临床随访研究中样本含量的估计

目的:介绍临床随访研究中生存分析资料的log-rank检验所需样本含量的估计法.方法:以离散性Markov链拟合生存过程,据此计算log-rank统计量的数学期望和方差,导出样本含量估计公式.结果:实例分析表明,该法能较好反映实际情况,应用灵活.结论:本法是一种有效、可行的样本含量估计法,值得推荐.     

单因素重复测量设计样本含量的估算及不同计算方法之间的比较

目的:介绍并比较几种重复测量设计样本含量的估算方法。方法:通过实例分析,分别采用PASS 11,stata统计学软件以及相关的计算公式计算其所需样本含量。结果:对同一案例,PASS 11软件中Compound Symmetry法需27例,AR法需19例,Banded法需12例,Simple法需6例;Stata软件中post法需27例,change法需13例,ancova法需10例;公式计算结果为14例。结论:PASS 11,stata统计学软件可以方便地用来估计重复测量设计的样本含量;正确分析研究设计性质并针对性地设置软件中对应参数是获得合适估计结果的关键。     

心电轴的计算公式法及其应用

目的介绍心电轴计算公式,通过对公式法与查表法比较,说明公式法的实用有效。方法介绍心电轴计算公式及其原理,应用公式法制定心电轴表记作表1,将表1中的数值与表2中的数值进行配对设计以及对40例心电图实例应用上述两种方法所得值进行配对设计。结果对配对样本t检验的结果（P〉0．05）表明这两种方法无显著差别,公式法与查表法取得一致性结果。结论公式法是一种准确实用的方法。     

晒黑或可降低患皮肤癌风险

正与肤色白皙的人相比,肤色深的人的皮肤黑色素含量更高,患皮肤癌的风险也更低。黑色素产生在称为黑色素体的细胞器中,并受黑色素体pH值的调节。美国魏尔·康奈尔医学院的周大雷(音译)等研究人员发现,由可溶性腺苷环化酶产生的环磷酸腺苷,能导致黑色素体pH值和酪氨酸酶(抑制黑色素合成的酶)活性降低。可溶性腺苷环化酶缺乏会增加小鼠黑     

个体生物等效性检验的样本含量估计

目的:对两种设计方法、三种检验方法的个体生物等效性的检验效能进行比较,并估计样本含量。方法:采用Monte-Carlo模拟研究。结果:2×4交叉设计所需的样本含量低于2×3设计。在个体内变异小于0.2时,可以采用估计法进行样本含量的估计;在个体内变异接近0.2时,可以采用检验法进行样本含量的估计;在个体内变异大于0.3时,可以选任一方法(估计法和检验法)估计样本含量,并选择合适的方法进行样本含量的估计。结论:个体生物等效性的样本含量因不同的个体内变异和个体与药物间的交互作用、设计而不同。     

免疫比浊法测定血清淀粉样蛋白A的钩状效应及其解决方案

目的探讨研制的血清淀粉样蛋白A(SAA)试剂盒的钩状效应及其解决方法。方法以83个西门子定值血清为研究对象,分析研制的SAA试剂盒的线性范围、准确度和精密度等性能;用试剂盒检测超高值血清样本,验证是否存在钩状效应,并研究稀释法能否解决钩状效应。结果 SAA试剂盒线性范围为1～200 mg/L,测定值与样本定值之间的偏差在20%以内,精密度CV均3.0%。浓度超出200 mg/L样本的实测值明显低于定值,浓度范围在1～1000 mg/L的拟合曲线未出现明显的下降趋势,而1～2000 mg/L、1～3000 mg/L拟合曲线出现明显的下降趋势,存在钩状效应。用稀释法测定异常值样本,测定值与定值相近。结论所发现的非正常测定值由钩状效应所致,稀释法能够解决钩状效应问题。     

清炒法炮制粉葛过程中主要化学成分与工艺、物性及颜色变化的相关性分析

目的：研究清炒法炮制过程中粉葛主要化学成分与工艺、物性及颜色的动态变化,以及其相关性。方法：测定不同炮制阶段粉葛样品的物性参数（氧化值、膨胀度、堆密度、pH值）,利用影像设备、Photoshop软件等获取炮制品图片的颜色变化值,采用紫外分光光度苯酚-硫酸显色法测定粉葛中可溶性多糖的含量,运用双波长法测定粉葛中总淀粉含量,最后对参数进行配对样本t检查、方差分析及线性回归分析。结果：随着炮制程度的加强,粉葛中总淀粉含量降低,水溶性多糖的含量先增高再降低,两者呈负相关。粉葛中可溶性多糖的含量与氧化性、红-绿色轴值呈明显正相关性,与膨胀度成明显负相关,淀粉含量与堆密度呈明显负相关。主要化学成分与部分物性参数及色度值线性回归显著。结论：粉葛在清炒法炮制过程中,参数间可能存在转化。部分颜色变化和物性参数数据可以作为评价炮制程度及合格与否的标准,弥补传统人为判断造成炮制品质量无法统一的不足,从而规范生产工艺。     

检测尿液中尿酸含量范围的试纸条的研制

目的:研制一种检测尿液中尿酸含量范围的试纸条。方法:将一定量的显色试剂吸附在试纸上,此试纸条上粘附的试剂能与尿液中的尿酸生成一种红色物质,而红色物质的生成量与样本中尿酸的浓度成正比,将显色试纸条与标准色卡比较,从而能快速检测出尿液中尿酸含量范围。结果:此试纸条能确定尿液中尿酸含量的范围,重现性好。结论:该试纸条临床应用方便、安全、经济。     

凝血检验中的影响因素和注意事项

目的探讨分析凝血检验中可能会对结果产生影响的因素和注意事项。方法使用我院2011年1月至2012年1月从住院部以及门诊部就诊患者采集的血液样本800份为研究对象,对样本进行标记和核查,如果发现不合格样本需要重新采血。根据获得结果对患者和相关医护人员进行回访调查,记录调查结果。结果样本检验结果发现136例可疑样本。占总样本的17%,可疑样本检测结果显示样本量偏少的样本第一次检测和第二次检测结果(PT值和APTT值)差异明显,P<0.05,具有统计学意义;样本量偏多的样本第一次检测和第二次检测结果(PT值和APTT值)差异明显,P<0.05;具有统计学意义。结论检测时应该对各个细节和操作步骤都谨慎小心才可以确保检测结果的准确性和可靠性,对患者的诊断和治疗方案的制定做出指导性地贡献。     

临床试验Williams设计中样本含量的估算方法

在临床试验中,2组交叉设计应用已相当广泛,其样本含量估算方法也被研究者所熟悉。多组交叉试验由Williams首先提出,因此被称为Wil-liams设计。本文介绍基于Williams设计的样本含量估算方法,并提供示例分析,供研究者参考使用。     

Population pharmacokinetic measures, their estimation and selection of sampling times

In pharmacokinetic (PK) studies, including bioavailability assessment, various population PK measures, such as area under the curve (AUC), maximal concentration (C(max)) and time to maximal concentration (T(max)) are estimated. In this paper we compare a model-based approach, where parameters of a compartmental model are estimated and the explicit formulae for PK measures are used, and a model-independent approach, where numerical integration algorithms are used for AUC and sample estimates for C(max) and T(max). Since regulatory agencies usually require the model-independent estimation of PK measures, we focus on the empirical approach while using the model-based approach and corresponding measures as a benchmark. We show how to "split" a single sampling grid into two or more subsets, which substantially reduces the number of samples taken for each patient, but often has little effect on the precision of estimation of PK measures in terms of mean squared error (MSE). We give explicit formulae for the MSE of the empirical estimator of AUC for a simple example and discuss how costs may be taken into account.     

Prediction of netilmicin disposition in neonates.

Multiple regression analyses of data from 33 neonates who received netilmicin therapy showed that concurrent treatment with other drugs (Drg), creatinine clearance (CLcr), gestational age (GA), and an apgar score of less than 6 at 1 min (Agl') were significant determinants of netilmicin clearance. Apparent volume of distribution was significantly affected by postnatal age (PNA), gender, the presence of ascites and/or oedema (A/O), and whether or not the neonate was small for gestational age (SGA). The following formulae were obtained: [formula: see text] The regression formulae were shown to predict netilmicin plasma concentrations with good precision and a non-significant bias in a further 15 neonates studied prospectively.     

Pharmacokinetic-pharmacodynamic modeling in the data analysis and interpretation of drug-induced QT/QTc prolongation

In this review, factors affecting the QT interval and the methods that are currently in use in the analysis of drug effects on the QT interval duration are overviewed with the emphasis on (population) pharmacokinetic-pharmacodynamic (PK-PD) modeling. Among which the heart rate (HR) and the circadian rhythm are most important since they may interfere with the drug effect and need to be taken into account in the data analysis. The HR effect or the RR interval (the distance between 2 consecutive R peaks) effect is commonly eliminated before any further analysis, and many formulae have been suggested to correct QT intervals for changes in RR intervals. The most often used are Bazett and Fridericia formulae introduced in 1920. They are both based on the power function and differ in the exponent parameter. However, both assume the same exponent for different individuals. More recent findings do not confirm this assumption, and individualized correction is necessary to avoid under- or overcorrection that may lead to artificial observations of drug-induced QT interval prolongation. Despite the fact that circadian rhythm in QT and QTc intervals is a well-documented phenomenon, it is usually overlooked when drug effects are evaluated. This may result in a false-positive outcome of the analysis as the QTc peak due to the circadian rhythm may coincide with the peak of the drug plasma concentration. In view of these effects interfering with a potential drug effect on the QTc interval and having in mind low precision of QT interval measurements, a preferable way to evaluate the drug effect is to apply a population PK-PD modeling. In the literature, however, there are only a few publications in which population PK-PD modeling is applied to QT interval prolongation data, and they all refer to antiarrhythmic agents. In this review, after the most important sources of variability are outlined, a comprehensive population PK-PD model is presented that incorporates an individualized QT interval correction, a circadian rhythm in the individually corrected QT intervals, and a drug effect. The model application is illustrated using real data obtained with 2 compounds differing in their QT interval prolongation potential. The usefulness of combining data of several studies is stressed. Finally, the standard approach based on the raw observations and formal statistics, as described in the Preliminary Concept paper of the International Conference on Harmonization, is briefly compared with the method based on population PK-PD modeling, and the advantages of the latter are outlined.     

Population Pharmacokinetic Measures,Their Estimation and Selection of Sampling Times

In pharmacokinetic (PK) studies, including bioavailability assessment, various population PK measures, such as area under the curve (AUC), maximal concentration (C _max ) and time to maximal concentration (T _max ) are estimated. In this paper we compare a model-based approach, where parameters of a compartmental model are estimated and the explicit formulae for PK measures are used, and a model-independent approach, where numerical integration algorithms are used for AUC and sample estimates for C _max and T _max . Since regulatory agencies usually require the model-independent estimation of PK measures, we focus on the empirical approach while using the model-based approach and corresponding measures as a benchmark. We show how to “split” a single sampling grid into two or more subsets, which substantially reduces the number of samples taken for each patient, but often has little effect on the precision of estimation of PK measures in terms of mean squared error (MSE). We give explicit formulae for the MSE of the empirical estimator of AUC for a simple example and discuss how costs may be taken into account.     

Simultaneous UPLC analysis of three major flavonoids in granule decoctions of Fructus aurantii-type formulae

A simple, rapid, and sensitive liquid chromatographic method has been established for the simultaneous analysis of three compounds (narirutin, hesperidin and naringin), in granule decoctions of Fructus Aurantii-type formulae. The compounds were separated in less than 10 min using a C18 column with gradient elution using (A) acetonitrile, (B) water, and (C) acetic acid at a flow rate of 0.3 mL/min, and with a PDA detector. The method was validated for specificity, accuracy, precision, and limits of detection. Good linear regression data (r2 > 0.9980) were obtained for all the calibration plots within the ranges tested. The method is an attractive alternative for quality control and clinical monitor of granule decoctions of Fructus Aurantii-type formulae.     

Estimation of particle number by stereology: an update.

Sampling designs dictated by stereology have proven very useful in recent years to estimate in situ the total number of deposited particles, or of macrophages, in different lung compartments at the light microscopical level. The sampling methods are based on parallel slabs which are subsequently subsampled by disectors. The resulting number estimators are unbiased irrespective of tissue shrinkage or swelling, and they are readily applicable in other contexts (notably in neuroscience). Several variants of the design are available, however, and, although they all yield the same number estimates, their precision, and the mathematical prediction of it, vary among the different estimators and are subjected to theoretical improvement. The present paper constitutes a detailed survey of the latest advances, and it illustrates methods and formulae alike by way of a real example stemming from an earlier study on particle retention and clearance.     

Interactive effect of water level and flushing rate on population dynamics of a harmful cyanobacterial species: Raphidiopsis raciborskii

Changes in water level and flushing rate directly affect to a large extent the biomass of harmful cyanobacteria, and drive the shift of phytoplankton composition between cyanobacteria dominance/non-dominance in eutrophic waters. Here, we gave a theoretical formula describing the combinational effect of water level and flushing rate on cyanobacterial biomass in eutrophic and well-mixed waters. We also formulated an equation predicting the water level and flushing rate at which cyanobacteria become non-dominating in such water columns. The formulae were confronted with field observations of a low-light adapted cyanobacterium in a large coastal reservoir of southern China. Our formulae demonstrate that water level and flushing rate have an interactive effect on the equilibrium biomass of low-light adapted cyanobacteria in mixed and turbid waters. The formulae were well fitted to the field observation of Raphidiopsis raciborskii population in the reservoir during four dry seasons. In agreement with the theoretical analysis, multiple regression analysis also showed that the interaction between water level and flushing rate is able to interpret the variation of R. raciborskii biomass in the water column. The two formulae are applicable for predicting the response of low-light adapted cyanobacteria to local climate change. Our findings have practical significance in designing measures against the dominance of low light-adapted cyanobacteria in reservoirs.

     

Assessment of the validity of a population pharmacokinetic model for epirubicin

AIMS: The aim of this study was to evaluate a population model for epirubicin clearance using internal and external validation techniques. METHODS: Jackknife samples were used to identify outliers in the population dataset and individuals influencing covariate selection. Sensitivity analyses were performed in which serum aspartate transaminase (AST) values (a covariate in the population model) or epirubicin concentrations were randomly changed by +/-10%. Cross-validation was performed five times, on each occasion using 80% of the data for model development and 20% to assess the performance of the model. External validation was conducted by assessing the ability of the population model to predict concentrations and clearances in a separate group of 79 patients. RESULTS: Structural parameter estimates from all jackknife samples were within 7.5% of the final population estimates and examination of log likelihood values indicated that the selection of AST in the final model was not due to the presence of outliers. Alteration of AST or epirubicin concentrations by +/-10% had a negligible effect on population parameter estimates and their precision. In the cross-validation analysis, the precision of clearance estimates was better in patients with AST concentrations>150 U l-1. In the external validation, epirubicin concentrations were over-predicted by 81.4% using the population model and clearance values were also poorly predicted (imprecision 43%). CONCLUSIONS: The results of internal validation of population pharmacokinetic models should be interpreted with caution, especially when the dataset is relatively small.     

Selenium status of Christchurch infants and the effect of diet.

OBJECT: New Zealanders, because of a soil deficiency, have a low intake of selenium. To determine the impact of this on the infant population in Christchurch. METHODS: we have measured red cell and plasma selenium and the selenoenzyme, glutathione peroxidase, in 70 infants less than 12 months old and related these to age and diet. RESULTS: the infant population as a whole had mean plasma levels of selenium and glutathione peroxidase of 33 micrograms/L and 97 U/L compared with adult values of 74 micrograms/L and 150 U/L. Infant red cell levels of 0.30 mu g selenium and 9.0 U glutathione peroxidase per g haemoglobin were similar to those in adults. The selenium status of most breast fed infants after birth remained similar to that of cord blood. Mean plasma selenium and glutathione peroxidase levels in formula fed infants were about half those of breast fed infants, and their red cell selenium was also significantly lower. These did not increase until solids were introduced into the diet. The status of the infants reflected their diet, with the concentration of selenium in formulae being 3.9-5.2 micrograms/mL compared with a mean of 13.4 micrograms/mL in breast milk. CONCLUSIONS: since infants in more replete selenium areas show a gradual rise in blood selenium parameters after birth, this study suggests that formula fed and some breast fed infants in Christchurch receive an inadequate selenium intake. Consideration should be given to supplementing infant formulae and perhaps also the diet of pregnant and/or breast feeding mothers.     

两个大样本均数比较u检验公式探讨

对两个大样本均数比较的 u检验计算公式进行了详细的探讨 ,介绍了总体标准差已知、未知、相等和不等各种情况下 u检验的计算公式 ,认为在大样本的情况下进行均数比较的检验 ,应根据具体情况选择计算公式。