Survival analysis with change-points in covariate effects

2020 ◽  
Vol 29 (11) ◽  
pp. 3235-3248
Author(s):  
Chun Yin Lee ◽  
KF Lam
Keyword(s):  
Survival Analysis ◽  
Change Point ◽  
Cox Regression ◽  
Bootstrap Method ◽  
Bernstein Polynomials ◽  
Change Points ◽  
Ratio Test ◽  
Covariate Effect ◽  
Sequential Approach ◽  
Covariate Effects

We apply a maximal likelihood ratio test for the presence of multiple change-points in the covariate effects based on the Cox regression model. The covariate effect is assumed to change smoothly at one or more unknown change-points. The number of change-points is inferred by a sequential approach. Confidence intervals for the regression and change-point parameters are constructed by a bootstrap method based on Bernstein polynomials conditionally on the number of change-points. The methods are assessed by simulations and are applied to two datasets.

scholarly journals Testing the proportional hazards assumption in cox regression and dealing with possible non-proportionality in total joint arthroplasty research: methodological perspectives and review

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ilari Kuitunen ◽  
Ville T. Ponkilainen ◽  
Mikko M. Uimonen ◽  
Antti Eskelinen ◽  
Aleksi Reito
Keyword(s):  
Survival Analysis ◽  
Regression Model ◽  
Total Joint Arthroplasty ◽  
Full Text ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Joint Arthroplasty ◽  
Central Research ◽  
Cox Regression Model ◽  
Pubmed Database

Abstract Background Survival analysis and effect of covariates on survival time is a central research interest. Cox proportional hazards regression remains as a gold standard in the survival analysis. The Cox model relies on the assumption of proportional hazards (PH) across different covariates. PH assumptions should be assessed and handled if violated. Our aim was to investigate the reporting of the Cox regression model details and testing of the PH assumption in survival analysis in total joint arthroplasty (TJA) studies. Methods We conducted a review in the PubMed database on 28th August 2019. A total of 1154 studies were identified. The abstracts of these studies were screened for words “cox and “hazard*” and if either was found the abstract was read. The abstract had to fulfill the following criteria to be included in the full-text phase: topic was knee or hip TJA surgery; survival analysis was used, and hazard ratio reported. If all the presented criteria were met, the full-text version of the article was then read. The full-text was included if Cox method was used to analyze TJA survival. After accessing the full-texts 318 articles were included in final analysis. Results The PH assumption was mentioned in 114 of the included studies (36%). KM analysis was used in 281 (88%) studies and the KM curves were presented graphically in 243 of these (87%). In 110 (45%) studies, the KM survival curves crossed in at least one of the presented figures. The most common way to test the PH assumption was to inspect the log-minus-log plots (n = 59). The time-axis division method was the most used corrected model (n = 30) in cox analysis. Of the 318 included studies only 63 (20%) met the following criteria: PH assumption mentioned, PH assumption tested, testing method of the PH assumption named, the result of the testing mentioned, and the Cox regression model corrected, if required. Conclusions Reporting and testing of the PH assumption and dealing with non-proportionality in hip and knee TJA studies was limited. More awareness and education regarding the assumptions behind the used statistical models among researchers, reviewers and editors are needed to improve the quality of TJA research. This could be achieved by better collaboration with methodologists and statisticians and introducing more specific reporting guidelines for TJA studies. Neglecting obvious non-proportionality undermines the overall research efforts since causes of non-proportionality, such as possible underlying pathomechanisms, are not considered and discussed.

scholarly journals Change Point Enhanced Anomaly Detection for IoT Time Series Data

Water ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 1633
Author(s):  
Elena-Simona Apostol ◽  
Ciprian-Octavian Truică ◽  
Florin Pop ◽  
Christian Esposito
Keyword(s):  
Time Series ◽  
Anomaly Detection ◽  
Change Point ◽  
Time Series Data ◽  
Multivariate Time Series ◽  
Change Point Detection ◽  
Change Points ◽  
Series Data ◽  
Prediction And Forecasting ◽  
Point Detection

Due to the exponential growth of the Internet of Things networks and the massive amount of time series data collected from these networks, it is essential to apply efficient methods for Big Data analysis in order to extract meaningful information and statistics. Anomaly detection is an important part of time series analysis, improving the quality of further analysis, such as prediction and forecasting. Thus, detecting sudden change points with normal behavior and using them to discriminate between abnormal behavior, i.e., outliers, is a crucial step used to minimize the false positive rate and to build accurate machine learning models for prediction and forecasting. In this paper, we propose a rule-based decision system that enhances anomaly detection in multivariate time series using change point detection. Our architecture uses a pipeline that automatically manages to detect real anomalies and remove the false positives introduced by change points. We employ both traditional and deep learning unsupervised algorithms, in total, five anomaly detection and five change point detection algorithms. Additionally, we propose a new confidence metric based on the support for a time series point to be an anomaly and the support for the same point to be a change point. In our experiments, we use a large real-world dataset containing multivariate time series about water consumption collected from smart meters. As an evaluation metric, we use Mean Absolute Error (MAE). The low MAE values show that the algorithms accurately determine anomalies and change points. The experimental results strengthen our assumption that anomaly detection can be improved by determining and removing change points as well as validates the correctness of our proposed rules in real-world scenarios. Furthermore, the proposed rule-based decision support systems enable users to make informed decisions regarding the status of the water distribution network and perform effectively predictive and proactive maintenance.

scholarly journals Cox regression survival analysis with compositional covariates: Application to modelling mortality risk from 24-h physical activity patterns

2019 ◽  
Vol 29 (5) ◽  
pp. 1447-1465 ◽  
Author(s):  
DE McGregor ◽  
J Palarea-Albaladejo ◽  
PM Dall ◽  
K Hron ◽  
SFM Chastin
Keyword(s):  
Public Health ◽  
Physical Activity ◽  
Survival Analysis ◽  
Regression Model ◽  
Cox Regression ◽  
Public Health Problem ◽  
Sitting Time ◽  
Cox Regression Model ◽  
Log Ratio ◽  
Activity Behaviour

Survival analysis is commonly conducted in medical and public health research to assess the association of an exposure or intervention with a hard end outcome such as mortality. The Cox (proportional hazards) regression model is probably the most popular statistical tool used in this context. However, when the exposure includes compositional covariables (that is, variables representing a relative makeup such as a nutritional or physical activity behaviour composition), some basic assumptions of the Cox regression model and associated significance tests are violated. Compositional variables involve an intrinsic interplay between one another which precludes results and conclusions based on considering them in isolation as is ordinarily done. In this work, we introduce a formulation of the Cox regression model in terms of log-ratio coordinates which suitably deals with the constraints of compositional covariates, facilitates the use of common statistical inference methods, and allows for scientifically meaningful interpretations. We illustrate its practical application to a public health problem: the estimation of the mortality hazard associated with the composition of daily activity behaviour (physical activity, sitting time and sleep) using data from the U.S. National Health and Nutrition Examination Survey (NHANES).

Testing for long memory in the presence of a general trend

2001 ◽  
Vol 38 (04) ◽  
pp. 1033-1054 ◽  
Author(s):  
Liudas Giraitis ◽  
Piotr Kokoszka ◽  
Remigijus Leipus
Keyword(s):  
Long Memory ◽  
Change Point ◽  
General Trend ◽  
Quantitative Description ◽  
Stationary Sequence ◽  
Change Points ◽  
Asymptotic Size ◽  
Short Memory ◽  
The Impact ◽  
Do So

The paper studies the impact of a broadly understood trend, which includes a change point in mean and monotonic trends studied by Bhattacharyaet al.(1983), on the asymptotic behaviour of a class of tests designed to detect long memory in a stationary sequence. Our results pertain to a family of tests which are similar to Lo's (1991) modifiedR/Stest. We show that both long memory and nonstationarity (presence of trend or change points) can lead to rejection of the null hypothesis of short memory, so that further testing is needed to discriminate between long memory and some forms of nonstationarity. We provide quantitative description of trends which do or do not fool theR/S-type long memory tests. We show, in particular, that a shift in mean of a magnitude larger thanN-½, whereNis the sample size, affects the asymptotic size of the tests, whereas smaller shifts do not do so.

scholarly journals Constructing the Logical Regression Model to Predict the Target of Jianpi Jiedu Decoction in the Treatment of Hepatocellular Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Rongjie Zhang ◽  
Yan Chen ◽  
Ge Zhou ◽  
Baoguo Sun ◽  
Yue Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Survival Analysis ◽  
Regression Model ◽  
Target Genes ◽  
Cox Regression ◽  
Risk Group ◽  
Cox Regression Analysis ◽  
Expression Levels ◽  
Prognostic Analysis ◽  
Significant Difference

Objectives. The purpose of this study was to identify the molecular mechanism and prognosis-related genes of Jianpi Jiedu decoction in the treatment of hepatocellular carcinoma. Methods. The gene expression data of hepatocellular carcinoma samples and normal tissue samples were downloaded from TCGA database, and the potential targets of drug composition of Jianpi Jiedu decoction were obtained from TCMSP database. The genes were screened out in order to obtain the expression of these target genes in patients with hepatocellular carcinoma. The differential expression of target genes was analyzed by R software, and the genes related to prognosis were screened by univariate Cox regression analysis. Then, the LASSO model was constructed for risk assessment and survival analysis between different risk groups. At the same time, independent prognostic analysis, GSEA analysis, and prognostic analysis of single gene in patients with hepatocellular carcinoma were performed. Results. 174 compounds of traditional Chinese medicine were screened by TCMSP database, corresponding to 122 potential targets. 39 upregulated genes and 9 downregulated genes were screened out. A total of 20 candidate prognostic related genes were screened out by univariate Cox analysis, of which 12 prognostic genes were involved in the construction of the LASSO regression model. There was a significant difference in survival time between the high-risk group and low-risk group ( p < 0.05 ). Among the genes related to prognosis, the expression levels of CCNB1, NQO1, NUF2, and CHEK1 were high in tumor tissues ( p < 0.05 ). Survival analysis showed that the high expression levels of these four genes were significantly correlated with poor prognosis of HCC ( p < 0.05 ). GSEA analysis showed that the main KEGG enrichment pathways were lysine degradation, folate carbon pool, citrate cycle, and transcription factors. Conclusions. In the study, we found that therapy target genes of Jianpi Jiedu decoction were mainly involved in metabolism and apoptosis in hepatocellular carcinoma, and there was a close relationship between the prognosis of hepatocellular carcinoma and the genes of CCNB1, NQO1, NUF2, and CHEK1.

scholarly journals Identification of Immune-Related Prognostic mRNA and lncRNA in Patients with Hepatocellular Carcinoma

2022 ◽  
Vol 2022 ◽  
pp. 1-16
Author(s):  
Dan Chen ◽  
Xiaoting Li ◽  
Hui Li ◽  
Kai Wang ◽  
Xianghua Tian
Keyword(s):  
Hepatocellular Carcinoma ◽  
Flow Cytometry ◽  
T Cells ◽  
Regression Analysis ◽  
Survival Analysis ◽  
Immune Cells ◽  
Cox Regression ◽  
Differentially Expressed ◽  
Cox Regression Analysis ◽  
Immune Related Genes

Background. As the most common hepatic malignancy, hepatocellular carcinoma (HCC) has a high incidence; therefore, in this paper, the immune-related genes were sought as biomarkers in liver cancer. Methods. In this study, a differential expression analysis of lncRNA and mRNA in The Cancer Genome Atlas (TCGA) dataset between the HCC group and the normal control group was performed. Enrichment analysis was used to screen immune-related differentially expressed genes. Cox regression analysis and survival analysis were used to determine prognostic genes of HCC, whose expression was detected by molecular experiments. Finally, important immune cells were identified by immune cell infiltration and detected by flow cytometry. Results. Compared with the normal group, 1613 differentially expressed mRNAs (DEmRs) and 1237 differentially expressed lncRNAs (DElncRs) were found in HCC. Among them, 143 immune-related DEmRs and 39 immune-related DElncRs were screened out. These genes were mainly related to MAPK cascade, PI3K-AKT signaling pathway, and TGF-beta. Through Cox regression analysis and survival analysis, MMP9, SPP1, HAGLR, LINC02202, and RP11-598F7.3 were finally determined as the potential diagnostic biomarkers for HCC. The gene expression was verified by RT-qPCR and western blot. In addition, CD4 + memory resting T cells and CD8 + T cells were identified as protective factors for overall survival of HCC, and they were found highly expressed in HCC through flow cytometry. Conclusion. The study explored the dysregulation mechanism and potential biomarkers of immune-related genes and further identified the influence of immune cells on the prognosis of HCC, providing a theoretical basis for the prognosis prediction and immunotherapy in HCC patients.

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