Cox比例风险模型影响点的识别

目的 探讨Ｃｏｘ比例风险模型影响点的有效识别方法。方法 介绍了剩余残差、加权Ｓｃｏｒｅ残差、似然距离、最大影响曲率诊断量及相应的诊断图。结果 实例分析表明，上述诊断量可从不同角度识别Ｃｏｘ模型影响点。结论 影响分析应是Ｃｏｘ模型分析的一个重要组成部分。     

Cox模型影响点识别诊断统计量的模拟研究

目的 探讨Cox比例风险模型影响点的有效识别方法 .方法 通过Monte-Carlo模拟研究,比较了六种诊断统计量及相应诊断图对影响点的诊断效能.结果 模拟研究表明,加权score残差、似然距离和最大影响曲率及其诊断图可从模型拟合不同角度有效识别影响点.结论 影响分析应是Cox模型分析的一个重要组成部分,加权score残差、似然距离和最大影响曲率是有效识别影响点的诊断统计量.     

Cox回归模型中强影响点的诊断

目的：识别Cox回归模型中的强影响点,方法：从似然距离的观点出发,应用局部影响的分析方法,介绍Δk诊断量和最大影响曲率度量诊断量。结果：对参数估计有强影响的点,两种诊断量的绝对值远远大于其它点,结论：此法可有效地识别影响参数估计的强影响点,从而避免参数估计时得出错误的结论。如参数较多时,最大曲率度量方法更为方便。     

鞅残差在Cox回归模型诊断中的应用

目的：探讨Cox模型中某给定连续变量对生存效应的最佳函数形式。方法：不含该变量的Cox模型下的鞅残差对该协变量作图可揭示该变量在全模型中的函数形式。结果：实例分析表明,Loess平滑鞅残差图可用于Cox模型中协变量函数形式的确定。结论：建议分析者把鞅残差图纳入Cox模型分析中,对协变量的生存效应作出正确估计。     

灰色多段函数残差辨识法在季节性疾病预测中的应用

目的:探讨季节性疾病的建模预测问题.方法:多段函数残差辨识的灰色建模方法.结果:经后验差比值和小误差概率检验知该模型预测精度为第一级"好".结论:实例证明该模型有计算简便、对资料要求不严、适应范围较宽、残差信息利用率及拟合预测精度较高等特点,可用于季节性疾病发病时间序列的建模预测.     

条件logistic回归模型的残差分析和影响诊断

对条件ｌｏｇｉｓｔｉｃ回归模型配合适度的分析，除了总配合适度检验统计量外，还包括有对匹配组和匹配组内每一个体的残差分析和影响诊断。本文介绍了离差残差和Ｐｅａｒｓｏｎ残差的理论，采用一步近似法计算删除某匹配组或匹配组内某个体后的配合适度变化，包括参数估计值的改变量、参数可信区间的位移以及Ｐｅａｒｓｏｎ卡方改变量，用来识别影响大的匹配组和匹配个体。用１∶２匹配子宫内膜癌病例－对照研究资料为例，进行了残差和影响诊断的分析，并提出了对待强影响点的意见。     

检查Cox模型比例风险假定的几种图示法

目的 检查Ｃｏｘ模型比例风险假定图示法的应用与比较。方法 介绍了基于Ｃｏｘ模型与ｋａｐｌｑｎ－ｍｅｉｅｒ法生存估计比较、Ｃｏｘ模型累积风险函数、ｓｃｈｏｅｎｆｅｌｄ残差和ｓｃｏｒｅ残差的图示法。结果 上述几种图示法均可不同程度地检查ＰＨ假定。结论 建议使用ｓｃｈｏｅｎｆｅｌｄ残差图和ｓｃｏｒｅ残差图,除评价ＰＨ假定外,前者可提供ＬＨＲＦ的非参数估计,后者可用于诊断观测对Ｃｏｘ模型参数估计的杠杆。     

主成分回归中异常点的稳健诊断

目的探讨主成分回归模型中存在异常点时的稳健诊断方法。方法采用基于MVT和LMS方法的一种稳健主成分回归方法来诊断异常点，并结合实例进行方法的对比。结果与未去除异常点时得到的回归方程相比较，具有较小的残差平方和，拟合效果较好。解决了主成分回归中存在异常点的问题。结论当主成分回归中存在异常点时，本文中所述的稳健诊断方法具有较高的稳健性，在主成分回归分析中有较好的应用前景。     

广义加性模型配合时间序列资料时消除残差自相关性的一种方法

目的广义加性模型假定观察是独立的,但时间序列资料往往存在自相关性。本文探讨在使用广义加性模型配合时间序列资料时消除残差自相关性的一种方法。方法在广义加性模型基础上加入反应变量函数的非参数匀滑函数项。结果本文实例中采用反应变量的滞后项作为反应变量的函数,使1-12阶的残差自相关系数由加入反应变量函数的非参数匀滑函数项之前的0.50～0.25下降为0.09～-0.09,取得了较满意的效果。结论在用广义加性模型配合时间序列资料时,加入反应变量函数的非参数匀滑函数项可以有效控制自相关带给参数假设检验的影响。     

logistic回归中两种不同杠杆点诊断方法的初步探讨

目的探讨logistic回归模型中两种不同杠杆点诊断方法间的异同,为杠杆点诊断及其软件应用提供参考。方法选取分类型和连续型两种协变量数据类型的实例,分别建立logistic回归模型,并采用代表不同估计方法的SPSS与STATA软件对回归模型进行杠杆点诊断。结果两种杠杆点诊断方法在处理不同类型数据时并不完全一致,当模型协变量组数远小于研究对象个体数时,两种方法所得结果有所不同。结论研究者应根据研究目的和资料类型正确选用不同软件进行杠杆点诊断。     

强影响点的诊断

强影响点指对参数估计的稳定性及真实性具有很大影响的数据，一般用经验影响函数θ－θ（ｉ）度量，θ－θ（ｉ）为多维向量，为方便，常用θ－θ（ｉ）的某种数量函数ｇ（θ－θ（ｉ））来刻划，但ｇ的确定较为困难，目前仅限于线性回归分析有Ｃｏｏｋ距离法。本文提出一种确定方法，它适用于任何参数统计分析，并且就线性回归分析而言，用该方法较Ｃｏｏｋ距离法更合理，将该方法用于ＣＯＸ模型，从应用实例看，效果也较好     

线性回归中的影响点与多元共线性关系初探

目的: 探讨线性回归模型中各数据点对多元共线性的影响。方法: 通过计算剔除每个数据前后条件数的相对变化来检查该点对共线性影响的程度和方向。结果: 通过两个实例分析说明数据中的杠杆点或影响点可夸大或掩盖多元共线性。结论: 检查数据中各点对多元共线性的影响可深入揭示数据结构特征并提示正确的回归估计方法     

调查点不足偏倚对疾病空间分布趋势面分析结果的影响

[目的 ]探讨调查点不足偏倚对趋势面分析结果的影响。 [方法 ]以基准面为基础 ,在保证调查点分布均匀化的前提下 ,依次减少调查点个数 ,并拟合同阶趋势面模型 ,观察模型的趋势等值线图和剩余等值线图 ,评价随调查点的递减 ,趋势面形态的变化情况。 [结果 ]随调查点数的递减 ,趋势等值线图的偏倚较小 ,但剩余等值线图的偏倚严重。 [结论 ]当用趋势面模型反映疾病发病水平在大尺度范围内的空间变化趋势时 ,用较少的调查点就能反映出来 ,不至于发生严重偏倚 ,但调查点数必须大于多项式的项数 ;当用趋势面模型寻找有地理流行病学意义的异常区域时 ,调查点太少会发生严重偏倚。     

Glutamine restores myocardial cytochrome C oxidase activity and improves cardiac function during experimental sepsis

Background: Cardiac dysfunction occurs commonly in sepsis. Impaired mitochondrial function is a potential cause of sepsis‐associated myocardial depression. Cytochrome oxidase (COX), the terminal oxidase of the electron transport chain, is inhibited in the septic heart. Glutamine (GLN) increases Krebs cycle intermediates and supports oxidative phosphorylation. Exogenous GLN has been shown to restore myocardial adenosine triphosphate levels and cardiac function following ischemia–reperfusion injury. The authors hypothesize that exogenous GLN will abrogate sepsis‐induced myocardial COX inhibition and improve sepsis‐associated myocardial depression. Methods: Under general anesthesia, male Sprague‐Dawley rats underwent cecal ligation and double puncture (CLP) or sham operation. At the time of operation, rats underwent intraperitoneal injection of either GLN (0.75 g/kg) or an equal volume of saline. Twenty‐four hours after the procedure, animals were killed, cardiac ventricles harvested, and mitochondria isolated. Steady‐state COX kinetic activity was measured and normalized to citrate synthase activity. Steady‐state levels of COX subunit I protein were determined with immunoblot analysis. Cardiac function was assessed using an isolated rat heart preparation. Five animals per group were evaluated. Significance was determined with analysis of variance and post hoc Tukey test. Results: CLP significantly decreased myocardial COX activity, oxygen consumption, left ventricular pressure (LVP), and pressure developed during isovolumic contraction (+dP/dt) and relaxation (?dP/dt). GLN restored COX activity to sham levels, significantly increased myocardial oxygen extraction and consumption, increased LVP toward sham values, and increased ±dP/dt by >30% following CLP. Conclusion: The beneficial effects of GLN therapy during sepsis may be in part due to restoration of oxidative phosphorylation and abrogation of sepsis‐associated myocardial depression.     

Adjusting for unmeasured confounders in pharmacoepidemiologic claims data using external information: the example of COX2 inhibitors and myocardial infarction

BACKGROUND: Large health care utilization datasets are frequently used to analyze the incidence of rare adverse events from medications. However, possible confounders are typically not measured in such datasets. We show how to assess the impact of confounding by factors not measured in Medicare claims data in a study of the association between selective COX2 inhibitors and acute myocardial infarction (MI). METHODS: Using the Medicare Current Beneficiary Survey, we assessed the association between use of selective COX2 inhibitors and 5 potential confounders not measured in Medicare claims data: body-mass index, aspirin use, smoking, income, and educational attainment. For 8,785 participants > or =65 years, we estimated the prevalence of selective COX2 inhibitor use and also of each confounder, as well as the association between drug exposure and confounders. Estimates of the confounder-disease associations from the medical literature were used to calculate the extent of residual confounding bias for each potential confounder. RESULTS: Selective COX2 inhibitor users were less likely to be smokers (8% versus 10%) than nonselective NSAID users, while the prevalence of obesity was comparable (24%). Aspirin use was also balanced among all drug exposure categories. Failure to adjust for 5 potential confounders led to a small underestimation of the association between selective COX2 inhibitors and MI; comparing selective COX2 inhibitors with NSAIDs, the net bias was estimated to be -1.0% of the unknown true effect size (maximum range: -6% to 0%). CONCLUSIONS: In this example of the relationship between selective COX2 inhibitors and MI, not adjusting for 5 potential confounders in Medicare claims data analyses tended to slightly underestimate the association, but is unlikely to cause important bias.     

穴位按摩对宫颈癌术后患者膀胱功能恢复的效果观察

目的：探讨穴位按摩对促进宫颈癌根治术后患者膀胱功能恢复的效果。方法：将140例宫颈癌根治术后患者随机分为两组,对照组70例,观察组70例;对照组采用盆底肌功能锻炼法,观察组采用盆底肌功能锻炼联合手法按压穴位法。观察两组患者拔除尿管第一次排尿后的膀胱残余尿量及尿潴留的发生率。结果：对照组平均残余尿量为（105.43±50.11）ml,观察组平均残余尿量为（51.79±24.14）ml;对照组患者尿潴留的发生率为45.71%,观察组发生率为5.71%;两者比较差异均有统计学意义（P<0.05）。结论：盆底肌功能锻炼联合手法按压穴位有利于促进宫颈癌根治术后患者膀胱功能的恢复。     

A Monte Carlo approach for change-point detection in the Cox proportional hazards model

Detecting a time lag of treatment effect or identifying change points in a hazard function is of great interest and importance in survival analysis. The testing procedures hereto are primarily based on analytical approximations for the asymptotic null distribution of either the likelihood ratio test or the score test. In the presence of random censoring and/or covariates, however, the justification for the limiting distribution often requires some technical assumptions and conditions that are difficult to verify in practice. Moreover, a satisfactory asymptotic theory for testing the existence of multiple change points in hazard function has not emerged. In this paper, we consider maximal score tests for detecting change point(s) in the Cox proportional hazards model with censored data. We propose to use a simple Monte Carlo approach for assessing the statistical significance of tests. The proposed approach is applicable for testing a single change point in the Cox model with covariates and sample stratifications over various types of candidate regions, including discrete time-point sets or disjoint intervals. We also show that the proposed test statistics and the Monte Carlo procedure are well applicable under situations with multiple change points. Simulation studies and an analysis of a real data from a randomized cancer trial are conducted to demonstrate the finite-sample performance of the proposed approach.     

高浓度葡萄糖对小鼠囊胚细胞线粒体和细胞色素氧化酶的影响

目的:探讨高浓度葡萄糖对小鼠囊胚细胞线粒体和细胞色素氧化酶的影响,探讨高浓度葡萄糖对小鼠囊胚有氧代谢的影响,为糖尿病妊娠导致胎儿畸形的机制和预防提供理论依据。方法:通过促超排卵,获取妊娠3.5天小鼠囊胚,随机分成三组,即对照组(空白)、低糖组(葡萄糖浓度为7.5 mmol/L)和高糖组(葡萄糖浓度为28.0 mmol/L),分别培养在含0、7.5 mmol/L和28.0 mmol/L葡萄糖的M199培养基中,培养24 h后,然后再吸山囊胚。每组随机吸取30个囊胚用罗丹明123荧光染料标记线粒体和组织化学方法显示细胞色素C氧化酶,观察囊胚细胞线粒体和细胞色素C氧化酶(Cytochrome C Oxidase)的变化。结果:①高糖组小鼠囊胚线粒体功能活性明显降低,荧光密度值较低,且线粒体的位置分布发生了明显变化,空白组和低糖组囊胚胞浆中线粒体分布均匀,荧光密度值较高,线粒体仍具有一定的活性。空白组与低糖组囊胚荧光密度值无显著性差异(P>0.05),高糖组与空白组和低糖组相比均存在显著性差异(P<0.05);②细胞色素氧化酶(COX)活性的变化:高糖组小鼠囊胚胞浆淡染,反应产物呈浅黄色,COX活性明显降低;空白组和低糖组囊胚胞浆可见明显的棕褐色物质,COX活性较高,统计学分析,空白组与低糖组囊胚灰度值无显著性差异(P>0.05),高糖组与空白组和低糖组相比均存在显著性差异(P<0.05)。结论:高浓度葡萄糖对小鼠囊胚线粒体的分布、功能以及COX活性均有影响。     

A regression model with unexplained residuals was preferred in the analysis of the fetal origins of adult diseases hypothesis

BACKGROUND AND OBJECTIVE: A continued controversy exists whether the assessment of the influence of low birth weight on adult blood pressure necessitates adjustment for adult weight in the analysis on the fetal origins of adult diseases hypothesis. Here we first explain the difficulty in understanding an adjusted multivariate regression model, and then propose another way of writing the regression model to make the interpretation of the separate influence of birth weight and changes in weight later in life more straightforward. STUDY DESIGN AND SETTING: We used a multivariate regression model containing birth weight (standard deviation score; SDS), and residual adult weight (SDS) to explore the effect on blood pressure (or any other outcome) separately. Residual adult weight was calculated as the difference between actual adult weight and the expected adult weight (SDS) given on a certain birth weight (SDS). RESULTS: The coefficients of birth weight and residual adult weight show directly the effect on the analyzed outcome variable. CONCLUSIONS: We prefer to use this regression model with unexplained residuals when the adjusted variable is in the causal pathway in the analyses of data referring to the fetal origins of adult diseases hypothesis.