Multivariate Cox Proportional Hazards Research Articles

Recompensation of Liver Cirrhosis by TIPS Reduces Epithelial Cell Death Markers, Translating Into Improved Clinical Outcome

ABSTRACTBackground and AimsPortal hypertension is the main pathophysiological driver of decompensation in patients with liver cirrhosis. Epithelial cell death markers, m30 and m65, correlate with hepatic injury and predict outcomes across various stages of liver disease. We aim (i) to evaluate whether portal hypertension itself contributes to liver outcome‐relevant epithelial injury, and (ii) to analyse the capacity of m30/m65 to predict outcome in patients receiving a transjugular intrahepatic portosystemic shunt (TIPS) for refractory ascites.MethodsSixty‐six patients undergoing TIPS placement for refractory ascites and 20 patients with compensated cirrhosis as controls were prospectively enrolled in this monocentric cohort study. Epithelial cell death markers were analysed pre‐TIPS, as well as 1–3 and 6–9 months post‐TIPS. The capacity of baseline levels of m30/m65 in predicting six‐month transplant‐free survival rates was analysed by multivariable Cox proportional hazards regression.ResultsLevels of m30 and m65 were higher in patients with decompensated cirrhosis (pre‐TIPS) compared with compensated cirrhosis (controls). Following correction of portal hypertension by TIPS and recompensation, both markers decreased over time, reaching levels comparable to patients with compensated cirrhosis. On multivariable analysis, pre‐TIPS baseline levels of m30 and m65 were not predictive for six‐month survival.ConclusionCorrection of portal hypertension via TIPS reduces levels of epithelial cell death markers, indicating that portal hypertension is a driver of outcome‐relevant, hepatic cell death in patients with decompensated cirrhosis. Baseline m30/m65 values do not affect six‐month survival rates, which suggests that TIPS placement overcomes the unfavourable spontaneous prognosis otherwise indicated by elevated baseline m30/65 levels.

Abstract 4124457: Socioeconomic Deprivation is Associated with Readmission Within One Year After Atrial Fibrillation Ablation

Introduction: Gender and race have been shown to impact access and outcomes regarding rhythm control management such as atrial fibrillation (AF) ablation. We aimed to evaluate the role of the Area Deprivation Index (ADI), a validated metric that represents the social disadvantage of communities, to determine if socioeconomic disadvantage (SED) increases the risk of readmission within one year after AF ablation. Methods: Patients ages ≥18 were identified in the Healthcare Cost and Utilization Project State Ambulatory Surgery and Services Databases in New York and Florida from 2016-2019 with follow-up into 2020 into the inpatient setting. These states were chosen due to availability for linkage of the 2020 ADI. International Classification of Diseases 10 and Current Procedural Terminology codes for AF and AF ablation were used. The risk of readmission was assessed using multivariable Cox proportional hazards with covariates age, sex, race, insurance, Charlson Comorbidity Index (0 vs ≥ 1 comorbidity), and ADI quartiles. ADI is scored 1-100 with higher scores representing more disadvantage. Results: 14,078 patients met inclusion criteria. The readmission rate at one, three, and twelve months was 6.1%, 9.9%, and 20.9% respectively. The most common readmission diagnoses at twelve months were AF (22.8%), followed by symptoms such as chest pain, dyspnea, palpitations, and syncope (13%). In the adjusted model, older age, female sex, federal insurance, ≥ 1 Charlson comorbidity, and higher ADI had higher one-, three-, and twelve-month risks of readmission. Hispanic ethnicity had a higher risk of one month readmission. Conclusion: Readmission for AF after ablation is common at twelve months. Higher risk of readmission after AF ablation was observed with SED. Enhanced awareness and additional research regarding SED as a risk factor for readmission may help improve post-ablation AF outcomes and equitable access to cardiovascular care.

Abstract 4137689: Artificial Intelligence Assessment of Diastolic Dysfunction by Electrocardiogram: Outcomes in Cardiac Intensive Care Unit Patients

Background: Left ventricular diastolic dysfunction (LVDD) predicts mortality in cardiac intensive care unit (CICU) patients. A novel artificial intelligence enhanced electrocardiogram (AIECG) algorithm can predict LVDD and mortality in general populations but has not been examined in the cardiac intensive care unit (CICU). We aim to assess if LVDD by AI-ECG is associated with in-hospital and one-year mortality in CICU patients. Methods: In this retrospective cohort study, we included consecutive unique adults admitted to the Mayo Clinic CICU from 2007 to 2018 with an admission AIECG, which AI assigned LVDD grade (0 to 3). Medial mitral E/e’ ratio >15 on transthoracic echocardiogram (TTE) defined elevated filling pressures. AIECG and TTE assessment of LVDD were used to assign patients to four groups based on TTE as gold standard: true and false negative, and true and false positive. In-hospital mortality was evaluated using multivariable logistic regression. One-year survival was evaluated using Kaplan-Meier curves and multivariable Cox proportional-hazards. Results: We included 11,868 patients (median age 69.5 years, 37.7% females); 48% had heart failure and 44% had acute coronary syndromes. AIECG LVDD grades were: grade 0 (normal), 33%; grade 1, 7%; grade 2, 39%; grade 3, 21%. In-hospital (adjusted OR) and one-year (adjusted HR) mortality increased in each higher AIECG LVDD grade (Figure A/B), before and after adjustment including TTE measurements. Patients with grade 2-3 LVDD by AIECG and medial mitral E/e’ ratio >15 by TTE (true positive) had the highest in-hospital (adjusted OR 2.5 [1.7-3.9]) and one-year (adjusted HR 1.9 [1.5-2.5]) mortality (Figure C/D), and mortality was elevated similarly in patients with either grade 2-3 LVDD by AIECG (false positive) or medial mitral E/e’ ratio >15 by TTE (false negative). Conclusions: The AIECG LVDD grade was strongly associated with in-hospital and one-year mortality in CICU patients, even after adjusting for clinical variables and TTE measurements. Patients with concordant AIECG and TTE for elevated filling pressures (true positive) were at highest risk.

Prognostic value of neutrophil to lymphocyte ratio and lymphocyte counts before durvalumab consolidation after radio-chemotherapy in locally advanced non-small cell lung cancer

BackgroundDurvalumab, an anti-PD-L1 immune checkpoint inhibitor, after radio-chemotherapy (RCT) has changed the management of locally advanced non-small cell lung cancer (LA NSCLC). A series of retrospective studies have investigated different cut-off of lymphocyte count (LyC) and neutrophil-to-lymphocyte ratio (NLR) to predict survival in LA NSCLC. None of these studies has validated their threshold in an independent group of patients. We wanted to assess the OS prognostic value of NLR and LyC in patients with LA NSCLC treated by RCT and durvalumab, with threshold determination and their validation in an external cohort.MethodsPatients were enrolled in four institutions between Oct. 2017 and Jan. 2022. Pre durvalumab LyC, neutrophils count (NC) and NLR were collected. To define NLR and LyC cut-off value predicting survival event, time dependent Receiver Operating Characteristics (ROC) curves was performed. Survival outcomes were estimated by the Kaplan-Meier method and differences were compared using univariate and multivariate Cox proportional hazard models.ResultsWe included 76 patients in the training set and 85 in the test set. The best cut off were 2,94 for NLR and 0,61 G/l for LyC to predict OS in the training set. For patients with NLR > 2,94, univariate analysis showed no significant deterioration in OS in either the training set (p = 0,066) or the test set (p = 0,12). Patients with LyC > 0,61 G/L, in univariate analysis, had longer OS in training set (p = 0,030) and in test set (p = 0,0062). This OS increase was not found in multivariate analysis (p = 0,057) in training set but was confirmed in test set (0,039).ConclusionLyC > 0,61 G/l is associated with longer OS for LA NSCLC patient’s treated with RCT and durvalumab in univariate analysis. In this context, a particular expectation for organs at risk sparing during RT to avoid lymphopenia seems important.Trial registrationRetrospectively registered.

Heart failure burden among adults with congenital heart disease

Abstract Background Adult congenital heart disease (ACHD) is associated with high rates of healthcare utilization and mortality. Data on Heart failure (HF) burden among ACHD patients are limited. Purpose To study the association between HF and healthcare utilization and mortality among ACHD patients in the community. Methods The retrospective cohort study comprised 11,653≥ 18 year old ACHD patients insured by two large Israeli healthcare providers between January 2007 and December 2011. We used multivariable Cox proportional hazard and negative binomial models to study the associations of HF with mortality and healthcare utilization, respectively. Inverse treatment probability weighting accounted for drug indication. Results ACHD-HF patients (N=908; 7.8%) were older (median: 69 vs. 45 years), more likely men (53% vs. 45%), with complex congenital heart disease (14% vs. 4%), and higher comorbidity rates than ACHD patients without HF. HF was associated with higher healthcare utilization. Compared to patients without HF, ACHD-HF patients had higher adjusted relative rates (RR) of primary care (1.26, 95% confidence interval [CI]: 1.17-1.3), and cardiology clinic visits (1.9, 95% CI: 1.7-2.0), higher hospitalization rates (RR=2.0, 95% CI: 1.7-2.1), and higher risk of death (mortality hazard ratio [HR]: 1.9, 95% CI: 1.5-20.) over the study period. Among ACHD-HF patients, Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers, and diuretics were associated with a lower mortality risk (treated vs. untreated HR=0.56, 95% CI: 0.48-0.65; HR=0.7, 95% CI: 0.6-0.8; HR=0.84, 95% CI: 0.73-0.97; respectively). Conclusions HF presents a major burden on ACHD patients and health care systems. Drugs recommended to the general HF patient population are also associated with lower risk of hospitalization and mortality in ACHD patients. Clinical trials are needed to establish the benefit of HF pharmacotherapy in ACHD patients.Age adjusted ACHD patient survival by HF

A standards-based software tool to support prognostic modelling: application to exemplar heart failure risk scores

Abstract Introduction Heart failure prognosis is an active research area, with the development of several new risk scores each year. While risk score derivation and evaluation have become common practices, these processes currently lack standardisation. Purpose We aimed to: i) develop a standards-based software tool to support prognostic modelling; and ii) apply the tool to derive, evaluate and compare exemplar heart failure risk models to address a hypothetical question of whether using only non-invasive measurements provides similar prognosis value compared to adding invasive measurements. Methods A software tool was developed based on a prognostic modelling workflow defined using the Common Workflow Language and containing 7 steps: univariate Cox proportional hazard (PH) regression, multivariable Cox PH regression with assessment of proportional hazards and linearity with outcome (Schoenfeld and Martingale residuals), derivation of points per risk factor, risk calculation and stratification, discrimination and calibration assessment. Using data from the PEOPLE heart failure cohort [1], two integer-based risk scores were developed to predict 2-year all-cause mortality. The first model utilised 12 variables available at recruitment informed by prior analysis of the PEOPLE cohort to provide a benchmark for comparison, while the second model is based on 9 non-invasive parameters. The analysis was conducted on cases with complete data (n=781), with no internal or external validation. Results By inputting the dataset and indicating the variables of interest for each model, our software tool automatically generated the patient-specific risk scores, risk strata, c-index, and discrimination and calibration plots. A 12-parameter model based on age, sex, ejection fraction, hypertension, diabetes, atrial fibrillation, ischaemic history, NYHA class, heart rate, systolic blood pressure, creatinine and NT-proBNP yielded reasonable discrimination (c-index=0.77). Graphical assessment of risk strata and calibration (Fig. 1.a and c) revealed good performance overall, apart from the highest risk decile where survival was overestimated. The reduced 9-parameter model excluded creatinine, NT-proBNP, and automatically dropped diabetes status for non-linearity. It showed a substantial drop in discrimination (c-index=0.67), confirmed in graphical assessment of risk strata (Fig. 1.b). Calibration was more variable per decile than seen with the 12-parameter model but was more robust to survival overestimation (Fig. 1.d). Conclusion Our software tool ensures the uniformity and comparability of the two risk models derived by a common statistical process. In this example, we showed how the addition of NT-proBNP, creatinine, and diabetes status improves discrimination for predicting heart failure survival. This tool can be leveraged to test new hypotheses in a standardised and reproducible manner to enhance research in heart failure prognosis.

Metoprolol use is associated with improved outcomes in patients with sepsis-induced cardiomyopathy: an analysis of the MIMIC-IV database

BackgroundMetoprolol is commonly administered to critically ill patients; however, its effect on mortality in patients with sepsis-induced cardiomyopathy (SICM) remains uncertain. This study aimed to investigate the relationship between metoprolol use and mortality in patients with SICM.MethodsAdults with SICM were identified from the MIMIC-IV database. The exposure of interest was metoprolol treatment. The outcomes assessed were 30-day mortality, 1-year mortality, and in-hospital mortality. Kaplan–Meier survival analysis evaluated the effect of metoprolol on these outcomes. Multivariable Cox proportional hazards and logistic regression analyses were performed to determine the correlation between metoprolol treatment and mortality in patients with SICM.Results1163 patients with SICM were identified, with 882 receiving metoprolol treatment (MET group) and 281 not receiving metoprolol treatment (NOMET group). Overall, the 30-day, 1-year, and in-hospital mortality rates were 10.2%, 18.2%, and 8.9%, respectively. Significant differences in mortality existed between the groups. Multivariable Cox analysis revealed that patients in the NOMET group had a higher risk of 1-year mortality (adjusted hazard ratio [HR] 2.493; 95% confidence interval [CI] 1.800–3.451; P < 0.001) and 30-day mortality (adjusted HR 4.280; 95%CI 2.760–6.637; P < 0.001). Metoprolol treatment was associated with lower in-hospital mortality (odds ratio [OR] 5.076; 95% CI 2.848–9.047; P < 0.001). Subgroup analysis supported these findings.ConclusionMetoprolol treatment is associated with reduced all-cause mortality in patients with SICM. Prospective studies are required to validate these findings.

Association between loneliness and incident atrial fibrillation across different genetic predisposition: findings from the UK Biobank

BackgroundLoneliness has garnered significant attention globally, with extensive exploration of its association with cardiovascular disease. However, a notable research gap persists concerning loneliness and its potential link to atrial fibrillation (AF).MethodsThis prospective cohort study utilized data from the UK Biobank (UKB), encompassing 441,056 participants. Loneliness was assessed through self-reported questionnaires gauging feelings of isolation and willingness to confide. AF diagnoses were ascertained using hospitalization records and cause-of-death registry data. The association between loneliness and AF risk was analyzed through multivariable Cox proportional hazard models.ResultsOver a median follow-up period of 13.9 years, 25,386 AF cases were identified. In comparison to individuals without reported loneliness, those in the loneliness group exhibited a significantly higher risk of AF (loneliness vs. non-loneliness: hazard ratio [HR]: 1.11, 95% confidence interval [CI] 1.07–1.16). Subgroup analysis revealed that the association between loneliness and increased AF risk was significant solely in individuals without heart valve disease (HR: 1.12, 95% CI 1.07–1.16). Additionally, significant associations between loneliness and heightened AF risk were noted across strata of genetic susceptibility to AF, with no observable impact on these associations by genetic susceptibility (P for interaction = 0.070).ConclusionsThis study establishes a robust association between loneliness and an elevated long-term risk of AF. Notably, this association is particularly pronounced in individuals without valvular disease and does not appear to be influenced by genetic predisposition to AF.

Time to recovery from necrotizing enterocolitis and its predictors among neonates admitted to Neonatal Intensive Care Unit in Bahir Dar, Ethiopia: A retrospective follow up study, 2022.

Necrotizing enterocolitis is one of the most common, life-threatening, gastrointestinal disorders in neonates. The recovery time for neonates with NEC varies depending on disease severity, prompt diagnosis, and effective treatment. Therefore, this study was intended to assess the time to recover from necrotizing enterocolitis and its' predictors among neonates admitted to Neonatal Intensive Care Unit in Bahir Dar City, Ethiopia. An institution-based retrospective follow-up study design was employed. A sample of 361 medical records of neonates with necrotizing enterocolitis was selected using systematic random sampling. Diagnosis of NEC in this study required clinical, laboratory and radiographic findings. The survival function was described using Kaplan Meier survival curve and log-rank test. Bivariate and multivariate Cox-proportional hazard (Cox-PH) regression models were used for analysis. The median recovery time from necrotizing enterocolitis for neonates in the neonatal intensive care unit was 12 days. The multivariable Cox-PH model showed that neonates classified as Stage III NEC (AHR: 0.42, 95% CI = 0.23-0.77) and those exposed to perinatal asphyxia (AHR: 0.51, 95% CI: 0.35-0.74) had a negative impact on NEC recovery time. However, neonates with a birth weight of 1500-2499gm (AHR: 1.65, 95% CI: 1.05-2.58) and a platelet count greater than 150,000 (AHR: 1.75, 95% CI: 1.24-2.48) had a positive effect on NEC recovery time. The recovery time for neonates in the neonatal intensive care unit with necrotizing enterocolitis was longer. Comorbidities and advanced stage of NEC were associated with prolonged recovery time from NEC. However, neonates with better platelet count and birth weight greater than 1500mg had shorter recovery time from NEC.

8455 Denosumab Is Associated With Decreased Mortality Compared To Zoledronic Acid In Diabetic Osteoporotic Patients: A Population-Based Cohort Study

Abstract Disclosure: V. Rouach: Consulting Fee; Self; Amgen Inc. H. Gortler: None. Y. Greenman: None. C. Gabriel: None. G. inbalL: None. Background: Anti-resorptive therapies are the mainstay of osteoporosis management, but evidence of their efficacy in the diabetic population is limited and comparison between treatments is lacking. A retrospective analysis, presented at the American Society for Bone and Mineral Research (ASBMR) 2023 Annual Meeting, suggests that denosumab leads to greater reduction in fracture risk than zoledronic acid among treatment-naive postmenopausal women with osteoporosis. However, a comparative study recently published suggests higher mortality with denosumab versus oral bisphosphonates. Aim: To assess the association between zoledronic acid or denosumab and the risk of major osteoporotic fracture and mortality in osteoporotic patients with diabetes type 2. Methods: The study population was identified by electronic records of a diabetes registry cross-linked with an osteoporosis registry of a large provider healthcare organization in Israel. Index date was at osteoporosis registry entry. Demographics, Comorbidity Index (CCI), diabetes complications, bone mineral density (BMD) T-scores, hemoglobin A1c levels, eGFR, purchase of statins, and anti-resorptive agents were collected. Propensity score matching was performed. Kaplan-Meier curves were generated to assess the time to outcomes. Multivariable Cox's proportional hazards survival model was performed. Results: A total of 27503 diabetic osteoporotic patients were identified, 13343 (48%) patients initiated treatment; 12214 (91.5%) started an oral bisphosphonate, 627 (4.7%) zoledronic acid and 502 (3.7%) denosumab. The median follow-up was 8.9 years. The denosumab treated patients were older (75.7 vs 71.9, p&amp;lt;0.01), had longer diabetes duration (8.4 vs 7.2, p&amp;lt;0.01), were more frequently treated with insulin (29.7 vs 23.9, p=0.02) and had a lower eGFR (59.4 vs 75.3, p&amp;lt;0.01). Male/Female ratio, BMI, CCI, smoking status, alcohol consumption, Hip BMD, HbA1c levels, microvascular complications, hypoglycemic events and statins prescriptions were similar. After propensity weighting, we observed a significant reduced risk of death among the denosumab treated patients (RR=0.72 [0.58-0.91]) without a significant difference in the risk of fracture (RR=0.9 [0.82-1.12]). Conclusions: In this cohort of diabetic osteoporotic patients, denosumab was associated with a significantly reduced mortality compared to zoledronic acid, without a significant difference in the risk of fractures. The effect of denosumab on mortality is yet to be explored. Presentation: 6/1/2024

9236 Denosumab Is Associated With Decreased Mortality Compared To Zoledronic Acid In Diabetic Osteoporotic Patients: A Population-Based Cohort Study

Abstract Disclosure: V. Rouach: Consulting Fee; Self; Amgen Inc. H. Gortler: None. Y. Greenman: None. C. Gabriel: None. G. inbalL: None. Background: Anti-resorptive therapies are the mainstay of osteoporosis management, but evidence of their efficacy in the diabetic population is limited and comparison between treatments is lacking. A retrospective analysis, presented at the American Society for Bone and Mineral Research (ASBMR) 2023 Annual Meeting, suggests that denosumab leads to greater reduction in fracture risk than zoledronic acid among treatment-naive postmenopausal women with osteoporosis. However, a comparative study recently published suggests higher mortality with denosumab versus oral bisphosphonates. Aim: To assess the association between zoledronic acid or denosumab and the risk of major osteoporotic fracture and mortality in osteoporotic patients with diabetes type 2. Methods: The study population was identified by electronic records of a diabetes registry cross-linked with an osteoporosis registry of a large provider healthcare organization in Israel. Index date was at osteoporosis registry entry. Demographics, Comorbidity Index (CCI), diabetes complications, bone mineral density (BMD) T-scores, hemoglobin A1c levels, eGFR, purchase of statins, and anti-resorptive agents were collected. Propensity score matching was performed. Kaplan-Meier curves were generated to assess the time to outcomes. Multivariable Cox's proportional hazards survival model was performed. Results: A total of 27503 diabetic osteoporotic patients were identified, 13343 (48%) patients initiated treatment; 12214 (91.5%) started an oral bisphosphonate, 627 (4.7%) zoledronic acid and 502 (3.7%) denosumab. The median follow-up was 8.9 years. The denosumab treated patients were older (75.7 vs 71.9, p&amp;lt;0.01), had longer diabetes duration (8.4 vs 7.2, p&amp;lt;0.01), were more frequently treated with insulin (29.7 vs 23.9, p=0.02) and had a lower eGFR (59.4 vs 75.3, p&amp;lt;0.01). Male/Female ratio, BMI, CCI, smoking status, alcohol consumption, Hip BMD, HbA1c levels, microvascular complications, hypoglycemic events and statins prescriptions were similar. After propensity weighting, we observed a significant reduced risk of death among the denosumab treated patients (RR=0.72 [0.58-0.91]) without a significant difference in the risk of fracture (RR=0.9 [0.82-1.12]). Conclusions: In this cohort of diabetic osteoporotic patients, denosumab was associated with a significantly reduced mortality compared to zoledronic acid, without a significant difference in the risk of fractures. The effect of denosumab on mortality is yet to be explored. Presentation: 6/1/2024

Young-onset type 2 diabetes mellitus enhances proteinuria, but not glomerular filtration rate decline: A Japanese cohort study.

The time course of chronic kidney disease in young-onset type 2 diabetes mellitus remains unclear. We compared the trajectories of proteinuria and estimated glomerular filtration rate (eGFR) decline between young-onset (aged ≤40 years) and late-onset (aged >40 years) type 2 diabetes mellitus in a Japanese multicenter cohort. Participants without diabetic kidney disease were divided into two groups according to age at diagnosis: young- and late-onset. The primary endpoint was eGFR <60 mL/min/1.73 m2, proteinuria or both. Multivariable Cox proportional hazards were calculated to estimate incidence. Among 626 participants with type 2 diabetes mellitus, 78 (12.4%) had young-onset and 548 (87.6%) had late-onset diabetes. The incidence of eGFR <60 mL/min/1.73 m2 was lower (16.7% vs 33.5%, P = 0.003), but that of proteinuria was higher (46.2% vs 28.9%, P = 0.002) in the young-onset type 2 diabetes mellitus group. The Kaplan-Meyer curve showed that young-onset type 2 diabetes mellitus was associated with a decreased hazard ratio (HR) for eGFR <60 mL/min/1.73 m2 and an increased HR for proteinuria compared with late-onset type 2 diabetes mellitus. In the multivariate Cox analysis, young-onset type 2 diabetes mellitus increased the HR (95% confidence interval) of proteinuria (1.53, 95% confidence interval 1.03-2.26), but did not change the eGFR <60 mL/min/1.73 m2 HR. Young-onset type 2 diabetes mellitus has a lower HR of eGFR <60 mL/min/1.73 m2 and an increased HR of proteinuria compared with late-onset type 2 diabetes mellitus, indicating that young-onset type 2 diabetes mellitus has a different time course for the development of proteinuria and subsequent eGFR decline.

Adaptation of a modified Elixhauser comorbidity index to isolate the impact of body mass index on survival outcomes in patients with cancer in a large integrated healthcare system.

124 Background: Variable impacts of body mass index (BMI) on overall survival (OS) and cancer-specific survival (CSS) have been described in patients with cancer, with existing data highlighting both detrimental effects and malignancy-specific benefits. Real-world data derived from integrated healthcare systems are underexplored in this context, and tight control of confounding using validated tools such as the Elixhauser Comorbidity Index (ECI) is rarely employed in pre-existing studies. Herein, we offer a highly refined description of the impact of BMI on cancer-specific outcomes in a large patient cohort using a targeted ECI model. Methods: 153,270 patient records were abstracted from an integrated healthcare system from 2010-2018, including descriptors of age, race/ethnicity, income, disease stage, and treatment regimens. Standardized derivation of BMI within one year prior to diagnosis was performed and categorized by World Health Organization definitions. A custom ECI was designed to exclude ICD codes for obesity to effectively isolate the impact of BMI on downstream analyses. Kaplan-Meier survival estimates of OS and CSS were constructed, and univariate and multivariate Cox proportional hazard (PH) modeling was performed to determine hazard ratios (HR). Results: When normalized to healthy BMI in multivariate modeling, we found a favorable dose-dependent relationship of overweight and obese BMI on OS and CSS independent of age, race/ethnicity, income, modified ECI score, cancer stage, or therapeutic regimen (Table). This advantage to OS and CSS was not as strongly reflected in severely obese patients, though still significant compared to healthy BMI counterparts. Being underweight was a negative prognostic indicator for OS and CSS in all patients compared to a healthy BMI. Conclusions: We demonstrate a beneficial impact of increased BMI on OS and CSS in a large cohort of patients treated in an integrated healthcare model independent of tightly controlled confounding. Specifically, we highlight the utility of isolating obesity using a targeted ECI model for comorbidity adjustment, which may provide a more robust measure of the influence of BMI on survival. Our findings raise questions regarding attention to adequate control of confounding in prior studies, as well as the potential benefit of removing variation in healthcare delivery in understanding these outcomes. Adjusted HR of OS and CSS stratified by BMI category (*95% Confidence Interval). BMI Category Adjusted OS Adjusted CSS Normal Weight(18.5 – 24.9) 1 (reference) 1 (reference) Underweight(&lt; 18.5) 1.35 (1.25 – 1.45*) 1.28 (1.15 – 1.41) Overweight(25 – 29.9) 0.83 (0.81 – 0.85) 0.84 (0.81 – 0.87) Obese(30 – 39.9) 0.81 (0.79 – 0.83) 0.81 (0.78 – 0.84) Severe Obesity(≥ 40) 0.86 (0.82 – 0.90) 0.82 (0.77 – 0.87) Unknown 1.33 (1.24 – 1.43) 1.19 (1.07 – 1.31)

Development and validation of a deep learning-based survival prediction model for pediatric glioma patients: A retrospective study using the SEER database and Chinese data

ObjectiveDevelop a time-dependent deep learning model to accurately predict the prognosis of pediatric glioma patients, which can assist clinicians in making precise treatment decisions and reducing patient risk. Study designThe study involved pediatric glioma patients from the Surveillance, Epidemiology, and End Results (SEER) Registry (2000–2018) and Tangdu Hospital in China (2010–2018) within specific time frames. For training, we selected two neural network-based algorithms (DeepSurv, neural multi-task logistic regression [N-MTLR]) and one ensemble learning-based algorithm (random survival forest [RSF]). Additionally, a multivariable Cox proportional hazard (CoxPH) model was developed for comparison purposes. The SEER dataset was randomly divided into 80 % for training and 20 % for testing, while the Tangdu Hospital dataset served as an external validation cohort. Super-parameters were fine-tuned through 1000 repeated random searches and 5-fold cross-validation on the training cohort. Model performance was assessed using the concordance index (C-index), Brier score, and Integrated Brier Score (IBS). Furthermore, the accuracy of predicting survival at 1, 3, and 5 years was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and the area under the ROC curves (AUC). The generalization ability of the model was assessed using the C-index of the Tangdu Hospital data, ROC curves for 1, 3, and 5 years, and AUC values. Lastly, decision curve analysis (DCA) curves for 1, 3, and 5-year time frames are provided to assess the net benefits across different models. ResultsA total of 9532 patients with pediatric glioma were included in this study, comprising 9274 patients from the SEER database and 258 patients from Tangdu Hospital in China. The average age at diagnosis was 9.4 ± 6.2 years, and the average survival time was 96 ± 66 months. Through comprehensive performance comparison, the DeepSurv model demonstrated the highest effectiveness, with a C-index of 0.881 on the training cohort. Furthermore, it exhibited excellent accuracy in predicting the 1-year, 3-year, and 5-year survival rates (AUC: 0.903–0.939). Notably, the DeepSurv model also achieved remarkable performance and accuracy on the Chinese dataset (C-index: 0.782, AUC: 0.761–0.852). Comprehensive analysis of DeepSurv, N-MTLR, and RSF revealed that tumor stage, radiotherapy, histological type, tumor size, chemotherapy, age, and surgical method are all significant factors influencing the prognosis of pediatric glioma. Finally, an online version of the pediatric glioma survival predictor based on the DeepSurv model has been established and can be accessed through https://pediatricglioma-tangdu.streamlit.app. ConclusionsThe DeepSurv model exhibits exceptional efficacy in predicting the survival of pediatric glioma patients, demonstrating strong performance in discrimination, calibration, stability, and generalization. By utilizing the online version of the pediatric glioma survival predictor, which is based on the DeepSurv model, clinicians can accurately predict patient survival and offer personalized treatment options.

Long-Term Mortality Following SARS-CoV-2 Infection in Rural Versus Urban Dwellers With Autoimmune or Inflammatory Rheumatic Disease: A Retrospective Cohort Analysis From the National COVID Cohort Collaborative.

Autoimmune or inflammatory rheumatic diseases (AIRDs) increase the risk for poor COVID-19 outcomes. Although rurality is associated with higher post-COVID-19 mortality in the general population, whether rurality elevates this risk among people with AIRD is unknown. We assessed associations between rurality and post-COVID-19 all-cause mortality, up to two years post infection, among people with AIRD using a large nationally sampled US cohort. This retrospective study used the National COVID Cohort Collaborative, a medical records repository containing COVID-19 patient data. We included adults with two or more AIRD diagnostic codes and a COVID-19 diagnosis documented between April 2020 and March 2023. Rural residency was categorized using patient residential zip codes. We adjusted for AIRD medications and glucocorticoid prescription, age, sex, race and ethnicity, tobacco or substance use, comorbid burden, and SARS-CoV-2 variant-dominant periods. Multivariable Cox proportional hazards with inverse probability treatment weighting assessed associations between rurality and two-year all-cause mortality. Among the 86,467 SARS-CoV-2-infected persons with AIRD, we observed a higher risk for two-year post-COVID-19 mortality in rural versus urban dwellers. Rural-residing persons with AIRD had higher two-year all-cause mortality risk (adjusted hazard ratio 1.24, 95% confidence interval 1.19-1.29). Glucocorticoid, immunosuppressive, and rituximab prescriptions were associated with a higher risk for two-year post-COVID-19 mortality, whereas risk with nonbiologic or biologic disease-modifying antirheumatic drugs was lower. Rural residence in people with AIRD was independently associated with higher two-year post-COVID-19 mortality in a large US cohort after adjusting for background risk factors. Policymakers and health care providers should consider these findings when designing interventions to improve outcomes in people with AIRD following SARS-CoV-2 infection, especially among high-risk rural residents.

Platelet count as a prognostic marker for acute respiratory distress syndrome

BackgroundThis study aimed to evaluate the role of platelet count (PLT) in the prognosis of patients with acute respiratory distress syndrome (ARDS).MethodsThe data were extracted from the Medical Information Mart for Intensive Care database (version 2.2). Patients diagnosed with ARDS according to criteria from Berlin Definition and had the platelet count (PLT) measured within the first day after intensive care unit admission were analyzed. Based on PLT, ARDS patients were divided into four groups: PLT ≤ 100 × 109/L, PLT 101–200 × 109/L, PLT 201–300 × 109/L, and PLT > 300 × 109/L. The primary outcome was 28-day mortality. Survival probabilities were analyzed using Kaplan–Meier. Furthermore, the association between PLT and mortality in ARDS patients was assessed using a univariate and multivariable Cox proportional hazards model.ResultsOverall, the final analysis included 3,207 eligible participants with ARDS. According to the Kaplan–Meier curves for 28-day mortality of PLT, PLT ≤ 100 × 109/L was associated with a higher incidence of mortality (P = 0.001), the same trends were observed in the 60-day (P = 0.001) and 90‐day mortality (P = 0.001). In the multivariate model adjusted for the potential factors, the adjusted hazard ratio at PLT 101–200 × 109/L group, PLT 201–300 × 109/L, and PLT > 300 × 109/L was 0.681 [95% confidence interval (CI): 0.576–0.805, P < 0.001], 0.733 (95% CI: 0.604–0.889, P = 0.002), and 0.787 (95% CI: 0.624–0.994, P = 0.044) compared to the reference group (PLT ≤ 100 × 109/L), respectively. Similar relationships between the PLT ≤ 100 × 109/L group and 28-day mortality were obtained in most subgroups.ConclusionPLT appeared to be an independent predictor of mortality in critically ill patients with ARDS.

The observational EURACAN prospective clinical registry dedicated to epithelioid hemangioendothelioma: The protocol of an international and collaborative effort on an ultra-rare entity.

Epithelioid hemangioendothelioma (EHE) is an ultra-rare sarcoma, marked by distinctive molecular and pathological features and with a variable clinical behavior. Its natural history is still partially understood, reliable prognostic and predictive factors are lacking and many questions are still open on the optimal management. In the context of EURACAN, a prospective registry specifically dedicated to EHE was developed and launched with the aim of providing, through high-quality prospective data collection, a better understanding of this disease. Registry-based cohort study including only new cases of patients with a pathological and molecularly confirmed diagnosis of EHE. To improve the understanding of EHE natural history, validate and identify new prognostic and predictive factors, clarify the activity and efficacy of currently available treatment options, describe treatment pattern. Settings and participantsIt is an hospital-based registry established in centers with expertise in EHE including adult patients with a new pathological and molecularly confirmed diagnosis of EHE starting from the 1st December 2023. The characteristics of each patient in the facility who meets the above-mentioned inclusion criteria will be collected prospectively and longitudinally with follow-up at cancer progression and / or cancer relapse or patient death. It is a secondary use of data which will be collected from the clinical records. The data collected for the registry will not entail further examinations or admissions to the facility and/or additional appointments to those normally provided for routine patient follow-up. VariablesFull details on patients and disease features, treatment and outcome will be collected, according to common clinical practice guidelines developed and shared with all the contributing centers. In addition, data on potential confounders (e.g. comorbidity; functional status etc.) will also be collected. Statistical methodsThe data analyses will include descriptive statistics and analytical analyses. Multivariable Cox's proportional hazards model and Hazard ratios (HR) for all-cause or cause-specific mortality will be used to determine independent predictors of overall survival, recurrence and progression. The registry has been joined by 21 sarcoma reference centers across EU and UK, covering 10 countries. Patients' recruitment started in December 2023. The estimated completion date is December 2033 upon agreement on the achievement of all the registry objectives. The already established collaboration and participation of EHE patient's associations involved in the project will help in promoting the registry and fostering accrual.

Predictors of mortality among multidrug-resistant tuberculosis patients after decentralization of services in Tanzania from 2017 to 2019: retrospective cohort study

BackgroundMultidrug-resistant tuberculosis (MDR-TB) presents persistent global health challenges, characterized by low treatment success rates among patients enrolled for treatment. The World Health Organization recommends decentralization to improve outcomes. This study aims to assess predictors of mortality among MDR-TB patients after decentralization of services in Tanzania. This was a retrospective cohort study involving all MDR-TB patients enrolled in treatment in all 31 regions in Tanzania from 2017 to 2019. The overall mortality rate among MDR-TB patients was calculated using the incidence rate. Additionally, independent factors of MDR-TB mortality were determined using multivariable cox proportional hazards models.ResultsThe study followed 985 patients for a total of 12,929 months. During this time, it found that approximately 12 out of every 1000 patients died each month. Specifically, the death rates were about 18 out of 1000 patients at 6 months, 8 out of 1000 at 12 months, and 7 out of 1000 at 24 months. Patients who had both MDR-TB and HIV, as well as those who were malnourished, had a lower chance of surviving at 6, 12, and 24 months. Malnourished patients had almost three times the risk of dying [adjusted hazard ratio (aHR) 2.96, with a 95% confidence interval (CI) of 2.10–4.19], while those with HIV had nearly double the risk [aHR 1.91, with a 95% CI of 1.37–2.65].ConclusionIn summary, our study on MDR-TB patient outcomes in Tanzania between 2017 and 2019 reveals a pattern of high mortality rates within the first 6 months of treatment. Furthermore, malnutrition and HIV co-infection were found to be significant predictors of mortality. To decrease mortality, it is crucial to closely monitor patients during the initial 6 months of treatment, especially those who are malnourished or co-infected with HIV, and ensure they receive appropriate and timely care. Additionally, further investigation is needed to find out what may be contributing to possible rise in mortality rate.

Incidence of mortality and its predictors among preterm neonates in nigist eleni mohammed memmorial comprehensive specialized hospital, Hossana, Ethiopia: a prospective follow-up study

BackgroundPreterm birth is the leading cause of neonatal mortality accounting for 35% of all neonatal deaths worldwide, and the second most frequent cause of death for under five children. Despite different efforts, preterm neonatal mortality is still persistently high in Ethiopia. Little is known about death and its predictors among preterm neonates in the study area.ObjectiveThis study is aimed at estimating the incidence of mortality and its predictors among preterm neonates admitted to the NICU of NEMMCSH.Methods and materials: A hospital-based prospective follow-up study was conducted from January to November 2022. A total of 197 preterm neonates were selected consecutively and followed. The Kaplan-Meier survival and failure curves were used to describe the proportion of deaths over time and to compare groups. The independent effects of covariates on the hazard of death were analyzed using a multivariable Cox proportional hazard model.ResultsPreterm neonates were followed for 1840 person-days. The mean time to death was 5.68 days (SD = 5.54). The incidence of mortality was 26.08 (95% CI: 19.65, 34.61) per 1000 person days. Preterm neonates of mothers with eclamsia (AHR = 3.03), preterm neonates who have not received KMC (AHR = 2.26), and preterm neonates who have not exclusively breastfed (AHR = 4.4) had higher hazards of death as compared to their counterparts.Conclusion and recommendation: The mean time to death was 5.68 days (SD = 5.54). The incidence of mortality was 26.08 per 1000 person days. Eclamsia, KMC, and exclusive breastfeeding were significant predictors of death among preterm neonates. The role of KMC in reducing mortality rates and improving outcomes has to be emphasized for mothers and families. Caregivers have to ensure that mothers and families receive adequate support and resources to facilitate KMC, including access to lactation support, counseling, and assistance with practical aspects of caregiving. Counseling and practical support to enhance exclusive breastfeeding initiation and continuation have to be strengthened. Special attention has to be given to the preterm neonates of mothers with eclampsia.

Fragmentation of care in breast cancer: greater than the sum of its parts

IntroductionFragmentation of care (FC, the receipt of care at > 1 institution) has been shown to negatively impact cancer outcomes. Given the multimodal nature of breast cancer treatment, we sought to identify factors associated with FC and its effects on survival of breast cancer patients.MethodsA retrospective analysis was performed of surgically treated, stage I–III breast cancer patients in the 2004–2020 National Cancer Database, excluding neoadjuvant therapy recipients. Patients were stratified into two groups: FC or non-FC care. Treatment delay was defined as definitive surgery > 60 days after diagnosis. Multivariable logistic regression was performed to identify factors predictive of FC, and survival was compared using Kaplan–Meier and multivariable Cox proportional hazards methods.ResultsOf the 531,644 patients identified, 340,297 (64.0%) received FC. After adjustment, FC (OR 1.27, 95% CI 1.25–1.29) was independently associated with treatment delay. Factors predictive of FC included Hispanic ethnicity (OR 1.04, 95% CI: 1.01–1.07), treatment at comprehensive community cancer programs (OR 1.06, 95% CI: 1.03–1.08) and integrated network cancer programs (OR 1.55, 95% CI: 1.51–1.59), AJCC stage II (OR 1.06, 95% CI 1.05–1.07) and stage III tumors (OR 1.06, 95% CI: 1.02–1.10), and HR + /HER2 + tumors (OR 1.05, 95% CI: 1.02–1.07). Treatment delay was independently associated with increased risk of mortality (HR 1.23, 95% CI 1.20–1.26), whereas FC (HR 0.87, 95% CI 0.86–0.88) showed survival benefit.ConclusionsWhile treatment delay negatively impacts survival in breast cancer patients, our findings suggest FC could be a marker for multispecialty care that may mitigate some of these effects.