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Farooq, Fabiha Binte, and Md Jamil Hasan Karami. "Model Selection Strategy for Cox Proportional Hazards Model." Dhaka University Journal of Science 67, no. 2 (July 30, 2019): 111–16. http://dx.doi.org/10.3329/dujs.v67i2.54582.
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Often in survival regression modelling, not all predictors are relevant to the outcome variable. Discarding such irrelevant variables is very crucial in model selection. In this research, under Cox Proportional Hazards (PH) model we study different model selection criteria including Stepwise selection, Least Absolute Shrinkage and Selection Operator (LASSO), Akaike Information Criterion (AIC), Bayesian Information Criterion (BIC) and the extended versions of AIC and BIC to the Cox model. The simulation study shows that varying censoring proportions and correlation coefficients among the covariates have great impact on the performances of the criteria to identify a true model. In the presence of high correlation among the covariates, the success rate for identifying the true model is higher for LASSO compared to other criteria. The extended version of BIC always shows better result than the traditional BIC. We have also applied these techniques to real world data.
Dhaka Univ. J. Sci. 67(2): 111-116, 2019 (July)
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Asadi, Majid, Nader Ebrahimi, and Ehsan S. Soofi. "Connections of Gini, Fisher, and Shannon by Bayes risk under proportional hazards." Journal of Applied Probability 54, no. 4 (November 30, 2017): 1027–50. http://dx.doi.org/10.1017/jpr.2017.51.
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Abstract The proportional hazards (PH) model and its associated distributions provide suitable media for exploring connections between the Gini coefficient, Fisher information, and Shannon entropy. The connecting threads are Bayes risks of the mean excess of a random variable with the PH distribution and Bayes risks of the Fisher information of the equilibrium distribution of the PH model. Under various priors, these Bayes risks are generalized entropy functionals of the survival functions of the baseline and PH models and the expected asymptotic age of the renewal process with the PH renewal time distribution. Bounds for a Bayes risk of the mean excess and the Gini's coefficient are given. The Shannon entropy integral of the equilibrium distribution of the PH model is represented in derivative forms. Several examples illustrate implementation of the results and provide insights for potential applications.
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ZHANG, HAO, and ELSAYED A. ELSAYED. "NONPARAMETRIC ACCELERATED LIFE TESTING BASED ON PROPORTIONAL ODDS MODEL." International Journal of Reliability, Quality and Safety Engineering 13, no. 04 (August 2006): 365–78. http://dx.doi.org/10.1142/s0218539306002318.
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Accelerated life testing (ALT) is used to obtain failure time data in short duration under high stress levels in order to predict product life and performance under design conditions. The proportional hazards (PH) model, a widely used reliability prediction model, assumes constant ratio between the failure rate at high stress levels and the failure rate at the normal operating conditions. However, this assumption might be violated under some conditions and the prediction of the failure rate at normal conditions becomes inaccurate. We investigate the proportional odds (PO) model, which assumes that the odds ratio under different stress levels is constant, for accelerating life testing. In this research, we propose a nonparametric ALT approach based on the proportional odds model to predict reliability at normal operating conditions. We estimate the parameters of the proposed ALT model using the maximum likelihood estimation method. To verify the new approach, we fit the PO model with simulated failure time datasets and experimental failure data and compare its performance with the PH model. The results show that the new approach based on the PO model is a viable complement to the PH model in estimating reliability of products possessing property of converging hazard rate functions.
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Equeter, Lucas, François Ducobu, Edouard Rivière-Lorphèvre, Roger Serra, and Pierre Dehombreux. "An Analytic Approach to the Cox Proportional Hazards Model for Estimating the Lifespan of Cutting Tools." Journal of Manufacturing and Materials Processing 4, no. 1 (March 24, 2020): 27. http://dx.doi.org/10.3390/jmmp4010027.
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The machining industry raises an ever-growing concern for the significant cost of cutting tools in the production process of mechanical parts, with a focus on the replacement policy of these inserts. While an early maintenance induces lower tool return on investment, scraps and inherent costs stem from late replacement. The framework of this paper is the attempt to predict the tool inserts Mean Up Time, based solely on the value of a cutting parameter (the cutting speed in this particular turning application). More specifically, the use of the Cox Proportional Hazards (PH) Model for this prediction is demonstrated. The main contribution of this paper is the analytic approach that was conducted about the relevance on data transformation prior to using the Cox PH Model. It is shown that the logarithm of the cutting speed is analytically much more relevant in the prediction of the Mean Up Time through the Cox PH model than the raw cutting speed value. The paper also covers a numerical validation designed to show and discuss the benefits of this data transformation and the overall interest of the Cox PH model for the lifetime prognosis. This methodology, however, necessitates the knowledge of an analytical law linking the covariate to the Mean Up Time. It also shows how the necessary data for the numerical experiment was obtained through a gamma process simulating the degradation of cutting inserts. The results of this paper are expected to help manufacturers in the assessment of tool lifespan.
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Tebbi, O., F. Guérin, and B. Dumon. "Standard Accelerated Life Testing Model Applied to Mechanical Components." Journal of the IEST 48, no. 1 (September 1, 2005): 103–14. http://dx.doi.org/10.17764/jiet.48.1.b0640u145jw81346.
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This paper provides an overview of the application of accelerated life testing (ALT) models to mechanical components. Estimates are based upon a classical test plan using a sample system tested under accelerated conditions (not under operating conditions). The time transfer regression model is considered log-linear. The parametric model, proportional hazards (PH) model, and semiparametric model are studied. This paper illustrates an experimental example on a paper clip.
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Sharma, Reema, Richa Srivastava, and Satyanshu K. Upadhyay. "A Hierarchical Bayes Analysis and Comparison of PH Weibull and PH Exponential Models for One-Shot Device Testing Experiment." International Journal of Reliability, Quality and Safety Engineering 28, no. 05 (July 30, 2021): 2150036. http://dx.doi.org/10.1142/s0218539321500364.
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The one-shot devices are highly reliable and, therefore, accelerated life tests are often employed to perform the experiments on such devices. Obviously, in the process, some covariates are introduced. This paper considers the proportional hazards model to observe the effect of covariates on the failure rates under the assumption of two commonly used models, namely the exponential and the Weibull for the lifetimes. The Bayes implementation is proposed using the hybridization of Gibbs and Metropolis algorithms that routinely extend to missing data situations as well. The entertained models are compared using the Bayesian and deviance information criteria and the expected posterior predictive loss criterion. Finally, the results based on two real data examples are given as an illustration.
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Spirko-Burns, Lauren, and Karthik Devarajan. "Unified methods for feature selection in large-scale genomic studies with censored survival outcomes." Bioinformatics 36, no. 11 (March 10, 2020): 3409–17. http://dx.doi.org/10.1093/bioinformatics/btaa161.
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Abstract Motivation One of the major goals in large-scale genomic studies is to identify genes with a prognostic impact on time-to-event outcomes which provide insight into the disease process. With rapid developments in high-throughput genomic technologies in the past two decades, the scientific community is able to monitor the expression levels of tens of thousands of genes and proteins resulting in enormous datasets where the number of genomic features is far greater than the number of subjects. Methods based on univariate Cox regression are often used to select genomic features related to survival outcome; however, the Cox model assumes proportional hazards (PH), which is unlikely to hold for each feature. When applied to genomic features exhibiting some form of non-proportional hazards (NPH), these methods could lead to an under- or over-estimation of the effects. We propose a broad array of marginal screening techniques that aid in feature ranking and selection by accommodating various forms of NPH. First, we develop an approach based on Kullback–Leibler information divergence and the Yang–Prentice model that includes methods for the PH and proportional odds (PO) models as special cases. Next, we propose R2 measures for the PH and PO models that can be interpreted in terms of explained randomness. Lastly, we propose a generalized pseudo-R2 index that includes PH, PO, crossing hazards and crossing odds models as special cases and can be interpreted as the percentage of separability between subjects experiencing the event and not experiencing the event according to feature measurements. Results We evaluate the performance of our measures using extensive simulation studies and publicly available datasets in cancer genomics. We demonstrate that the proposed methods successfully address the issue of NPH in genomic feature selection and outperform existing methods. Availability and implementation R code for the proposed methods is available at github.com/lburns27/Feature-Selection. Contact karthik.devarajan@fccc.edu Supplementary information Supplementary data are available at Bioinformatics online.
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Apeagee, Bemgba, P. O. Agada, D. A. Dzaar, and A. A. Ede. "APPLICATION OF COX PROPORTIONAL HAZARDS MODEL IN TIME TO EVENT ANALYSIS OF HIV/AIDS PATIENTS." FUDMA JOURNAL OF SCIENCES 4, no. 3 (September 12, 2020): 185–91. http://dx.doi.org/10.33003/fjs-2020-0403-360.
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The Human Immunodeficiency Virus (HIV) and Acquired Immunodeficiency Syndrome (AIDS) remains a public health crisis that has contributed to the majority of deaths recorded in the past decade, affecting Nigeria and other countries of the world as it has become drug resistance in some patients. This study was aimed at estimating the effects of covariates on the survival time for HIV/AIDS patients using the Cox PH model. The KM results indicated that 91 patients were males, out of which 31 experienced the event of interest, and 60 (68.9%) were censored, 209 were females, 65 died due to AIDS, and 144 were censored (68.9%) respectively. The results of the Cox PHM indicated that sex, age, and health of patients are positively associated with death due to AIDS with the associated negative length of survival for HIV/AIDS patients with HR (1.149, 1.235, 1.887, and 1.306) respectively. The study concluded that CD4 cell counts are the only variable or covariate that showed a lower risk of death due to AIDS. The results further stated that patients with high CD4 cell counts have lower risks of death due to AIDS but an increase in survival time considering other factors. The study, therefore recommends that survival analysis should be used to assess the various risk factors and the confounding effects associated with them stressing that a patient’s lifestyle should be improved to live healthy as they continue to age older.
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Ren, Yi, Chung-Chou H. Chang, Gabriel L. Zenarosa, Heather E. Tomko, Drew Michael S. Donnell, Hyung-joo Kang, Mark S. Roberts, and Cindy L. Bryce. "Gray’s Time-Varying Coefficients Model for Posttransplant Survival of Pediatric Liver Transplant Recipients with a Diagnosis of Cancer." Computational and Mathematical Methods in Medicine 2013 (2013): 1–13. http://dx.doi.org/10.1155/2013/719389.
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Transplantation is often the only viable treatment for pediatric patients with end-stage liver disease. Making well-informed decisions on when to proceed with transplantation requires accurate predictors of transplant survival. The standard Cox proportional hazards (PH) model assumes that covariate effects are time-invariant on right-censored failure time; however, this assumption may not always hold. Gray’s piecewise constant time-varying coefficients (PC-TVC) model offers greater flexibility to capture the temporal changes of covariate effects without losing the mathematical simplicity of Cox PH model. In the present work, we examined the Cox PH and Gray PC-TVC models on the posttransplant survival analysis of 288 pediatric liver transplant patients diagnosed with cancer. We obtained potential predictors through univariable(P<0.15)and multivariable models with forward selection(P<0.05)for the Cox PH and Gray PC-TVC models, which coincide. While the Cox PH model provided reasonable average results in estimating covariate effects on posttransplant survival, the Gray model using piecewise constant penalized splines showed more details of how those effects change over time.
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Tsai, Bor-Wen, John T. Harvey, and Carl L. Monismith. "Application of Weibull Theory in Prediction of Asphalt Concrete Fatigue Performance." Transportation Research Record: Journal of the Transportation Research Board 1832, no. 1 (January 2003): 121–30. http://dx.doi.org/10.3141/1832-15.
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The objectives are to present the feasibility of utilizing the Weibull proportional hazards (PH) model and the Weibull accelerated failure time model of survival analysis to predict in situ pavement fatigue performance from laboratory fatigue test results. A set of WesTrack temperature sensitivity fatigue tests is used as an example to demonstrate how the Weibull PH model works. An example utilizing the deflection data from a heavy vehicle simulator test is given to verify the feasibility of the failure time model. The relationship between mode factor and controlled-deformation fatigue test is discussed using the same example. The Weibull theory approach has potential for use in recursive mechanistic-empirical design procedures.
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Asano, Junichi, Akihiro Hirakawa, Chikuma Hamada, Kan Yonemori, Taizo Hirata, Chikako Shimizu, Kenji Tamura, and Yasuhiro Fujiwara. "Use of Cox’s Cure Model to Establish Clinical Determinants of Long-Term Disease-Free Survival in Neoadjuvant-Chemotherapy-Treated Breast Cancer Patients without Pathologic Complete Response." International Journal of Breast Cancer 2013 (2013): 1–9. http://dx.doi.org/10.1155/2013/354579.
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In prognostic studies for breast cancer patients treated with neoadjuvant chemotherapy (NAC), the ordinary Cox proportional-hazards (PH) model has been often used to identify prognostic factors for disease-free survival (DFS). This model assumes that all patients eventually experience relapse or death. However, a subset of NAC-treated breast cancer patients never experience these events during long-term follow-up (>10 years) and may be considered clinically “cured.” Clinical factors associated with cure have not been studied adequately. Because the ordinary Cox PH model cannot be used to identify such clinical factors, we used the Cox PH cure model, a recently developed statistical method. This model includes both a logistic regression component for the cure rate and a Cox regression component for the hazard for uncured patients. The purpose of this study was to identify the clinical factors associated with cure and the variables associated with the time to recurrence or death in NAC-treated breast cancer patients without a pathologic complete response, by using the Cox PH cure model. We found that hormone receptor status, clinical response, human epidermal growth factor receptor 2 status, histological grade, and the number of lymph node metastases were associated with cure.
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Zhang, Tang, Yao-Zong Guan, and Hao Liu. "Association of Acidemia With Short-Term Mortality of Acute Myocardial Infarction: A Retrospective Study Base on MIMIC-III Database." Clinical and Applied Thrombosis/Hemostasis 26 (January 1, 2020): 107602962095083. http://dx.doi.org/10.1177/1076029620950837.
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Acute myocardial infarction (AMI) is a leading cause of death and not a few of these patients are combined with acidemia. This study aimed to detect the association of acidemia with short-term mortality of AMI patients. A total of 972 AMI patients were selected from the Medical Information Mart for Intensive Care (MIMIC) III database for analysis. Propensity-score matching (PSM) was used to reduce the imbalance. Kaplan-Meier survival analysis was used to compare the mortality, and Cox-proportional hazards model was used to detect related factors associated with mortality. After PSM, a total of 345 non-acidemia patients and 345 matched acidemia patients were included. The non-acidemia patients had a significantly lower 30-day mortality (20.0% vs. 28.7%) and lower 90-day mortality (24.9% vs. 31.9%) than the acidemia patients ( P < 0.001 for all). The severe-acidemia patients (PH < 7.25) had the highest 30-day mortality (52.6%) and 90-day mortality (53.9%) than non-acidemia patients and mild-acidemia (7.25 ≤ PH < 7.35) patients ( P < 0.001). In Cox-proportional hazards model, acidemia was associated with improved 30-day mortality (HR = 1.518; 95%CI = 1.110-2.076, P = 0.009) and 90-day mortality (HR = 1.378; 95%CI = 1.034 -1.837, P = 0.029). These results suggest that severe acidemia is associated with improved 30-day mortality and 90-day mortality of AMI patients.
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Chandra, Novita Eka, and Siti Alfiatur Rohmaniah. "ANALISIS SURVIVAL MODEL REGRESI SEMIPARAMETRIK PADA LAMA STUDI MAHASISWA." Jurnal Ilmiah Teknosains 5, no. 2 (February 3, 2020): 94. http://dx.doi.org/10.26877/jitek.v5i2.4256.
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In survival analysis to determine the relationship between variables is used a regression model, one of which uses the semiparametric regression model. The semiparametric regression model is a model that does not require assumptions or information on survival data distribution. That way, this model is more flexible in its use. In this study, the semiparametric regression model used the Cox Proportional Hazard (Cox PH) regression model. Estimation of Cox PH regression parameters can be done without determining the function baseline hazard. The purpose of this study is to determine the factors that influence the duration of student studies. If there are many students whose studies have not been on time, it shows that there is a lack of professionalism in the academic field of the educator. Thus, the community will assess the low quality of the university, resulting in a decrease in the number of students who want to study at the university. The samples in this study were students of class 2014 Universitas Islam Darul Ulum Lamongan. The variables have used the length of study for students, gender, GPA, school origin, organization, and work. Based on the results of the assumption Proportional Hazard (PH) conducted, all independent variables have fulfilled these assumptions, so that these variables can be used in Cox PH regression. After parameter estimation by Cox PH regression, the GPA and organizational factors significantly influence the duration of student study. Students with high GPA and participating in organizations more quickly complete their studies.
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Mdzinarishvili, Tengiz, Michael X. Gleason, Leo Kinarsky, and Simon Sherman. "Extension of Cox Proportional Hazard Model for Estimation of Interrelated Age-period-Cohort Effects on Cancer Survival." Cancer Informatics 10 (January 2011): CIN.S6770. http://dx.doi.org/10.4137/cin.s6770.
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In the frame of the Cox proportional hazard (PH) model, a novel two-step procedure for estimating age-period-cohort (APC) effects on the hazard function of death from cancer was developed. In the first step, the procedure estimates the influence of joint APC effects on the hazard function, using Cox PH regression procedures from a standard software package. In the second step, the coefficients for age at diagnosis, time period and birth cohort effects are estimated. To solve the identifiability problem that arises in estimating these coefficients, an assumption that neighboring birth cohorts almost equally affect the hazard function was utilized. Using an anchoring technique, simple procedures for obtaining estimates of interrelated age at diagnosis, time period and birth cohort effect coefficients were developed. As a proof-of-concept these procedures were used to analyze survival data, collected in the SEER database, on white men and women diagnosed with LC in 1975–1999 and the age at diagnosis, time period and birth cohort effect coefficients were estimated. The PH assumption was evaluated by a graphical approach using log-log plots. Analysis of trends of these coefficients suggests that the hazard of death from LC for a given time from cancer diagnosis: (i) decreases between 1975 and 1999; (ii) increases with increasing the age at diagnosis; and (iii) depends upon birth cohort effects. The proposed computing procedure can be used for estimating joint APC effects, as well as interrelated age at diagnosis, time period and birth cohort effects in survival analysis of different types of cancer.
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MEKKI, Reem Yousif, Mohamed Hassan MUDAWI, Manahil Saidahmed MUSTAFA, Altaiyb Omer Ahmed MOHMMED, Ahmed Bakheet Abd ALLA, and Abdel Rahman AHMED. "Parametric Survival Models of Hemodialysis Patients in Relation with Patient-Related Factors." Medicina Moderna - Modern Medicine 27, no. 4 (December 20, 2020): 295–304. http://dx.doi.org/10.31689/rmm.2020.27.4.295.
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Background: Survival analysis refers to analyzing of statistical data for which the outcome variable of interest is time until an event occurs. This research aimed at comparing different models of parametric Proportional Hazards (PH) models (Weibull, exponential, Gompertz) in patients with hemodialysis to determine the best model for assessing the survival of patient. Study consists of 325 hemodialysis patients who referred to public hospitals in Khartoum state in the period from December 2005 to December 2015. Data was used to estimate the survival function with view to identify risk factors influencing among end-stage renal disease (ESRD) population. Based on the Cox-Snell Residuals and AIC, BIC, and Gompertz (PH) model is an efficient model than other when the values of (AIC=662.21), (BIC=703.83) and (R2=0.211) where maintained Study assessed that the variables dealing with univariate models were significant but had a significant effect on hemodialysis survival. The Gompertz model had the smallest AIC and BIC value; therefore; it was selected as the most appropriate model. In multivariable analysis, the BIC had the lowest value and the highest value in each analysis. The study assessed that diabetes mellitus and hypertension, regular, and hospital, had a. significant effect.
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Morin, Amy A., Alisha Albert-Green, Douglas G. Woolford, and David L. Martell. "The use of survival analysis methods to model the control time of forest fires in Ontario, Canada." International Journal of Wildland Fire 24, no. 7 (2015): 964. http://dx.doi.org/10.1071/wf14158.
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This paper presents the results from employing survival analysis methods to model the probability distribution of the control time of forest fires. The Kaplan–Meier estimator, log–location–scale models, accelerated failure time models, and Cox proportional hazards (PH) models are described. Historical lightning and people-caused forest fire data from the Province of Ontario, Canada from 1989 through 2004 are employed to illustrate the use of the Cox PH model. We demonstrate how this methodology can be used to examine the association between the control time of a suppressed forest fire and local factors such as weather, vegetation and fuel moisture, as well as fire management variables including the response time between when a fire is reported and the initiation of suppression action. Significant covariates common to both the lightning and people-caused models were the size of the fire at the onset of initial attack, the Fine Fuel Moisture Code and the Initial Spread Index. The response time was also a significant predictor for the control time of lightning-caused fires, whereas the Drought Code and time of day of initial attack were significant for people-caused fires. Larger values of the covariates in these models were associated with larger survival probabilities.
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Shah, Ronak Jagdeep, Lisa E. Vaughan, Felicity T. Enders, Dawn S. Milliner, and John C. Lieske. "Plasma Oxalate as a Predictor of Kidney Function Decline in a Primary Hyperoxaluria Cohort." International Journal of Molecular Sciences 21, no. 10 (May 20, 2020): 3608. http://dx.doi.org/10.3390/ijms21103608.
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This retrospective analysis investigated plasma oxalate (POx) as a potential predictor of end-stage kidney disease (ESKD) among primary hyperoxaluria (PH) patients. PH patients with type 1, 2, and 3, age 2 or older, were identified in the Rare Kidney Stone Consortium (RKSC) PH Registry. Since POx increased with falling estimated glomerular filtration rate (eGFR), patients were stratified by chronic kidney disease (CKD) subgroups (stages 1, 2, 3a, and 3b). POx values were categorized into quartiles for analysis. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for risk of ESKD were estimated using the Cox proportional hazards model with a time-dependent covariate. There were 118 patients in the CKD1 group (nine ESKD events during follow-up), 135 in the CKD 2 (29 events), 72 in CKD3a (34 events), and 45 patients in CKD 3b (31 events). During follow-up, POx Q4 was a significant predictor of ESKD compared to Q1 across CKD2 (HR 14.2, 95% CI 1.8–115), 3a (HR 13.7, 95% CI 3.0–62), and 3b stages (HR 5.2, 95% CI 1.1–25), p < 0.05 for all. Within each POx quartile, the ESKD rate was higher in Q4 compared to Q1–Q3. In conclusion, among patients with PH, higher POx concentration was a risk factor for ESKD, particularly in advanced CKD stages.
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Emmert-Streib, Frank, and Matthias Dehmer. "Introduction to Survival Analysis in Practice." Machine Learning and Knowledge Extraction 1, no. 3 (September 8, 2019): 1013–38. http://dx.doi.org/10.3390/make1030058.
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The modeling of time to event data is an important topic with many applications in diverse areas. The collective of methods to analyze such data are called survival analysis, event history analysis or duration analysis. Survival analysis is widely applicable because the definition of an ’event’ can be manifold and examples include death, graduation, purchase or bankruptcy. Hence, application areas range from medicine and sociology to marketing and economics. In this paper, we review the theoretical basics of survival analysis including estimators for survival and hazard functions. We discuss the Cox Proportional Hazard Model in detail and also approaches for testing the proportional hazard (PH) assumption. Furthermore, we discuss stratified Cox models for cases when the PH assumption does not hold. Our discussion is complemented with a worked example using the statistical programming language R to enable the practical application of the methodology.
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Nilima, Shahnaz. "Under-five child mortality in Bangladesh: Classical and Bayesian approaches to Cox proportional hazard model." Bangladesh Journal of Scientific Research 30, no. 1-2 (March 25, 2018): 45–54. http://dx.doi.org/10.3329/bjsr.v30i1-2.36119.
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This study examines the determinants of under-five child mortality in Bangladesh using the data extracted from the Bangladesh Demographic and Health Survey (BDHS), 2011 and 2014. Product-Limit method and Log-Rank test have been used for bivariate analysis. Cox proportional hazard model has been employed under both classical and Bayesian approaches. Cox regression analysis reveals that region (Barisal and Sylhet), maternal education (higher education), mother’s membership of NGO have significant impact on child mortality. The results obtained using Bayesian Cox PH model are almost similar except one key finding. Under Bayesian analysis, child’s size at birth appeared as potential determinant of under-five mortality whereas it has insignificant effect on child survival when classical Cox model has been applied.Bangladesh J. Sci. Res. 30(1&2): 45-54, December-2017
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Sha, Naijun, and Hao Yang Teng. "A Bayes Inference for Step-Stress Accelerated Life Testing." International Journal of Statistics and Probability 6, no. 6 (September 15, 2017): 1. http://dx.doi.org/10.5539/ijsp.v6n6p1.
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In this article, we present a Bayesian analysis with convex tent priors for step-stress accelerated life testing (SSALT) using a proportional hazard (PH) model. As flexible as the cumulative exposure (CE) model in fitting step-stress data and its attractive mathematical properties, the PH model makes Bayesian inference much more accessible than the CE model. Two sampling methods through Markov chain Monte Carlo algorithms are employed for posterior inference of parameters. The performance of the methodology is investigated using both simulated and real data sets.
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Kohne, Claus-Henning, Ralf Hofheinz, Laurent Mineur, Henry Letocha, Richard Greil, Josef Thaler, Brian Twomey, et al. "Amphiregulin (AREG) expression and response to first-line panitumumab (pmab) plus FOLFIRI in metastatic colorectal cancer (mCRC)." Journal of Clinical Oncology 33, no. 3_suppl (January 20, 2015): 731. http://dx.doi.org/10.1200/jco.2015.33.3_suppl.731.
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731 Background: Biomarker analyses have shown that patients (pts) with RAS wild-type (WT) mCRC can achieve overall survival (OS) benefits with first-line pmab plus chemotherapy. Other biomarkers may exist that could optimize pt selection. Epidermal growth factor receptor ligand (eg AREG) levels have been correlated with OS during anti-EGFR therapy. Here we investigate the relationship between AREG expression and treatment outcome in a single-arm first-line mCRC study of pmab + FOLFIRI. Methods: Qualified reverse transcription quantitative polymerase chain reaction (RT-qPCR) assays were used to measure AREG RNA expression in archival formalin-fixed, paraffin embedded tumor samples from mCRC pts in two pmab trials (STEPP and 314). The STEPP analysis was used to establish a cut-off point in AREG expression that identified the best responders. This cut-off was applied prospectively to samples previously analyzed for KRAS in the 314 trial. Using the KRASMT subgroup as a non-responding comparator, Cox proportional hazards (PH) models were used to evaluate AREG expression levels as a continuous covariate. Decision curves were used to estimate the progression-free survival (PFS) hazard ratio (HR) with increasing levels of baseline AREG expression. Results: In the 314 trial 100 pts had evaluable AREG levels. Among 50 KRAS WT pts, high AREG expression was associated with objective response (OR) (Table). The high AREG group had better PFS HRs (KRAS WT/KRAS MT: 0.30 [95% CI, 0.12–0.75]) compared with the low AREG group (PFS HR 0.49 [95% CI 0.21–1.1]). There was a significant biomarker-by-AREG expression interaction in the Cox PH model (p=0.03). Conclusions: Treatment decision curves based on the PH model suggest that most KRAS WT patients express AREG at levels where treatment benefit is predicted. Future analysis of samples from a RASWT population may provide further insights. Clinical trial information: NCT00508404. [Table: see text]
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Lara, Matthew Stephen, Ann Brunson, Ben Kent Tomlinson, Theodore Wun, Lihong Qi, Rosemary Cress, Primo Lara, David R. Gandara, and Karen Kelly. "Predictors of survival for younger patients (pts) less than 50 years of age with non-small cell lung cancer (NSCLC): A California Cancer Registry (CCR) analysis." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 8049. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.8049.
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8049 Background: Lung cancer is often seen in older pts, with a median age at diagnosis of 70 years (yrs). Epidemiology and outcomes are reportedly different among younger NSCLC pts (< 50 yrs). We hypothesized that these pts have longer cause-specific survival (CSS) and that baseline clinical features prognostic for CSS would be identified. Methods: NSCLC pts in the CCR diagnosed between 1/98 through 12/09 were included. The primary outcome was CSS. Hazard ratios (HR) for CSS were calculated using Cox Proportional Hazards (PH) models for all ages & for pts <50 years, adjusted for baseline variables. Results: We identified 132,671 lung cancer pts: 114,451 (86.3%) had NSCLC. 6,389 (5.6%) were < 50 yrs (median, 46 yrs). Demographics: White (3,557, 56%); Histology: AdenoCA (AC) (3,406, 53%), Squamous (781, 12%), BAC (291, 4.6%); Stage IV (3,655, 57%). Fewer pts < 50 yrs were diagnosed in later yrs: from 37% in ‘98-’01 to 29% in ‘06-‘09. Results of Cox PH models for all ages and < 50 years are shown. Conclusions: The relative proportion of pts < 50 yrs has declined by 22% over the past decade. Age < 50 years was an independent predictor of improved CSS (HR 0.83, p<0.001). In younger pts, AC histology was not prognostic for CSS (versus squamous) despite known differences in clinical and biologic behavior between subtypes.Importantly, clinical variables strongly prognostic for CSS were identified in pts < 50 yrs. [Table: see text]
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Lin, Emily Pei-Ying, Chih-Yuan Hsu, Pan-Chyr Yang, and Yu Shyr. "Changing paradigm in oncology clinical trials: Cox-TEL—Adjustment made ready for early crossover and tail tale." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e15067-e15067. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e15067.
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e15067 Background: Approvals of immune checkpoint inhibitors (ICI) were made based on positive clinical trial results analyzed by the Cox proportional hazards (PH) model. With ICI data, however, long tails and early crossover in survival curves, which violate the Cox PH assumption, can lead to misinterpretation of clinical significance of findings. Here we introduce the Cox-TEL and show the differences of study results before and after Cox-TEL adjustment using KEYNOTE 042 and 045 as examples. Methods: Cox-TEL is built on the mathematical foundation of Taylor expansion. As an easily implemented alternative of PH cure model, it not only infers associations between survival probabilities of the two study arms among patients without long-term survival (poor-responders), but also estimates differences in proportion (DP) between arms among patients in the long-tail segment of the survival curve (true-responders). Results: In KEYNOTE 042, the Cox-TEL HRs for death were statistically insignificant across all subgroups. The trend of DP, on the other hand, is positively related to that of PD-L1 TPS and inverted related to that of Cox HR when the PD-L1 ≥50% cohort is covered. In KEYNOTE 045, the Cox-TEL HRs suggested that for the poor-responders, pembrolizumab did not do better than chemotherapy in terms of overall survival (OS) and might do harm to the patients in terms of progression-free survival (PFS). For the true-responders, DPs of OS and PFS were both statistically significant (Table). Conclusions: Our data demonstrated the biases derived from insufficient data analyses and strengthened the necessity of analytic model revisits in the new oncology era of which cure for advanced cancers is no longer impossible. [Table: see text]
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Halabi, Susan, Andrew J. Armstrong, A. Oliver Sartor, Johann Sebastian De Bono, Ellen B. Kaplan, and Eric Jay Small. "Prostate-specific antigen decline (PSA) as a surrogate for overall survival (OS) in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC) who failed first-line chemotherapy." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 4515. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.4515.
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4515 Background: PSA kinetics, and more specifically a 30% decline in PSA following initiation of first-line chemotherapy with docetaxel, has been reported to be a surrogate endpoint for OS in mCRPC pts. The objective of this analysis was to evaluate PSA kinetics as surrogate endpoints for overall survival (OS) in patients who were receiving second line chemotherapy following progression after docetaxel front line therapy. Methods: Data from a phase III trial of 755 mCRPC pts randomized to treatment with cabazitaxel in combination with prednisone (C+P) every 3 weeks or mitoxantrone in combination with prednisone (M+P) were used. All pts were previously treated with a docetaxel-containing regimen. PSA decline (≥30% and ≥50% ) and PSA velocity within the first three months of treatment were evaluated as potential surrogate endpoints for OS. The proportional hazards (PH) model was used to test for Prentice’s criteria and the proportion of treatment explained (PTE) was computed as a second test of surrogacy. PTE was defined as one minus the ratio of the treatment coefficient in the adjusted PH model (includes PSA decline or velocity) to the treatment coefficient in the unadjusted PH model. Results: Of 755 men, 654 had sufficient PSA data to be included in the analysis. Treatment arm (C+P vs. M+P) was prognostic of OS with a hazard ratio (HR) of 0.65 (95% CI=0.54-0.79, p<0.001). A 30% PSA decline within three months of treatment was associated with a HR of 0.46 (95% CI 0.37-0.57, p-value<0.001) for OS. After adjusting for treatment effect, the HR for 30% PSA decline was 0.50 (95% CI= 0.40-0.62, p<0.001) but treatment arm remained statistically significant thus failing Prentice’s third criterion. The PTE for ≥30% decline in PSA within three months was 0.39 (95% CI= 0.36-0.42) indicating a lack of surrogacy for OS. Similar results were observed for pts who experienced ≥50% decline in PSA and PSA velocity. Conclusions: Neither PSA decline (≥30% and ≥50%) nor PSA velocity within the first three months of therapy are surrogate endpoints for OS in pts receiving second line chemotherapy.
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Anwar, Samsul. "Perbandingan Nilai Hazard Kejadian Tsunami di Indonesia Berdasarkan Posisi Garis Khatulistiwa (Katalog Tsunami Indonesia 1802 - 2018)." Jurnal Lingkungan dan Bencana Geologi 12, no. 1 (July 1, 2021): 33. http://dx.doi.org/10.34126/jlbg.v12i1.303.
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ABSTRAKIndonesia merupakan salah satu negara yang rawan terjadinya tsunami. Berdasarkan Katalog Tsunami BMKG, sepanjang tahun 1802 hingga 2018 telah terjadi 219 tsunami di Indonesia. Dengan mempelajari kejadian tsunami pada masa lalu berarti merupakan salah satu langkah mitigasi bencana dalam upaya meminimalisir kerugian yang disebabkan oleh tsunami pada masa yang akan datang. Tujuan penelitian ini adalah menghitung nilai hazard rasio kejadian tsunami berdasarkan lokasi kejadiannya relatif terhadap garis khatulistiwa. Model Cox Proportional Hazard (Cox PH) menunjukkan bahwa tsunami di wilayah selatan garis khatulistiwa cenderung 50,5% lebih cepat terjadi dibandingkan dengan wilayah utara. Hal ini disebabkan karena wilayah selatan berpotensi lebih besar akan terjadinya kejadian tsunamigenik termasuk gempa bumi, erupsi gunungapi dan penyebab lainnya dari pada wilayah utara. Adanya zona subduksi aktif akibat pertemuan lempeng tektonik Indo-Australia dan Eurasia di wilayah selatan meningkatkan potensi terjadinya tsunamigenik di wilayah tersebut. Penelitian lebih lanjut diperlukan untuk menjelaskan hubungan antara garis khatulistiwa dengan kejadian tsunamigenik di Indonesia.Kata kunci: garis khatulistiwa, hazard rasio, Indonesia, model cox ph, tsunami, tsunamigenikABSTRACTIndonesia is a tsunami-prone country. Based on the BMKG Tsunami Catalog, from 1802 to 2018 there were 219 tsunamis in Indonesia. By studying tsunami events in the past means one disaster mitigation measure in an effort to minimize losses caused by tsunamis in the future. The objective of the study is to measure the tsunami hazard ratio based on its location relative to the equator position. Cox Proportional Hazard Model (Cox PH) showed that tsunamis in the southern area tended to happen 50.5% faster compared to the northern area. This is because the southern region has greater potential for tsunamigenic events including earthquakes, volcanic eruptions, and other causes than the northern region. The existence of an active subduction zone due to the confluence of Indo-Australian and Eurasian tectonic plates in the southern region increases the potential for tsunamigenic events in the region. Further research is necessarily needed to explain the relationship between the equator and tsunamigenic events in Indonesia.Keywords: equator, hazard ratio, Indonesia, cox ph model, tsunami, tsunamigenic
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Ou, Shuo-Ming, Wen-Chien Fan, Kun-Ta Cho, Chiu-Mei Yeh, Vincent Yi-Fong Su, Man-Hsin Hung, Yu-Sheng Chang, et al. "Systemic Sclerosis and the Risk of Tuberculosis." Journal of Rheumatology 41, no. 8 (July 15, 2014): 1662–69. http://dx.doi.org/10.3899/jrheum.131125.
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Objective.Pulmonary involvement is common in patients with systemic sclerosis (SSc), and this condition causes substantial morbidity and mortality. Disrupted immunity from the disease or associated medication may render such patients subject to tuberculosis (TB) infection. However, the relationship between SSc and TB has not yet been investigated.Methods.Using the Taiwan National Health Insurance Research Database, 838 patients with SSc diagnosed in Taiwan during 2000–2006 were identified and followed for emergence of TB infection. Incidence rate ratios (IRR) of TB compared to 8380 randomly selected age-, sex-, and comorbidity-matched controls without SSc were calculated. The Cox proportional hazards model was used for multivariate adjustment to identify independent risk factors for TB infection.Results.The risk of TB infection was higher in the SSc cohort than in controls (IRR 2.81, 95% CI 1.36–5.37; p = 0.004), particularly for pulmonary TB (IRR 2.53, 95% CI 1.08–5.30; p = 0.022). Other independent risk factors for TB infection in patients with SSc were age ≥ 60 years [hazard ratio (HR) 3.52, 95% CI 1.10–11.33; p = 0.035] and pulmonary hypertension (PH; HR 6.06, 95% CI 1.59–23.17; p = 0.008). Mortality did not differ for SSc patients with or without TB.Conclusion.In this nationwide study, the incidence of TB infection was significantly higher among patients with SSc than in controls without SSc. Special care should be taken in managing patients with SSc who are at high risk for TB, especially those aged ≥ 60 years or who also have PH.
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Raboud, Janet, Sandra Blitz, Tony Antoniou, Mona Loutfy, and Sharon Walmsley. "Recent Immigrants Show improved Clinical Outcomes at a Tertiary Care HIV Clinic." Canadian Journal of Infectious Diseases and Medical Microbiology 23, no. 1 (2012): 9–14. http://dx.doi.org/10.1155/2012/963474.
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BACKGROUND: In recent years, the proportion of patients attending tertiary care HIV clinics who are recent immigrants to Canada has increased dramatically.METHODS: Among patients first seen at the Toronto Hospital Immunodeficiency Clinic (Toronto, Ontario) between January 1, 2000 and August 31, 2009, the time to death from the first positive HIV test was compared between individuals who had immigrated to Canada within 10 years of their first visit and individuals who were either Canadian-born or who had immigrated more than 10 years before their first clinic visit. In addition, for the antiretroviral-naive patients in these two groups who initiated combination antiretroviral therapy, the time to and the duration of virologic suppression were compared.RESULTS: In a multivariable proportional hazards (PH) model, recent immigrant status was associated with decreased mortality (HR 0.11, P=0.03) after adjusting for age, CD4 count and the risk factor for men having sex with men. In multivariable PH models, recent female immigrants achieved virologic suppression more quickly (HR 1.51, P=0.02), while male immigrants (HR 1.14, P=0.44) and female nonimmigrants (HR 0.90, P=0.61) had similar times to virologic suppression as male nonimmigrants, respectively, after adjusting for the year of and viral load at combination antiretroviral therapy initiation. When pregnant women were removed from the analysis, there were no significant differences in the rates of virologic rebound according to sex or immigration status.DISCUSSION: Despite the perceived barriers of newcomers to Canada, mortality was lower among recent immigrants and virologic suppression was achieved more quickly in recent female immigrants.
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Costello, R. E., B. Birlie Yimer, M. Jani, and W. Dixon. "FRI0120 ORAL GLUCOCORTICOID USE IS ASSOCIATED WITH HYPERTENSION IN PATIENTS WITH RHEUMATOID ARTHRITIS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 641.1–641. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1000.
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Background:Oral glucocorticoids (GC) are frequently prescribed to patients with rheumatoid arthritis (RA), however GC use is associated with a number of potential side effects. Hypertension is cited as a possible side effect, but few studies have specifically investigated GC-associated hypertension in patients with RA with conflicting results.Objectives:The aim of this study was to determine whether GCs were associated with an increased risk of incident hypertension in a cohort of patients with RA.Methods:A retrospective cohort of patients with incident RA and no hypertension at RA diagnosis were identified from UK primary care electronic health records (Clinical Practice Research Datalink). GC prescriptions were used to determine time-varying GC use and dose, categorised as: no use, >0–4.9 mg/day, 5–7.4 mg/day, 7.5–14.9 mg/day, ≥15mg/day. A 3-month risk attribution model was used where patients continued to remain at risk for 3 months after the end of prescriptions. Hypertension was identified if a patient had either: 1) 2 consecutive systolic blood pressure (BP) measurements >140mmHg within a year, 2) 2 consecutive diastolic BP measurements >90mmHg within a year or 3) antihypertensive prescriptions on at least two occasions and a Read code for hypertension. Unadjusted and adjusted Cox proportional hazards (PH) regression models were fitted to determine if there was an association between GC use and hypertension. Models were adjusted for baseline age, gender, baseline body mass index, baseline ever smoking, time-varying synthetic disease-modifying anti-rheumatic drug use, time-varying non-steroidal anti-inflammatory drug use and baseline Charlson comorbidity index.Results:There were 17,760 patients with incident RA and no hypertension. The cohort had a mean age of 56.3 ± 12.7 years and were predominantly female (68%). 7,421 (42%) were prescribed GCs during follow-up. There were 6,243 cases of incident hypertension over 97547 person years (pyrs) of follow-up, giving an incident rate of 64.1 per 1000 pyrs. Of those 1321 cases were in those exposed to GCs and 4922 were in those unexposed, giving incident rates of 87.6 per 1000 pyrs and 59.7 per 1000 pyrs, respectively. The adjusted Cox PH model indicated that recent GC use was associated with a 17% increased hazard of hypertension (hazard ratio: 1.17 (95% CI 1.10 to 1.24)). When categorised by dose, the adjusted model indicated only doses above 7.5mg were significantly associated with hypertension (Table 1).Table 1.Unadjusted and adjusted Cox proportional hazards regression model resultsUnadjustedHR (95% CI)Age and gender adjustedHR (95% CI)Fully adjusted* HR (95% CI)Recent GC use1.44(1.35 to 1.53)1.23(1.16 to 1.31)1.17(1.10 to 1.24)Recent GC doseNo GC useReferenceReferenceReference>0 – 4.9mg1.35(1.21 to 1.53)1.13(1.01 to 1.28)1.10(0.98 to 1.24)5mg – 7.4mg1.40(1.22 to 1.60)1.11(0.97 to 1.27)1.07(0.93 to 1.23)7.5mg – 14.9mg1.44(1.33 to 1.57)1.26(1.16 to 1.38)1.18(1.08 to 1.29)15mg and over1.60(1.40 to 1.84)1.45(1.27 to 1.66)1.36(1.18 to 1.56)* Adjusted for: Baseline age, gender, baseline body mass index, baseline ever smoking, synthetic disease-modifying anti-rheumatic drug use (time-varying), non-steroidal anti-inflammatory drug use (time-varying) and baseline Charlson comorbidity index.Conclusion:In this large cohort of patients with RA and without hypertension, recent GC use was associated with incident hypertension. In particular doses ≥7.5mg were associated with hypertension while the association with lower doses was inconclusive. Clinicians need to consider cardiovascular risk when prescribing GCs and ensure BP is regularly monitored.Disclosure of Interests:Ruth E Costello: None declared, Belay Birlie Yimer: None declared, Meghna Jani Speakers bureau: Grifols, William Dixon Consultant of: Bayer and Google
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Hou, Ziming, Jun Yang, Hao Wang, Dongyuan Liu, and Hongbing Zhang. "A Potential Prognostic Gene Signature for Predicting Survival for Glioblastoma Patients." BioMed Research International 2019 (March 26, 2019): 1–9. http://dx.doi.org/10.1155/2019/9506461.
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Objective. This study aimed to screen prognostic gene signature of glioblastoma (GBM) to construct prognostic model.Methods. Based on the GBM information in the Cancer Genome Atlas (TCGA, training set), prognostic genes (Set X) were screened by Cox regression. Then, the optimized prognostic gene signature (Set Y) was further screened by the Cox-Proportional Hazards (Cox-PH). Next, two prognostic models were constructed: model A was based on the Set Y; model B was based on part of the Set X. The samples were divided into low- and high-risk groups according to the median prognosis index (PI). GBM datasets in Gene Expression Ominous (GEO, GSE13041) and Chinese Glioma Genome Atlas (CGGA) were used as the testing datasets to confirm the prognostic models constructed based on TCGA.Results. We identified that the prognostic 14-gene signature was significantly associated with the overall survival (OS) in the TCGA. In model A, patients in high- and low-risk groups showed the significantly different OS (P = 7.47 × 10−9, area under curve (AUC) 0.995) and the prognostic ability were also confirmed in testing sets (P=0.0098 and 0.037). The model B in training set was significant but failed in testing sets.Conclusion. The prognostic model which was constructed based on the prognostic 14-gene signature presented a high predictive ability for GBM. The 14-gene signature may have clinical implications in the subclassification of GBM.
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Tabassum, Tasnuva, and Wasimul Bari. "Competing risks analysis of under-five child mortality in Bangladesh." Bangladesh Journal of Scientific Research 27, no. 1 (January 4, 2016): 27–38. http://dx.doi.org/10.3329/bjsr.v27i1.26222.
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This study implements an analysis of under five mortality to the Bangladesh Demographic and Health Survey, 2011 data from a competing risks perspective. Kaplan - Meier overall survival curves along with log-rank test p-values are employed to determine the prospective covariates for the Cox proportional hazard (PH) model. Later the typical Cox PH model is used to model the causespecific hazard for the two competing causes, namely disease and non-disease on the selected covariates. It is revealed that mothers primary and secondary education, birth order of the index child in case of disease model; mothers higher education, wealth index of the index child in case of non-disease model and mothers aged greater than 30 years at the time of giving birth, home as a place of child delivery in both model played significant role in decreasing under five child mortality.Bangladesh J. Sci. Res. 27(1): 27-38, June-2014
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Hafid, Herawati, Muhammad Nadjib Bustan, and Muhammad Kasim Aidid. "Penanganan Ties Event dalam Regresi Cox Proportional Hazard Menggunakan Metode Breslow (Kasus: Pasien Rawat Inap DBD di RSAL Jala Ammari Makassar)." VARIANSI: Journal of Statistics and Its application on Teaching and Research 2, no. 1 (March 13, 2020): 13. http://dx.doi.org/10.35580/variansiunm12897.
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Abstrak Analisis Survival adalah prosedur statistika yang digunakan untuk menganalisis data dimana peubah yang diperhatikan adalah waktu sampai terjadinya suatu event. Waktu dapat dinyatakan dalam hitungan hari, minggu, bulan dan tahun. Salah satu tujuan dari analisis survival adalah untuk mengetahui hubungan antara waktu kejadian peubah bebas yang terukur pada saat dilakukan penelitian. Metode yang sering digunakan dalam analisis survival khususnya data kesehatan adalah Regresi Cox Proportional Hazard (PH) karena distribusinya tidak tergantung pada asumsi waktu kejadian. Dalam suatu data seperti data pasien penderita penyakit Demam Berdarah Dengue (DBD) ditemukan adanya data kejadian bersama (ties event) yang berpengaruh pada pembentukan himpunan risikonya pada bagian estimasi parameter model cox,pada kasus kejadian bersama (ties event) dilakukan modifikasi pada partial likelihood untuk mengetahui faktor-faktor yang mempengaruhi laju kesembuhan pasien penderita penyakit DBD. Adapun hasil analisisnya, diperoleh faktor yang paling berpengaruh terhadap laju kesembuhan penyakit DBD yakni leukosit dengan p-value =0,097< α 0,05, dan nilai hazard ratio sebesar 1,1024 serta faktor yang kedua yaitu hematokrit dengan p-value =0,0141< α 0,05, dan nilai hazard ratio sebesar 1,595. Kata Kunci: Analisis Survival, Regresi Cox PH, Ties Event, Metode Breslow, Demam Berdarah Dengue (DBD). Abstract Survival analysis is a statistical procedure that is used to analyze data where the variables considered are the time until the occurrence of an event. Time can be expressed in days, weeks, months and years. One of the objectives of survival analysis is to find out the relationship between the time of occurrence of independent variables measured at the time of the study. The method often used in survival analysis, especially health data, is Cox Proportional Hazard (PH) Regression because its distribution does not depend on the assumption of the time of the event. In a data such as data on patients with Dengue Hemorrhagic Fever (DHF) data, there were ties event data that influenced the formation of risk sets in the cox model parameter estimation section, in the case of ties event modifications were made to the partial likelihood for know the factors that influence the recovery rate of patients with DHF. As for the results of the analysis, the factors that most influence the recovery rate of leucocyte dengue fever with p-value = 0,097 < α = 0,05 and the hazard ratio of 1.1024 and the second factor is the hematocrit with p-value = 0,0141 < α = 0,05 and the hazard ratio valueamounting to 1,595. Keywords: Survival Analysis, Cox PH Regression, Ties Event, Breslow Method, Dengue Hemorrhagic Fever (DHF).
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Madariaga, Rafa, Ramon Oller, and Joan Carles Martori. "Discrete choice and survival models in employee turnover analysis." Employee Relations 40, no. 2 (February 12, 2018): 381–95. http://dx.doi.org/10.1108/er-03-2017-0058.
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Purpose The purpose of this paper is to assess the capacity of two methodological approaches – discrete choice and survival analysis models – to investigate the relationship between socio-economic characteristics and turnover in a retailing company. A comparison of the estimation results under each model and their interpretation is carried out. The study provides a guide to determine, assess and interpret the effects of different driving factors behind turnover. Design/methodology/approach The authors use a data set containing information about 1,199 workers followed up between January 2007 and December 2009. First, not distinguishing voluntary and involuntary resignation, a binary logistic regression model and a Cox proportional hazards (PH) model for univariate survival data are set up and estimated. Second, distinguishing voluntary and involuntary resignation, a multinomial logistic regression model and a Cox PH model for competing risk data are set up and estimated. Findings When no distinction is made, the results point that wage and age exert a negative effect on turnover. Risk of resignation is higher for male, single, not married and Spanish nationals. When the distinction is made, previous results hold for voluntary turnover: wage, age, gender, marital status and nationality are significant. However, when explaining involuntary turnover, all variables except wage lose explaining power. The survival analysis approach is better suited as it measures risk of resignation in a longitudinal way. Discrete choice models only study the risk at a particular cut-off point (24 months in case of this study). Originality/value This paper is a systematic application, evaluation and comparison of four different statistical models for analysing employee turnover in a single firm. This work is original because no systematic comparison has been done in the context of turnover.
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Hsu, Vivien M., Lorinda Chung, Laura K. Hummers, Ami Shah, Robert Simms, Marcy Bolster, Faye N. Hant, et al. "Risk Factors for Mortality and Cardiopulmonary Hospitalization in Systemic Sclerosis Patients At Risk for Pulmonary Hypertension, in the PHAROS Registry." Journal of Rheumatology 46, no. 2 (October 1, 2018): 176–83. http://dx.doi.org/10.3899/jrheum.180018.
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Objective.We sought to identify predictors of mortality and cardiopulmonary hospitalizations in patients at risk for pulmonary hypertension (PH) and enrolled in PHAROS, a prospective cohort study to investigate the natural history of PH in systemic sclerosis (SSc).Methods.The at-risk population for PH was defined by the following entry criteria: echocardiogram systolic pulmonary arterial pressure > 40 mmHg, or DLCO < 55% predicted or ratio of % forced vital capacity/%DLCO > 1.6, measured by pulmonary function testing. Baseline clinical measures were evaluated as predictors of hospitalization and death between 2005 and 2014. Cox proportional hazards models were censored at date of PH onset or latest study visit and adjusted for age, sex, race, and disease duration.Results.Of the 236 at-risk subjects who were followed for a median of 4 years (range 0.4–8.5 yrs), 35 developed PH after entering PHAROS (reclassified as PH group). In the at-risk group, higher mortality was strongly associated with male sex, low %DLCO, exercise oxygen desaturation, anemia, abnormal dyspnea scores, and baseline pericardial effusion. Risks for cardiopulmonary hospitalization were associated with increased dyspnea and pericardial effusions, although PH patients with DLCO < 50% had the highest risk of cardiopulmonary hospitalizations.Conclusion.Risk factors for poor outcome in patients with SSc who are at risk for PH were similar to others with SSc-PH and SSc-pulmonary arterial hypertension, including male sex, DLCO < 50%, exercise oxygen desaturation, and pericardial effusions. This group should undergo right heart catheterization and receive appropriate intervention if PH is confirmed.
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Nevskaya, T., Y. Jiang, M. Wang, M. Baron, J. Pope, Janet E. Pope, Murray Baron, et al. "FRI0258 CUMULATIVE INCIDENCE, SURVIVAL AND PREDICTORS OF PULMONARY HYPERTENSION IN SYSTEMIC SCLEROSIS SUBSETS: PAH IS NOT INCREASED IN LIMITED VS DIFFUSE PATIENTS BY ADJUSTED COMPETING RISK ANALYSIS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 713. http://dx.doi.org/10.1136/annrheumdis-2020-eular.3847.
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Background:Pulmonary hypertension (PH) is a life-threatening complication of systemic sclerosis (SSc), thought to be more commonly found in limited cutaneous (lcSSc) compared to diffuse (dcSSc) subset. Since lcSSc has a better prognosis, it is unclear whether a higher occurrence of PH in lcSSc reflects survival bias.Objectives:To compare the cumulative PH incidence in disease subsets, after accounting for death as a competing event, in a large multi-center SSc cohort.Methods:Cumulative incidence of PH was studied in 1431 Canadian Scleroderma Research Group (CSRG) database patients (57% lcSSc; follow-up 3.5±2.9 years, range 1-14) by Fine-Gray analysis, unadjusted and adjusted for sex, age and SSc-related autoantibodies (SAS 9.4). Survival curves, predictors of PH development and survival were analyzed by Kaplan-Meier and Cox proportional hazards analyses (SPSS 25.0). Subgroup analysis was performed for PAH.Results:157 SSc patients had PH (including 117 PAH), either confirmed by RHC or postmortem. Compared to those without PH, lcSSc-PH patients had longer disease and older age at SSc diagnosis, while dcSSc-PH patients - more severe peripheral vascular and gastrointestinal involvement. The cumulative incidences of PH/PAH were similar in dcSSc and lcSSc after accounting for death in the adjusted competitive risk model (Table 1; Fig.1). 47% of PH- and 42% of PAH-patients died over a FU period. Male gender (p<0.0001) and anti-Scl-70 (p<0.001) were associated with earlier PH development, while older age (p=0.006) - with PAH (Table 2). ACA-negativity and older age predicted worse PH prognosis.Figure 1.Cumulative incidence curves for PH (A) and PAH (B).Conclusion:Cumulative incidence of PH, after accounting for death as competing event, was comparable in SSc subsets. Vigilance should be considered in males, Scl-70 positive and late age-onset SSc.Table 1.Sub-distribution Hazard ratio of incident PH and PAH.PHPAHHazard ratio (95% CIs)P valuesHazard ratio (95% CIs)P valuesCrude ModelDcSSc vs lcSSc2.03 (1.13, 3.66)0.01861.60 (0.82, 3.16)0.1710Adjusted modelDcSSc vs lcSSc1.82 (0.93, 3.57)0.08181.57 (0.69, 3.59)0.2812Female vs male0.98 (0.42, 2.32)0.96602.10 (0.51, 8.65)0.3040Age1.00 (0.99, 1.02)0.70411.01 (0.98, 1.03)0.5498AntibodiesACA vs negative0.95 (0.46, 1.96)0.89911.08 (0.50, 2.35)0.8391ATA vs negative1.93 (0.84, 4.42)0.11980.59 (0.13, 2.73)0.4970Anti-RNAP vs negative1.24 (0.45, 3.43)0.68411.77 (0.58, 5.44)0.3181Disclosure of Interests:Tatiana Nevskaya: None declared, Yuxuan Jiang: None declared, Mianbo Wang: None declared, Murray Baron: None declared, Janet Pope Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly & Company, Merck, Roche, Seattle Genetics, UCB, Consultant of: AbbVie, Actelion, Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eicos Sciences, Eli Lilly & Company, Emerald, Gilead Sciences, Inc., Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Speakers bureau: UCB
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Ghofrani, Faeze, Qing He, Reza Mohammadi, Abhishek Pathak, and Amjad Aref. "Bayesian Survival Approach to Analyzing the Risk of Recurrent Rail Defects." Transportation Research Record: Journal of the Transportation Research Board 2673, no. 7 (May 2, 2019): 281–93. http://dx.doi.org/10.1177/0361198119844241.
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This paper develops a Bayesian framework to explore the impact of different factors and to predict the risk of recurrence of rail defects, based upon datasets collected from a US Class I railroad between 2011 and 2016. To this end, this study constructs a parametric Weibull baseline hazard function and a proportional hazard (PH) model under a Gaussian frailty approach. The analysis is performed using Markov chain Monte Carlo simulation methods and the fit of the model is checked using a Cox–Snell residual plot. The results of the model show that the recurrence of a defect is correlated with different factors such as the type of rail defect, the location of the defect, train speed limit, the number of geometry defects in the last three years, and the weight of the rail. First, unlike the ordinary PH model in which the occurrence times of rail defects at the same location are assumed to be independent, a PH model under frailty induces the correlation between times to the recurrence of rail defects for the same segment, which is essential in the case of recurrent events. Second, considering Gaussian frailties is useful for exploring the influence of unobserved covariates in the model. Third, integrating a Bayesian framework for the parameters of the Weibull baseline hazard function as well as other parameters provides greater flexibility to the model. Fourth, the findings are useful for responsive maintenance planning, capital planning, and even preventive maintenance planning.
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Das, Prantik, James Price, Michael Jones, Cristina Martin-Fernandez, Akram Ali, Thangrarajh Mugunthan, and Chandrani Mallick. "Abiraterone acetate plus prednisone/prednisolone compared with enzalutamide in metastatic castration resistant prostate cancer before or after chemotherapy: A retrospective study of real-world data (ACES)." Journal of Clinical Oncology 37, no. 7_suppl (March 1, 2019): 303. http://dx.doi.org/10.1200/jco.2019.37.7_suppl.303.
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303 Background: Abiraterone acetate (a prodrug of abiraterone, which is a selective inhibitor of androgen biosynthesis) combined with prednisone/prednisolone (AA+P) and enzalutamide (ENZ) (an androgen-receptor–signalling inhibitor) have proven survival benefit in men with metastatic castration resistant prostate cancer (mCRPC) in chemo naïve and prior chemo patients. There have been no studies directly comparing the effectiveness of ENZ to AA+P in mCRPC patients. Methods: A retrospective, survival analysis study of 143 real world mCRPC patients (90 in AA+P and 53 in ENZ group) was conducted. Patients who started their treatment between 1st February 2012 and 31st May 2016 were included. The primary endpoint was biochemical progression free survival (PFS). Secondary end points were radiographic progression free survival (rPFS) and overall survival (OS). Data was analysed using Cox proportional hazards models, adjusting for covariates: prior radical or palliative treatment; Gleason score; baseline PSA; age; and chemo naïve or not. Results: After median follow up of 15 months (IQR 7 to 23) 112 events of biochemical progression were observed (71 in AA+P and 41 in ENZ). 41%in AA+P group and 30% patients in ENZ group received prior chemo. The chance of biochemical progression was significantly lower among ENZ patients than AA+P patients, when adjusting for all covariates in the Cox PH model (Hazard Ratio 0.54, 95% CI 0.35 to 0.82, p=0.004. There was a trend implying the chance of rPFS could be higher among ENZ patients than AA+P patients (HR 1.24, 95% CI 0.76 to 2.02, p=0.4). OS is lower among ENZ patients than AA+P patients, when adjusting for all covariates in the Cox PH model (HR 0.91, 95% CI 0.59 to 1.41, p=0.7). 38% of ENZ patients reported fatigue compared to 16% of AA+P patients while hypertension was reported slightly more in AA+P patients than in ENZ patients. Conclusions: This study showed a statistically significant difference in biochemical progression-free survival, favouring ENZ, but no significant difference in radiographic progression-free survival or overall survival.
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Udland, Carley J., William A. Carey, Amy L. Weaver, Kristin C. Mara, Reese H. Clark, and Kevin R. Ellsworth. "Birth Size and Gestational Age Specific Outcomes of Inhaled Nitric Oxide Therapy in Preterm Neonates with Clinically Diagnosed Pulmonary Hypertension." American Journal of Perinatology 36, no. 14 (January 23, 2019): 1471–80. http://dx.doi.org/10.1055/s-0039-1677799.
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Objective Among neonates of 22 to 29 weeks' gestational age (GA) who required mechanical ventilation for the treatment of respiratory distress syndrome (RDS) and clinically diagnosed pulmonary hypertension (PH), we tested our hypothesis that the association between early treatment with inhaled nitric oxide (iNO) and survival would vary according to birth size and GA. Study Design Because iNO was not randomly prescribed to patients in this cohort, we used propensity score matching to pair a neonate who received iNO at a chronological age of ≤7 days with an unexposed neonate with similar baseline characteristics. The primary outcome was inhospital mortality, which we evaluated based on size for GA and GA strata using the Cox proportional hazards regression model. Results Among 1,531 neonates who met study criteria, we created a propensity score matched cohort of 615 pairs of neonates (iNO-exposed and unexposed). The risk of inhospital mortality for iNO-exposed neonates was observed only in the minority (<10%) who were large for GA, though this finding did not persist when matching for illness severity. Conclusion Early treatment with iNO is not associated with survival in most extremely premature neonates with RDS and clinically diagnosed PH when stratified for birth size or GA.
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Lo, Chia-Lun, Ya-Hui Yang, Chien-Jen Hsu, Chun-Yu Chen, Wei-Chun Huang, Pei-Ling Tang, and Jenn-Huei Renn. "Development of a Mortality Risk Model in Elderly Hip Fracture Patients by Different Analytical Approaches." Applied Sciences 10, no. 19 (September 28, 2020): 6787. http://dx.doi.org/10.3390/app10196787.
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Hip fracture is a major health issue that accompanies community aging. The most critical time after a hip fracture should be the first year. Care systems and surgical techniques for hip fractures have improved, so the trend of mortality in elderly hip fracture could be changed with them. Therefore, we observed the changes in the trend and critical factors for first-year mortality for the hip fractures in an elderly population in Taiwan, and mortality of prognosis prediction model was developed for the early diagnosis using a population-based database in Taiwan (National Health Insurance Research Database, NHIRD). A total of 166,274 elderly subjects with an age greater than 60-years-old from 2001 to 2010 were collected for this study. Cox proportional-hazards (PH) regression and logistic regression were calculated to odds ratio and hazard ratio for mortality of those patients and compared it. Data mining algorithms were also used to generate a risk stratification prediction model. The first-year mortality rate of the overall study group was 21.5% in 2001 and 15.0% in 2010 (p for trend < 0.001). In the male subgroup, the first-year mortality rate was 29.3% in 2001 and decreased to 17.3% in 2010; the trend of standardized mortality ratio was significantly decreased from 4.4 to 2.6 (p for trend < 0.001). By logistic regression, mortality significantly increased with age and male gender. Furthermore, gender, age, patients with diabetes mellitus (DM), cardiovascular (CV), and renal comorbidity, and surgical intervention can be variables for constructing the risk stratification model. The findings of the study will be used for helping related field physicians to predict the prognosis risk of hip fracture patients, and provide evidence-based tailored treatment recommendations for those patients. It may consider to build various models for predicting the prognosis of hip fracture or integrating prediction algorithms into the computerized physician order entry system, thus creating a practical clinical decision support system with warning functions.
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KENDLER, K. S., K. SHETH, C. O. GARDNER, and C. A. PRESCOTT. "Childhood parental loss and risk for first-onset of major depression and alcohol dependence: the time-decay of risk and sex differences." Psychological Medicine 32, no. 7 (October 2002): 1187–94. http://dx.doi.org/10.1017/s0033291702006219.
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Background. Whereas a number of studies have suggested that parental loss is associated with increased risk for major depression (MD), much less is known about possible gender differences, diagnostic specificity and the time course of the impact of loss.Method. First-onsets for MD and alcohol dependence (AD) were assessed at personal interviews in 5070 twins from same-sex (SS) and 2118 from opposite-sex (OS) twin pairs ascertained from a population-based registry. Cox Proportional Hazard (PH) and Non-Proportional Hazard (NPH) models, examining first onsets of MD and AD, were used with twins from SS pairs and conditional logistic regression for OS pairs. Parent–child separations prior to age 17 were divided into death and separation from other causes.Results. The PH assumptions of constant increased risk were rejected for the impact of loss on risk for MD but not for AD. NPH models found significantly increased risk for MD after both death and separation with the risk lasting much longer for separations. For AD, the PH model found significantly increased risk after parental separation but not death. In both SS and OS twin pairs, no sex differences were seen in the impact of parental loss on risk for MD whereas the association between separation and risk for AD was significantly stronger in females than in males.Conclusion. Consistent sex differences in the association with parental loss were seen for AD but not MD. The analysis of the time-course of increased risk after loss suggests three different patterns which may reflect different relationships: parental death and MD (return to baseline within ∼12 years), separation and MD (return to baseline within ∼30 years) and separation and AD (no change in risk over time).
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Altit, Gabriel, Shazia Bhombal, Jeffrey Feinstein, Rachel K. Hopper, and Theresa A. Tacy. "Diminished right ventricular function at diagnosis of pulmonary hypertension is associated with mortality in bronchopulmonary dysplasia." Pulmonary Circulation 9, no. 3 (July 2019): 204589401987859. http://dx.doi.org/10.1177/2045894019878598.
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Pulmonary vascular disease and resultant pulmonary hypertension (PH) have been increasingly recognized in the preterm population, particularly among patients with bronchopulmonary dysplasia (BPD). Limited data exist on the impact of PH severity and right ventricular (RV) dysfunction at PH diagnosis on outcome. The purpose of this study was to evaluate if echocardiography measures of cardiac dysfunction and PH severity in BPD-PH were associated with mortality. The study is a retrospective analysis of the echocardiography at three months or less from time of PH diagnosis. Survival analysis using a univariate Cox proportional hazard model is presented and expressed using hazard ratios (HR). We included 52 patients with BPD and PH of which 16 (31%) died at follow-up. Average gestational age at birth was 26.3 ± 2.3 weeks. Echocardiography was performed at a median of 43.3 weeks (IQR: 39.0–54.7). The median time between PH diagnosis and death was 117 days (range: 49–262 days). Multiple measures of PH severity and RV performance were associated with mortality (sPAP/sBP: HR 1.02, eccentricity index: HR 2.02, tricuspid annular plane systolic excursion Z-score: HR 0.65, fractional area change: HR 0.88, peak longitudinal strain: HR 1.22). Hence, PH severity and underlying RV dysfunction at PH diagnosis were associated with mortality in BPD-PH patients. While absolute estimation of pulmonary pressures is not feasible in every screening echocardiography, thorough evaluation of RV function and other markers of PH may allow to discriminate the most at-risk population and should be considered as standard add-ons to the current screening at 36 weeks.
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Sharaf, Taysseer, and Chris P. Tsokos. "Two Artificial Neural Networks for Modeling Discrete Survival Time of Censored Data." Advances in Artificial Intelligence 2015 (March 15, 2015): 1–7. http://dx.doi.org/10.1155/2015/270165.
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Artificial neural network (ANN) theory is emerging as an alternative to conventional statistical methods in modeling nonlinear functions. The popular Cox proportional hazard model falls short in modeling survival data with nonlinear behaviors. ANN is a good alternative to the Cox PH as the proportionality of the hazard assumption and model relaxations are not required. In addition, ANN possesses a powerful capability of handling complex nonlinear relations within the risk factors associated with survival time. In this study, we present a comprehensive comparison of two different approaches of utilizing ANN in modeling smooth conditional hazard probability function. We use real melanoma cancer data to illustrate the usefulness of the proposed ANN methods. We report some significant results in comparing the survival time of male and female melanoma patients.
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Cheng, Chun-Gu, Wu-Chien Chien, Chia-Peng Yu, Chi-Hsiang Chung, and Chun-An Cheng. "Association between Reflux Esophagitis Incidence and Palmar Hyperhidrosis." International Journal of Environmental Research and Public Health 17, no. 12 (June 23, 2020): 4502. http://dx.doi.org/10.3390/ijerph17124502.
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The autonomic dysfunction in palmar hyperhidrosis (PH) includes not only sympathetic overactivity but also parasympathetic impairment. A decrease of parasympathetic tone has been noted in gastroesophageal reflux disease of neonates and adults. Patients with reflux esophagitis have a defective anti-reflux barrier. The association between reflux esophagitis and PH is deliberated in this article. The National Health Insurance Database in Taiwan was used. At first-time visits, PH patients were identified by the International Classification of Disease, 9th Revision, Clinical Modification disease code of 780.8 without endoscopic thoracic sympathectomy. Patients were matched by age and gender as control groups. The reflux esophagitis incidence was assessed using disease codes 530.11, 530.81, and 530.85. The factors related to reflux esophagitis were established by the Cox proportional regression model. The risk of reflux esophagitis in PH patients had a hazard ratio of 3.457 (95% confidence interval: 3.043–3.928) after adjustment of the other factors. We confirmed the association between reflux esophagitis and PH. Health care providers must be alerted to this relationship and other risk factors of reflux esophagitis to support suitable treatments to improve the quality of life of patients.
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Hassan, M. Kabir, Jennifer Brodmann, Blake Rayfield, and Makeen Huda. "Modeling credit risk in credit unions using survival analysis." International Journal of Bank Marketing 36, no. 3 (May 8, 2018): 482–95. http://dx.doi.org/10.1108/ijbm-05-2017-0091.
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Purpose The purpose of this paper is to investigate proprietary data from customers of a Southern Louisiana credit union. It analyzes the factors that contribute to an accelerated failure time (AFT) using information from customers’ credit applications as well as information provided in their credit report. Design/methodology/approach This paper investigates the factors that affect credit risk using survival analysis by employing two primary models – the AFT model and the Cox proportional hazard (PH) model. While several studies employ the Cox PH model, few use the AFT model. However, this paper concludes that the AFT model has superior predictive qualities. Findings This paper finds that the factors specific to borrowers and local factors play an important role in the duration of a loan. Practical implications This paper offers an easily interpretable model for determining the duration of a potential borrower. The marketing department of credit unions can then use this information to predict when a customer will default, thus allowing the credit union to intervene in a timely manner to prevent defaults. Further, the credit union can use this information to seek out customers who are less likely to default. Originality/value This study is different from the previous research due to its focus on credit unions, which have distinct characteristics. Compared to similar lending institutions, the charter of the credit union does not allow management to sell off loans to other investors.
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Chuang, Li-Yeh, Guang-Yu Chen, Sin-Hua Moi, Fu Ou-Yang, Ming-Feng Hou, and Cheng-Hong Yang. "Relationship between Clinicopathologic Variables in Breast Cancer Overall Survival Using Biogeography-Based Optimization Algorithm." BioMed Research International 2019 (April 1, 2019): 1–12. http://dx.doi.org/10.1155/2019/2304128.
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Breast cancer is the most common cancer among women and is considered a major public health concern worldwide. Biogeography-based optimization (BBO) is a novel metaheuristic algorithm. This study analyzed the relationship between the clinicopathologic variables of breast cancer using Cox proportional hazard (PH) regression on the basis of the BBO algorithm. The dataset is prospectively maintained by the Division of Breast Surgery at Kaohsiung Medical University Hospital. A total of 1896 patients with breast cancer were included and tracked from 2005 to 2017. Fifteen general breast cancer clinicopathologic variables were collected. We used the BBO algorithm to select the clinicopathologic variables that could potentially contribute to predicting breast cancer prognosis. Subsequently, Cox PH regression analysis was used to demonstrate the association between overall survival and the selected clinicopathologic variables. C-statistics were used to test predictive accuracy and the concordance of various survival models. The BBO-selected clinicopathologic variables model obtained the highest C-statistic value (80%) for predicting the overall survival of patients with breast cancer. The selected clinicopathologic variables included tumor size (hazard ratio [HR] 2.372, p = 0.006), lymph node metastasis (HR 1.301, p = 0.038), lymphovascular invasion (HR 1.606, p = 0.096), perineural invasion (HR 1.546, p = 0.168), dermal invasion (HR 1.548, p = 0.028), total mastectomy (HR 1.633, p = 0.092), without hormone therapy (HR 2.178, p = 0.003), and without chemotherapy (HR 1.234, p = 0.491). This number was the minimum number of discriminators required for optimal discrimination in the breast cancer overall survival model with acceptable prediction ability. Therefore, on the basis of the clinicopathologic variables, the survival prediction model in this study could contribute to breast cancer follow-up and management.
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Lee, MinJae, Mohammad H. Rahbar, and Hooshang Talebi. "A nonparametric method for assessment of interactions in a median regression model for analyzing right censored data." Statistical Methods in Medical Research 28, no. 4 (January 9, 2018): 1170–87. http://dx.doi.org/10.1177/0962280217751518.
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We propose a nonparametric test for interactions when we are concerned with investigation of the simultaneous effects of two or more factors in a median regression model with right censored survival data. Our approach is developed to detect interaction in special situations, when the covariates have a finite number of levels with a limited number of observations in each level, and it allows varying levels of variance and censorship at different levels of the covariates. Through simulation studies, we compare the power of detecting an interaction between the study group variable and a covariate using our proposed procedure with that of the Cox Proportional Hazard (PH) model and censored quantile regression model. We also assess the impact of censoring rate and type on the standard error of the estimators of parameters. Finally, we illustrate application of our proposed method to real life data from Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study to test an interaction effect between type of injury and study sites using median time for a trauma patient to receive three units of red blood cells. The results from simulation studies indicate that our procedure performs better than both Cox PH model and censored quantile regression model based on statistical power for detecting the interaction, especially when the number of observations is small. It is also relatively less sensitive to censoring rates or even the presence of conditionally independent censoring that is conditional on the levels of covariates.
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Nater, A., LA Tetreault, B. Kopjar, PM Arnold, MB Dekutoski, JA Finkelstein, CG Fisher, et al. "C.02 Predictors of survival in a surgical series of Metastatic Spinal Cord Compression and a complete external validation of 8 models in a prospective multi-centre study." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 45, s2 (June 2018): S14. http://dx.doi.org/10.1017/cjn.2018.97.
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Background: We aimed to identify preoperative predictors of survival in Metastatic Epidural Spinal Cord Compression (MESCC) patients surgically treated, examine how these predictors relate to eight prognostic models, and to perform the first full external validation of these models in accordance with the TRIPOD statement. Methods: 142 surgically treated MESCC patients were enrolled in a prospective, multicenter cohort study and followed for 12 months or until death. Cox proportional hazards (PH) regressions were used. Non-collinear predictors with <10% missing data, ≥10 events per stratum and p<0.05 in univariable analysis were tested through a backward stepwise selection. For the original and revised Tokuhashi, Tomita, modified Bauer, van der Linden, Bartels, OSRI, Bartels and Bollen, we examined calibration and discrimination; survival stratified by risk groups with the Kaplan-Meier method and log-rank test. Results: Primary tumor, organ metastasis and SF-36v2 PC were associated with survival in multivariable analysis; corrected discrimination was 0.68. These three predictors were common to most current prognostic models. However, calibration was poor overall while discrimation was possibly helpful. Conclusions: Primary tumor type (breast, prostate and thyroid), absence of organ metastasis, and a lower degree of physical disability are preoperative predictors of longer survival in surgical MESCC patients. Clinicians should use these 8 prognostic models with caution.
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Cullen, Jennifer, Yongmei Chen, Huai-Ching Kuo, Kevin R. Rice, Inger L. Rosner, and Jonathan Forsberg. "Modeling time from bone metastasis to death in a racially diverse cohort of military health care beneficiaries." Journal of Clinical Oncology 37, no. 7_suppl (March 1, 2019): 246. http://dx.doi.org/10.1200/jco.2019.37.7_suppl.246.
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246 Background: Development of prostate cancer (PCa) metastasis, while uncommonly observed in US men, typically occurs to bone and ultimately leads to disease-specific death. The goal of this study was to estimate OS in a racially diverse cohort of military health care beneficiaries diagnosed with metastatic PCa to bone, to enhance understanding of factors such as patient race and receipt of palliative treatment, that potentially affect OS in advanced PCa patients. Methods: A retrospective cohort study was conducted, examining men consented to participate in the CPDR multi-center national database who underwent biopsy for suspicion of prostate cancer between 1989-2017 and subsequently diagnosed with bone metastasis, confirmed by bone scan, bone biopsy and/or MRI. Multivariable Cox proportional hazards (PH) analysis was used to model OS as a function of race and palliative treatment, controlling for clinical covariates. Hazard ratios (HR) and 95% Confidence intervals (CI) are reported. Results: Among 17,356 patients diagnosed with prostate cancer (PCa) between 1989 and 2017, 869 (5.0%) developed bone metastasis. Median patient age was 67 years; median follow-up time following diagnosis with bone metastasis was 2.4 years. Over one-fifth of patients (22.5%) self-reported as African American. Only 11.5% of all patients with metastasis received palliative treatment (radiation (RT) only, RT+ hormone therapy (HT), RT+HT, or RT+HT+chemotherapy). While race did not predict OS, receipt of palliative treatment was strongly predictive of better OS (p<0.0005). Conclusions: Patient race did not predict OS among those with distant metastatic PCa but receipt of palliative care and slower PSADT were critical factors in lengthening OS. This work is being extended to examine the combinations and sequencing of palliative care on OS, to provide improved patient-tailored prediction tools for men with advanced prostate cancer. [Table: see text]
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Lu-Yao, Grace L., William Kevin Kelly, and Andrew E. Chapman. "Advanced age and prostate cancer specific mortality among geriatric patients with metastatic prostate cancer." Journal of Clinical Oncology 36, no. 6_suppl (February 20, 2018): 319. http://dx.doi.org/10.1200/jco.2018.36.6_suppl.319.
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319 Background: Data from clinical trials has shown that octogenarians are at increased risk for prostate cancer specific mortality (PCSM). Patients with significant comorbidities were excluded from the trials; consequently, the findings from clinical trials may not be applicable to the general population. Data on patients age 80+ with metastatic prostate cancer in the general population are limited. This population-based study assesses PCSM for metastatic prostate cancer patients diagnosed at age 70+. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, identified 418,982 patients diagnosed with prostate cancer at age 70+ between 01/01/2004-12/31/13, of which 12,749 had metastatic prostate cancer. The SEER database covers about 28% of the US population from all racial/ethnic groups. We used Cox proportional hazards (PH) model to calculate cause specific hazard ratio adjusted by age, race, marital status, urban-rural classification, income level, insurance type, primary cancer therapy, stage, and diagnosis period. Results: Of the 12,749 patients, 49.4% of the patients were in their 70's and 8.3% in their 90's+, with 79.1% of patients white and 57.1% married. About 17% of these patients received radiotherapy as their primary cancer treatment. The distribution of M1 subtype is: M1a (4.2%), M1b (68.5%), M1c (22.7%), M1 Not Otherwise Specified (or NOS,4.6%). The median survival for patients with M1 prostate cancer aged 70-79, 80-89 and 90+ were 25, 15, and 7 months, respectively. Compared to patients diagnosed in their 70's, there was 38% and 109% increase in PCSM among those diagnosed at ages 80-89 and 90+ respectively (Table). Conclusions: PCSM increases among geriatric patients with metastatic prostate cancer after accounting for potential confounding factors. Further investigation is needed to shed light on the underlying biological mechanisms. [Table: see text]
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Nicolini, Franck E., Giovanni Martinelli, Dong-Wook Kim, Andreas Hochhaus, Michael J. Mauro, Jorge Cortes, Charles Chuah, et al. "Epidemiological Study on Survival of Chronic Myeloid Leukemia (CML) and Ph+ Acute Lymphoblastic Leukemia (ALL) Patients with T315I Mutation. Final Analysis." Blood 112, no. 11 (November 16, 2008): 188. http://dx.doi.org/10.1182/blood.v112.11.188.188.
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Abstract The BCR-ABL T315I mutation is one of the major mechanisms of resistance to tyrosine kinase inhibitors (TKIs). Limited data have suggested that patients harboring a T315I mutation have poor outcomes. The objectives of this study were to estimate overall (OS) and progression-free survival (PFS) for CML in chronic (CP), accelerated (AP), or blastic (BP) phase, and Ph+ ALL patients who developed a T315I mutation; and describe the treatment pattern after T315I detection. Methods: This was a retrospective, multicenter observational study. Eligible patients included CML and Ph+ ALL patients who developed T315I mutation between 1999 and 2008. The medical records of 222 patients from 9 countries (France, Italy, Korea, USA, Germany, Singapore, Denmark, UK and Japan) were abstracted, and Kaplan-Meier plots and Cox proportional hazard models were used for survival analysis. Results: Median age at T315I detection was 54 (range, 18–84) years; 57% were male; 75% were Caucasian and 22% were Asian. Before T315I detection, 97% patients received imatinib (25% as a 1st line) and 50% received second generation TKIs. 16% of patients had other mutations detected before T315I detection. The median time between TKI treatment start and T315I detection was 29 months for CP, 15 for AP, 6 for BP, and 9 for Ph+ ALL. After T315I detection, 56% patients received second generation TKIs (30% started after T315I detection), 39% received hydroxyurea (33% started after T315I detection), 35% received imatinib (13% started after T315I detection), 26% received cytarabine, 21% received investigational drugs including 11% MK-0457, 17% underwent stem cell transplantation, and 6% received interferon alpha (5% started after T315I detection). At the time of T315I detection, T315I formed the predominant clone in 87% of patients; 23% had additional mutations detected (11% of these P-loop mutations). OS and PFS from T315I mutation detection are summarized in Table 1. In a preliminary analysis, the following covariates were associated with worse OS in Cox proportional hazard model (adjusted hazard ratio, 95% confidence interval): older age (by median, 2.30, 1.04–5.09) in Ph+ ALL patients, female gender in BP (1.73, 0.96–3.10); worse performance status in Ph+ ALL (1+ vs. 0; 2.18, 1.02–4.68); and detection of T315I by direct sequencing (vs. other methods) in AP (3.03, 0.89–10.29) and Ph+ ALL (2.33, 1.06–5.12). The effect of different treatments on OS will be available at the time of presentation. Conclusion: These results confirm that survival of patients harboring a T315I mutation is dependent on the disease phase at T315I detection. No clear treatment pattern after T315I detection was observed. Age, gender, performance status, and techniques used for T315I detection might be important prognosis factors affecting OS across different phases of CML and Ph+ ALL. Table 1. OS and PFS of CML and Ph+ ALL patients from T315I detection CML CP (N=82) CML AP (N=38) CML BP (N=56) Ph+ ALL (N=46) * Median survival and survival rates were calculated using Kaplan-Meier method. Median follow up time (months) 12.4 15.2 3.0 3.6 Median OS (months) (95% CI) 22.4 (18.2, 48.5) 28.4 (15.9, 49.8) 4.0 (2.0, 5.0) 4.9 (3.4, 7.3) 1-year OS Rate (95% CI) 71% (58–80%) 69% (50–81%) 23% (13–36%) 12% (3–27%) Median PFS (months) (95% CI) 11.5 (9.2, 15.7) 22.2 (9.0, N/A ) 1.8 (1.2, 4.0) 2.5 (1.8, 3.6) 1-year PFS Rate (95% CI) 46% (34–57%) 56% (38–70%) 16% (7–27%) 7% (1–19%)
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Takeda, Tsuyoshi, Takashi Sasaki, Takafumi Mie, Takaaki Furukawa, Ryo Kanata, Akiyoshi Kasuga, Masato Matsuyama, Masato Ozaka, and Naoki Sasahira. "Comparison of clinicopathological characteristics and prognosis of borderline resectable pancreatic cancer according to the location of the primary tumor." Journal of Clinical Oncology 38, no. 4_suppl (February 1, 2020): 662. http://dx.doi.org/10.1200/jco.2020.38.4_suppl.662.
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662 Background: Little is known about the clinicopathological and prognostic differences between borderline resectable (BR) pancreatic head (Ph) and pancreatic body/tail (Pbt) cancer. Therefore, we conducted this study to compare the clinicopathological features and prognosis of BR pancreatic cancer (PC) according to the location of the primary tumor. Methods: We retrospectively investigated consecutive patients with BR PC who initiated neoadjuvant chemotherapy (NAC) between March 2015 and April 2019. We compared clinicopathological characteristics and prognosis between Ph and Pbt cancer. Furthermore, multivariate survival analysis was performed using cox proportional hazard model. Results: A total of 104 patients with BR PC (median age 68, male 49%) were included in this study. The location of the tumor was Ph 72 and Pbt 32, respectively. The initial regimen of NAC was nab-paclitaxel/gemcitabine in 102 and gemcitabine in 2, respectively. The median cycle of NAC was 4. Median age, sex, primary tumor size, performance status, neutrophil to lymphocyte ratio, and serum level of carbohydrate antigen 19-9 at the time of the initiation of NAC were not significantly different between Ph and Pbt cancer, while the modified glasgow prognostic score (mGPS) was lower in Pbt cancer (mGPS = 0; 78% vs. 94%, p = 0.05). R0/R1 resection rate (81% vs. 69%, p = 0.21) and median survival time (928 days vs. NA, p = 0.13) were also not different between Ph and Pbt cancer. Multivariate survival analysis revealed that R0/R1 resection (HR, 0.11; p < 0.01) and Ph (HR, 2.29; p = 0.03) were independent prognostic factors for survival in patients with BR PC. Conclusions: Although R0/R1 resection rate was similar between BR Ph and Pbt cancer, Pbt cancer had a higher rate of mGPS score of 0 compared to Ph cancer. Furthermore, R0/R1 resection (HR, 0.11) and Ph (HR, 2.29) were independent prognostic factors for survival in patients with BR PC.