A goodness-of-fit test for the marginal Cox model for correlated interval-censored failure time data

The marginal Cox model approach is perhaps the most commonly used method in the analysis of correlated failure time data (Cai, 1999; Cai and Prentice, 1995; Lin, 1994; Wei, Lin and Weissfeld, 1989). It assumes that the marginal distributions for the correlated failure times can be described by the Cox model and leaves the dependence structure completely unspecified. This paper discusses the assessment of the marginal Cox model for correlated interval-censored data and a goodness-of-fit test is presented for the problem. The method is applied to a set of correlated interval-censored data arising from an AIDS clinical trial.     

抗阻训练联合八段锦对慢性心力衰竭患者心功能、生活质量和不良心脏事件的影响

摘要 目的：观察抗阻训练联合八段锦对慢性心力衰竭（CHF）患者心功能、生活质量和不良心脏事件的影响。方法：纳入2019年6月~2020年7月期间湖南中医药大学第一附属医院心血管内科收治的120例CHF患者,按随机数表法分为对照组、研究组各60例。两组均采取常规抗心衰治疗,在此基础上,对照组接受抗阻训练,研究组接受抗阻训练联合八段锦训练,两组均干预6个月。对比两组疗效以及干预前、干预6个月后的心功能、生活质量,记录随访期间不良心脏事件发生情况。结果：研究组的临床总有效率高于对照组（P<0.05）。干预6个月后,研究组左室收缩末期内径（LVESD）、左室舒张末期内径（LVEDD）小于对照组,左心室射血分数（LVEF）大于对照组（P<0.05）。干预6个月后,研究组SF-36各维度（躯体健康、心理健康、总体健康、情绪功能、躯体功能、社会功能、躯体疼痛、精力）评分高于对照组（P<0.05）。研究组的不良心脏事件发生率低于对照组（P<0.05）。结论：抗阻训练联合八段锦可有效改善CHF患者心功能,提高其生活质量,并降低不良心脏事件发生率。     

Modified GEE and Goodness of the Marginal Fit (GOMF) Test with Correlated Binary Responses for Contingency Tables

This paper addresses testing the goodness of fit of models for marginal probabilities estimated by generalized estimating equations. We develop a modified version of generalized estimating equation and a goodness‐of‐fit test based on the fitted marginal means. The test statistic is easy to compute and has a simple reference distribution. Its performance is evaluated asymptotically and in small samples. It is also compared to the deviance and Pearson X² statistics. Example applications are given. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Inferring the location and effect of tumor suppressor genes by instability-selection modeling of allelic-loss data

Cancerous tumor growth creates cells with abnormal DNA. Allelic-loss experiments identify genomic deletions in cancer cells, but sources of variation and intrinsic dependencies complicate inference about the location and effect of suppressor genes; such genes are the target of these experiments and are thought to be involved in tumor development. We investigate properties of an instability-selection model of allelic-loss data, including likelihood-based parameter estimation and hypothesis testing. By considering a special complete-data case, we derive an approximate calibration method for hypothesis tests of sporadic deletion. Parametric bootstrap and Bayesian computations are also developed. Data from three allelic-loss studies are reanalyzed to illustrate the methods.     

Derivation of normative data for the COPD assessment test (CAT)

Background

The tradition classification of the severity of COPD, based on spirometry, fails to encompass the heterogeneity of the disease. The COPD assessment test (CAT), a multi-dimensional, patient-filled questionnaire, assesses the overall health status of patients, and is recommended as part of the assessment of individuals with COPD. However, information regarding the range of values for the test in a non-COPD population (normative values) is limited, and consequently, knowledge regarding the optimal cut-off, and the minimum clinically important difference (MCID) for the test remain largely empirical.

Methods

CanCOLD is a population-based multi-center cohort study conducted across Canada, the methodology of which is based on the international BOLD initiative. The study includes subjects with COPD, at-risk individuals who smoke, and healthy control subjects. CAT questionnaires were administered at baseline to all subjects. Among non-COPD subjects, normative values for the CAT questionnaire, and psychometric properties of the test were characterized. Predictors of high CAT scores were identified using multivariable logistic regression.

Results

Of the 525 non-COPD subjects enrolled, 500 were included in the analysis. Mean FEV₁/FVC ratio among the 500 included subjects was 0.77 (SD 0.49); the mean predicted FEV₁ was 99.38% (SD 16.88%). The overall mean CAT score was 6 (SD 5.09); scores were higher among females (6.43, SD 5.59), and subjects over 80 years of age (mean 7.58, SD 6.82). Cronbach alpha for the CAT was 0.79, suggesting a high internal consistency for the test. A score of 16 was the 95th percentile for the population, and 27 subjects (5.4%) were found to have a CAT score > =16. Current smoking (aOR 3.41, 95% CI 1.05, 11.02), subject-reported physician-diagnosed asthma (aOR 7.59, 95% CI 2.71, 21.25) and musculoskeletal disease (aOR 4.09, 95% CI 1.72, 9.71) were found to be significantly associated with a score ≥16.

Conclusions

The characterization of CAT scores in the general population will be useful for norm-based comparisons. Longitudinal follow-up of these subjects will help in the optimization of cut-offs for the test.     

Prediction of response and adverse drug reaction of pemetrexed plus platinum-based chemotherapy in lung adenocarcinoma by serum metabolomic profiling

BackgroundPemetrexed plus platinum doublet chemotherapy regimen remains to be the standard first-line treatment for lung adenocarcinoma patients. However, few biomarkers can be used to identify potential beneficiaries with maximal efficacy and minimal toxicity. This study aimed to explore potential biomarker models predictive of efficacy and toxicity after pemetrexed plus platinum chemotherapy based on metabolomics profiling.MethodsA total of 144 patients who received at least two cycles of pemetrexed plus platinum chemotherapy were enroled in the study. Serum samples were collected before initial treatment to perform metabolomics profiling analysis. Logistic regression analysis was performed to establish prediction models.Results157 metabolites were found to be differentially expressed between the response group and the nonresponse group. A panel of Phosphatidylserine 20:4/20:1, Sphingomyelin d18:1/18:0, and Phosphatidic Acid 18:1/20:0 could predict pemetrexed and platinum chemotherapy response with an Area Under the Receiver Operating Characteristic curve (AUROC) of 0.7968. 76 metabolites were associated with hematological toxicity of pemetrexed plus platinum chemotherapy. A panel incorporating triglyceride 14:0/22:3/22:5, 3-(3-Hydroxyphenyl) Propionate Acid, and Carnitine C18:0 was the best predictive ability of hematological toxicity with an AUROC of 0.7954. 54 differential expressed metabolites were found to be associated with hepatotoxicity of pemetrexed plus platinum chemotherapy. A model incorporating stearidonic acid, Thromboxane B3, l-Homocitrulline, and phosphoinositide 20:3/18:0 showed the best predictive ability of hepatotoxicity with an AUROC of 0.8186.ConclusionsThis study established effective and convenient models that can predict the efficacy and toxicity of pemetrexed plus platinum chemotherapy in lung adenocarcinoma patients before treatment delivery.