假单胞菌易产生多源耐药,加强耐药性监测,控制医院内感染,对临床医生选用有效的抗生素具有十分重要的意义.     

Evidence based medicine: an approach to clinical problem-solving.

Doctors within the NHS are confronting major changes at work. While we endeavour to improve the quality of health care, junior doctors'' hours have been reduced and the emphasis on continuing medical education has increased. We are confronted by a growing body of information, much of it invalid or irrelevant to clinical practice. This article discusses evidence based medicine, a process of turning clinical problems into questions and then systematically locating, appraising, and using contemporaneous research findings as the basis for clinical decisions. The computerisation of bibliographies and the development of software that permits the rapid location of relevant evidence have made it easier for busy clinicians to make best use of the published literature. Critical appraisal can be used to determine the validity and applicability of the evidence, which is then used to inform clinical decisions. Evidence based medicine can be taught to, and practised by, clinicians at all levels of seniority and can be used to close the gulf between good clinical research and clinical practice. In addition it can help to promote self directed learning and teamwork and produce faster and better doctors.     

Fast and accurate method for quantitating E. coli host-cell DNA contamination in plasmid DNA preparations

Plasmid DNA is being used successfully as a gene delivery vector in a variety of clinical applications. Similar to other pharmaceutical products for clinical use, the plasmid vectors must meet rigorous purity standards. One important contaminant is the DNA of the host cell used to produce the plasmids. We have developed a new method to accurately quantitate E. coli host-cell DNA in plasmid preparations. This method is based on kinetic PCR using the ABI PRISM 7700 with 23S rDNA as a target. This precise assay is significantly faster and has a lower limit of quantitation than the currently used Southern-based methods.     

Clinical application of antifungal pharmacodynamics

Studies of pharmacodynamics are used to develop dosing regimens that maximize safety and efficacy in clinical practice. Antifungal pharmacodynamics is a growing field, and studies are increasingly moving from the in vitro phase to animal models to clinical evaluations. Preclinical studies that determine pharmacodynamic predictors of efficacy and safety provide valuable data in the determination of a dosage regimen, but evaluations of antifungal pharmacodynamic parameters in vivo are less common. This article reviews areas where antifungal pharmacodynamics has been evaluated in clinical trials to develop principles that may be used in the pharmacotherapy of invasive mycoses.     

Nonparametric confidence intervals for the ratio of marginal hazard rates of paired survival times

Paired survival times with potential censoring are often observed from two treatment groups in clinical trials and other types of clinical studies. The ratio of marginal hazard rates may be used to quantify the treatment effect in these studies. In this paper, a recently proposed nonparametric kernel method is used to estimate the marginal hazard rate, and the method of variance estimates recovery (MOVER) is used for the construction of the confidence intervals of a time‐dependent hazard ratio based on the confidence limits of a single marginal hazard rate. Two methods are proposed: one uses the delta method and another adopts the transformation method to construct confidence limits for the marginal hazard rate. Simulations are performed to evaluate the performance of the proposed methods. Real data from two clinical trials are analyzed using the proposed methods.     

Quid des produits de contraste en TEP/TDM ?

It is important that PET/CT in its current technical form is used to its fullest clinical capability. In order to achieve this, training has to be such that PET/CT readers are capable PET as well as CT readers. Imaging protocols have to be devised such that contrast media enhancement in CT minimizes artefacts since the CT data are also used for attenuation correction. The easiest and most flexible way is to perform a low dose pre-PET/CT scan and add a CE-CT at the end of the examination, if necessary. Necessity is dictated by the clinical question and clinical experience is accumulating telling us that depending on the question asked from the PET/CT examination, CE is mandatory, recommended, optional or unnecessary.     

药物基因组学在新药临床试验及个体化用药中的应用

药物安全性和有效性评价是药物临床试验和个体化用药的核心,也是药物基因组学研究的主要内容。药物基因组学研究贯穿于药物 研发、上市评价和临床应用整个过程, 根据药物代谢酶、转运体、受体相关基因多态性对用药者进行分层分析,评价与药物体内的处置过程、 安全性、有效性个体差异的相关性。综述药物基因组学在新药临床试验、个体化用药中的应用研究新进展。     

A Markov model for a clinical episode of recurrent genital herpes

A time-homogeneous Markov process is proposed for modeling the clinical course of recurrent genital herpes and is used to obtain estimators for various characteristics of the disease episode. The model has a finite, discrete time parameter and discrete state space, with six transient states corresponding to the six stages a herpes lesion may enter. The healed condition is represented as an absorbing state. The number of lesions present at the onset of the clinical episode and the number of lesions appearing during the course of the episode are assumed to have negative binomial distributions. Clinical trial data are used to examine the assumptions of the model and to estimate its parameters. Estimates of clinical variables based on the model are computed and are compared with those calculated directly to assess how well the model represents the biological process of the disease.     

脑电双频指数监测技术及其临床应用

适宜的麻醉深度是保证患者的生命安全和创造良好手术条件的关键。脑电双频指数(bispectralindex,BIS)是用于监测镇静程度的一种新方法,自从临床应用以来它已得到多方面关注和研究,本文就其概念、原理及临床应用等方面进行综述。