Estimation in additive cox models by marginal integration

2005 ◽  
Vol 57 (3) ◽  
pp. 403-423 ◽  
Author(s):  
Toshio Honda
Keyword(s):  
Cox Models ◽  
Marginal Integration

Toxicities of axitinib, sunitinib and temsirolimus: implications for progression-free and overall survival in metastatic renal cell cancer

2020 ◽  
Author(s):  
Annemarie Uhlig ◽  
Johannes Uhlig ◽  
Lutz Trojan ◽  
Michael Woike ◽  
Marianne Leitsmann ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cancer Patients ◽  
Skin Reaction ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Cox Models ◽  
Metastatic Renal Cell Cancer ◽  
Hand Foot Skin Reaction

The aim of this study was to evaluate the association between axitinib, sunitinib and temsirolimus toxicities and patient survival in metastatic renal cell cancer patients. Overall survival (OS) and progression-free survival (PFS) of metastatic renal cell cancer patients from the prospective multicenter STAR-TOR study were assessed using multivariable Cox models. A total of 1195 patients were included (n = 149 axitinib; n = 546 sunitinib; n = 500 temsirolimus). The following toxicities significantly predicted outcomes: hand–foot skin reaction (hazard ratio [HR] = 0.29) for PFS with axitinib; stomatitis (HR = 0.62) and pneumonitis (HR = 0.23) for PFS with temsirolimus; stomatitis (HR = 0.52) and thrombocytopenia (HR = 0.6) for OS with temsirolimus; fatigue (HR = 0.71) for PFS with sunitinib; hand–foot skin reaction (HR = 0.56) and fatigue (HR = 0.58) for OS with sunitinib. In conclusion, in metastatic renal cell cancer, axitinib, sunitinib and temsirolimus demonstrate specific toxicities that are protective OS/PFS predictors.

Lynch syndrome-related non-endometrioid endometrial cancer: analysis of outcomes

2019 ◽  
Vol 30 (1) ◽  
pp. 56-61
Author(s):  
Giorgio Bogani ◽  
Maria Grazia Tibiletti ◽  
Maria Teresa Ricci ◽  
Ileana Carnevali ◽  
Viola Liberale ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Lynch Syndrome ◽  
Disease Free Survival ◽  
Oncologic Outcomes ◽  
Cox Models ◽  
Matching Algorithm ◽  
Pathogenic Variants ◽  
Propensity Matching ◽  
Endometrioid Endometrial Cancer

ObjectiveWomen with Lynch syndrome have a risk up to 40–60% of developing endometrial cancer, which is higher than their risk of developing colorectal or ovarian cancer. To date, no data on the outcomes of patients with Lynch syndrome diagnosed with non-endometrioid endometrial cancer are available. The goal of this study was to evaluate the outcome of patients with Lynch syndrome diagnosed with non-endometrioid endometrial cancer.MethodsData from consecutive patients diagnosed with Lynch syndrome and with a histological diagnosis of non-endometrioid endometrial cancer were retrospectively collected in two referral institutes in Italy. A case–control comparison (applying a propensity matching algorithm) was performed in order to compare patients with proven Lynch syndrome and controls. Inclusion criteria were: (a) histologically-proven endometrial cancer; (b) detection of a germline pathogenic variant in one of the MMR genes; (c) adequate follow-up. Only carriers of pathogenic or likely pathogenic variants (ie, class 5 and 4 according to the InSiGHT classification) were included in the study. Survival outcomes were assessed using KaplanMeier and Cox models.ResultsOverall, 137 patients with Lynch syndrome were collected. Mean patient age was 49.2 (10.9) years. Genes involved in the Lynch syndrome included MLH1, MSH2, and MSH6 in 43%, 39%, and 18% of cases, respectively. The study population included 27 patients with non-endometrioid endometrial cancer, who were matched 1:2 with patients with sporadic cancers using a propensity matching algorithm. After a median follow-up of 134 months (range 1–295), 2 (7.4%) of the 27 patients developed recurrent disease (3 and 36 months) and subsequently died of disease (7 and 91 months). Patients diagnosed with Lynch syndrome experienced better disease-free survival (HR 7.86 (95% CI 1.79 to 34.5); p=0.006) and overall survival (HR 5.33 (95% CI 1.18 to 23.9); p=0.029) than controls.ConclusionsNon-endometrioid endometrial cancer occurring in patients with Lynch syndrome might be associated with improved oncologic outcomes compared with controls. Genetic/molecular profiling should be investigated in order to better understand the mechanism underlying the prognosis.

Association between self-care and prognosis in 1123 patients with chronic heart failure

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Calero ◽  
E Hidalgo ◽  
R Marin ◽  
L Rosenfeld ◽  
I Fernandez ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Acute Heart Failure ◽  
Nyha Class ◽  
Self Care ◽  
P Value ◽  
Funding Source ◽  
Class Iii ◽  
Cox Models ◽  
Lower Tertile

Abstract Background Self-care is a crucial factor in the education of patients with heart failure (HF) and directly impacts in the progression of the disease. However, little is published about its major clinical implications as admission or mortality in patients with HF. Aims and methods The aim of the study was to analyze time to admission due to acute heart failure and mortality associated with poor self-care in patients with chronic HF. We prospectively recruited consecutive patients with stable chronic HF referred to a nurse-led HF programme. Selfcare was evaluated at baseline with the 9 item European Heart Failure Self-Care Behavior Scale. Scores were standardized and reversed from 0 (worst selfcare) to 100 (better self care). For the purpose of this study we analyzed the associations of worse self-care (defined as scores below the lower tertile of the scale) with demographic, disease-related (clinical) and psychosocial factors in all patients at baseline. Results We included 1123 patients, mean age 72±11, 639 (60%) were male, mean LVEF 45±17 and 454 (40,4%) were in NYHA class III or IV. Mean score of the 9-item ESCBE was 69±28. Score below 55 (lower tertile) defined impaired selfcare behaviour. Those patients with worse self-care had more ischaemic heart disease, more COPD, and they achieved less distance in the 6 minute walking test. Regarding psychosocial items patients in lower tertile of self-care needed a caregiver more frequently, they present more cognitive impairment, depressive symptoms and worse score in terms of health self-perception. Multivariate Cox Models showed that a score below 55 points in 9-item ESCBE was independently associated with higher readmission due to acute heart failure [HR 1.26 (1.02–1.57), p value=0.034] and with mortality [HR 1.24 CI95% (1.02–1.50), p value=0.028] Conclusion Poor self-care measured with the modified 9-item ESCBE was associated with higher risk of admission due to acute decompensation and higher risk of mortality in patients with chronic heart failure. These results highlight the importance of assessing self-care and provide measures to improve them. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Hospital Univesitario de Bellvitge

scholarly journals Dual Decline in Gait and Cognition Is Associated With Future Dementia: Evidence for a Phenotype

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 264-264
Author(s):  
Manuel Montero Odasso ◽  
Mark Speechley ◽  
Richard Camicioli ◽  
Nellie Kamkar ◽  
Qu Tian ◽  
...  
Keyword(s):  
Older Adults ◽  
Gait Speed ◽  
Regression Models ◽  
Community Dwelling ◽  
Hierarchical Regression ◽  
Chi Square ◽  
Cox Models ◽  
Incident Dementia ◽  
Risk Of Progression ◽  
Community Dwelling Older Adults

Abstract BACKGROUND: The concurrent decline in gait speed and cognition are associated with future dementia. However, the clinical profile of those who present with dual-decline has not yet been described. We aimed to describe the phenotype and risk for incident dementia of individuals who present a dual-decline in comparison with non dual-decliners. METHODS: Prospective cohort of community-dwelling older adults free of dementia at baseline. We evaluated participants’ gait speed, cognition, medical status, functionality, incidence of adverse events, and dementia biannually over 7 years. Gait speed was assessed with a 6-meter electronic-walkway, and global cognition was assessed using the MoCA test. We compared characteristics between dual-decliners and non dual-decliners using t-test, Chi-square, and hierarchical regression models. We estimated incident dementia using Cox models. RESULTS: Among 144 participants (mean age 74.23 ± 6.72 years, 54% women), 17% progressed to dementia. Dual-decliners had a three-fold risk (HR: 3.12, 95%CI:1.23-7.93, p=0.017) of progression to dementia compared with non dual-decliners. Dual-decliners were significantly older with a higher prevalence of hypertension and dyslipidemia (p=0.002). Hierarchical regression models show that age and sex alone explained 3% of the variation in the dual-decliners group, while adding hypertension and dyslipidemia increased the explained variation to 8% and 10 %, respectively. The risk of becoming a dual-decliner was 4-fold if hypertension was present. CONCLUSION: Older adults with concurrent decline in gait speed and cognition represent a group at the highest risk of progression to dementia. These dual-decliners have a distinct phenotype with a higher prevalence of hypertension, a potentially treatable condition.

scholarly journals Identification of novel cell glycolysis related gene signature predicting survival in patients with breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Feng Jiang ◽  
Chuyan Wu ◽  
Ming Wang ◽  
Ke Wei ◽  
Jimei Wang
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Single Gene ◽  
Prediction Method ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Cox Models ◽  
Normal Tissues ◽  
Predictive Risk

AbstractOne of the most frequently identified tumors and a contributing cause of death in women is breast cancer (BC). Many biomarkers associated with survival and prognosis were identified in previous studies through database mining. Nevertheless, the predictive capabilities of single-gene biomarkers are not accurate enough. Genetic signatures can be an enhanced prediction method. This research analyzed data from The Cancer Genome Atlas (TCGA) for the detection of a new genetic signature to predict BC prognosis. Profiling of mRNA expression was carried out in samples of patients with TCGA BC (n = 1222). Gene set enrichment research has been undertaken to classify gene sets that vary greatly between BC tissues and normal tissues. Cox models for additive hazards regression were used to classify genes that were strongly linked to overall survival. A subsequent Cox regression multivariate analysis was used to construct a predictive risk parameter model. Kaplan–Meier survival predictions and log-rank validation have been used to verify the value of risk prediction parameters. Seven genes (PGK1, CACNA1H, IL13RA1, SDC1, AK3, NUP43, SDC3) correlated with glycolysis were shown to be strongly linked to overall survival. Depending on the 7-gene-signature, 1222 BC patients were classified into subgroups of high/low-risk. Certain variables have not impaired the prognostic potential of the seven-gene signature. A seven-gene signature correlated with cellular glycolysis was developed to predict the survival of BC patients. The results include insight into cellular glycolysis mechanisms and the detection of patients with poor BC prognosis.

scholarly journals Association of early glycemic change with short-term mortality in lobar and non-lobar intracerebral hemorrhage

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paola Forti ◽  
Fabiola Maioli ◽  
Marco Zoli
Keyword(s):  
Intracerebral Hemorrhage ◽  
Continuous Variable ◽  
Serum Glucose ◽  
Diabetic Patients ◽  
Short Term ◽  
Cox Models ◽  
Short Term Mortality ◽  
Glucose Test ◽  
Acute Intracerebral Hemorrhage ◽  
Persistent Hyperglycemia

AbstractThe association between early glycemic change and short-term mortality in non-diabetic patients with acute intracerebral hemorrhage (ICH) is unclear. We retrospectively investigated non-diabetic patients with lobar (n = 262) and non-lobar ICH (n = 370). Each patient had a random serum glucose test on hospital admission and a fasting serum glucose test within the following 48 h. Hyperglycemia was defined as serum glucose ≥ 7.8 mmol/l. Four patterns were determined: no hyperglycemia (reference category), persistent hyperglycemia, delayed hyperglycemia, and decreasing hyperglycemia. Associations with 30-day mortality were estimated using Cox models adjusted for major features of ICH severity. Persistent hyperglycemia was associated with 30-day mortality in both lobar (HR 3.00; 95% CI 1.28–7.02) and non-lobar ICH (HR 4.95; 95% CI 2.20–11.09). In lobar ICH, 30-day mortality was also associated with delayed (HR 4.10; 95% CI 1.77–9.49) and decreasing hyperglycemia (HR 2.01, 95% CI 1.09–3.70). These findings were confirmed in Cox models using glycemic change (fasting minus random serum glucose) as a continuous variable. Our study shows that, in non-diabetic patients with ICH, early persistent hyperglycemia is an independent predictor of short-term mortality regardless of hematoma location. Moreover, in non-diabetic patients with lobar ICH, both a positive and a negative glycemic change are associated with short-term mortality.

scholarly journals Comparing the characteristics and predicting the survival of patients with head and neck melanoma versus body melanoma: a population-based study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yuxin Ding ◽  
Runyi Jiang ◽  
Yuhong Chen ◽  
Jing Jing ◽  
Xiaoshuang Yang ◽  
...  
Keyword(s):  
Head And Neck ◽  
Health Management ◽  
External Validation ◽  
Area Under The Curve ◽  
Population Based ◽  
Survival Prediction ◽  
Cancer Specific Survival ◽  
Cox Models ◽  
Lentigo Maligna Melanoma ◽  
Clinical Tools

Abstract Background Previous studies reported cutaneous melanoma in head and neck (HNM) differed from those in other regions (body melanoma, BM). Individualized tools to predict the survival of patients with HNM or BM remain insufficient. We aimed at comparing the characteristics of HNM and BM, developing and validating nomograms for predicting the survival of patients with HNM or BM. Methods The information of patients with HNM or BM from 2004 to 2015 was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The HNM group and BM group were randomly divided into training and validation cohorts. We used the Kaplan-Meier method and multivariate Cox models to identify independent prognostic factors. Nomograms were developed via the rms and dynnom packages, and were measured by the concordance index (C-index), the area under the curve (AUC) of the receiver operating characteristic (ROC) curve and calibration plots. Results Of 70,605 patients acquired, 21% had HNM and 79% had BM. The HNM group contained more older patients, male sex and lentigo maligna melanoma, and more frequently had thicker tumors and metastases than the BM group. The 5-year cancer-specific survival (CSS) and overall survival (OS) rates were 88.1 ± 0.3% and 74.4 ± 0.4% in the HNM group and 92.5 ± 0.1% and 85.8 ± 0.2% in the BM group, respectively. Eight variables (age, sex, histology, thickness, ulceration, stage, metastases, and surgery) were identified to construct nomograms of CSS and OS for patients with HNM or BM. Additionally, four dynamic nomograms were available on web. The internal and external validation of each nomogram showed high C-index values (0.785–0.896) and AUC values (0.81–0.925), and the calibration plots showed great consistency. Conclusions The characteristics of HNM and BM are heterogeneous. We constructed and validated four nomograms for predicting the 3-, 5- and 10-year CSS and OS probabilities of patients with HNM or BM. These nomograms can serve as practical clinical tools for survival prediction and individual health management.

scholarly journals The sentinel node invasion level (SNIL) as a prognostic parameter in melanoma

2021 ◽  
Author(s):  
Lutz Kretschmer ◽  
Christina Mitteldorf ◽  
Simin Hellriegel ◽  
Andreas Leha ◽  
Alexander Fichtner ◽  
...  
Keyword(s):  
Lymph Node ◽  
Prognostic Significance ◽  
Tumor Burden ◽  
Recurrence Rates ◽  
Cox Models ◽  
Nodal Basin ◽  
Lymph Vessels ◽  
Kaplan Meier ◽  
Metastasis Patterns ◽  
Transverse Sinuses

AbstractSentinel lymph node (SN) tumor burden is becoming increasingly important and is likely to be included in future N classifications in melanoma. Our aim was to investigate the prognostic significance of melanoma infiltration of various anatomically defined lymph node substructures. This retrospective cohort study included 1250 consecutive patients with SN biopsy. The pathology protocol required description of metastatic infiltration of each of the following lymph node substructures: intracapsular lymph vessels, subcapsular and transverse sinuses, cortex, paracortex, medulla, and capsule. Within the SN with the highest tumor burden, the SN invasion level (SNIL) was defined as follows: SNIL 1 = melanoma cells confined to intracapsular lymph vessels, subcapsular or transverse sinuses; SNIL 2 = melanoma infiltrating the cortex or paracortex; SNIL 3 = melanoma infiltrating the medulla or capsule. We classified 338 SN-positive patients according to the non-metric SNIL. Using Kaplan–Meier estimates and Cox models, recurrence-free survival (RFS), melanoma-specific survival (MSS) and nodal basin recurrence rates were analyzed. The median follow-up time was 75 months. The SNIL divided the SN-positive population into three groups with significantly different RFS, MSS, and nodal basin recurrence probabilities. The MSS of patients with SNIL 1 was virtually identical to that of SN-negative patients, whereas outgrowth of the metastasis from the parenchyma into the fibrous capsule or the medulla of the lymph node indicated a very poor prognosis. Thus, the SNIL may help to better assess the benefit-risk ratio of adjuvant therapies in patients with different SN metastasis patterns.

scholarly journals Alcohol and early mortality (before 65 years) in the “Seguimiento Universidad de Navarra” (SUN) cohort: does any level reduce mortality?

2021 ◽  
pp. 1-33
Author(s):  
Miguel A. Martínez-González ◽  
María Barbería-Latasa ◽  
Javier Pérez de Rojas ◽  
Ligia J. Domínguez ◽  
Alfredo Gea
Keyword(s):  
Alcohol Intake ◽  
Premature Mortality ◽  
Continuous Variable ◽  
Early Mortality ◽  
Repeated Measurements ◽  
University Graduates ◽  
Inverse Association ◽  
Cox Models ◽  
Highly Educated ◽  
Heavy Drinkers

Abstract The aim of this study was to assess the association between alcohol intake and premature mortality (younger than 65 years) and to explore the effect of potential alcohol underreporting by heavy drinkers. We followed-up 20,272 university graduates. Four categories of alcohol intake were considered (abstainer, light, moderate and heavy consumption). Repeated measurements of alcohol intake and updated information on confounders were used in time-dependent Cox models. Potential underreporting of alcohol intake by some heavy drinkers (likely misclassified as light or moderate drinkers) was explicitly addressed in an attempt to correct potential underreporting by using indirect information. During 12.3 years of median follow-up (interquartile range: 6.8-15.0), 226 participants died before their 65th birthday. A higher risk of early mortality was found for the highest category of alcohol intake (≥50 g/d) in comparison with abstention (multivariable-adjusted hazard ratio (HR) =2.82, 95% confidence interval (CI): 1.38-5.79). In analyses of alcohol as a continuous variable, the multivariable-adjusted HR was 1.17 (95% CI: 1.08-1.26), for each 10 g/d of alcohol. This harmful linear association was present both in uncorrected models and in models corrected for potential underreporting. No significant inverse association between light or moderate alcohol intake and premature mortality was observed, even after correcting for potential misclassification. Alcohol intake exhibited a harmful linear dose-response association with premature mortality (<65 years) in this young and highly-educated Mediterranean cohort. Our attempts to correct for potential misclassification did not substantially change these results.

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