Change point detection in Cox proportional hazards mixture cure model

2020 ◽  
pp. 096228022095911
Author(s):  
Bing Wang ◽  
Jialiang Li ◽  
Xiaoguang Wang
Keyword(s):  
Survival Data ◽  
Change Point ◽  
Proportional Hazards ◽  
Test Procedure ◽  
Cox Proportional Hazards ◽  
Change Point Detection ◽  
Parameter Estimates ◽  
Finite Sample ◽  
Cure Model ◽  
Mixture Cure Model

The mixture cure model has been widely applied to survival data in which a fraction of the observations never experience the event of interest, despite long-term follow-up. In this paper, we study the Cox proportional hazards mixture cure model where the covariate effects on the distribution of uncured subjects’ failure time may jump when a covariate exceeds a change point. The nonparametric maximum likelihood estimation is used to obtain the semiparametric estimates. We employ a two-step computational procedure involving the Expectation-Maximization algorithm to implement the estimation. The consistency, convergence rate and asymptotic distributions of the estimators are carefully established under technical conditions and we show that the change point estimator is n consistency. The m out of n bootstrap and the Louis algorithm are used to obtain the standard errors of the estimated change point and other regression parameter estimates, respectively. We also contribute a test procedure to check the existence of the change point. The finite sample performance of the proposed method is demonstrated via simulation studies and real data examples.

scholarly journals 1388. Dose Discrimination for ASN100: Bridging from Rabbit Survival Data to Predicted Activity in Humans Using a Minimal Physiologically Based Pharmacokinetic (mPBPK) Model

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S426-S426
Author(s):  
Christopher M Rubino ◽  
Lukas Stulik ◽  
Harald Rouha ◽  
Zehra Visram ◽  
Adriana Badarau ◽  
...  
Keyword(s):  
Survival Data ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Model ◽  
Virulent Strain ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Simulated Patients ◽  
Research Support ◽  
Mpbpk Model

Abstract Background ASN100 is a combination of two co-administered fully human monoclonal antibodies (mAbs), ASN-1 and ASN-2, that together neutralize the six cytotoxins critical to S. aureus pneumonia pathogenesis. ASN100 is in development for prevention of S. aureus pneumonia in mechanically ventilated patients. A pharmacometric approach to dose discrimination in humans was taken in order to bridge from dose-ranging, survival studies in rabbits to anticipated human exposures using a mPBPK model derived from data from rabbits (infected and noninfected) and noninfected humans [IDWeek 2017, Poster 1849]. Survival in rabbits was assumed to be indicative of a protective effect through ASN100 neutralization of S. aureus toxins. Methods Data from studies in rabbits (placebo through 20 mg/kg single doses of ASN100, four strains representing MRSA and MSSA isolates with different toxin profiles) were pooled with data from a PK and efficacy study in infected rabbits (placebo and 40 mg/kg ASN100) [IDWeek 2017, Poster 1844]. A Cox proportional hazards model was used to relate survival to both strain and mAb exposure. Monte Carlo simulation was then applied to generate ASN100 exposures for simulated patients given a range of ASN100 doses and infection with each strain (n = 500 per scenario) using a mPBPK model. Using the Cox model, the probability of full protection from toxins (i.e., predicted survival) was estimated for each simulated patient. Results Cox models showed that survival in rabbits is dependent on both strain and ASN100 exposure in lung epithelial lining fluid (ELF). At human doses simulated (360–10,000 mg of ASN100), full or substantial protection is expected for all four strains tested. For the most virulent strain tested in the rabbit pneumonia study (a PVL-negative MSSA, Figure 1), the clinical dose of 3,600 mg of ASN100 provides substantially higher predicted effect relative to lower doses, while doses above 3,600 mg are not predicted to provide significant additional protection. Conclusion A pharmacometric approach allowed for the translation of rabbit survival data to infected patients as well as discrimination of potential clinical doses. These results support the ASN100 dose of 3,600 mg currently being evaluated in a Phase 2 S. aureus pneumonia prevention trial. Disclosures C. M. Rubino, Arsanis, Inc.: Research Contractor, Research support. L. Stulik, Arsanis Biosciences GmbH: Employee, Salary. H. Rouha, 3Arsanis Biosciences GmbH: Employee, Salary. Z. Visram, Arsanis Biosciences GmbH: Employee, Salary. A. Badarau, Arsanis Biosciences GmbH: Employee, Salary. S. A. Van Wart, Arsanis, Inc.: Research Contractor, Research support. P. G. Ambrose, Arsanis, Inc.: Research Contractor, Research support. M. M. Goodwin, Arsanis, Inc.: Employee, Salary. E. Nagy, Arsanis Biosciences GmbH: Employee, Salary.

P1810 Impact of pulmonary hypertension on survival in patients with degenerative aortic stenosis, prospective clinical trial

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
D Mercea ◽  
R Ianos ◽  
C Pop ◽  
D Pop ◽  
D Zdrenghea ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Survival Rate ◽  
Aortic Stenosis ◽  
Survival Data ◽  
Proportional Hazards ◽  
Negative Impact ◽  
Severe Aortic Stenosis ◽  
Cox Proportional Hazards ◽  
Logrank Test ◽  
Pulmonary Pressure

Abstract Introduction Aortic stenosis has become the most common degenerative valvular heart disease, due to aging of the population. It represents 43% of degenerative valvular disease. Methods We prospectively followed 196 patients with degenerative aortic stenosis, for a period of 6 years. Of these, 106 had mild aortic stenosis, 28 had moderate aortic stenosis and 62 patients had severe aortic stenosis. Of the 196 patients, 54 had mild pulmonary hypertension (PH), 22 had moderate PH and 7 had severe PH. The survival data were estimated by the Kaplan - Meier method and the logrank test. The Cox proportional- hazards regression was performed to assess the differences between the groups. Results During the follow-up period, of a total of 196 patients, 61 patients died. We studied if the presence of PH has an influence on survival in patients with aortic stenosis and we found out that the patients who had PH had reduced survival rates, compared with those who hadn"t. The survival rate at 5 years was lower in the group with mild PH compared with the group with normal pulmonary pressure ( p = 0.045, HR 1.84, 95%CI 1.01-3.36). In the group with mild PH, 20 patients (37.03%) died at 5 years, compared with 23 in the group without PH (20.35%). The survival rate at 5 years was also lower in the group with moderate PH compared with the group with normal pulmonary pressure ( p = 0.001, HR 5.82, 95% CI 3.02-11.22). At 5 years, 15 patients with moderate PH died ( 68.18% compared with 20.35 in the group without PH). Comparing the group with severe PH with the group with normal pulmonary pressure the results showed a reduced survival rate in those with severe pulmonary hypertension ( p = 0.139, HR 2.48, 95% CI 0.74-8.27). At 5 years, 3 patients with severe PH died (42.85% compared with 20.35 in the group without PH). Conclusion The presence of PH in patients with degenerative aortic stenosis has a negative impact on survival, highly statistically significant (p <0.001, HR 1.03, 95% CI, 1.02-1.04). Given these findings, perhaps an increased attention should be paid to the treatment of the patients with PH compared to those without PH.

Effect of HPV Status on Survival of Oropharynx Cancer with Distant Metastasis

2020 ◽  
Vol 163 (2) ◽  
pp. 372-374 ◽  
Author(s):  
Adam W. Kaplon ◽  
Thomas J. Galloway ◽  
Mihir K. Bhayani ◽  
Jeffrey C. Liu
Keyword(s):  
Distant Metastasis ◽  
Survival Data ◽  
Regression Models ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
National Cancer Database ◽  
Proportional Hazards Regression ◽  
Kaplan Meier ◽  
Hpv Status ◽  
Oropharynx Squamous Cell Carcinoma

Human papillomavirus (HPV)–positive oropharynx squamous cell carcinoma (OPSCC) is known to have improved survival over HPV-negative disease. However, it is largely unknown whether HPV status similarly affects survival in patients presenting with distant metastatic disease. We queried the National Cancer Database for OPSCC with distant metastasis. Kaplan-Meier curves and Cox proportional hazards regression models controlling for relevant demographics were used to evaluate overall survival. In total, 768 OPSCC cases were available for analysis with HPV and survival data: 50% of cases were HPV negative and 50% were HPV positive. The 1- and 2-year survival for HPV-negative disease was 49% and 27%, respectively, as compared with 67% and 42% in the HPV-positive cohort. HPV positivity was associated with improved median survival in treated and untreated patients. Age, comorbidities, and HPV status were predictive of improved survival on multivariate analysis. HPV-positive OPSCC has improved survival in the setting of distant metastatic presentation as compared with HPV-negative disease and shows greater responsiveness to treatment.

scholarly journals High SALM3 Expression in Tumor Cells and Fibroblasts Is Correlated with Poor Prognosis in Gastric Cancer Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Ying Liu ◽  
Xiaoli Chen ◽  
Xi Chen ◽  
Xiaobing Yang ◽  
Qingjie Song ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prognostic Factor ◽  
Tumor Cells ◽  
Survival Data ◽  
Proportional Hazards ◽  
Synapse Formation ◽  
Tissue Microarrays ◽  
Cox Proportional Hazards ◽  
Kaplan Meier ◽  
Kaplan Meier Plotter

Objective. The synaptic adhesion-like molecule (SALM) family is largely restricted to neural tissues and is involved in the regulation of neurite outgrowth and synapse formation. However, the expression of SALM3 in gastric cancer (GC) and its clinical significance remain unclear. The aim of the present study was to investigate the prognostic value of SALM3 in patients with GC.Patients and Methods. Expression of SALM3 was validated by tissue microarrays from 730 GC patients and statistically assessed for correlations with the clinical parameters and the prognosis of the patients. The transcriptional and survival data of SALM3 in GC patients were also mined through the Oncomine and Kaplan-Meier Plotter databases.Results. SALM3 is overexpressed in the tumor cells and fibroblasts of clinical GC tissues, and a high level of SALM3 was significantly associated with tumor invasive characteristics. Cox proportional hazards univariate and multivariate regression analyses revealed SALM3 expression in tumor cells or stroma as an independent prognostic factor in the overall survival rate of GC patients. Furthermore, the survival of GC patients with high SALM3 expression in both tumor cells and fibroblasts was significantly poorer than that of the other groups. Oncomine and Kaplan-Meier Plotter analyses further confirmed high levels of SALM3 expression in GC, and high levels of SALM3 expression were associated with shorter survival in patients.Conclusion. SALM3 may be a prognostic factor for GC and may potentially be a high-priority therapeutic target.

Depressive Symptoms

2016 ◽  
Vol 39 (4) ◽  
pp. 539-552
Author(s):  
Muna H. Hammash ◽  
Terry A. Lennie ◽  
Timothy Crawford ◽  
Seongkum Heo ◽  
Misook L. Chung ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Survival Data ◽  
Proportional Hazards ◽  
Heart Association ◽  
Cox Proportional Hazards ◽  
Health Perceptions ◽  
Class Iii ◽  
Event Free Survival ◽  
Free Survival ◽  
The Relationship

Depressive symptoms and poor health perceptions are predictors of higher hospitalization and mortality rates (heart failure [HF]). However, the association between depressive symptoms and health perceptions as they affect event-free survival outcomes in patients with HF has not been studied. The purpose of this secondary analysis was to determine whether depressive symptoms mediate the relationship between health perceptions and event-free survival in patients with HF. A total of 458 HF patients (61.6 ± 12 years, 55% New York Heart Association Class III/IV) responded to one-item health perception question and completed the Patient Health Questionnaire–9. Event-free survival data were collected for up to 4 years. Multiple regression and Cox proportional hazards regression analysis showed that depressive symptoms mediated the relationship between health perceptions and event-free survival. Decreasing depressive symptoms is essential to improve event-free survival in patients with HF.

scholarly journals Application of Modified Generalized–Gamma Mixture Cure Model in the Analysis of Ovarian Cancer Data

2021 ◽  
Vol 2123 (1) ◽  
pp. 012041
Author(s):  
Serifat A. Folorunso ◽  
Timothy A.O. Oluwasola ◽  
Angela U. Chukwu ◽  
Akintunde A. Odukogbe
Keyword(s):  
Ovarian Cancer ◽  
Survival Data ◽  
Information Criterion ◽  
Cure Model ◽  
Modeling And Analysis ◽  
Cancer Data ◽  
Mixture Cure Model ◽  
Generalized Gamma ◽  
Ovarian Cancer Data ◽  
Cure Models

Abstract The modeling and analysis of lifetime for terminal diseases such as cancer is a significant aspect of statistical work. This study considered data from thirty-seven women diagnosed with Ovarian Cancer and hospitalized for care at theDepartment of Obstetrics and Gynecology, University of Ibadan, Nigeria. Focus was on the application of a parametric mixture cure model that can handle skewness associated with survival data – a modified generalized-gamma mixture cure model (MGGMCM). The effectiveness of MGGMCM was compared with existing parametric mixture cure models using Akaike Information Criterion, median time-to-cure and variance of the cure rate. It was observed that the MGGMCM is an improved parametric model for the mixture cure model.

scholarly journals Assessment of preparation time and 1-year Invisalign aligner attachment survival using flowable and packable composites:

2021 ◽  
Author(s):  
Shuang Lin ◽  
Ling Huang ◽  
Jialing Li ◽  
Juan Wen ◽  
Li Mei ◽  
...  
Keyword(s):  
Survival Data ◽  
Tooth Extraction ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Secondary Outcome ◽  
Preparation Time ◽  
Cox Models ◽  
Significant Difference

ABSTRACT Objectives To compare preparation time and 1-year Invisalign aligner attachment survival between a flowable composite (FC) and a packable composite (PC). Materials and Methods Fifty-five participants (13 men and 42 women, mean age ± SD: 24.2 ± 5.9 years) were included in the study. Ipsilateral quadrants (ie, maxillary and mandibular right, or vice versa) of attachments were randomly assigned to the FC group (Filtek Z350XT Flowable Restorative) and the PC group (Filtek Z350XT Universal Restorative) by tossing a coin. The primary outcome was preparation time. The secondary outcome was time to the first damage of an attachment. Preparation times were compared using the paired t-test, and the survival data were analyzed by the Cox proportional hazards model with a shared frailty term, with α = .05. Results The preparation times were significantly shorter with the FC (6.22 ± 0.22 seconds per attachment) than with the PC (32.83 ± 2.16 seconds per attachment; P < .001). The attachment damage rates were 14.79% for the FC and 9.70% for the PC. According to the Cox models, attachment damage was not significantly affected by the attachment material, sex, arch, tooth location, attachment type, presence of overbite, or occurrence of tooth extraction. Conclusions The use of a FC may save time as compared with the use of a PC. With regard to attachment survival, there was no significant difference between the two composites. None of the covariates of attachment materials (sex, arch, tooth location, attachment type, presence of overbite, oir occurrence of tooth extraction) affected attachment damage.

A retrospective analysis of all non-AIDS defining cancers (NADC): A subset analysis of the County Hospital AIDS Malignancy Project (CHAMP).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1611-1611
Author(s):  
Shweta Gupta ◽  
Prantesh Jain ◽  
Emilio Araujo Mino ◽  
Audrey L. French ◽  
Fred R Rosen ◽  
...  
Keyword(s):  
Inner City ◽  
Survival Data ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Cd4 Count ◽  
County Hospital ◽  
Male Population ◽  
Poorly Differentiated

1611 Background: County Hospital (CCH) with its HIV clinic, the CORE Center (CC) is the largest provider for HIV patients (pts) in Chicago, treating over 5,500 HIV pts yearly. There is paucity of data on characteristics of HIV+ cancers (ca) in the inner city. The CHAMP cohort is a retrospective study of all HIV associated cancers at CC and CCH over past 14 years (yrs). We analyzed all of the NADC from this cohort. Methods: All HIV pts with NADC were identified from the CHAMP cohort and retrospectively reviewed for HIV and cancer characteristics, overall survival (OS), and pt demographics. Statistics: Survival data was analyzed using Kaplan-Meier analysis and Cox Proportional Hazards model. Results: Of 438 pts identified, 157 were NADC representing 21 ca. The average (ave) age was 48 yrs (range 44-57), with prostate ca having highest age presentation. Over the past 10 yrs, the number of NADC has risen from 10 to over 20 each yr. Unlike historical controls (HC) where lung ca is most common, anal ca (21%) was most frequent followed by lung ca (17%). Prostate, head and neck (HNSCC), liver, and colorectal ca were seen in 9, 9, 8, and 7% respectively. 65% of pts were African Americans (AA) and 18% Caucasians. 78% of all NADC were men. 45% of anal ca present with stage IIIa/b disease, moderately to poorly differentiated ca in 48%, with a median OS of 34 mo. CD4 count did not alter OS but stage predicted better outcomes. 86% lung ca presented as stage III/IV disease with ave CD4 count 204. Histologically, 36% were SCC, 28% adenosquamous and 20% adenocarcinoma. OS was 5.5 mo and did not change by histology, CD4, or age. 68% HNSCC present with stage IVa/b but no IVc. Ave age was 48 yrs with an OS of 18mo. 50% were oropharyngeal compared to 22% in HC. Conclusions: Based on data by Sheilds et. al, CCH treats just over 1% of the country’s NADC population. We demonstrate a higher incidence of NADC over time, dominated by a younger, AA and male population. Each ca presents with advanced stage 45-86% and poorly differentiated tumors ranging from 15-30%. The OS of each cancer is consistent with HC with exception of HNSCC. As HIV pts age becoming prone to cancers of elderly, education and screening of inner city HIV pts will help improve cancer rates.

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