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CoxKAN: Kolmogorov-Arnold networks for interpretable, high-performance survival analysis.

MOTIVATION: Survival analysis is a branch of statistics that is crucial in medicine for modeling the time to critical events such as death or relapse, in order to improve treatment strategies and patient outcomes. Selecting survival models often involves a trade-off between performance and interpretability; deep learning models offer high performance but lack the transparency of more traditional approaches. This poses a significant issue in medicine, where practitioners are reluctant to use black-box models for critical patient decisions. RESULTS: We introduce CoxKAN, a Cox proportional hazards Kolmogorov-Arnold Network for interpretable, high-performance survival analysis. Kolmogorov-Arnold Networks (KANs) were recently proposed as an interpretable and accurate alternative to multi-layer perceptrons. We evaluated CoxKAN on four synthetic and nine real datasets, including five cohorts with clinical data and four with genomics biomarkers. In synthetic experiments, CoxKAN accurately recovered interpretable hazard function formulae and excelled in automatic feature selection. Evaluations on real datasets showed that CoxKAN consistently outperformed the traditional Cox proportional hazards model (by up to 4% in C-index) and matched or surpassed the performance of deep learning-based models. Importantly, CoxKAN revealed complex interactions between predictor variables and uncovered symbolic formulae, which are key capabilities that other survival analysis methods lack, to provide clear insights into the impact of key biomarkers on patient risk. AVAILABILITY AND IMPLEMENTATION: CoxKAN is available at GitHub and Zenodo.

Humans

Descriptive epidemiology and survival analysis of nasopharyngeal carcinoma in the United States.

Population-based incidence data on nasopharyngeal carcinomas (NPC) from the Surveillance, Epidemiology and End Results program in the United States were examined for the years 1973-1986. The 1,645 cases showed incidence rates varying according to ethnic origin, with chinese having the highest, followed by Filipinos, Blacks and Whites. In females the incidence was about half of that seen in males, in each of these groups. There was no evidence of changes in incidence rates during the study period. An analysis of survival with NPC was undertaken using hazard function regression models to allow for control of multiple variables. Survival was found to be independently influenced by age and stage at diagnosis, histologic type, grade and sex. Significant ethnic differences in survival remained after adjustment for these factors, with Chinese surviving longest followed by Filipinos, Whites and Blacks. These difference in survival remained after control for the variation in population-wide mortality rates associated with age, ethnicity, sex and calendar year. We present evidence that survival has improved for this disease over time.

Adolescent

Repeated assessment of risk factors in survival analysis.

Regression models for survival data with time-dependent covariates are considered. We review estimation in the Cox regression model and discuss problems in connection with data requirements for the analysis, with interpretation of results and with prediction based on such a model. In particular, we discuss how the latter problems may be approached within an extended (Markov process) model. A clinical trial in liver cirrhosis is used for illustration.

Clinical Trials as Topic

Survival analysis of octogenarian patients with coronary artery disease managed by elective coronary artery bypass surgery versus conventional medical treatment.

BACKGROUND: In view of the increasing age of the U.S. population, the use of coronary artery bypass surgery in the management of the elderly patients with coronary artery disease needs to be better defined. METHODS AND RESULTS: To evaluate the effects of medical and surgical therapy on octogenarian patients with coronary artery disease in our institution, we retrospectively reviewed 177 consecutive octogenarians who underwent cardiac catheterization over a 5-year period. Sixty-five of these patients were found to have significant coronary artery disease without severe valvular disease. Elective coronary artery bypass surgery was performed in 36 patients, whereas 29 patients were continued on maximization of medical therapy and not referred to the surgical service. Left ventricular ejection fractions (LVEF) were similar for the two groups, whereas the surgical patients had slightly higher average number of diseased coronary vessels and slightly higher levels of angina. Univariate survival analysis of 20 variables, including the choice of medical versus surgical treatment and the associated conditions, was performed by Mantel-Cox testing of the paired Kaplan-Meier product limit survival curves stratified by the subgroups of each variable. The variables found to be significant were then included in a multivariate survival analysis using the Cox proportional hazards regression model. The treatment choice, LVEF, level of angina, and presence of any aortic and/or mitral valvular disease at the time of cardiac catheterization were found to be independent prognostic indicators of survival in the follow-up period of 26 +/- 16 months. The 3-year probability of survival rates for the surgical patients and medical patients were 77.4% and 55.2%, respectively (p = 0.0294). The New York Heart Association functional class of the surgical group decreased significantly from a mean preoperative level of 3.4 +/- 0.5 to a mean level of 1.2 +/- 0.6 at the follow-up interview (p < 0.01), whereas it did not significantly change for the medical group from a baseline mean level of 2.8 +/- 1.3 to a mean follow-up level of 2.5 +/- 1.0. CONCLUSIONS: We conclude that coronary artery bypass surgery provided improved long-term survival and functional benefit compared with conventional medical treatment in a small group of octogenarian patients in our institution.

Aged

[AIDS: descriptive study and survival analysis of the 1st 40 cases].

AIM: To analyze the epidemiologic and clinical features, the survival as well as length of stay of the first 40 AIDS cases seen at the internal Medicine Department of the Virgen de la Arrixaca Hospital (Murcia, Spain). METHODS: Prospective study from September 1988 through July 1991. AIDS criteria used were the CDC (1987) ones. The survival analysis was performed using the Kaplan-Meier method. RESULTS: Thirty-four patients were male (85%) and six female (15%), with a mean age of 39 years. Eighteen (45%) were homo or bisexual, 11 drug addicts (27.5%), 8 (20%) had sexual contacts with prostitutes and/or drug addicts. Two patients were recipients of blood products and in one case no risk could be determined. Opportunistic infections were the first AIDS criteria in 75% of cases. Among the most frequent are P. carinii pneumonia (17.5%), CNS toxoplasmosis (15%) and cryptosporidiosis (12.5%). In 20% of cases a Kaposi's sarcoma developed. The probability of survival after three months was 91% +/- 9.6, at 7 months 79.5% +/- 15.0 and at 15 months 72.5 +/- 18. Overall, 90% of patients had at least one hospital admission, and 27.7% were hospitalized for 50% of more of their survival time. CONCLUSIONS: We recorded an increased number of AIDS cases since 1988, being most of them homo-bisexual male patients, with opportunistic infections as first manifestation. We noticed also high proportion of cases of heterosexual transmission.

Acquired Immunodeficiency Syndrome

Foundation model based multimodal transformer framework for survival analysis in HER2 stratified breast cancer.

Objective. To improve survival prediction for HER2-positive breast cancer by integrating histopathological, molecular, and clinical data using a multimodal transformer framework.Approach. We propose a multimodal transformer framework for breast cancer survival prediction using HER2 stratified (SurvMBC), a foundation model-enhanced architecture that fuses three data modalities: whole-slide images, clinical narratives, and molecular features. Tumor microenvironment features are extracted using a pathology language and image pre-training (PLIP), clinical narratives are processed with BioBERT, and miRNA expression plus DNA methylation data are embedded using Gen2Vec. These representations are integrated through a cross-modal transformer with attention mechanisms for survival prediction.Main results. The model was evaluated on 1,095 HER2-positive breast cancer patients from The Cancer Genome Atlas. SurvMBC achieved a concordance index (C-index) of 0.857 (95% CI: 0.834, 0.880), a low integrated Brier score, and a strong inverse negative binomial log-likelihood. Risk stratification based on model outputs significantly separated high- and low-risk groups (log-rankp< 0.01) and showed strong associations with tumor stage, grade, and hormone receptor status (allp< 0.05).Significance. SurvMBC demonstrates the effectiveness of multimodal fusion in addressing tumor heterogeneity and improving prognostic accuracy. The attention-based integration enables context-aware learning of survival-relevant features across modalities, supporting individualized risk stratification and risk-adaptive treatment planning for HER2 stratified breast cancer patients.

Breast Neoplasms

Polygenic risk factors for comorbid diagnoses in individuals with substance use disorders: A phenome-wide survival analysis.

OBJECTIVE: Persons with substance use disorders (SUD) often suffer from additional comorbidities. Researchers have explored this overlap via phenome-wide association studies (PheWASs). However, PheWASs are largely cross-sectional, limiting our understanding of whether diagnoses predate the development of an SUD. We characterize whether polygenic scores (PGSs) are associated with time to comorbid diagnoses in electronic health records (EHR) after the first documented SUD diagnosis. METHODS: Using data from All of Us (N&#xa0;=&#xa0;393,596), we explored: (1) whether social determinants of health (SDoHs) are associated with lifetime risk of SUD (N cases&#xa0;=&#xa0;42,568) and (2) within a subset those with a diagnosed SUD and available genetic data SUD (N&#xa0;=&#xa0;21,357), whether PGS for alcohol use disorders, cannabis use disorders, depression, externalizing, posttraumatic stress disorder, and schizophrenia were associated with subsequent diagnoses via a phenome-wide survival analysis. RESULTS: Multiple SDoHs were associated with lifetime SUD diagnosis, with annual household income having the largest overall associations (e.g. <$10&#xa0;K annually vs $100&#xa0;K-$150&#xa0;K annually: OR&#xa0;=&#xa0;4.18; 95% CI&#xa0;=&#xa0;3.92, 4.45). There were 86 phenome-wide significant PGS associations with subsequent diagnoses across various bodily systems. PGSs for alcohol use disorders, posttraumatic stress disorder, and schizophrenia were each associated with time to their respective diagnoses. CONCLUSIONS: Social determinants, especially those related to income, have profound associations with lifetime SUD risk. Additionally, PGSs for psychiatric conditions are associated with multiple post-SUD diagnoses within those with a SUD, suggesting PGS may capture information beyond lifetime risk, including timing and severity of comorbidities related to SUD.

Humans

Polygenic Risk Factors for Comorbid Diagnoses in Individuals with Substance Use Disorders: A Phenome-Wide Survival Analysis.

OBJECTIVE: Persons with substance use disorders (SUD) often suffer from additional comorbidities. Researchers have explored this overlap via phenome wide association studies (PheWAS). However, PheWAS are largely cross-sectional, limiting our understanding of whether diagnoses predate development of an SUD. We characterize whether polygenic scores (PGS) are associated with time to comorbid diagnoses in electronic health records (EHR) after the first documented SUD diagnosis. METHODS: Using data from All of Us (N = 393,596), we explored: 1) whether social determinants of health (SDoH) are associated with lifetime risk of SUD (N cases = 42,568) and 2) within a subset those with a diagnosed SUD and available genetic data SUD (N = 21,357), whether PGS for alcohol use disorders, cannabis use disorders, depression, externalizing, post-traumatic stress disorder, and schizophrenia were associated with subsequent diagnoses via a phenome-wide survival analysis. RESULTS: Multiple SDoH were associated with lifetime SUD diagnosis, with annual household income having the largest overall associations (e.g., <$10K annually vs $100K-$150K annually: OR = 3.89, 95% CI = 3.66, 4.13). There were 101 phenome-wide significant PGS associations with subsequent diagnoses across various bodily systems. PGSs for alcohol use disorders, post-traumatic stress disorder, and schizophrenia were each associated with time to their respective diagnoses. CONCLUSIONS: Social determinants, especially those related to income, have profound associations with lifetime SUD risk. Additionally, PGS for psychiatric conditions are associated with multiple post-SUD diagnoses within those with a SUD, suggesting PGS may capture information beyond lifetime risk, including timing and severity of comorbidities related to SUD.

Journal Article

[Survival analysis of 487 patients with kidney transplantation].

The causes of graft loss were analysed in a group of 487 kidney transplants, of which 252 (51.46%) concerned related donors, 139 (28.5%) cadaver donors and 96 (19.7%) non-related donors. A total of 74 kidneys were lost in the first 3 months after transplantation (15.19%). In 34 cases the loss was due to immunological factors (45.9%) in 21 cases (28.3%) to the death of the patients and in 19 cases (25.7%) to the technical causes. From 34 losses by immunological problems, 32 were rejections with humoral character (acute vascular rejection in 11 cases, late humoral rejection in 11 cases, immediate humoral rejection in 9 cases, ABO incompatibility in one case) and recurrence of original disease in one case. Acute cellular rejection was observed in only one patient. None of the patients died from immunological loss of the graft. The most frequent cause of death were sepsis (13 out of 21 patients) and the most common focus of infection was pulmonary (5 patients). It occurred most frequently with cadaveric donor, (10.07%). Death related to cardiovascular causes occurred in four patients, digestive in two and in consequence of arterial bleeding in two. Among the 23 losses by technical factors renal artery thrombosis was the most frequent (11 cases); renal rupture occurred in three cases, renal vein thrombosis in two rupture of arterial anastomosis in one and inviable kidney in another one. The technical loss was most frequent with cadaver donors (8.63%), followed by non-related donors (4.16%) and related donors (2.77%). Four patients died from causes directly related to technical factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Brazil

[Use of Cox's model in long-term survival analysis of cerebrovascular disease].

A long-term survival study on 885 cases of cerebrovascular disease was carried out. The results showed that after follow-up for 3, 5, and 8 years, the survival rates were 86.98%, 75.70% and 64.26% respectively, and all were lower obviously than that of the general population in the same district. The results of Cox's model analysis showed that recurrence, hypertension and age were the risk factors influencing the long-term survival of cerebrovascular disease, and the relative risks were 3.29, 2.17 and 1.65 respectively.

Adult

[Epithelioma of the pyriform sinus: retrospective study and survival analysis after 5 years].

We have studied 27 clinical records of patients with piriform sinus epidermoid carcinoma diagnosed and treated in our department during a period of 6 years. All the patients underwent surgery and radiotherapy. We have analyzed the survival and recurrence rates together with other parameters that may have some influence in them. We have tried to show the factors that might be in relation with the prognosis of pyriform sinus carcinoma. The statistical analysis show a survival rate of 29.6% after 5 years follow up, being the node invasion, wither clinical or histological, the main fact to have a prognostic value.

Aged

[Small-cell lung cancer: survival analysis over the last 10 years: 1980-1990].

A review of 269 papers published between 1980 and 1990 has been performed in order to evaluate the median survival (MS) of patients with small cell lung cancer (SCLC) in relationship with different therapeutic modalities. We found that therapies with cisplatin and etoposide were associated with a significantly longer MS than those without these drugs. Alternating regimens, short therapies (< or = 6 months) and maintenance treatments have a similar MS. Initial and late intensification does not significantly prolong the MS as compared to conventional treatments. Neither radiation therapy to the chest and/or to the brain does increase the MS. Overall, MS of patients with limited SCLC is significantly longer than that of patients with extensive disease.

Antineoplastic Combined Chemotherapy Protocols

Machine learning prognostic model and drug survival analysis for lung adenocarcinoma in the context of radiotherapy.

BACKGROUND: Patients with lung adenocarcinoma (LUAD) receiving radiotherapy represent an important but underexplored clinical subgroup. These patients often undergo concomitant pharmacologic treatments, yet the prognostic impact and underlying determinants of such combined regimens remain poorly understood. OBJECTIVE: This retrospective observational study aimed to develop and validate a radiotherapy-specific machine learning prognostic model for LUAD and to compare survival across concomitant pharmacologic regimens. METHODS: In this retrospective observational study, using genomic and clinical data from TCGA, a radiotherapy-specific prognostic model for LUAD was developed and validated through ten machine learning algorithms. Survival analyses were conducted across distinct concomitant pharmacologic strategies, followed by functional enrichment to elucidate molecular mechanisms underlying differential outcomes. RESULTS: Demonstrating robust prognostic abilities, the model efficiently sorted patients into high- and low-risk categories. Both treatment type and risk score independently predicted overall survival, with significant interaction effects. Low-risk patients receiving targeted or combination therapy-mainly erlotinib, gefitinib, or bevacizumab-exhibited substantially improved survival compared with those receiving conventional chemotherapy. Enrichment of "Exogenous peptide presentation," "MHC class II assembly," "Peptide-MHC II assembly," and "Symbiotic interaction" pathways indicated immune modulation and host-tumor crosstalk as key mediators of treatment efficacy. CONCLUSION: This study establishes a radiotherapy-specific prognostic model for lung adenocarcinoma, demonstrating distinct molecular and therapeutic heterogeneity and highlighting the superior survival benefit of targeted combination therapy in low-risk patients.

Humans

Wheezing in infants with cystic fibrosis: clinical course, pulmonary function, and survival analysis.

Wheezing is a common finding in infants with cystic fibrosis (CF). This study was undertaken to determine the prevalence of wheezing in infants with CF and to compare the clinical outcome of those who wheezed in infancy with that of those who did not. The study cohort included 229 CF patients born between 1965 and 1979 with CF diagnosed before 2 years of age. Fifty-seven (25%) had physician-documented wheezing during the first 2 years of life. Wheezing had resolved by the age of 2 years in 50% of the patients and by the age of 4 years in 75%. Although wheezing seemed to be linked to a family history of allergy and asthma, the frequency of the delta F508 mutation was similar to that of the non-wheezers. There was no significant difference in survival at the age of 13 years between the two groups. At the age of 7 years, patients who had wheezed had significantly lower forced expiratory flow rate at mid-expiratory phase (85 +/- 34% predicted) compared with those with no wheezing history (101 +/- 34% predicted). At the age of 13 years, forced expiratory volume in 1 second values was lower in the wheezing group (69 +/- 24% predicted vs 78 +/- 21% predicted), as was forced expiratory flow rate at mid-expiratory phase (56 +/- 33% predicted vs 69 +/- 30% predicted). In conclusion, although wheezing in infants with CF seems to have diminished with age, pulmonary function abnormalities were more evident at 7 and 13 years of age in the group that wheezed than in the group that did not.

Cohort Studies

Hepatocellular carcinoma. Prognostic factors and survival analysis in 135 Italian patients.

This is a retrospective study to evaluate the history of hepatocellular carcinoma and find the relationship between clinical, biochemical and ultrasonographic features and survival in Italian patients. In 135 consecutive patients median follow-up was 16 months (range 1-66 months) and median survival from the time of diagnosis was 12 months. Univariate analysis showed that individual variables associated with significantly decreased survival included: absence of therapy, Okuda's Stage III, Child-Pugh's Class C, alpha-fetoprotein greater than 400 ng/ml, presence of symptoms, moderate or severe ascites, tumor involving both lobes, mixed internal echo pattern, and multinodular or massive type. Multiple regression analysis (Cox model) revealed that the mixed internal echo pattern of hepatocellular carcinoma, the presence of moderate or severe ascites and Okuda's Stage III were independent predictors of high risk of death. These data can help in selecting patients whose probability of survival is considered high enough to undergo treatment and may be useful for stratifying patients in randomized controlled trials.

Adult

scSurv: a deep generative model for single-cell survival analysis.

MOTIVATION: Single-cell omics analysis has unveiled the heterogeneity of various cell types within tumors. However, no methodology currently reveals how this heterogeneity influences cancer patient survival at single-cell resolution. Here, we introduce scSurv, combining a Cox proportional hazards model with a deep generative model of single-cell transcriptome, to estimate individual cellular contributions to clinical outcomes. RESULTS: The accuracy of scSurv was validated using both simulated and real datasets. This method identifies cells associated with favorable or adverse prognoses and extracts genes correlated with their contribution levels. In melanoma, scSurv reproduces known prognostic macrophage classifications and facilitates hazard mapping through spatial transcriptomics in renal cell carcinoma. We also identified genes consistently associated with prognosis across multiple cancers and demonstrated the applicability of this method to infectious diseases. scSurv is a novel framework for quantifying the heterogeneity of individual cellular effects on clinical outcomes. AVAILABILITY: The implementation of scSurv is available on GitHub (https://github.com/3254c/scSurv) and Zenodo (https://doi.org/10.5281/zenodo.17793054).

Humans

The effect of mixed distributions on the methods of survival analysis.

A study of the effectiveness of preoperative radiation as an adjuvant for surgery for patients with invasive bladder carcinoma revealed a subpopulation of patients having advanced disease who could not benefit from radiation treatment. The effect of such a group of patients on the efficiency of 2 common nonparametric tests is investigated here. Both Gehan's tests and Greenwood's tests were shown to have a very low efficiency when compared with a parametric test when this group of patients is present.

Humans

Whole -genome survival analysis of 144&#x200a;286 people from the UK Biobank identifies novel loci associated with blood pressure.

This study utilized UK Biobank data from 144&#x200a;286 participants and employed whole-genome sequencing (WGS) data and time-to-event data over a 12-year follow-up period to identify susceptibility in genetic variants associated with hypertension. Following genotype quality control, 6&#x200a;319&#x200a;822 single nucleotide polymorphisms underwent analysis, revealing 31 significant variant-level associations. Among these, 29 were novel - 15 in Fibrillin-2 ( FBN2 ) and 4 in Junctophilin-2 ( JPH2 ). Mendelian randomization utilizing two identified variants (rs17677724 and rs1014754) suggested that a genetically induced decrease in heart FBN2 expression and an increase in adrenal gland JPH2 expression were causally linked to hypertension. Phenome-wide association (PheWAS) analysis using the FinnGen dataset confirmed positive associations of rs17677724 and rs1014754 with hypertension, assessed across 2727 traits in 377&#x200a;277 individuals. Lastly, rs1014754 positively associated with kallistatin, whereas rs17677724 negatively associated with renin in the Fenland study, suggesting a counterregulatory response to high blood pressure. This study, employing WGS data, identified novel genetic loci and potential therapeutic targets for hypertension.

Humans