scholarly journals An online updating approach for testing the proportional hazards assumption with streams of survival data

Biometrics ◽  
2019 ◽  
Vol 76 (1) ◽  
pp. 171-182 ◽  
Author(s):  
Yishu Xue ◽  
HaiYing Wang ◽  
Jun Yan ◽  
Elizabeth D. Schifano
Keyword(s):  
Survival Data ◽  
Proportional Hazards ◽  
Proportional Hazards Assumption

Reporting of Multivariable Methods in the Medical Literature

2008 ◽  
Vol 56 (7) ◽  
pp. 954-957 ◽  
Author(s):  
Jeanette M. Tetrault ◽  
Maor Sauler ◽  
Carolyn K. Wells ◽  
John Concato
Keyword(s):  
Logistic Regression ◽  
New England ◽  
Proportional Hazards ◽  
Medical Literature ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Primary Method ◽  
Primary Analysis ◽  
Proportional Hazards Assumption ◽  
Complete Reporting

BackgroundMultivariable models are frequently used in the medical literature, but many clinicians have limited training in these analytic methods. Our objective was to assess the prevalence of multivariable methods in medical literature, quantify reporting of methodological criteria applicable to most methods, and determine if assumptions specific to logistic regression or proportional hazards analysis were evaluated.MethodsWe examined all original articles in Annals of Internal Medicine, British Medical Journal, Journal of the American Medical Association, Lancet, and New England Journal of Medicine, from January through June 2006. Articles reporting multivariable methods underwent a comprehensive review; reporting of methodological criteria was based on each article's primary analysis.ResultsAmong 452 articles, 272 (60%) used multivariable analysis; logistic regression (89 [33%] of 272) and proportional hazards (76 [28%] of 272) were most prominent. Reporting of methodological criteria, when applicable, ranged from 5% (12/265) for assessing influential observations to 84% (222/265) for description of variable coding. Discussion of interpreting odds ratios occurred in 13% (12/89) of articles reporting logistic regression as the primary method and discussion of the proportional hazards assumption occurred in 21% (16/76) of articles using Cox proportional hazards as the primary method.ConclusionsMore complete reporting of multivariable analysis in the medical literature can improve understanding, interpretation, and perhaps application of these methods.

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.

scholarly journals Del(6)(q22) and BCL6 Rearrangements in Primary CNS Lymphoma Are Indicators of an Aggressive Clinical Course

2008 ◽  
Vol 26 (29) ◽  
pp. 4814-4819 ◽  
Author(s):  
Francois M. Cady ◽  
Brian Patrick O'Neill ◽  
Mark E. Law ◽  
Paul A. Decker ◽  
David M. Kurtz ◽  
...  
Keyword(s):  
Survival Data ◽  
Proportional Hazards ◽  
Deep Structure ◽  
Primary Cns Lymphoma ◽  
B Cell Lymphoma ◽  
Aggressive Lymphoma ◽  
Cns Lymphoma ◽  
High Dose ◽  
Putative Tumor Suppressor Gene ◽  
Thin Sections

Purpose Primary CNS lymphoma (PCNSL) is an aggressive lymphoma but clinically validated biologic markers that can predict natural history to tailor treatment according to risk are lacking. Several genetic changes including BCL6 rearrangements and deletion of 6q22, containing the putative tumor suppressor gene PTPRK, are potential risk predictors. Herein we determined the prevalence and survival impact of del(6)(q22) and BCL6, immunoglobulin heavy chain (IGH), and MYC gene rearrangements in a large PCNSL cohort treated in a single center. Patients and Methods Interphase fluorescence in situ hybridization was performed using two-color probes for BCL6, MYC, IGH-BCL6, and del(6)(q22) on thin sections of 75 paraffin-embedded samples from 75 HIV-negative, immunocompetent patients newly diagnosed with PCNSL. Survival data were analyzed using Kaplan-Meier survival curves, log-rank tests, and proportional hazards regression adjusting for age, deep structure involvement, and high-dose methotrexate (HDMTX) treatment. Results The prevalence of del(6)(q22) and BCL6, IGH, and MYC translocations was 45%,17%, 13%, and 3%, respectively. The presence of del(6)(q22) and/or a BCL6 translocation was associated with inferior overall survival (OS; P = .0097). The presence of either del(6)(q22) alone or a BCL6 translocation alone was also associated with inferior OS (P = .0087). Univariable results held after adjusting for age, deep structure involvement, and HDMTX. Conclusion Del (6)(q22) and BCL6 rearrangements are common in PCNSL and predict for decreased OS independent of deep structure involvement and HDMTX. Unlike systemic diffuse large B-cell lymphoma, del(6)(q22) is common and IGH translocations are infrequent and usually involve BCL6 rather than BCL2, suggesting a distinct pathogenesis.

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.

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