Cox Proportional Hazards Research Articles

Modeling the output from a commercial chemical process using regression models from survival analysis

This article is concerned with the modeling of the gas output of a commercial chemical plant using the coal sources as predictor variables. We consider the use of two models to incorporate these predictors; the Cox proportional hazards and accelerated failure time regression models. These models are chosen for their simplicity and for the ease with which the effects of explanatory variables can be interpreted. The contribution of this article lies therein that these models are used in the current context for the first time. We show, using both graphical and formal hypothesis testing procedures that these models (with a Weibull baseline distribution) fit observed gas production data well. We provide a discussion of the interpretation of the estimated model parameters and we comment on how these estimates can be of substantial practical value. The large scale of production from the chemical plant in question ensures that potential cost savings and increases in production associated with more accurate models are of great practical importance.

Enhancing outcomes in extensive-stage small cell lung cancer brain metastases: a retrospective study on the synergistic effects of immune checkpoint inhibitor, brain radiotherapy, and chemotherapy.

Brain metastasis is a frequent complication in small cell lung cancer (SCLC), and there is an urgent need for new treatment modalities, given the limited success of traditional approaches. This study evaluates the combined efficacy and safety of brain radiotherapy (BRT), chemotherapy, and immune checkpoint inhibitors (ICIs) in the treatment of brain metastases in patients with extensive-stage SCLC (ES-SCLC). Additionally, it seeks to identify prognostic factors in these cases. A retrospective analysis was performed on 187 patients with ES-SCLC and brain metastases treated at Zhejiang Cancer Hospital from January 2017 to October 2023. Patients were divided into three groups based on their initial treatment: BRT alone, ICI alone, and a combined ICI + BRT approach, with chemotherapy included in all regimens. Variables such as age, number of brain metastases, symptoms, comorbidities, Karnofsky Performance Status (KPS) scores, smoking history, Graded Prognostic Assessment (GPA) scores, survival time, and treatment-related adverse events (TRAEs), including hematologic and hepatic toxicities were evaluated. Prognostic factors were assessed using univariate and multivariate analyses via Cox's proportional hazards model. The study also compared outcomes and TRAEs between patients undergoing synchronous treatment (ICI and BRT within four weeks) versus those with asynchronous therapy (more than four weeks apart). Median overall survival (OS) times differed significantly across the groups: 11.6 months for BRT, 11.6 months for ICI, and 20.9 months for ICI + BRT (P<0.001). The ICI + BRT group also exhibited notably better progression-free survival (PFS) and intracranial PFS (iPFS), with medians of 12.6 and 14.9 months, respectively (P<0.001). This group demonstrated significantly improved systemic and intracranial objective response rates (ORR) and disease control rates (DCR). No significant differences in acute radiation injury rates were observed between the BRT and ICI + BRT groups. Multivariate analysis identified several factors influencing OS, including treatment regimen, number of chemotherapy and ICI cycles, presence of bone and multiple brain metastases, and antiangiogenesis therapies and extracranial radiotherapy. Both atezolizumab and serplulimab ICIs, in combination with various radiotherapy regimens [whole BRT (WBRT), WBRT with boost], were effective. Notably, asynchronous ICI and BRT treatment demonstrated advantages in PFS and iPFS over concurrent therapy, with no significant differences in other therapeutic indices or TRAE incidence rates. For ES-SCLC patients with synchronous brain metastases, combined ICI and BRT, alongside chemotherapy, surpasses the efficacy of either treatment alone with manageable TRAEs. Importantly, asynchronous ICI and BRT therapy showed superior outcomes compared to synchronous treatment modalities.

Mortality follow-up of Fernald Feed Materials Production Center workers exposed to uranium from 1951 to 1985

ObjectiveThis follow-up study of uranium processing workers at the Fernald Feed Materials Production Center examines the relationship between radiation exposure and cancer and non-cancer mortality among 6403 workers employed for...

Identifying Survival Subtypes of Esophageal Squamous Cell Carcinoma Patients: An Application of Deep Learning in Gene Expression Data Analysis

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most lethal types of cancer. Late diagnosis significantly decreases patient survival rates. Objectives: The study aimed to identify survival groups for patients with ESCC and find predictive biomarkers of time-to-death from ESCC using state-of-the-art deep learning (DL) and machine learning algorithms. Methods: Expression profiles of 60 ESCC patients, along with their demographic and clinical variables, were downloaded from the GEO dataset. A DL autoencoder model was employed to extract lncRNA features. The univariate Cox proportional hazard (Cox-PH) model was used to select significant extracted features related to patient survival. Hierarchical clustering (HC) identified risk groups, followed by a decision trees algorithm which was used to identify lncRNA profiles. We used Python.3.7 and R.4.0.1 software. Results: Inputs of the autoencoder were 8,900 long noncoding RNAs (lncRNAs), of which 1000 features were extracted. Out of the features, 42 lncRNAs were significantly related to time-to-death using the Cox-PH model and used as input for clustering of patients into high and low-risk groups (P-value of log-rank test = 0.022). These groups were then labeled for supervised HC. The C5.0 algorithm achieved an overall accuracy of 0.929 on the test set and identified four hub lncRNAs associated with time-to-death. Conclusions: Novel discovered lncRNAs lnc-FAM84A-1, LINC01866, lnc-KCNE4-2 and lnc-NUDT12-4 implicated in the pathogenesis of death from ESCC. Our findings represent a significant advancement in understanding the role of lncRNAs on ESCC prognosis. Further research is necessary to confirm the potential and clinical application of these lncRNAs.

Predictors of mortality by an artificial intelligence enhanced electrocardiogram model for cardiac amyloidosis.

We aim to determine if our previously validated, diagnostic artificial intelligence (AI) electrocardiogram (ECG) model is prognostic for survival among patients with cardiac amyloidosis (CA). A total of 2533 patients with CA (1834 with light chain amyloidosis (AL), 530 with wild-type transthyretin amyloid protein (ATTRwt) and 169 with hereditary transthyretin amyloid (ATTRv)] were included. An amyloid AI ECG (A2E) score was calculated for each patient reflecting the likelihood of CA. CA stage was calculated using the European modification of the Mayo 2004 criteria for AL and Mayo stage for transthyretin amyloid (ATTR). Risk of death was modelled using Cox proportional hazards, and Kaplan-Meier was used to estimate survival. Median age of the cohort was 67 [inter-quartile ratio (IQR) 59, 74], and 71.6% were male. The median overall survival for the cohort was 35.6months [95% confidence interval (CI) 32.3, 39.5]. For AL, ATTRwt and ATTRv, respectively, median survival was 22.9 (95% CI 19.2, 28.2), 47.2 (95% CI 43.4, 52.3) and 61.4 (95% CI 48.7, 75.9) months. On univariate analysis, an increasing A2E score was associated with more than a two-fold risk of all-cause death. On multivariable analysis, the A2E score retained its importance with a risk ratio of 2.0 (95% CI 1.58, 2.55) in the AL group and 2.7 (95% CI 1.81, 4.24) in the ATTR group. Among patients with AL and ATTR amyloidosis, the A2E model helps to stratify risk of CA and adds another dimension of prognostication.

Tislelizumab synergizes with surgery to augment the survival benefit in stage II-III non-small cell lung cancer

ObjectivesThis retrospective study evaluated the individual benefits of tislelizumab and surgery, as well as their synergistic effect on progression-free survival (PFS) and overall survival (OS) of stage II-III non-small cell lung cancer (NSCLC) patients.MethodsFrom September 2019 to June 2022, all participants with potentially resectable NSCLC who received chemotherapy (C) or tislelizumab plus chemotherapy (T) were included in the study. Participants were categorized into four groups based on surgery or not (S or NS) and the utilization of tislelizumab (T or C). Progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan–Meier method and log-rank test, as well as Cox proportional hazards models.ResultsCompared to C, T was associated with significantly higher objective response rate (64.54% vs. 34.78%, p = 0.003), higher pathological complete response rate (40.00% vs. 14.06%, p = 0.007), and higher major pathological response rate (60.00% vs. 20.31%, p < 0.001). The T + S group exhibited a proportionately higher reduction in the risk of disease progression or death compared to the sum of the T + NS group and C + S group. Regardless of C or T, surgery was associated with improved OS (p < 0.01). Without surgery, T did not show significant improvement in PFS or OS. However, with surgery, T significantly improved both PFS and OS (ps < 0.01).ConclusionTislelizumab with subsequent surgery synergistically improves the survival benefits in patients with NSCLC.

Volunteering and Risk of Heart Attack in Later Life: The Moderating Role of Purpose in Life?

Objectives: We investigate whether volunteering is associated with a reduced risk of first heart attack in later life and whether purpose in life moderates this relationship. Methods: Cox proportional hazards were used to examine seven waves of data (2006-2018) from the Health and Retirement Study-a nationally representative survey of adults 50 years and older (N = 5,079). Results: Volunteering a moderate number of hours was associated with a 46% lower risk of heart attack compared to non-volunteers. The association between high time-commitment volunteering and heart attack risk was contingent on level of purpose in life: compared to non-volunteers, people with high purpose in life who volunteered 100 + hours had the lowest risk of heart attack. Discussion: Meaningful volunteer activities may be one way for older adults to reduce their risk of heart attack.

An evaluation of the racial equity of the actuarial Family risk assessment instrument used in Queensland, Australia

BackgroundRisk assessment instruments used in child protection to guide intervention decisions should be equitable. To be considered equitable, two criteria are necessary: instruments should avoid discriminatory logic and display comparative validity for children of different races. Empirical evidence about the equity of risk assessment instruments is limited. Objective: To investigate the racial equity of a widely used risk assessment instrument, the Structured Decision Making Family Risk Assessment (FRA). Participants and setting: Administrative data were obtained for all children subject to investigation in Queensland, Australia in 2018, for whom an FRA was completed (n = 17,851). MethodsRelationships between FRA items, race, and recurrence (subsequent investigation within 12 months) were explored using crosstabulations and Cox Proportional Hazards. Accuracy of FRA recommendations and practitioner decisions were compared using sensitivity and specificity for Indigenous and non-Indigenous children. ResultsMost FRA items predicted race better than recurrence. Differences in recurrence by race were only partially explained by FRA items. The FRA produced high rates of false positives for Indigenous children (incorrectly classifying 48.9% of children who did not recur compared to 31.7% for non-Indigenous children) and high rates of false negatives for non-Indigenous children (incorrectly classifying 59% of children who did recur compared to 39% for Indigenous children). Practitioner discretion did not mitigate inequitable FRA recommendations. ConclusionsThe FRA failed both criteria of equity, discriminating indirectly by relying heavily on factors correlated with race, and demonstrating less accuracy for Indigenous children. High rates of false positives for Indigenous children exacerbate Indigenous overrepresentation in child protection.

Post-discharge functional outcomes in older patients with sepsis

BackgroundThe post-discharge prognosis of patients with sepsis remains a crucial issue; however, few studies have investigated the relationship between pre-sepsis health status and subsequent prognosis in a large population. This study aimed to examine the effect of the pre-sepsis care needs level on changes in care needs and mortality in patients with sepsis 1 year post-discharge.MethodsThis was a population-based retrospective cohort study including twelve municipalities in Japan that participated in the Longevity Improvement & Fair Evidence study between April 2014 and March 2022, with a total of 1,491,608 persons. The pre-hospitalization levels of care needs (baseline) were classified from low to high, as no care needs, support level and care needs level 1, care needs levels 2–3, and care needs levels 4–5 (fully dependent). The outcomes were changes in care needs level and mortality 1 year post-discharge, assessed by baseline care needs level using Cox proportional hazard models.ResultsThe care needs levels of 17,648 patients analyzed at baseline were as follows: no care needs, 7982 (45.2%); support level and care needs level 1, 3736 (21.2%); care needs levels 2–3, 3089 (17.5%); and care needs levels 4–5, 2841 (16.1%). At 1 year post-discharge, the distribution of care needs were as follows: no care needs, 4791 (27.1%); support level and care needs level 1, 2390 (13.5%); care needs levels 2–3, 2629 (14.9%); care needs levels 4–5, 3373 (19.1%); and death, 4465 (25.3%). Patients with higher levels of care needs exhibited an increased association of all-cause mortality 1 year post-discharge after adjusting for confounders [hazard ratios and 95% confidence intervals: support level and care needs level 1, 1.05 (0.96, 1.15); care needs levels 2–3, 1.46 (1.33, 1.60); and care needs levels 4–5, 1.92 (1.75, 2.10); P for trend < 0.001].ConclusionsElevated care needs and mortality were observed in patients with sepsis within 1 year post-discharge. Older patients with sepsis and higher baseline levels of care needs had a high association of all-cause mortality 1 year post-discharge.

Risk analysis of blood pressure changes on cardiovascular disease in Chinese population.

The study aimed to assess the impact of changes in blood pressure on cardiovascular events in the Chinese population. It enrolled 33 179 Chinese participants aged ≥35 years (57.1% women) without CVD at baseline. BP status was defined according to the 2017 ACC/AHA hypertension guidelines. The type of BP change was defined as change in BP status from baseline to the end of follow-up, included stable BP<130/80, <130/80 to ≥130/80, ≥130/80 to<130/80mm Hg, persistent BP ≥130/80mm Hg. The hazard ratio (HR) of incident CVD by change in BP category was estimated using Cox proportional hazards and Fine-Gray models. During median follow-up of 3.17 years, 2023 CVD events occurred. Compared with BP<120/80, 120-129/<80mm Hg at baseline (HR=1.66, 95% CI: 1.09-2.53), 130-139/80-89mm Hg (HR=1.35, 95% CI: 0.94-1.95), and ≥140/90mm Hg (HR=2.46, 95% CI: 1.78-3.40) were risk factors for CVD. Compared with the group with stable BP<130/80mm Hg, the risk of CVD was 1.88 (95% CI: 1.40-2.53) in the group with persistent BP ≥130/80mm Hg and 1.40 (95% CI: 1.01-1.94) in the group of BP decreased to<130/80mm Hg. These results showed that BP 120-129/<80, 130-139/80-89, and ≥140/90mm Hg were associated with a high risk of CVD. Over time, persistent BP ≥130/80mm Hg increased the risk of CVD, but a return to<130/80mm Hg from hypertension decreased the risk of CVD.

Skin autofluorescence and cause-specific mortality in a population-based cohort

We aimed to assess the association of SAF with cardiovascular mortality in the general population and the possible association between SAF with other disease-specific mortality rates. We evaluated 77,143 participants without known diabetes or cardiovascular disease. The cause of death was ascertained by the municipality database. The associations between SAF and all-cause mortality, cardiovascular mortality and cancer mortality were assessed with Cox proportional hazard analysis.After a median follow-up of 115 months, 1447 participants were deceased (1.9%). SAF and age-adjusted SAF-z score were higher in all mortality groups. Cox regression analysis revealed that the highest quartile of SAF was associated with increased odds of cardiovascular mortality, (HR) 12.6 (7.3–21.7) and after adjusting for age (HR 1.8 (1.0–3.2)). Significance was lost after additional adjustments for sex, smoking status, and BMI (HR 1.4 (0.8–2.5). For cancer-related mortality the highest quartile of SAF was associated with higher probability of mortality in all models (unadjusted HR 8.6 (6.6–11.3), adjusted for age HR 2.1 (1.6–2.8)), adjusted for age, sex, smoking status, and BMI HR 1.7 (1.3–2.4)). SAF is associated with all-cause mortality as well as cardiovascular and cancer-related mortality in the general population.

Cohort Study in Outcome and One-Year Mortality of Acute Stroke Patient in Academic Hospital Universitas Gadjah Mada

Background: Stroke is still becoming one of the most common non-communicable diseases in Indonesia. Sample Registration System survey in 2016 showed that in Indonesia stroke has become the most common cause of death at all age, about 19.9%. 4 Research conducted by Novbakht found that age, sex, BMI, type of stroke, family history of stroke, hyperlipidaemia, diabetes, and severity of stroke was related and increased the mortality rate. 6 Academic Hospital Universitas Gadjah Mada had not conducted this type of research, so that researcher wanted to know the one-year mortality rate after stroke, factors that related to mortality, and to improve the quality of stroke treatment at Academic Hospital Universitas Gadjah Mada.Objective: To know one-year mortality rate in acute stroke patients in Academic Hospital Universitas Gadjah Mada by looking for the acute stroke characteristic, outcome of stroke patients, and risk factors that cause mortality in stroke patients.Method: This is an analytic research using retrospective cohort study through data collection of acute stroke patients (patients with &lt;5 days stroke onset) during July 2019 until June 2022 then we followed up the condition in the first year after stroke by using medical records, direct examination, or via telephone or video call. Mortality rates were assessed one year after stroke and the predictors of death were evaluated using the cox proportional hazard model.Result: One-year mortality after stroke in our study were related to age (&gt;67 years old) (OR=2,29; 95% CI 1,18-4,46; p=0,015) and the severity of stroke was related to higher NIHSS score (NIHSS score during admission 16-42, (OR=38,49; 95% CI 8,92-166,0; p&lt;0,001)) and ICU admission ((OR=8,01; 95% CI 4,03-15,90; p&lt;0,001)). Conclusion: An association was found between stroke severity and one-year outcomes of acute stroke patients with old age (&gt;67 years), high NIHSS scores, and ICU admissions

Investigating the Obesity Paradox in Colorectal Cancer: An Analysis of Prospectively Collected Data in a Diverse Cohort.

Prior studies are inconclusive regarding the effect of obesity on mortality in persons with colorectal cancer (CRC). We sought to determine the association of pre-diagnosis body mass index (BMI) trajectories on mortality after CRC diagnosis. Utilizing the Multiethnic Cohort, we included adults aged 18-75 between 1 January 1993 and 1 January 2019 with a diagnosis of CRC and at least three available BMIs. The primary exposure, BMI, was subjected to group-based trajectory modeling (GBTM). We evaluated all-cause and CRC-specific mortality, using Cox proportional hazard (PH) models. Of 924 persons, the median age was 60 years, and 54% were female. There was no statistically significant association between pre-cancer BMI trajectory and either all-cause or cancer-specific mortality. In competing risk analysis, the risk of CRC-specific mortality was higher for African Americans (HR = 1.56, 95% CI [1.00-2.43], p = 0.048) and smokers (HR = 1.59, 95% CI [1.10-2.32], p = 0.015). Risk of all-cause mortality was higher for Hawaiian persons (HR = 2.85, 95% CI [1.31-6.21], p = 0.009) and persons with diabetes (HR = 1.83, 95% CI [1.08-3.10], p = 0.026). Pre-diagnosis BMI trajectories were not associated with mortality after CRC diagnosis, whereas race/ethnicity, diabetes, and smoking were associated with an increased risk of death. Our findings suggest the obesity paradox alone does not account for mortality after CRC diagnosis.

The role of ultra-processed foods in plant-based diets: associations with human health and environmental sustainability.

Investigate the associations of ultra-processed foods (UPF) in healthful (hPDI) and unhealthful (uPDI) plant-based diets with all-cause mortality, greenhouse gas emissions (GHGE), and blue water consumption (BWC). Analyses were based on 35,030 participants (20-70 years; 74% females) from the EPIC-NL cohort who were followed up from 1993 to 1997 through 2014. Plant-based diet indices (hPDI and uPDI) and UPF consumption were calculated from a validated FFQ, assessed at baseline. Cox proportional hazard and multiple linear regression models were used to estimate associations between combined quartiles of the PDI indices and UPF consumption. With lower hPDI and higher UPF diets as the reference, we observed the following. Risk estimates of all-cause mortality were 0.98 (95% CI: 0.83, 1.16) for lower UPF consumption, 0.86 (95% CI: 0.68, 1.08) for higher hPDI, and 0.78 (95% CI: 0.66, 0.89) for combined higher hPDI and lower UPF consumption. Results with the uPDI were inconclusive. Mean differences in GHGE and BWC were 1.4% (95% CI: 0.3, 2.4) and 1.6% (95% CI: -0.5, 3.7) for lower UPF consumption, -7.4% (95% CI: -8.6, -6.4) and 9.6% (95% CI: 7.2, 12.0) for higher hPDI, and - 6.8% (95% CI: -7.4, -6.1) and 13.1% (95% CI: 11.6, 14.8) for combined higher hPDI and lower UPF consumption. No apparent conflict between environmental impacts was observed for the uPDI; GHGE and BWC were lower for higher uPDI scores. Mortality risk and environmental impacts were mostly associated with the amount of plant-based foods and to a lesser extent UPF in the diet. Shifting to a more healthful plant-based diet could improve human health and reduce most aspects of environmental impact (GHGE, but not BWC) irrespective of UPF consumption.

Moderately hypofractionated prostate-only versus whole-pelvis radiotherapy for high-risk prostate cancer: A retrospective real-world single-center cohort study

BackgroundThe benefit of prophylactic whole pelvis radiation therapy (WPRT) in prostate cancer has been debated for decades, with evidence based mainly on conventional fractionation targeting pelvic nodes. AimThis retrospective cohort study aimed to explore the impact of adding moderately hypofractionated pelvic radiotherapy to prostate-only irradiation (PORT) on prognosis, toxicity, and quality of life in real-world settings. Materials and methodsPatients with high-risk and conventionally staged prostate cancer (cT1-3N0M0) treated with moderately hypofractionated WPRT or PORT, using external beam radiotherapy alone or combined with high-dose-rate brachytherapy, at Örebro University Hospital between 2008 and 2021 were identified. Biochemical failure-free survival (BFFS), metastasis-free survival (MFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were compared using Kaplan-Meier method and Cox proportional hazards. Toxicity and quality of life measures were also analysed. ResultsAmong 516 patients (227 PORT, 289 WPRT), 5-year BFFS rates were 77 % (PORT) and 74 % (WPRT), adjusted HR=1.50 (95 % CI=0.88–2.55). No significant differences were found in MFS, PCSS, or OS in main analyses. WPRT was associated with a higher risk of acute grade ≥ 2 and 3 genitourinary toxicities whereas no differences in late toxicities or quality of life between PORT and WPRT were observed. ConclusionWe found no significant differences in oncological outcomes or quality of life when comparing moderately hypofractionated PORT to WPRT. Some differences in toxicity patterns were observed. Despite caveats related to study design, our findings support the need for further research on WPRT’s impact on treatment-related and patient-reported outcomes.

Influence of HIV status on outcomes of children admitted with sepsis at a paediatric hospital in Zambia: protocol for a prospective longitudinal study

IntroductionSepsis, a condition of global public health concern, is a major cause of morbidity and mortality, especially in patients with underlying HIV infection. This study aims to determine outcomes, aetiology...

Disparities in postdischarge follow-up and risk of readmission between Medicaid and privately insured patients.

Studies have identified higher risk of readmission for patients with Medicaid compared to those with private insurance. Postdischarge follow-up is utilized as an intervention to reduce readmissions in the Medicare population, but it is unclear whether follow-up reduces risk of readmission for patients with Medicaid. To assess whether follow-up within 30 days of discharge reduces risk of readmission and mitigates readmission disparities based upon insurance status. This retrospective cohort study used Cox proportional hazard and competing risk models to estimate associations between sociodemographic and clinical characteristics, follow-up, and readmission. We analyzed data from 4281 patients aged 21-64 years with Medicaid or private insurance who were hospitalized from January 2017 to December 2019 for one of five conditions associated with high risk of readmission. Outpatient follow-up within 30 days of discharge and 30-day all-cause readmission were outcomes. Overall risk of readmission was similar for Medicaid and privately insured patients in this cohort (13.7% and 14.5%, respectively). Patients with Medicaid were 23% points less likely to complete outpatient follow-up within 30 days compared to patients with private insurance (p < .001). However, outpatient follow-up before readmission within 30 days of discharge was not associated with a significant difference in readmission rate (hazard ratio: 1.10, 95% confidence interval: 0.91-1.32) in the overall sample or in analysis stratified by payer. We found similar rates of readmission for Medicaid and privately insured patients despite significant disparities in postdischarge follow-up. Timely follow-up care alone may not be sufficient as an intervention to reduce readmissions.

Economic Benefits of Surgical Aortic Valve Replacement on Patients With Symptomatic Aortic Valve Regurgitation.

Aortic regurgitation is distinguished by the backflow of blood from the aorta into the left ventricle. American College of Cardiology/American Heart Association guidelines recommend surgical aortic valve replacement (SAVR) for patients with symptomatic aortic regurgitation (sAR). This study estimates the difference in mortality, health care use, and costs between patients with sAR who receive SAVR within 12 months of diagnosis versus those who do not. We used the Optum United Healthcare database to identify 132 317 patients diagnosed with sAR from 2016 to 2021 who had at least 6 months of enrollment before sAR and 12 months of enrollment after. Criteria were no history of aortic stenosis or transcatheter aortic valve replacement and ≥2 visits for heart failure, angina, dyspnea, or syncope. Outcomes were all-cause mortality, health care use, and annualized cost. Baseline differences in demographics and comorbidities were adjusted with inverse propensity score weighting. We modeled survival and estimated health care use and costs using Cox proportional hazards and general linear models, respectively. Of the 132 317 patients, 400 underwent SAVR within 12 months of diagnosis. They were on average younger, more often men, and with a slightly higher Elixhauser Comorbidity Index score. After inverse propensity score weighting, patients with sAR who had SAVR had lower mortality, fewer inpatient and emergency department visits, fewer hospital days, and lower annualized cost. SAVR performed within 12 months of an sAR diagnosis is associated with improved mortality and lower annualized health care use and costs. These clinical and economic benefits should be considered when managing patients with sAR.

Prognostic Nomogram Predicting Survival and Propensity Score Matching with Demographics and Comparative Analysis of Prostate Small Cell and Large Cell Neuroendocrine Carcinoma.

Background: This retrospective study aims to examine the patient demographics, survival rates, and treatment methods for small-cell neuroendocrine carcinoma (SCNEC) and large-cell neuroendocrine carcinoma (LCNEC) of prostate origin while also identifying the main differences between common types of prostate cancer with comparative analysis for survival. Methods: Our analysis utilized the Surveillance, Epidemiology, and End Results database (SEER), and data was collected from 2000-2020. Cox proportional hazards and chi-squared analysis were used for statistical analysis. Results: A total of 718 cases of prostate small and large neuroendocrine carcinoma were identified. The median age was 71.5 years, and the median follow-up was 11.0 years (95% confidence interval (95% CI) = 9.2-12.8). Most patients were over the age of 80 years (33.8%) and Caucasian (74.4%). The overall 5-year survival was 8.0% (95% CI = 6.8-9.2). The 5-year OS for Caucasians was 7.3% (95% C.I. 6.0-8.3). For Black Americans, the 5-year OS was 11.9% (95% C.I. 7.3-16.5). For Hispanics, the 5-year OS was 12.2% (95% C.I. 7.7-16.7). The 5-year cause-specific survival (CSS) was 16.2% (95% CI = 14.3-18.1). For treatment modality, the five-year survival for each were as follows: chemotherapy, 3.5% (95% CI = 2.1-4.9); surgery, 18.2% (95% CI = 13.6-22.8); multimodality therapy (surgery and chemotherapy), 4.8% (95% CI = 1.7-7.9); and combination (chemoradiation with surgery), 5.0% (95% CI = 1.0-9.0). The prognostic nomogram created to predict patient survivability matched the findings from the statistical analysis with a statistical difference found in race, income, housing, stage, and nodal status. The nomogram also indicated a slight increase in mortality with tumors of greater size. This analysis showed a slight increase in mortality for patients of Asian race. In addition, there was a significant increase in death for patients with stage 3 tumors, as well as patients who underwent surgery and radiation. Furthermore, we performed propensity score matching for survival differences, and no survival difference was found between SCNEC and LCNEC. Conclusions: Asian patients, larger tumor size, and distant disease were associated with worse long-term clinical outcomes. By leveraging insights from registry-based studies, clinicians can better strategize treatment options, improving patient outcomes in this challenging oncology arena.

Visual predictive check of longitudinal models and dropout.

Visual predictive checks (VPC) are commonly used to evaluate pharmacometrics models. However their performance may be hampered if patients with worse outcomes drop out earlier, as often occurs in clinical trials, especially in oncology. While methods accounting for dropouts have appeared in literature, they vary in assumptions, flexibility, and performance, and the differences between them are not widely understood. This manuscript aims to elucidate which methods can be used to handle VPC with dropout and when, along with a more informative VPC approach using confidence intervals. Additionally, we propose constructing the confidence interval based on the observed data instead of the simulated data. The theoretical framework for incorporating dropout in VPCs is developed and applied to propose two approaches: full and conditional. The full approach is implemented using a parametric time-to-event model, while the conditional approach is implemented using both parametric and Cox proportional-hazard (CPH) models. The practical performances of these approaches are illustrated with an application to the tumor growth dynamics (TGD) modeling of data from two cancer clinical trials of nivolumab and docetaxel, where patients were followed until disease progression. The dataset consisted of 3504 tumor size measurements from 855 subjects, which were described by a TGD model. The dropout of subjects was described by a Weibull or CPH model. Simulated datasets were also used to further illustrate the properties of the VPC methods. The results showed that the more familiar full approach might not provide meaningful improvement for TGD model evaluation over the naive approach of not adjusting for dropout, and could be outperformed by the conditional approach using either the Weibull model or the Cox proportional hazard model. Overall, including confidence intervals in VPC should improve interpretation, the conditional approach was shown to be more generally applicable when dropout occurs, and the nonparametric approach could provide additional robustness.