Multivariable Competing Risk Models Research Articles

Folic acid supplementation is associated with a decreased mortality and reduced hospital readmission in patients with decompensated alcohol-related liver cirrhosis

Background and AimsThiamine and folic acid malnutrition is highly frequent in patients with decompensated alcohol-related liver cirrhosis (aLC). Current guidelines therefore recommend vitamin supplementation in these patients. However, implementation and its impact on the clinical outcome remains unknown. Therefore, we aimed to analyze the use of thiamine and folic acid and their effects on mortality and morbidity in patients with decompensated aLC. MethodsA number of 289 consecutive patients with decompensated aLC who received a paracentesis at Hannover Medical School between 2011 and 2023 were retrospectively investigated. The use of folic acid and thiamine-containing supplements was assessed in the discharge medication. Patients were followed for up to one year regarding liver transplant (LTx)-free survival and the incidence of hepatic encephalopathy, infections and hepatic decompensation requiring rehospitalization. ResultsMedian baseline MELD was 15, median age 56.6 years. 73.0% (n=211) were male patients. At hospital discharge, thiamine-containing supplements and folic acid were prescribed to 48.1% (n=139) and 18.0% (n=52) patients, respectively. Neither thiamine nor folic acid prescription were linked to improved clinical outcomes within 90 days. However, folic acid intake was associated with a higher one-year LTx-free survival (HR=0.48; p=0.04) in the multivariable analysis. Furthermore, folic acid substitution was linked to a decreased risk of rehospitalization within one year (HR=0.55; p=0.01) in the multivariable competing risk model. In contrast, thiamine prescription did neither affect LTx-free survival nor the here investigated liver-related complications. ConclusionFolic acid, but not thiamine substitution was linked to an improved outcome in patients with decompensated aLC.

The hepatocellular carcinoma risk in patients with HBV-related cirrhosis: a competing risk nomogram based on a 4-year retrospective cohort study.

The study aimed to build and validate a competitive risk nomogram to predict the cumulative incidence of hepatocellular carcinoma (HCC) for patients with hepatitis B virus (HBV)-related cirrhosis. A total of 1401 HBV-related cirrhosis patients were retrospectively enrolled from January 1, 2011 to December 31, 2014. Application of 20 times imputation dealt with missing data using multiple imputation by chained equations (MICE). The patients were randomly divided into a training set (n = 1017) and a validation set (n = 384) at a ratio of 3:1. A prediction study was carried out using a competing risk model, where the event of interest was HCC and the competing events were death and liver transplantation, and subdistribution hazard ratios (sHRs) with 95% CIs were reported. The multivariate competing risk model was constructed and validated. There was a negligible difference between the original database and the 20 imputed datasets. At the end of follow-up, the median follow-up time was 69.9 months (interquartile range: 43.8-86.6). There were 31.5% (442/1401) of the patients who developed HCC, with a 5-year cumulative incidence of 22.9 (95%CI, 20.8%-25.2%). The univariate and multivariate competing risk regression and construction of the nomogram were performed in 20 imputed training datasets. Age, sex, antiviral therapy history, hepatitis B e antigen, alcohol drinking history, and alpha-fetoprotein levels were included in the nomogram. The area under receiver operating characteristic curve values at 12, 24, 36, 60, and 96 months were 0.68, 0.69, 0.70, 0.68, and 0.80, and the Brier scores were 0.30, 0.25, 0.23, 0.21, and 0.20 in the validation set. According to the cumulative incidence function, the nomogram effectively screened out high-risk HCC patients from low-risk patients in the presence of competing events (Fine-Gray test p < 0.001). The competitive risk nomogram was allowed to be used for predicting HCC risk in individual patients with liver cirrhosis, taking into account both the association between risk factors and HCC and the modifying effect of competition events on this association.

Development and validation of a nomogram for predicting specific mortality risk: A study of competing risk model based on real endometrial cancer patients.

This study aimed to construct a competing risk prediction model for predicting specific mortality risks in endometrial cancer patients from the SEER database based on their demographic characteristics and tumor information. We collected relevant clinical data on patients with histologically confirmed endometrial cancer in the SEER database between 2010 and 2015. Univariate and multivariate competing risk models were used to analyze the risk factors for endometrial cancer-specific death, and a predictive nomogram was constructed. C-index and receiver operating characteristic curve (ROC) at different time points were used to verify the accuracy of the constructed nomogram. There were 26 109 eligible endometrial cancer patients in the training cohort and 11 189 in the validation cohort. Univariate and multivariate analyses revealed that Age, Marriage, Grade, Behav, FIGO, Size, Surgery, SurgOth, Radiation, ParaAortic_Nodes, Peritonea, N positive, DX_liver, and DX_lung were independent prognostic factors for specific mortality in endometrial cancer patients. Based on these factors, a nomogram was constructed. Internal validation showed that the nomogram had a good discriminative ability (C-index = 0.883 [95% confidence interval [CI]: 0.881-0.884]), and the 1-, 3-, and 5-year AUC values were 0.901, 0.886 and 0.874, respectively. External validation indicated similar results (C-index = 0.883 [95%CI: 0.882-0.883]), and the 1-, 3-, and 5- AUC values were 0.908, 0.885 and 0.870, respectively. We constructed a competing risk model to predict the specific mortality risk among endometrial cancer patients. This model has favorable accuracy and reliability and can provide a reference for the development and update of endometrial cancer prognostic risk assessment tools.

Chronic Obstructive Pulmonary Disease Mortality in Bladder Cancer Patients: A SEER-Based Competing Risk Analysis.

This study was designed to evaluate risk of mortality from chronic obstructive pulmonary disease (COPD) in patients with bladder cancer (BC). Data on patients diagnosed with BC by pathology between 2000 and 2016 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Based on reference data from the general population, the standardized mortality rate (SMR) is calculated. Nelson-Aalen cumulative hazard curves were used for assessment of the risk of COPD mortality in BC patients. Multivariable competing risk models were conducted. The proportional hazards assumption was tested using Schoenfeld residuals, which were scaled and plotted over time for each risk factor. A total of 237,563 BC patients were identified for further analysis from the SEER database, 5,198 of these patients experienced COPD mortality; the overall SMR for COPD mortality in BC patients was 1.58 (95% CI: 1.54-1.63). Age, race, year of diagnosis, histologic type, summary stage, surgery, marital status, college education level, and median household income independently predicted COPD mortality in BC patients. In comparison to the general population, the risk of COPD mortality is significantly higher in patients with BC. Pre-identification of high-risk groups and respiratory care provisions are important measures to effectively improve survival in this group of patients.

Bleeding complications, coagulation disorders, and their management in acute myocardial infarction-related cardiogenic shock rescued by veno-arterial ECMO: A retrospective cohort study

PurposeManagement of dual antiplatelet therapy (DAPT) in patients on venoarterial-extracorporeal membrane (VA-ECMO) after acute myocardial infarction (AMI) is challenging. Our objective was to describe the frequency, management and outcomes of severe bleeding complications and determine their occurrence risk factors. Material and methodsWe conducted a retrospective observational cohort study including post-AMI cardiogenic shock patients requiring VA-ECMO. Severe bleeding was defined based on the Bleeding Academic Research Consortium classification. We calculated multivariable Fine–Gray models to assess factors associated with risk of severe bleeding. ResultsFrom January 2015 to July 2019, 176 patients received VA-ECMO after AMI and 132 patients were included. Sixty-five (49%) patients died. Severe bleeding occurred in 39% of cases. Severe thrombocytopenia (< 50 G/L) and hypofibrinogenemia (<1,5 g/L) occurred in respectively 31% and 19% of patients. DAPT was stopped in 32% of patients with a 6% rate of stent thrombosis. Anticoagulation was stopped in 39% of patients. Using a multivariate competing risk model, female sex, time on ECMO, troponin at admission and Impella® implantation were independently associated with severe bleeding. ConclusionsBleeding complications and coagulation disorders were frequent and severe in patients on VA-ECMO after AMI, leading of antiplatelet therapy withdrawal in one third of patients.

Prediction of bronchopulmonary dysplasia in very preterm infants: competitive risk model nomogram.

To develop predictive clinical models of bronchopulmonary dysplasia (BPD) through competing risk analysis. Retrospective observational cohort study, including preterm newborns ≤32 weeks gestational age, conducted between January 1, 2013 and September 30, 2022 in a third-level Neonatal Intensive Care Unit in Spain. A prediction study was carried out using competing risk models, where the event of interest was BPD and the competing event was death. A multivariate competing risk model was developed separately for each postnatal day (days 1, 3, 7 and 14). Nomograms to predict BPD risk were developed from the coefficients of the final models and internally validated. A total of 306 patients were included in the study, of which 73 (23.9%) developed BPD and 29 (9.5%) died. On day 1, the model with the greatest predictive capacity was that including birth weight, days since rupture of membranes, and surfactant requirement (area under the receiver operating characteristic (ROC) curve (AUC), 0.896; 95% CI, 0.792-0.999). On day 3, the final predictive model was based on the variables birth weight, surfactant requirement, and Fraction of Inspired Oxygen (FiO2) (AUC, 0.891; 95% CI, 0.792-0.989). Competing risk analysis allowed accurate prediction of BPD, avoiding the potential bias resulting from the exclusion of deceased newborns or the use of combined outcomes. The resulting models are based on clinical variables measured at bedside during the first 3 days of life, can be easily implemented in clinical practice, and can enable earlier identification of patients at high risk of BPD.

Impact of prior cancer history on survival in brain malignancy: A propensity score-adjusted, population-based study.

Individuals with a Prior Cancer History (PCH) are often excluded from clinical trials. However, a growing body of evidence suggests that prior cancer history does not present adverse outcomes on cancer patients. The evidence on the survival of brain cancer patients in this regard remains widely unknown. We conducted a retrospective cohort study to estimate the prevalence and impact of prior cancer on survival of patients diagnosed with brain cancer. Data of patients who were diagnosed with brain cancer as their first or second primary malignancy between 2000 and 2019 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity Score Matching (PSM) was used to ensure comparable baseline characteristics among the patients. Survival analysis was conducted using the Kaplan-Meier method, as well as multivariate Cox proportional hazard and multivariate competing risk models. Out of 42 726 patients, 1189 (2.78%) had PCH. Genitourinary (40.4%), Breast (13.6%), Hematologic and Lymphatic (11.4%), and Gastrointestinal malignancies (11.3%) were the most common types of prior cancer. PCH served as a significant risk factor for Overall Survival (OS) (Adjusted Hazard Ratio [AHR] 1.26; 95% CI [1.15-1.39]; p < .001) but did not have a statistically significant impact on Brain Cancer-Specific Survival (BCSS) (AHR 0.97; 95% CI [0.88-1.07]; p = .54). Glioblastoma exhibited the most substantial and statistically significant impact on survival as compared to other histological types. Of all the organs systems, only prior Gastrointestinal and Hematologic and Lymphatic malignancies had a statistically significant impact on OS of patients. Our findings indicate that PCH does not exert a substantial impact on the survival of brain cancer patients, except in cases involving gastrointestinal or hematologic and lymphatic PCH, or when the brain cancer is glioblastoma.

Effect of different treatment modalities on ovarian cancer patients with liver metastases: A retrospective cohort study based on SEER.

To examine the trends in morbidity and mortality among ovarian cancer patients with liver metastases, and investigate the impact of different treatments on both overall survival (OS) and cancer-specific survival (CSS). 2,925 ovarian cancer patients with liver metastases from Surveillance, Epidemiology, and End Results 2010-2019 were included. The primary endpoint was considered as OS and CSS. We conducted trend analysis of the incidence, OS and CSS rates of liver metastases in ovarian cancer. Univariate and multivariate COX proportional risk models were used to investigate the association between different treatment methods and OS, and univariate and multivariate competing risk models were employed to evaluate the impact of treatment methods on CSS. At the end of follow-up, 689 patients remained alive. The OS and CSS rates were 76.44% and 72.99% for all patients, respectively. There was a significant decreasing trend in the incidence [average annual percent change (AAPC) = -2.3, 95% confidence interval (CI): -3.9, -0.7], all-cause mortality (AAPC = -12.8, 95% CI: -15.6, -9.9) and specific mortality (AAPC = -13.0, 95% CI: -16.1, -9.8) rate of liver metastases in ovarian cancer. After adjusting all confounding factor, only receiving surgery was associated with OS [hazard ratio (HR) = 0.39, 95%CI: 0.31-0.48]/CSS (HR = 0.37, 95%CI: 0.30-0.47). Chemotherapy was found to be protective factor for OS (HR = 0.33, 95%CI: 0.30-0.37)/CSS (HR = 0.44, 95%CI: 0.39-0.50) of ovarian cancer patients, while not receiving surgery remained a risk factor. Additionally, the result of subgroup analyses also showed that only receiving surgery and chemotherapy still were significant protective factor of OS and CSS for patients without other distant metastases, with distant metastases to the bone, lung, brain or other organs, with bone metastasis, and with lung metastasis. Our research has elucidated a downward trend in morbidity and mortality rates among patients with liver metastases originating from ovarian cancer. Only receiving surgery and chemotherapy as therapies methods confer survival benefits to patients.

Elevated Fibrinogen-to-Albumin Ratio Correlates with Incident Stroke in Cerebral Small Vessel Disease.

We aimed to explore the association between fibrinogen-to-albumin ratio (FAR) and the risk of incident stroke (IS) in a cohort of cerebral small vessel disease (CSVD) patients. Participants were screened from a prospective CSVD database. Clinical data, hematologic measures and imaging findings were collected. The primary outcome was IS during follow-up, with a secondary outcome of composite vascular events (CVE) including IS, myocardial infarction (MI), and vascular deaths. Univariate and multivariate COX proportional risk models, along with competing risk models, were employed to identify factors associated with outcomes. Restricted cubic spline (RCS) and subgroup analyses were conducted to assess the association between FAR and the risk of IS and CVE in CSVD patients. In the final analysis of 682 CSVD patients over a median observation period of 34.0 [24.0-53.0] months, there were 33 cases of IS (4.84%, 1.55/100 person-years), 4 incidents of MI (0.59%, 0.19/100 person-years), 15 non-vascular deaths (2.20%, 0.70/100 person-years), and 37 occurrences of CVE (5.43%, 1.74/100 person-years). Multivariate Cox regression analysis revealed a significant positive correlation between elevated FAR and both IS (HR 1.146; 95% CI 1.043-1.259; P=0.004) and CVE (HR 1.156; 95% CI 1.063-1.257; P=0.001) in CSVD patients. Multivariate competing risk model showed the similar results (IS: HR 1.16; 95% CI 1.06-1.27; P=0.001, CVE: HR 1.15; 95% CI 1.05-1.26; P=0.003). RCS analysis indicated a linear relationship between FAR and the risks of both IS (P for non-linearity =0.7016) and CVE (P for non-linearity =0.6475), with an optimal cutoff value of 8.69, particularly in individuals over 60 years of age. Elevated FAR demonstrated an independent and linear association with IS and the development of CVE in CSVD patients.

Mortality patterns of patients with tonsillar squamous cell carcinoma: a population-based study.

Tonsillar squamous cell carcinoma (TSCC) and second primary malignancies (SPMs) are the most common causes of mortality in patients with primary TSCC. However, the competing data on TSCC-specific death (TSD) or SPM-related death in patients with TSCC have not been evaluated. This study aimed to analyze the mortality patterns and formulate prediction models of mortality risk caused by TSCC and SPMs. Data on patients with a first diagnosis of TSCC were extracted as the training cohort from the 18 registries comprising the Surveillance, Epidemiology, and End Results (SEER) database. A competing risk approach of cumulation incidence function was used to estimate cumulative incidence curves. Fine and gray proportional sub-distributed hazard model analyses were performed to investigate the risk factors of TSD and SPMs. A nomogram was developed to predict the 5- and 10-year risk probabilities of death caused by TSCC and SPMs. Moreover, data from the 22 registries of the SEER database were also extracted to validate the nomograms. In the training cohort, we identified 14,530 patients with primary TSCC, with TSCC (46.84%) as the leading cause of death, followed by SPMs (26.86%) among all causes of death. In the proportion of SPMs, the lungs and bronchus (22.64%) were the most common sites for SPM-related deaths, followed by the larynx (9.99%), esophagus (8.46%), and Non-Melanoma skin (6.82%). Multivariate competing risk model showed that age, ethnicity, marital status, primary site, summary stage, radiotherapy, and surgery were independently associated with mortality caused by TSCC and SPMs. Such risk factors were selected to formulate prognostic nomograms. The nomograms showed preferable discrimination and calibration in both the training and validation cohorts. Patients with primary TSCC have a high mortality risk of SPMs, and the competing risk nomogram has an ideal performance for predicting TSD and SPMs-related mortality. Routine follow-up care for TSCC survivors should be expanded to monitor SPMs.

Exposure to Agent Orange and Hepatocellular Carcinoma Among US Military Personnel

Hepatocellular carcinoma (HCC) and its mortality are on the rise. Viral hepatitis and alcohol are leading risk factors; however, other risk factors among veterans are less defined, including Agent Orange (AO), an herbicide linked to several cancers. To assess the association of AO exposure and HCC in a national cohort of Vietnam veterans. This retrospective cohort study included Vietnam veterans who served between 1966 and 1975, were male, were older than 18 years at the time of deployment, and had established follow-up in the Veterans Affairs (VA) between 2000 and 2019. Veterans with AO exposure were identified in the disability data via validated clinical surveys. Relevant clinical risk factors for cirrhosis and HCC were collected. Patients were stratified based on cirrhosis status, as defined by consecutive diagnosis found by documented International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision scores or calculated Fibrosis-4 scores. Data were collected from January 1, 2019, to December 31, 2020, and analyzed from December 2020 to October 2023. Incident HCC was the primary outcome. AO and HCC association was estimated using a multivariable Cox regression analysis, with death and liver transplant as competing events. Of the 296 505 eligible veterans (222 545 [75.1%] White individuals and 44 342 [15.0%] Black individuals), 170 090 (57%) had AO exposure (mean [SD] age, 21.62 [3.49] years; 131 552 White individuals [83.2%] and 22 767 Black individuals [14.4%]) and 35 877 (12.1%) had cirrhosis. Veterans who were not exposed to AO were more likely to smoke (109 689 of 126 413 [86.8%] vs 146 061 of 170 090 [85.9%]); use alcohol (54 147 of 126 413 [42.8%] vs 71 951 of 170 090 [42.3%]) and have viral hepatitis (47 722 of 126 413 [37.8%] vs 58 942 of 170 090 [34.7%]). In a multivariable competing risk model, AO exposure was not associated with HCC. Among veterans with cirrhosis, self-identification as Hispanic individuals (aHR, 1.51; 95% CI, 1.30-1.75; P <.001) or Black individuals (aHR, 1.18; 95% CI, 1.05-1.32; P = .004), and having a diagnosis of viral hepatitis (aHR, 3.71; 95% CI, 3.26-4.24; P <.001), alcohol-associated liver disease (aHR, 1.32; 95% CI, 1.19-1.46; P <.001), and nonalcoholic fatty liver disease (NAFLD) (aHR, 1.92; 95% CI, 1.72-2.15; P <.001) were associated with HCC. Among veterans without cirrhosis, hypertension (aHR, 1.63; 95% CI, 1.23-2.15; P <.001) and diabetes (aHR, 1.52; 95% CI, 1.13-2.05; P = .005) were also associated with HCC. Early smoking and alcohol use were significant risk factors for HCC. In this large nationwide cohort study of Vietnam veterans, AO exposure was not associated with HCC. Smoking, alcohol, viral hepatitis, and NAFLD were the most important clinical risk factors for HCC.

Competing risk analysis of cardiovascular death in breast cancer: evidence from the SEER database.

Cardiovascular disease (CVD) is the leading cause of death for all non-cancer deaths among breast cancer (BC) patients. The aim of this study was to investigate the risk of cardiovascular mortality (CVM) in patients with BC. Patients diagnosed with primary BC between 2010 and 2018 were identified through the Surveillance, Epidemiology and End Results (SEER) database. The standardized mortality ratio (SMR) for CVD was calculated to compare the CVM of BC patients with that of the general population. Multivariate competing risk models were performed to identify predictors of CVM in BC patients. Overall, 399,014 BC patients were included from the SEER database, of whom 7,023 (1.8%) suffered death from CVD. The significantly higher overall SMR of CVM was observed in BC patients [SMR =4.84, 95% confidence interval (CI): 4.72-4.95]. Multivariate competing risk regression analysis revealed that age, race, American Joint Committee on Cancer (AJCC) stage, year of diagnosis, estrogen receptor (ER) status, progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status, BC subtype, surgery, chemotherapy, radiation therapy, and median household income as independent predictors of CVM in BC patients. Compared to the general population, BC patients have a higher risk of experiencing CVM during the follow-up period after diagnosis. Early detection and intervention of cardiovascular risk factors would improve overall survival (OS) of BC patients.

Risk Factors for the Development of New-Onset Persistent Atrial Fibrillation: Subanalysis of the VITAL Study.

Sustained forms of atrial fibrillation (AF) are associated with lower treatment success rates and poorer prognosis compared with paroxysmal AF. Yet, little is known about risk factors that predispose to persistent AF on initial presentation. Our objective was to define risk factors associated with new-onset persistent AF. We prospectively examined the differential associations between lifestyle, clinical, and socioeconomic risk factors and AF pattern (persistent versus paroxysmal) at the time of diagnosis among 25 119 participants without a history of cardiovascular disease, AF, or cancer in the VITAL rhythm study (Vitamin D and Omega-3). During a median follow-up of 5.3 years, 900 participants developed AF and 346 (38.4%) were classified as persistent at the time of diagnosis. In multivariable competing risk models, increasing age, male sex, White race, height, weight, body mass index ≥30 kg/m2, hypertension, current or past smoking, alcohol intake ≥2 drinks/day, postcollege education, and randomized treatment with vitamin D were significantly associated with incident persistent AF. Compared with paroxysmal AF, increasing age, male sex, weight, body mass index ≥30 kg/m2, and postcollege education were more strongly associated with persistent AF in multivariable models regardless of whether interim cardiovascular disease and heart failure events were censored. In a prospective cohort without baseline AF or cardiovascular disease, over one-third of AF at the time of diagnosis is persistent. Older age, male sex, postcollege education, and obesity were preferentially associated with persistent AF and represent a high-risk AF subset for population-based intervention.

The association between histological subtypes and lymph node metastasis and prognosis in early esophageal cancer: a population-based study.

There is still a lack of high-level clinical evidence and uniform conclusions on whether there are differences in lymph node metastasis (LNM) and prognosis between early esophageal adenocarcinoma (EAC) and squamous cell carcinoma (ESCC). Patients with surgically resected, histologically diagnosed, pT1 EAC or ESCC in the Surveillance, Epidemiology and End Results registries database from 2004 to 2015 were included. Multivariable logistic regression, Cox regression, multivariate competing risk model, and propensity score matching were used to analyze association the histology and LNM or prognosis. A total of 570 early esophageal cancer patients were included. The LNM rates were 13.8% and 15.1% for EAC and ESCC ( P = 0.757), respectively. Multivariate logistic regression analysis showed no significant association between histological type and LNM (odds ratio [OR], 1.209; 95% CI, 0.538-2.715; P = 0.646). Moreover, the prognosis of early EAC and ESCC was shown to be comparable in both multivariate Cox regression (hazard ratio [HR], 1.483; 95% CI, 0.699-3.150; P = 0.305) and the multivariate competing risk model (subdistribution HR, 1.451; 95% CI, 0.628-3.354; P = 0.383). After propensity score matching, there were no significant differences between early EAC and ESCC in terms of LNM (10.6% vs.18.2%, P = 0.215), 5-year CSS (89.8% [95% CI, 81.0%-98.6%] vs. 79.1% [95% CI, 67.9%-90.3%], P = 0.102) and 5-year cumulative incidence of CSS (10.2% [95% CI, 1.4%-19.0%] vs. 79.1% [95% CI, 9.7%-32.1%], P = 0.124). The risk of LNM and prognosis of early ESCC and EAC are comparable, so the treatment choice for early esophageal cancer does not depend on the histologic type.

Metastasis, characteristic, and treatment of breast cancer in young women and older women: A study from the Surveillance, Epidemiology, and End Results registration database.

Younger age is an independent risk factor for breast cancer (BC) prognosis, and BC in young women is often considered more aggressive. BC patients with different age and molecular subtypes have different metastasis patterns and survival. Herein, we aim to explore the metastasis patterns, characteristics and treatment methods of young patients with BC, and to compare them with older patients. Data of young patients (aged ≤40 years old) and older patients (aged >40 years old) with BC were extracted from the Surveillance, Epidemiology, and End Results (SEER) registration database in 2010-2019 in this retrospective cohort study. Univariate and multivariate competing risk models and proportional hazard models were used to explore the association between different metastasis patterns and treatments and BC prognoses in young and older patients. Kaplan-Meier (KM) curves were drawn to reflect the survival probability of patients with BC who have different metastasis patterns. Also, we performed subgroup analysis of different metastasis patterns to explore the association between different treatments and overall survival (OS)/cancer specific survival (CSS) in patients with BC. The evaluation index was hazard ratios (HRs) with 95% confidence intervals (CIs). Totally, 5,984 patients died, and 92.56% of them died from BC. There were respectively 1,089 young patients and 9,105 older patients, and we found some differences of characteristics and metastasis patterns between them. After adjusting for covariates, young patients who had brain metastasis and multiple sites metastasis seemed to have high risk of both lower OS and CSS. Among older patients with BC, brain metastasis, liver metastasis, and multiple sites metastasis were all positively associated with both lower OS and CSS. In young and older patients, those who not receive radiotherapy or surgery, or received non-surgery combined with radiotherapy seemed to have high risk of both lower OS and CSS. Breast-conserving surgery (BCS) and surgery combined with radiotherapy were associated with higher OS and CSS in young patients, while only older patients received surgery combined with radiotherapy had higher OS and CSS. Results of subgroup analysis indicated that for patients with different metastasis patterns, developing a personalized treatment plan is necessary. Characteristics of BC between young patients and older patients were different. Clinicians should focus on different metastasis sites and choose appropriate treatments in patients with different ages, which may improve the prognoses.

Sex Differences in the Development of Anthracycline-Associated Heart Failure

Female sex is frequently cited as a risk factor for anthracycline cardiotoxicity based on pediatric data, but the role of sex in the development of cardiotoxicity has not been clearly established in adults. To assess the effect of female sex on the development of incident heart failure (HF) in adult patients treated with anthracyclines. This was a retrospective cohort study of 1525 adult patients with no prior history of HF or cardiomyopathy who were treated with anthracyclines between 1992 and 2019. The primary outcome was new HF within 5 years of the first dose of anthracyclines. The effect of sex was assessed using Cox proportional hazards and competing risk models. Over a median (IQR) follow-up of 1.02 (0.30-3.01) years, 4.78% of patients developed HF (44 men and 29 women). Female sex was not associated with the primary outcome in a multivariable Cox proportional hazards model (HR 0.87; 95% CI 0.53-1.43; P = 0.58). Similar results were observed in a multivariable model accounting for the competing risk of death (HR 0.94; 95% CI 0.39-2.25; P = 0.88). Age, coronary artery disease and hematopoietic stem cell transplant were associated with the primary outcome in a multivariable Cox proportional hazards model. Age and body mass index were associated with the primary outcome in a multivariable competing risk model. In this large, single-center, retrospective cohort study, female sex was not associated with incident HF in adult patients treated with anthracyclines. Female sex is frequently cited as a risk factor for anthracycline cardiotoxicity based on pediatric data, but the role of sex in the development of cardiotoxicity has not been clearly established in adults. In this retrospective cohort study, we assessed the effect of female sex on the development of incident heart failure in adult patients treated with anthracyclines. Using Cox proportional hazards and competing risk regression models, we found that there was no association between female sex and heart failure after treatment with anthracyclines.

Competing risk analysis of cardiovascular-specific mortality in typical carcinoid neoplasms of the lung: A SEER database analysis.

Cardiovascular mortality (CVM) is a growing concern for cancer survivors. This study aimed to investigate the mortality patterns of individuals with typical carcinoid (TC) tumors, identify independent predictors of CVM, and compare these risk variables with those associated with TC deaths. The Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2019 was utilized for obtaining data on patients with TC. Standardized mortality rates were employed to evaluate the risk of CVM while multivariate competing risk models were used to determine the association between patient characteristics and the probability of CVM or TC-related deaths. Our findings show that TC patients had an increased risk of CVM, with an standardized mortality rates of 1.12 (95% CI:1.01-1.25). Furthermore, we discovered that age at diagnosis, marital status, year of diagnosis, SEER stage, site, year of diagnosis, surgery, radiotherapy, and chemotherapy all contributed independently to the risk of CVM in patients with TC, whereas age at diagnosis, sex, race, SEER stage, site, year of diagnosis, surgery, radiotherapy, and chemotherapy all contributed significantly to TC mortality. Compared to the general population in the United States, patients with TC are significantly more likely to acquire CVM. Timely introduction of cardioprotective treatments is critical for preventing CVM in patients with TC.

Statin use, survival and incidence of thrombosis among older patients with polycythemia vera and essential thrombocythemia.

Polycythemia vera (PV) and essential thrombocythemia (ET) are linked to increased risk of cardiovascular morbidity and mortality. In addition to the reduction in of arterial thrombotic events, statins may prevent venous thrombosis including among patients with cancer. As previous registry- and claims-based studies revealed that the use of statins may improve the survival of patients with various malignancies we evaluated their impact on outcomes of older adults with PV and ET. We identified 4010 older adults (aged 66-99 years at diagnosis) with PV (n = 1809) and ET (n = 2201) in a population-based cohort study using the Surveillance, Epidemiology, and End Results-Medicare database with median follow-up of 3.92 (interquartile range: 2.58-5.75) years. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) approaches were utilized to assess potential association between statins and overall survival. Multivariable competing risk models with death as a competing risk were used to evaluate possible relationship between statins and the incidence of thrombosis. 55.8% of the patients used statins within the first year after PV/ET diagnosis, and statin use was associated with a 22% reduction in all-cause mortality (PSM: hazard ratio [HR] = 0.78, 95% confidence interval [CI]: 0.63-0.98, p = 0.03; IPTW: HR = 0.79, 95% CI: 0.64-0.97, p = 0.03). Statins also reduced the risk of thrombosis in this patient population (PSM: HR = 0.63, 95% CI: 0.51-0.78, p < 0.01; IPTW: HR = 0.57, 95% CI: 0.49-0.66, p < 0.01) as well as in PV and ET subgroups. These findings suggest that it may be important to incorporate statins into the therapeutic strategy for older adults with PV and ET.

Rate of Kidney Function Decline is Associated With Kidney and Heart Failure in Individuals With Type 1 Diabetes

Diabetes is the most common cause of chronic kidney disease (CKD). Urinary albumin excretion rate (AER) and estimated glomerular filtration rate (eGFR) are commonly used to monitor the onset and progression of diabetic kidney disease (DKD). We studied if the preceding rate of kidney function decline, that is, the eGFR slope, is independently associated with incident clinical cardiorenal events. This study included longitudinal data for 2498 Finnish individuals with type 1 diabetes (T1D). The eGFR slope was calculated from 5 years preceding the study visit. Data on kidney failure, coronary heart disease (CHD), stroke, 3-point major adverse cardiovascular events (MACE), heart failure, and death were obtained from national registries. The associations between the eGFR slope and incident events were assessed with multivariable competing risk models during the average follow-up of 9.2 years. The eGFR slopes were associated (P≤ 0.001) with all outcomes when adjusted for age, sex, and HbA1c. However, eGFR slope remained associated only with the composite outcome of kidney failure or death when the albuminuria group and eGFR at the study visit were included in the model (P= 0.041). In addition, eGFR slope was independently associated with kidney failure in individuals without CKD (eGFR > 60 ml/min per 1.73 m2; P= 0.044), and with heart failure in those with CKD (P= 0.033). However, eGFR slope did not markedly improve the model C-index. The eGFR slope was independently associated with kidney failure in those without CKD, and with heart failure in those with CKD. However, it is unlikely to have major relevance for clinical practice when the current eGFR and albuminuria status are known.

Identification of risk factors and development of a predictive model for bloodstream infection in intensive care unit COVID-19 patients

To identify risk factors for nosocomial bloodstream infections (BSIs) in intensive care unit (ICU) patients with COVID-19 and to build a predictive model for BSIs. The retrospective case-control study included 236 ICU COVID-19 patients with BSIs group and 234 patients in the control group. Demographic and laboratory data, comorbidities, drug use, invasive procedures and identified pathogens were recorded separately for patients directly admitted and transferred to ICU. Fine and Gray's multi-variate competing risk model was used to build a predictive model for patients transferred to ICU. The risk factors were: interleukin inhibitors (HR= 6.1 (95% CI: 2.0-18.5)) and dexamethasone (HR= 3.0 (95% CI: 1.3-7.1)) use in previous hospitalization, glomerular filtration rate <60mL/min per 1.73m2 (HR= 4.0 (95% CI: 2.1-7.6)) and blood glucose >9mmol/L (HR= 2.5 (95% CI: 1.4-4.6)) in patients directly admitted to ICU; and dexamethasone use in previous hospitalization (HR= 4.5 (95% CI: 1.8-11)), the total dexamethasone dose before transfer to ICU (HR= 1.2 (95% CI: 1.06-1.37)), diabetes mellitus (HR= 1.4 (95% CI: 1.1-1.9)), alanine transaminase (ALT) ≥35.5 U/L on hospital admission (HR= 1.5 (95% CI: 1.1-2.1)), and the use of low-flow oxygen versus high-flow oxygen therapy or non-invasive mechanical ventilation on admission to ICU ((HR= 2.7 (95% CI: 5.6-11.1)) in patients transferred to ICU. A predictive model had sensitivity of 63-73% and specificity of 71-83% at different times of ICU stay. Our findings may help clinicians detect patients at high risk of developing BSIs.