Time-dependent Cox Regression Models Research Articles

#2477 Longitudinal serum bicarbonate and mortality risk in older patients with advanced chronic kidney disease: analyses from the EQUAL cohort

Abstract Background and Aims Serum bicarbonate (SBC) disorders have been consistently linked to mortality in chronic kidney disease (CKD) patients. Low SBC levels have been extensively associated with increased mortality in CKD patients, possibly due to the detrimental effects of acidosis on various organs and systems. Likewise, several studies have identified high levels of SBC as a risk factor for mortality in the CKD population. To date, most studies have focused on the association between SBC levels and patient survival during the pre-kidney replacement therapy (KRT) period or the period after KRT initiation, considered separately. None have explored this association across the continuum of CKD (e.g., from pre-KRT to post-KRT start), which is relevant since metabolic acidosis is expected to be managed through dialysis in the KRT population, and thus its clinical outcomes might change after KRT initiation. To provide new insights on this topic, we aimed to explore the relationship between SBC and mortality in advanced CKD during three distinct treatment periods: during the pre-KRT period, during the transition phase surrounding the start of KRT (transition-CKD), and during KRT. Method Using the European QUALity Study on treatment in advanced CKD (EQUAL) cohort, which includes patients aged ≥65 years and eGFR ≤20 ml/min per 1.73 m2 from six European countries, we explored the association between longitudinal SBC and all-cause mortality in three separate CKD populations: pre-KRT, transition-CKD and in the KRT populations, using multivariable time-dependent Cox regression models. The cumulative time-averaged, the cumulative exposure of SBC, and the slope of the SBC trajectory during the pre-KRT phase were calculated and evaluated for association with all-cause mortality in the transition-CKD population. Subgroup analysis were used to evaluate the effect modification by pre-specified variables on the relationship between SBC and mortality. Results We included 1485 patients with a median follow-up of 2.9 (IQR 2.7) years, during which 529 (35.6%) patients died. A U-shaped relationship between SBC levels and all-cause mortality was observed in the pre-KRT population (p = 0.03; Fig.). Low cumulative exposure, defined as the area under the SBC trajectory before KRT initiation, was associated with increased mortality risk after transitioning to KRT (p = 0.01). Similarly, in the KRT population, low SBC levels showed a trend towards increased mortality risk (p = 0.13). We observed effect modification on the relationship between SBC and mortality by subjective global assessment category (p-value for interaction = 0.02) and KRT initiation (p-value for interaction = 0.02). Conclusion Our study has provided important insights into the relationship between SBC and mortality in advanced CKD patients. A U-shaped relationship describes the association between SBC and mortality in the advanced CKD pre-KRT population, whereas in patients that initiate KRT only low SBC levels are associated with an increased mortality risk. Our findings suggest that the relationship between SBC and mortality varies across different stages of CKD and that this relationship is modified by KRT initiation. From this point of view, it would be appropriate to consider a personalized management of acid-base balance disorders based on a comprehensive evaluation of the clinical status of the patient.

#2509 Longitudinal haemoglobin levels and mortality in an elderly population with advanced chronic kidney disease: insights from the EQUAL Study

Abstract Background and Aims The relationship between haemoglobin (Hb) levels and clinical outcomes in chronic kidney disease (CKD) is more intricate than previously understood, as both low and high values can have detrimental effects. Although the association between Hb and patient outcomes is widely reported, few studies have focused on older patients with advanced CKD or have explored this relationship both before and after kidney replacement therapy (KRT) initiation. The primary objective of this study is to describe the relationship between Hb levels and mortality in older patients with advanced CKD in the continuum from pre-KRT phase to subsequent KRT initiation, and to evaluate any effect modification by KRT initiation. Method We used data from the European QUALity Study on treatment in advanced CKD (EQUAL) cohort which includes patients aged ≥65 years and eGFR ≤20 ml/min per 1.73 m2 from six European countries. The association between Hb and all-cause and cause-specific mortality (cardiovascular [CV] and non-cardiovascular [non-CV] mortality) was explored in three separate CKD populations: pre-KRT, KRT and transition-CKD (transition phase surrounding the start of KRT) population. Multivariable adjusted time-dependent Cox regression models and natural cubic splines were used to investigate the association between longitudinal Hb levels (as categorical and continuous variable) and mortality risk in the pre-KRT and KRT population. The area under the Hb trajectory (AUC Hb) before KRT initiation was calculated to evaluate the relationship between the cumulative exposure of Hb before KRT initiation and all-cause mortality after KRT initiation in the transition-CKD population. We evaluated effect modification by pre-specified variables on the relationship between Hb and mortality. Results Overall, 1716 CKD patients were included in the study. During a median follow up of 3.0 years (IQR 2.6), 614 patients died, resulting in a 5-year survival probability of 51% (95% CI 48, 55). Low Hb levels were consistently associated with increased mortality risk in all study populations (Figure). A U-shaped association between both the lowest and highest levels of Hb and mortality risk was observed (Figure). A similar association was observed for non-CV mortality, with lower Hb values associated with an increased mortality risk (Figure). Conversely, a trend towards higher risk of cardiovascular death was observed as Hb levels increase, especially in the whole population and pre-KRT population (Figure), albeit not statistically significant. Low cumulative exposure of Hb in the transition-CKD population was associated with increased mortality risk after transitioning to KRT (p = 0.047). In subgroup analysis diabetic patients were more susceptible to low Hb levels (p-value for interaction = 0.003) while patients on ESA therapy (p-value for interaction = 0.005) or initiating KRT (p-value for interaction = 0.024) showed increased mortality risk for high Hb levels. Conclusion The relationship between Hb levels and mortality in advanced CKD patients is complex. Low Hb levels consistently indicate an increased risk of mortality, while high Hb levels also appear to have a negative effect, increasing mortality risk, particularly in patients receiving ESA therapy and after KRT initiation. Our work emphasizes how different stages of advanced kidney disease (i.e., before and after initiating KRT), as well as comorbidities such as diabetes or medications such as ESA therapy can significantly influence the relationship between Hb and mortality.

Abstract PO4-01-13: Effect of interruption or discontinuation of endocrine therapy on the prognosis of breast cancer patients: a cohort study using the real-world database

Abstract Background:Adjuvant endocrine therapy is the most important treatment modality as long as one, which can reduce the mortality risk and the recurrence risk for patients with hormone receptor-positive breast cancer. Currently, few studies has reported the association in poor adherence with overall survival(OS) or disease-free-survival(DFS). However, the use of prescription coverage in previous studies to describe patient adherence to endocrine therapy may not be representative of the patient's actual medication. Additionally, previous studies did not distinguish between interruption and discontinuation of endocrine therapy, which is different to clinician. This research used rigorous follow-up data and aims on the effects of discontinuation and interruption on patients with early-stage hormone receptor-positive breast cancer. Methods: Based on the Breast Cancer Information Management System (BCIMS), we identified patients diagnosed with stage I-III breast cancer with hormone receptor-positive and received endocrine therapy during January 1, 1990 to January 1, 2018 in West China Hospital (WCH), Sichuan University, China. Briefly, all patients diagnosed with breast cancer were included and prospectively followed from the diagnosis at WCH or the first visit to WCH for breast cancer. Information, including demographic characteristics, medical history, laboratory results, pathological information, treatments and clinical outcomes, were obtained from clinical records and interviews. Kaplan-Meier analysis, Time-Dependent Cox Regression Model, and subgroup analysis were performed to evaluate the effectiveness of interruption or discontinuation of endocrine therapy. And “X-tile” software is used to select cutoff values in survivorship data. Results:A total of 3,418 eligible patients were included with 8.13(±1.96) years median follow-up. Of these patients, 19.5% did not adhere to standard endocrine regimens, with 6.9% discontinuing and 12.7% discontinuing. The multivariate cox analysis indicates that discontinuation group (DFS:HR=9.71, [95%CI]5.21-18.34,P <0.001; OS:HR=10.41, [95%CI]5.63-19.24,P <0.001) increased the risk of death and breast cancer events compared to the adherence group, but not shown statistical significance difference in the interruption (DFS:HR=1.03,[95%CI]0.23-4.66, P =0.975; OS:HR=1.17, [95%CI]0.26-5.28,P =0.840). We further analyzed the interruption and discontinuation group respectively. In the interruption group, we found cutoff value with 30 months in survival risks but didn't find statistical significance difference in DFS and OS compared to the adherence groups. For the discontinuation group, we divided the patients into low-risk and high-risk groups according to cutoff value (23 months), the final results showed that the high-risk group who took the endocrine therapy less than 23 months had increased the rate of OS(HR=23.98,[95%CI]11.71-49.14, P< 0.001) and DFS(HR=24.03,[95%CI]11.51-50.18, P< 0.001). Conclusion:This study found that interruption of endocrine therapy may not affect prognosis of HR+ breast cancer patients, but prolonged discontinuation increases the risk of relapse and death. Therefore, clinicians should educate patients taking endocrine therapy and encourage those who discontinue the drug to take the drug again as soon as possible. A.Kaplan-Meier Curve for OS B.A.Kaplan-Meier Curve for DFS Kaplan-Meier Curve for OS and DFS in the Interruption Group according to the events location Kaplan-Meier Curve for OS and DFS in the Discontinuation Group according to the total duration of medication Citation Format: Ya Huang, Jie Chen, Yunhao Wu. Effect of interruption or discontinuation of endocrine therapy on the prognosis of breast cancer patients: a cohort study using the real-world database [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-01-13.

Revisiting the potential value of vital signs in the real-time prediction of mortality risk in intensive care unit patients

BackgroundPredicting patient mortality risk facilitates early intervention in intensive care unit (ICU) patients at greater risk of disease progression. This study applies machine learning methods to multidimensional clinical data to dynamically predict mortality risk in ICU patients.MethodsA total of 33,798 patients in the MIMIC-III database were collected. An integrated model NIMRF (Network Integrating Memory Module and Random Forest) based on multidimensional variables such as vital sign variables and laboratory variables was developed to predict the risk of death for ICU patients in four non overlapping time windows of 0–1 h, 1–3 h, 3–6 h, and 6–12 h. Mortality risk in four nonoverlapping time windows of 12 h was externally validated on data from 889 patients in the respiratory critical care unit of the Chinese PLA General Hospital and compared with LSTM, random forest and time-dependent cox regression model (survival analysis) methods. We also interpret the developed model to obtain important factors for predicting mortality risk across time windows. The code can be found in https://github.com/wyuexiao/NIMRF.ResultsThe NIMRF model developed in this study could predict the risk of death in four nonoverlapping time windows (0–1 h, 1–3 h, 3–6 h, 6–12 h) after any time point in ICU patients, and in internal data validation, it is suggested that the model is more accurate than LSTM, random forest prediction and time-dependent cox regression model (area under receiver operating characteristic curve, or AUC, 0–1 h: 0.8015 [95% CI 0.7725–0.8304] vs. 0.7144 [95%] CI 0.6824–0.7464] vs. 0.7606 [95% CI 0.7300–0.7913] vs 0.3867 [95% CI 0.3573–0.4161]; 1–3 h: 0.7100 [95% CI 0.6777–0.7423] vs. 0.6389 [95% CI 0.6055–0.6723] vs. 0.6992 [95% CI 0.6667–0.7318] vs 0.3854 [95% CI 0.3559–0.4150]; 3–6 h: 0.6760 [95% CI 0.6425–0.7097] vs. 0.5964 [95% CI 0.5622–0.6306] vs. 0.6760 [95% CI 0.6427–0.7099] vs 0.3967 [95% CI 0.3662–0.4271]; 6–12 h: 0.6380 [0.6031–0.6729] vs. 0.6032 [0.5705–0.6406] vs. 0.6055 [0.5682–0.6383] vs 0.4023 [95% CI 0.3709–0.4337]). External validation was performed on the data of patients in the respiratory critical care unit of the Chinese PLA General Hospital. Compared with LSTM, random forest and time-dependent cox regression model, the NIMRF model was still the best, with an AUC of 0.9366 [95% CI 0.9157–0.9575 for predicting death risk in 0–1 h]. The corresponding AUCs of LSTM, random forest and time-dependent cox regression model were 0.9263 [95% CI 0.9039–0.9486], 0.7437 [95% CI 0.7083–0.7791] and 0.2447 [95% CI 0.2202–0.2692], respectively. Interpretation of the model revealed that vital signs (systolic blood pressure, heart rate, diastolic blood pressure, respiratory rate, and body temperature) were highly correlated with events of death.ConclusionUsing the NIMRF model can integrate ICU multidimensional variable data, especially vital sign variable data, to accurately predict the death events of ICU patients. These predictions can assist clinicians in choosing more timely and precise treatment methods and interventions and, more importantly, can reduce invasive procedures and save medical costs.

The association between mean arterial pressure and acute kidney injury reversal among patients with decompensated cirrhosis.

This study informs how mean arterial pressure (MAP) impacts acute kidney injury (AKI) recovery among all patients hospitalized with cirrhosis, regardless of etiology. We identified incident AKI episodes among subjects in our cohort of patients with decompensated cirrhosis. AKI was defined as a ≥50% increase in creatinine from an outpatient baseline (≥7 days prior) that required hospitalization. Linear mixed effects models were completed to determine the impact between AKI recovery, MAP, and time. To determine the impact of MAP on AKI reversal, we completed time-dependent Cox regression models with time beginning at the time of peak creatinine and ending at death, discharge, or AKI reversal, among those hospitalized with AKI and those with persistent AKI (≥48h) We identified 702 hospitalized patients with cirrhosis with AKI. We found those with AKI reversal had, on average, higher MAP (2.1mmHg, p <0.05) and a greater increase in MAP over time (0.1mmHg per hour, p <0.001). Among all 702 hospitalized patients with AKI and adjusted for confounders, each 5mmHg increase in MAP was associated with 1.07× the hazard of AKI reversal ( p <0.01). Similarly, among those with persistent AKI after adjusting for confounders, each 5mmHg increase in MAP was associated with a 1.19× greater likelihood of AKI reversal ( p <0.001). Our data demonstrate that MAP significantly increases the likelihood of AKI recovery regardless of severity or injury or AKI phenotype. We believe these data highlight the importance of MAP as a clinical tool to promote kidney function recovery among patients with cirrhosis hospitalized with AKI.

The dilution effect of healthy lifestyles on the risk of cognitive function attributed to socioeconomic status among Chinese older adults: A national wide prospective cohort study.

Lower socioeconomic status (SES) is a risk factor for poor cognitive function, while a healthy lifestyle is associated with better cognitive function. We examined the complex relationship between SES and a healthy lifestyle and cognitive function among older Chinese adults. We used a national prospective cohort of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2008-18, aged 65 years and older with normal cognition at baseline. Participants were categorised into the favourable group if they had four to six healthy lifestyle factors and the unfavourable group for zero to three factors. SES was classified as higher and lower by assessing the socioeconomic vulnerability index (SEVI) with six components. Cognitive function was measured using the Mini-Mental State Examination (MMSE) scores and the standardised Z-scores. We applied the linear mixed effects and time-dependent Cox regression models to explore associations and further stratified the analysis by healthy lifestyles. A total of 6851 participants were included (the mean age was 80.87, 43.44% had a favourable lifestyle, and 49.29% had higher SES). Over the 10-year follow-up period, SES status and lifestyle profiles significantly affected the decline in the standardised Z-scores (P < 0.05). The higher SES group with favourable lifestyles exhibited a slower cognitive decline than those with lower SES (by 0.031 points per year, P < 0.05). The association was not observed in those in the unfavourable group (0.010 points per year, P > 0.05). During a follow-up, 25.06% of participants developed cognitive impairment (MMSE<18). We also observed a significant interaction between SES and healthy lifestyles (P < 0.05), with the corresponding associations of SES being more pronounced among participants with unfavourable lifestyles (hazard ratio (HR) = 0.821; 95% confidence interval (CI) = 0.701-0.960) than those with favourable lifestyles (HR = 1.006; 95% CI = 0.844-1.200). A healthy lifestyle may attenuate the adverse impacts of lower SES on cognitive function among older adults. This study might provide important information for protecting cognitive function, especially in low- and middle-income countries.

Effects of treatment with clopidogrel with or without proton pump inhibitor omeprazole on the risk of ischemic stroke: a nationwide cohort study

Most proton pump inhibitors (PPIs) inhibit the bioactivation of clopidogrel to its active metabolite. There is controversy concerning whether PPIs alter the effectiveness of clopidogrel in reducing the risk of ischemic stroke (IS). We therefore aimed to examine the risk of IS associated with concomitant use of clopidogrel and omeprazole, a PPI commonly used in clinical settings. We conducted a retrospective cohort study using the National Health Insurance Research Database of Taiwan dated from 2000 to 2013. The study cohorts comprised 407 patients diagnosed with acute coronary syndrome (ACS) and with concomitant use of clopidogrel and omeprazole (the exposed cohort), 814 ACS patients with single use of clopidogrel (the comparison cohort), and 230 ACS patients with concurrent use of clopidogrel and pantoprazole (the reference cohort). The primary outcome was incident IS. The hazard ratios (HRs) and 95% confidence intervals (CIs) derived from the time-dependent Cox regression model were used to assess the association between concomitant use of clopidogrel and omeprazole and the risk of IS. The incidence rate of IS was significantly higher in the exposed cohort (81.67 per 1000 person-years) than in the comparison cohort (57.45 per 1000 person-years), resulting in an adjusted HR of 1.39 (95% CI 1.03–1.74). By contrast, there was no significant difference in the risk of IS between the exposed and reference cohorts (adjusted HR 1.11; 95% CI 0.81–1.52). The present study revealed that patients taking both clopidogrel and omeprazole was associated with an increased risk of IS.

Treatment of pancreatic adenocarcinoma in relation to survival in the U.S. Military Health System

BackgroundPancreatic cancer has a high case fatality and relatively short survival after diagnosis. Treatment is paramount to improving survival, but studies on the effects of standard treatment by surgery or chemotherapy on survival in U.S. healthcare settings is limited. Further, variability in access to care may impact treatment and outcomes for patients. We aimed to assess the relationship between standard treatment(s) and survival of pancreatic adenocarcinoma in a population with access to comprehensive healthcare. MethodsWe used the Military Cancer Epidemiology (MilCanEpi) database, which includes data from the Department of Defense cancer registry and medical encounter data from the Military Health System (MHS), to study a cohort of 1408 men and women who were diagnosed with pancreatic adenocarcinoma between 1998 and 2014. Treatment with surgery or chemotherapy in relation to overall survival was examined in multivariable time-dependent Cox regression models. ResultsOverall, 75 % of 441 patients with early-stage and 51 % of 967 patients with late-stage pancreatic adenocarcinoma received treatment. In early-stage disease, surgery alone or surgery with chemotherapy were both associated with statistically significant 52 % reduced risks of death, but chemotherapy alone was not. In late-stage disease, surgery alone, chemotherapy alone, or both surgery and chemotherapy significantly reduced the risk of death by 42 %, 25 %, and 52 %, respectively. ConclusionsOur findings from the MHS demonstrate improved survival after treatment with surgery or surgery with chemotherapy for early- or late-stage pancreatic cancer and after chemotherapy for late-stage pancreatic cancer. In the era of immunotherapy and personalized medicine, further research on treatment and survival of pancreatic cancer in observational settings is needed.

Heightened long-term cardiovascular risks after exacerbation of chronic obstructive pulmonary disease

ObjectiveTo examine the risk of adverse cardiovascular (CV) events following an exacerbation of chronic obstructive pulmonary disease (COPD).MethodsThis retrospective cohort study identified patients with COPD using administrative data from Alberta,...

Predictors of early and long-term readmissions and their association with survival after liver transplantation

BackgroundThe impact of post liver transplantation (LT) readmissions on mortality has not been well described. Thus, the primary objective of our study was to determine predictors of readmissions post-LT and assess impact on survival. MethodsSingle center retrospective observational study investigating adult patients who underwent LT between January 1, 2010 – December 31, 2019 at Toronto General Hospital (TGH). Time-dependent cox regression model was used to investigate risk factors for 30-day, 30–90-day, and >90-day readmissions to hospital. The effect of readmission on survival was assessed with the Kaplan–Meier estimator. Results987 patients fulfilled inclusion criteria. Significant predictors of 30-day readmissions were BMI > 30 kg/m2 (HR=0.64; CI 0.42–0.98; p-value 0.04) and autoimmune/cholestatic liver disease (HR=1.86; CI 1.01–3.42; p = 0.046) at 30-days. Post-LT length of stay (HR=1.05; CI 1.02–1.08; p<0.001) at 30–90 days. Meanwhile, living donor LT (HR=1.41; CI 1.06–1.89; p = 0.02) and distance from LT center (HR=1.05; CI 1.01–1.09; p = 0.011) after 90 days. Infection was the main reason for readmission across three time periods. An inpatient readmission across any time period was found to be significantly associated with mortality (HR=2.4; 1.6–3.6; p<0.0001). ConclusionHospital readmissions post-LT are associated with increased mortality. Although infection is a common risk factor for readmission other modifiable risk factors may be an area for target of interventions to reduce post-LT readmission.

Cause-specific mortality and comorbid neurodevelopmental disorder in 167,515 patients with bipolar disorder: An entire population longitudinal study

ObjectiveStudies addressing premature mortality in bipolar disorder (BD) patients are limited by small sample sizes. Herein, we used almost 99 % of the population of Taiwan to address this issue, and its association with comorbid neurodevelopmental disorders and severe BD. MethodsBetween 2003 and 2017, we enrolled 167,515 individuals with BD and controls matched 1:4 for sex and birth year from the National Health Insurance Database linked to the Database of National Death Registry in Taiwan. Time-dependent Cox regression models were used to examine cause-specific mortality (all-cause, natural, and unnatural causes [accidents or suicide]). ResultsWith adjustments of sex, age, income, urbanization, and physical conditions, suicide was associated with the highest risk of mortality (reported as hazard ratio with 95 % confidence interval: 9.15; 8.53–9.81) among BD patients, followed by unnatural (4.94; 4.72–5.17), accidental (2.15; 1.99–2.32), and natural causes (1.02; 1.00–1.05). Comorbid attention-deficiency hyperactivity disorder did not contribute to the increased risk of cause-specific mortality; however, comorbid autism spectrum disorder (ASD) increased such risks, particularly for natural (3.00; 1.85–4.88) and accidental causes (7.47; 1.80–31.1). Cause-specific mortality revealed a linear trend with the frequency of psychiatric hospitalization (all, p for trend <0.001), and BD patients hospitalized twice or more each year had 34.63-fold increased risk of suicide mortality (26.03–46.07). ConclusionsBD patients with a higher frequency of psychiatric hospitalization have the highest risk of suicide mortality, and comorbid ASD was associated with an increased risk of natural and accidental causes of mortality.

Class III Obesity Is Associated with Worse Overall Survival in Previously Untreated Younger Patients with Acute Myeloid Leukemia Enrolled on SWOG 1203

Mohamed Sorror and Mary-Elizabeth Percival contributed equally to this project. Introduction: There has been inconsistent evidence supporting the association between obesity and outcomes in patients with newly diagnosed acute myeloid leukemia (AML). Prior studies have studied obesity as defined by body mass index (BMI) ≥ 30. However, this general definition of obesity can be further subdivided into class I obesity (BMI 30 to &amp;lt;35), class II obesity (BMI 35 to &amp;lt;40) and class 3 obesity (BMI ≥40). Given the high prevalence of obesity in the United States (41.9%; with class III obesity 9.2%), distinctions in degree of obesity may be associated with outcomes for patients with AML (Stierman et al, 2021). We were interested in studying outcomes in patients with AML stratified by class I, class II and class III obesity after induction chemotherapy and allogeneic hematopoietic cell transplant (HCT). Identification of at-risk patient populations could aid in design of future interventions. Methods: We retrospectively reviewed a group of 738 previously untreated subjects with AML randomized to daunorubicin and cytarabine (DA), idarubicin and cytarabine (IA), and IA with vorinostat as part of clinical trial SWOG 1203, conducted by the SWOG Cancer Research Network between 2012 and 2015. Subjects with adverse risk cytogenetics were recommended to receive HCT in their first complete remission (CR1); subjects with intermediate risk cytogenetics were selected for HCT in CR1 per local institutional standards. Nine patients who did not receive protocol therapy or had missing BMI were excluded (final cohort 729 patients). Early death was defined as death within 56 days of induction chemotherapy. Multivariable time-dependent Cox regression model and Fisher's exact test were used for analysis of overall survival (OS). HCT in first complete remission (CR1) was included as a time-dependent covariate. Results: The median age was 49 years (range, 18 to 60), 51% were male, 90% had de novo disease, and 88% had a performance status (PS) of 0-1 (Table 1). Among these patients, 1% (n=9) were underweight, 25% (n=182) were normal weight, 31% (n=225) were overweight, 20% (n=145) had class I obesity, 11% (n= 82) had class II obesity and 12% (n= 86) had class III obesity. There was no difference in the rate of achieving composite CR (CR with or without count recovery) between different weight categories (p=0.17). There was no clear trend in early death rate by weight (underweight: 11%; normal weight: 4%; overweight: 6%;class I obesity: 7%; class II obesity: 4%; class III obesity: 17%), though class III obesity had a significantly higher early death rate as compared to all the other groups combined (p=0.004). In multivariable Cox regression analyses, class III obesity was significantly associated with worse OS when compared to normal weight (hazard ratio (HR) 2.56, 95% confidence interval (CI) 1.68-3.90; p&amp;lt;0.001); though not statistically significant, we identified a trend towards worse OS for patients with class I (HR 1.40, 95% CI 0.95-2.06; p=0.09) and class II obesity (HR 1.48, 95% CI 0.95-2.31; p=0.09) (Figure 1). Other co-variates with a significant association with OS included age (HR 1.03, 95% CI 1.01-1.04; p&amp;lt;0.001), intermediate cytogenetic risk (HR 2.45, 95% CI 1.33-4.51; p=0.004), and adverse cytogenetic risk (HR 5.86, CI 3.10-11.06; p&amp;lt;0.001). HCT during CR1 was not found to be significantly associated with OS (HR 0.88, CI 0.67-1.15; p=0.3). No significant difference was identified in time to HCT based on BMI category. In patients who underwent HCT during CR1, class III obesity (HR 2.32, 95% CI 1.22-4.43; p=0.01) and older age (HR 1.02, 95% CI 1.00-1.04; p=0.01) were significantly associated with worse OS; in contrast no significant association was identified between OS and class I obesity (HR 1.30, 95% CI 0.77-2.20;p=0.32), while a higher HR and a trend existed for class II obesity (HR 1.76, 95% CI 0.97-3.17; p=0.06). Conclusions: Our retrospective analysis suggests that among newly diagnosed younger patients with AML, those with class III obesity are at increased risk of early death and shorter overall survival. Future directions include assessing lean body mass in addition to BMI in patients with newly diagnosed AML, as sarcopenic obesity is known to portend poor outcomes. Identifying this at-risk patient population may help guide future investigation of early weight management interventions in patients with newly diagnosed AML.

FIB-4 as a Time-varying Covariate and Its Association With Severe Liver Disease in Primary Care: A Time-dependent Cox Regression Analysis.

The Fibrosis-4 Index (FIB-4) has demonstrated a strong association with severe liver disease (SLD) outcomes in primary care, but previous studies have only evaluated this relationship using 1 or 2 FIB-4 scores. In this study, we determined the association of FIB-4 as a time-varying covariate with SLD risk using time-dependent Cox regression models. This retrospective cohort study included primary care patients with at least 2 FIB-4 scores between 2012 and 2021. The outcome was the occurrence of an SLD event, a composite of cirrhosis, complications of cirrhosis, hepatocellular carcinoma, and liver transplantation. The primary predictor was FIB-4 advanced fibrosis risk, categorized as low-(<1.3), indeterminate-(1.3≤FIB to 4<2.67), and high-risk (≥2.67). FIB-4 scores were calculated and the index, last, and maximum FIB-4s were identified. Time-dependent Cox regression models were used to estimate hazard ratios (HR) and their corresponding 95% CI with adjustment for potentially confounding covariates. In the cohort, 20,828 patients had a median of 5 (IQR: 3 to 11) FIB-4 scores each and 3% (n=667) suffered an SLD outcome during follow-up. Maximum FIB-4 scores were indeterminate-risk for 34% (7149) and high-risk for 24% (4971) of the sample, and 32% (6692) of patients had an increase in fibrosis risk category compared with their index value. The adjusted Cox regression model demonstrated an association between indeterminate- (hazard ratio 3.21; 95% CI 2.33-4.42) and high-risk (hazard ratio 20.36; 95% CI 15.03-27.57) FIB-4 scores with SLD outcomes. Multiple FIB-4 values per patient are accessible in primary care, FIB-4 fibrosis risk assessments change over time, and high-risk FIB-4 scores (≥2.67) are strongly associated with severe liver disease outcomes when accounting for FIB-4 as a time-varying variable.

Large long-haul aircraft entry, survival, and exit in China's air transport market: The Airbus 380 and Boeing 747-8I

This study explores the dynamics of entry, survival, and exit of large long-haul aircraft in China's burgeoning air transport market, focusing on the Airbus 380 and Boeing 747–8I as case studies. Utilizing rare events logistic regression and the time-dependent Cox regression model, the determinants of route entrance and survival for these aircraft from 2011 to 2021 were analyzed. The data is based on the flight plans of pertinent air routes and aircraft. Key findings include: (1) Both aircraft types favored entry into home-airfield-related, long-haul routes with a substantial existing flight volume. (2) Both aircraft exhibited prolonged survival on international long-haul routes, especially when airlines used them to bolster market share with consistent frequency. (3) Without the home-airfield advantage enjoyed by Air China, China Southern Airlines trialed the Airbus 380 on multiple occasions. Notably, if the Airbus 380 maintains operation on a route for at least 16 weeks, it demonstrates a lower likelihood of exit compared to the Boeing 747–8I.

Time-Dependent Factors Influencing Cardiocerebral Vascular Events in Chronic Hemodialysis Patients: Insights from a Longitudinal Study.

BACKGROUND Cardiocerebral vascular events (CVCs) are significant complications in patients undergoing hemodialysis (HD). Given the increased morbidity and mortality associated with CVCs in this population, understanding the factors influencing CVC occurrence over time is crucial. This study aimed to investigate these time-dependent factors in HD patients. MATERIAL AND METHODS A total of 228 HD patients from 2 dialysis centers, with at least 3 months of treatment between 2017 and 2021, were included. Annual clinical data were collected, and patients were monitored until CVC development. Kaplan-Meier analysis and a time-dependent Cox regression model were used for data analysis. RESULTS The mean age of 228 patients was 55.0±15.0 years, and 64.76% were male. For 5 years of monitoring, the mean follow-up interval was 3.1±1.0 years for patients to develop CVCs. The 1-year, 3-year, and 5-year CVC-free rates were 97.47%, 81.31%, and 70.71%, respectively. Time-dependent Cox regression revealed that C-reactive protein was an independent time-dependent risk factor in HD patients and blood flow rate was an independent time-dependent protective factor. The male subgroup and non-diabetic subgroup had these same results. The following were was the independent time-dependent risk factors: white blood cell count for the female subgroup; blood flow rate for the non-elderly subgroup; and C-reactive protein for the diabetic subgroup. None were risk factors for the elderly subgroup. CONCLUSIONS It took an average of 3.1±1.0 years for patients with HD to develop CVCs. C-reactive protein and blood flow rate emerged as key time-dependent influencing factors for CVCs in this population.

Longitudinal association of premature atrial contractions with atrial fibrillation and brain ischemia in people with type 2 diabetes: The Hoorn Diabetes Care System cohort

BackgroundPremature atrial contractions (PACs) are potential markers for imminent onset of both atrial fibrillation (AF) and brain ischemia (BI; transient ischemic attack [TIA] or ischemic stroke). We investigated the association of PACs with incident AF and BI events separately, and of incident AF with BI events in people with type 2 diabetes (T2D) without pre-existing AF or cerebrovascular disease. MethodsA prospective longitudinal study of 12,242 people with T2D without known AF or cerebrovascular disease from the Hoorn Diabetes Care System cohort. Annual measurements (1998–2018) included cardiovascular risk factors, over 85,000 ECGs, and self-reported cardiovascular events. We assessed the association of PACs with incident AF and BI events and of incident AF with BI events using time-dependent Cox-regression models, adjusted for time-varying cardiovascular risk factors and medication use (Hazard Ratios with 95%CIs). ResultsThe baseline mean age was 62.2 ± 11.9 years. During a median follow-up of 7.0 (IQR 3.4–11.0) years, 1031 (8.4 %) participants had PACs, and 566 (4.6 %) had incident AF at any of the median 6 (IQR 3–10) annual ECG recordings. BI events occurred in 517 (4.2 %) people (304 TIAs, 213 ischemic strokes). After adjustment, PACs were associated with incident AF (Hazard Ratio, 1.96 (95%CI, 1.53–2.50)), but not with overall BI events (1.09 (0.76–1.56)), or with TIA (0.91 (0.57–1.46)) or ischemic stroke (1.50 (0.88–2.54)) separately. AF was not associated with BI events (0.95 (0.55–1.63)). ConclusionsIn people with T2D without a history of AF or BI events, PACs are associated with a two-fold increased risk of incident AF.

All Expanded Criteria Donor Kidneys are Equal But are Some More Equal Than Others? A Population-Cohort Analysis of UK Transplant Registry Data.

Survival outcomes for kidney transplant candidates based on expanded criteria donor (ECD) kidney type is unknown. A retrospective cohort study was undertaken of prospectively collected registry data of all waitlisted kidney failure patients receiving dialysis in the United Kingdom. All patients listed for their first kidney-alone transplant between 2000-2019 were included. Treatment types included; living donor; standard criteria donor (SCD); ECD60 (deceased donor aged ≥60years); ECD50-59 (deceased donor aged 50-59years with two from the following three; hypertension; raised creatinine and/or death from stroke) or remains on dialysis. The primary outcome was all-cause mortality, with time-to-death from listing analyzed using time-dependent non-proportional Cox regression models. The study cohort comprised 47,917 waitlisted kidney failure patients, of whom 34,558 (72.1%) received kidney transplantation. ECD kidneys (n = 7,356) were stratified as ECD60 (n = 7,009) or ECD50-59 (n = 347). Compared to SCD, both ECD60 (Hazard Ratio 1.126, 95% CI 1.093-1.161) and ECD50-59 (Hazard Ratio 1.228, 95% CI 1.113-1.356) kidney recipients have higher all-cause mortality. However, compared to dialysis, both ECD60 (Hazard Ratio 0.194, 95% CI 0.187-0.201) and ECD50-59 (Hazard Ratio 0.218, 95% CI 0.197-0.241) kidney recipients have lower all-cause mortality. ECD kidneys, regardless of definition, provide equivalent and superior survival benefits in comparison to remaining waitlisted.

Association of neighborhood physical activity facilities with incident cardiovascular disease

BackgroundThe availability of physical activity (PA) facilities in neighborhoods is hypothesized to influence cardiovascular disease (CVD), but evidence from individual-level long-term cohort studies is limited. We aimed to assess the association between neighborhood exposure to PA facilities and CVD incidence.MethodsA total of 4658 participants from the Chinese Multi-provincial Cohort Study without CVD at baseline (2007–2008) were followed for the incidence of CVD, coronary heart disease (CHD), and stroke. Availability of PA facilities was defined as both the presence and the density of PA facilities within a 500-m buffer zone around the participants’ residential addresses. Time-dependent Cox regression models were performed to estimate the associations between the availability of PA facilities and risks of incident CVD, CHD, and stroke.ResultsDuring a median follow-up of 12.1 years, there were 518 CVD events, 188 CHD events, and 355 stroke events. Analyses with the presence indicator revealed significantly lower risks of CVD (hazard ratio [HR] 0.80, 95% confidence interval ([CI] 0.65–0.99) and stroke (HR 0.76, 95% CI 0.60–0.97) in participants with PA facilities in the 500-m buffer zone compared with participants with no nearby facilities in fully adjusted models. In analyses with the density indicator, exposure to 2 and ≥ 3 PA facilities was associated with 35% (HR 0.65, 95% CI 0.47–0.91) and 28% (HR 0.72, 95% CI 0.56–0.92) lower risks of CVD and 40% (HR 0.60, 95% CI 0.40–0.90) and 38% (HR 0.62, 95% CI 0.46–0.84) lower risks of stroke compared with those without any PA facilities in 500-m buffer, respectively. Effect modifications between presence of PA facilities and a history of hypertension for incident stroke (P = 0.049), and a history of diabetes for incident CVD (P = 0.013) and stroke (P = 0.009) were noted.ConclusionsResiding in neighborhoods with better availability of PA facilities was associated with a lower risk of incident CVD. Urban planning intervention policies that increase the availability of PA facilities could contribute to CVD prevention.

Oral Glucocorticoid Use and Long-Term Mortality in Patients with Chronic Musculoskeletal Non-Cancer Pain: A Cross-Sectional Cohort Study.

This study aimed to examine the associated factors of oral glucocorticoid (GC) use in patients with chronic non-cancer pain (CNCP) associated with musculoskeletal diseases (MSDs) in South Korea. Moreover, we examined whether oral GC use was associated with long-term mortality in patients with CNCP. This population-based cohort study used data from the national registration database in South Korea. Using a stratified random sampling technique, we extracted the data from 2.5% of adult patients diagnosed with MSDs in 2010. Patients with CNCP-associated MSDs who were prescribed oral GC regularly for ≥30 days were defined as GC users, while the other patients were considered to be non-GC users. A total of 1,804,019 patients with CNCP were included in the final analysis, and 9038 (0.5%) patients were GC users, while 1,794,981 (95.5%) patients were non-GC users. Some factors (old age, comorbid status, pain medication use, and MSD) were associated with GC use among patients with CNCP. Moreover, in the multivariable time-dependent Cox regression model, GC users showed a 1.45-fold higher 10-year all-cause mortality (hazard ratio: 1.45, 95% confidence interval: 1.36-1.54; p < 0.001) than non-GC users. In South Korea, the 10-year all-cause mortality risk increased in the patients with CNCP using GC.

Glucocorticoid treatment in SLE is associated with infections, comorbidities and mortality-a national cohort study.

Patients with SLE have an increased risk of comorbidities and impaired survival. We aimed to assess whether various thresholds of oral CS (OCS) can predict development of infections, comorbidities, malignancies and survival in SLE using data from national health registries in Sweden. All incident SLE cases, age >18 years, in Sweden (n = 5309) between 2005 and 2020 and matched population controls (n = 26 545) were included and followed until 2020, a total of 257 942 patient years. Data from national registers were retrieved including information from the National Prescribed Drug Register. Risk factors were analysed using time-dependent Cox regression models. Compared with no OCS, >0 to <5.0 mg/day, 5.0-7.5 mg/day as well as >7.5 mg/day OCS predicted development of infections (pneumonia, influenza, herpes zoster and urinary tract infection), osteoporosis, osteonecrosis, gastroduodenal ulcers, cataracts, hypertension and mortality (all P < 0.05). OCS >0 to <5.0 mg/day was associated with lower hazard ratios for these comorbidities than higher doses of OCS. Fifteen years after diagnosis, 48% of patients were taking OCS at a median dose of 5.7 mg/day. A small reduction of OCS treatment 5 years after diagnosis in patients diagnosed with SLE 2006-10 compared with 2011-15 was observed, 49% vs 46% respectively (P = 0.039). Results highlight the potential harm associated with even low OCS dose treatment in SLE and the need to judiciously use OCS at the lowest possible dose to maximize efficacy and minimize harm.