Competing Risk Model Research Articles

Adverse cardiovascular events in patients with cancer: a biomarker-enhanced clinical risk score

Abstract Background/Introduction Continuously improving cancer-specific survival puts a growing proportion of cancer patients at risk of major adverse cardiovascular events (MACE), but reliable tools for cardiovascular risk prediction remain unavailable (1). Purpose To assess a broad panel of cardiovascular biomarkers and clinical risk factors and to provide a novel risk score for the prediction of MACE in cancer patients. Methods Among 2’192 patients with newly diagnosed or recurrent cancer, a broad panel of cardiovascular biomarkers, including NT-proBNP, P-/E-/L-selectins, ICAM-1, VCAM-1, sLOX-1, CRP, and Lp(a) were measured by blinded study personnel. Patients were followed prospectively for the occurrence of 2-year MACE and 5-year cardiovascular death (2,3). Uni- and multivariable competing risk models were fit to assess independent associations of cardiovascular risk factors and biomarkers with MACE, and a risk score was developed. Results Beyond clinical risk factors, ICAM-1, P-/E-/L-selectins and NT-proBNP levels were independently linked to 2-year MACE risk, though shape of associations differed markedly. A clinical risk score was derived, assigning +1 point for male sex, smoking, and age ≥60 years, and +2 points for ASCVD history, yielding a bootstrapped C-statistic of 0.76 (95%CI:0.71-0.81). Implementation of cardiovascular biomarkers conferred improved performance (0.83, 95%CI:0.78-0.88). A simplified model, solely informed by clinical variables and readily available NT-proBNP (+1 point for NT-proBNP≥230pg/mL), achieved similar performance (0.80, 95%CI:0.74-0.86), with a cumulative 2-year MACE incidence of 0% in low- and 11.0% in high-risk patients. Conclusions Cancer patients are at substantial MACE risk. The herein presented first-of-its-kind risk score, integrating traditional cardiovascular risk factors and biomarkers, including NT-proBNP, effectively predicts 2-year MACE and 5-year cardiovascular death.

Association between PCSK9 inhibitor with cause-specific morality amongst cancer survivors

Abstract Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor has emerged as a novel pharmacotherapy for dyslipidemia and been shown to be effective in reducing the risks of atherosclerotic cardiovascular diseases. PCSK9 is aberrantly expressed in a broad spectrum of cancers and has been demonstrated to contribute to cancer prognosis. However, no prior study has investigated the associations between PCSK9 inhibitors (PCSK9i) with cardiovascular and cancer mortality amongst cancer survivors. Purpose This study investigated the effects of PCSK9i on cause-specific mortality amongst cancer survivors. Methods This retrospective study used data from the Tianjin Coronary Artery Disease Cohort, which included medical data from 71 secondary or tertiary hospitals in Tianjin, China. Adult patients with coronary artery disease (CAD) diagnosed with incident cancer between 2017 and 2023 were enrolled in this study. Propensity score matching with a 1:3 ratio for PCSK9i users versus non-users was performed. The primary outcomes included all-cause mortality, cardiovascular mortality, and cancer mortality. Multivariable Cox regression was used to test associations between PCSK9i with outcomes, adjusting for age, gender, cardiovascular and non-cardiovascular comorbidities, lipid-lowing agents and other medication use, lipid level, as well as cancer characteristics. Multivariable competing risk analysis was used as sensitivity analysis. Results A total of 62,341 incident cancer patients were identified. After matching, 424 PCSK9i users and 1,272 non-users were included in this study. During a median follow-up of 1,009 days, 315 patients died, among which 98 died due to cardiovascular cause, 146 died due to cancer cause. Compared to non-users, cancer patients treated with PCSK9i presented with significantly lower risk of all-cause mortality (hazard ratio [HR], 0.33; 95% confidence interval [CI] 0.23-0.47; p <0.001), after adjusting for potential confounders. In addition, PCSK9i therapy was associated with a 63% lower risk of cardiovascular mortality (HR, 0.37; 95%CI 0.20-0.69; p=0.002) and a 75% lower risk of cancer-related mortality (HR, 0.25; 95%CI 0.14-0.45; p<0.001), in relation to non-PCSK9i group. Sensitivity analysis using multivariable competing risk model also suggested a significant association between PCSK9i treatment with reduced risk of cardiovascular mortality (HR, 0.41; 95%CI 0.22-0.76; p=0.005) and cancer mortality (HR, 0.26; 95%CI 0.15-0.48; p<0.001) among cancer survivors. Conclusion The use of PCSK9i was associated lower risks of all-cause, cardiovascular-related, and cancer-related mortality amongst cancer survivors. These findings potentially indicate benefits of PCSK9i beyond adverse cardiovascular events related to atherosclerosis.

Relative burden of cancer and noncancer mortality among long-term survivors of differentiated thyroid cancer in the US.

Limited information is available regarding the relative risks of cancer-specific mortality and noncancer-specific mortality among long-term survivors with differentiated thyroid cancer (DTC). In this retrospective study, nationwide data from the Surveillance, Epidemiology, and End Results database (1992-2020) were utilized. The Accelerated Failure Time Model was applied to calculate Survival Time Ratios (TR), with the primary focus on mortality resulting from DTC. The competing risks model was employed to investigate the relative risks of various outcomes in DTC patients with a survival duration of 5 years or more. In our cohort, 279 patients succumbed to DTC, while 748 died from other diseases. Notably, in DTC cohorts, noncancer-specific mortality rates were consistently higher than DTC-specific mortality rates across different age groups and genders. The risk of DTC and noncancer-specific mortality varied based on the TNM stage. With more advanced disease stages, the risk of DTC and other cancer-specific mortality gradually increased. The cumulative mortality from other cancer-specific causes was consistently the lowest. In long-term surviving DTC patients, noncancer-specific mortality outweighed DTC-specific mortality irrespective of age and gender. For stage I and II patients, increased attention should be directed toward noncancer-specific mortality in postoperative follow-ups. Conversely, for stage III and IV patients, greater consideration should be given to DTC-related causes of death. In addition, for stage III and IV DTC patients, the risk of death from other cancers was significantly higher than for stages I and II.

Clinical features, outcomes, and anticoagulant strategies in lung cancer-associated isolated distal deep vein thrombosis

IntroductionThe clinical presentation, outcomes, and anticoagulation strategies in patients with lung cancer-associated isolated distal deep vein thrombosis (LC-iDDVT) are not well-defined. Materials and methodsThe study included 593 patients with LC-iDDVT and 260 patients with lung cancer-associated proximal DVT (LC-Proximal DVT). LC-iDDVT was further classified into axial venous thrombosis (AVT; 112 patients) and muscular venous thrombosis (MVT; 481 patients). Cox proportional risk regression models with Fine-Gray tests and competing risk models were employed to evaluate short-term (90-day) and long-term (1-year) outcomes (hazard ratio [HR]; 95 % confidence interval [CI]). ResultsAt the 90-day follow-up, patients with MVT had lower adjusted risks of pulmonary embolism (PE; HR = 0.20 [0.07–0.55], p = 0.002) and venous thromboembolism (VTE) recurrence (HR = 0.54 [0.34–0.88], p = 0.013) than those with LC-Proximal DVT. Similar results were observed at the 1-year follow-up. However, adjusted risks for PE (HR = 0.74 [0.29–1.92], p = 0.540; HR = 0.87 [0.42–1.78], p = 0.700) and VTE recurrence (HR = 0.96 (0.54–1.71), p = 0.890; HR = 0.99 [0.63–1.56], p = 0.970) at 90-day and 1-year were not significantly different between patients with AVT and those with LC-Proximal DVT. Among patients with LC-iDDVT, those receiving anticoagulation had reduced risks of VTE recurrence (HR = 0.57 [0.35–0.95], p = 0.030) and DVT deterioration (HR = 0.28 [0.13–0.60], p = 0.001) compared to those without anticoagulation. Moreover, AVT patients on >3 months of anticoagulation had a lower VTE recurrence risk (HR = 0.23 [0.03–0.92], p = 0.038) than those on ≤3 months of anticoagulation. ConclusionIn the context of lung cancer, patients with AVT may have a higher tendency for recurrent thrombosis compared to those with MVT, especially if anticoagulation is refused or given briefly.

Extracorporeal Membrane Oxygenation for COVID-19 During the Delta and Omicron Waves in North America.

Clinical outcomes for patients with severe acute respiratory failure caused by different variants of the coronavirus disease 2019 (COVID-19) supported with extracorporeal membrane oxygenation (ECMO) are incompletely understood. Clinical characteristics, pre-ECMO management, and hospital mortality at 90 days for adults with COVID-19 who received venovenous ECMO (VV-ECMO) at North American centers during waves predominated by Delta (August 16 to December 12, 2021) and Omicron (January 31 to May 31, 2022) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants were compared in a competing risks framework. One thousand seven hundred and sixty-six patients (1,580 Delta, 186 Omicron) received VV-ECMO for COVID-19 during the Delta- and Omicron-predominant waves in North American centers. In the unadjusted competing risks model, no significant difference was observed in risk of hospital mortality at 90 days between patients during the Delta- versus Omicron-predominant wave (subhazard ratio [sHR], 0.94; 95% confidence interval [CI], 0.74-1.19), but patients supported with VV-ECMO during the Omicron-predominant wave had a significantly lower adjusted risk of hospital mortality at 90 days (subhazard ratio, 0.71; 95% CI, 0.51-0.99). Patients receiving VV-ECMO during the Omicron-predominant wave had a similar unadjusted risk of hospital mortality at 90 days, but a significantly lower adjusted risk of hospital mortality at 90 days than those receiving VV-ECMO during the Delta-predominant wave.

Suicide in people prescribed opioid-agonist therapy in Scotland, United Kingdom, 2011-2020: A national retrospective cohort study.

Opioid dependence is associated with an increased risk of suicide. Drug-related mortality among people with opioid dependence in Scotland has more than tripled since 2010; less is known about changes in suicide risk. We aimed to determine if opioid agonist therapy (OAT) in Scotland is protective against suicide and to measure trends in suicide rates in those with opioid dependence over time. Retrospective cohort study. Scotland, UK. 46 453 individuals in Scotland who received at least one prescription for OAT between 2011 and 2020 with over 304 000 person-years (pys) of follow-up. We calculated standardised mortality ratios (SMR) using the age- and sex-specific suicide rates in Scotland for years 2011-2020. We fitted multivariable competing-risk regression models to estimate suicide rates by OAT exposure and to estimate trends over time, adjusting for potential confounders. There were 575 deaths classed as suicide among the cohort and the overall suicide rate was 1.89 (95% confidence interval [CI] = 1.74-2.05) per 1000 pys. Age and sex SMR for suicide was 7.05 times (95% CI = 6.50-7.65) higher than in the general population. After adjustment, OAT was shown to be highly protective against suicide, with rates more than three times greater (adjusted hazard ratio: 3.07; 95% CI = 2.60-3.62) off OAT compared with on OAT. Suicide rates decreased over time, falling from 2.57 (95% CI = 2.19-3.02) per 1000 pys in 2011-12 to 1.48 (95% CI = 1.21-1.82) in 2019-20. People with opioid dependence in Scotland appear to have a greater risk of suicide than the general population. Treatment is protective, with rates of suicide lower among those on opioid agonist therapy. Suicide rates have decreased over time, during a period in which drug-related death rates in Scotland have risen to globally high levels.

‎The association between cumulative exposure to neighborhood walkability (NW) and diabetes risk, a prospective cohort study

PurposeTo examine the association between cumulative exposure to neighborhood walkability (NW) and diabetes risk. MethodsA total of 11,037 women free of diabetes at enrollment were included. We constructed a 4-item NW index at baseline, and a 2-item average annual NW across years of follow-up that captured both changes in neighborhood features and residential moves. We used multivariable Cox PH regression models with robust variance to estimate the hazard ratios (HRs) of diabetes by NW scores. ResultsCompared with women living in areas with lowest NW (Q1), those living in areas with highest NW (Q4) had 33 % (26 %−39 %) reduced risk of incident diabetes, using baseline NW, and 25 % (95 % CI 11 %−36 %), using average annual NW. Analysis using time-varying exposure showed that diabetes risks decreased by 13 % (10 %−16 %) per -standard deviation increase in NW. The associations remained similar when using inverse probability of attrition weights and/or competing risk models to account for the effect of censoring due to death or non-response. The associations of average annual NW with incident diabetes were stronger in postmenopausal women as compared to premenopausal women. ConclusionLong-term residence in more walkable neighborhoods may be protective against diabetes in women, especially postmenopausal women.

Competing and Noncompeting Risk Models for Predicting Kidney Allograft Failure.

Prognostic models are becoming increasingly relevant in clinical trials as potential surrogate endpoints, and for patient management as clinical decision support tools. However, the impact of competing risks on model performance remains poorly investigated. We aimed to carefully assess the performance of competing risk and noncompeting risk models in the context of kidney transplantation, where allograft failure and death with a functioning graft are two competing outcomes. We included 11,046 kidney transplant recipients enrolled in 10 countries. We developed prediction models for long-term kidney graft failure prediction, without accounting (i.e., censoring) and accounting for the competing risk of death with a functioning graft, using Cox, Fine-Gray, and cause-specific Cox regression models. To this aim, we followed a detailed and transparent analytical framework for competing and noncompeting risk modelling, and carefully assessed the models' development, stability, discrimination, calibration, overall fit, clinical utility, and generalizability in external validation cohorts and subpopulations. More than 15 metrics were used to provide an exhaustive assessment of model performance. Among 11,046 recipients in the derivation and validation cohorts, 1,497 (14%) lost their graft and 1,003 (9%) died with a functioning graft after a median follow-up post-risk evaluation of 4.7 years (IQR 2.7-7.0). The cumulative incidence of graft loss was similarly estimated by Kaplan-Meier and Aalen-Johansen methods (17% versus 16% in the derivation cohort). Cox and competing risk models showed similar and stable risk estimates for predicting long-term graft failure (average mean absolute prediction error of 0.0140, 0.0138 and 0.0135 for Cox, Fine-Gray, and cause-specific Cox models, respectively). Discrimination and overall fit were comparable in the validation cohorts, with concordance index ranging from 0.76 to 0.87. Across various subpopulations and clinical scenarios, the models performed well and similarly, although in some high-risk groups (such as donors over 65 years old), the findings suggest a trend towards moderately improved calibration when using a competing risk approach. Competing and noncompeting risk models performed similarly in predicting long-term kidney graft failure.

The relationship between serum HDL-cholesterol, cardiovascular disease and mortality in community-based people with type 2 diabetes: the Fremantle Diabetes Study phase 2

BackgroundOlder general population-based studies found an inverse association between serum HDL-cholesterol and both cardiovascular disease (CVD) events and mortality, but more recent data have suggested a U-shaped relationship. Whether this applies to type 2 diabetes is uncertain. The aim of this study was to assess the prognostic significance of serum HDL-cholesterol concentrations in representative, community-based participants from the Fremantle Diabetes Study Phase II (FDS2).MethodsWe followed 1,479 FDS2 participants with confirmed type 2 diabetes (713 females, mean age 65.6 years; 763 males, mean age 65.9 years) from entry (2008–2011) to death/end-2021. Major adverse cardiovascular events (non-fatal myocardial infarction (MI), non-fatal stroke, cardiovascular death; 3-point MACE), and all-cause mortality were ascertained from prospectively collected data and validated administrative databases. Independent associates of 3-point MACE by sex, excluding participants with prior MI/stroke, were assessed using Cox and competing risk models with sex-specific quintiles of HDL-cholesterol added to the most parsimonious models. Predictors of all-cause mortality were identified using Cox proportional hazards modelling.ResultsIn females, with baseline serum HDL-cholesterol quintile 2 (1.04–1.22 mmol/L) as reference, both quintiles 1 (< 1.04 mmol/L) and 5 (> 1.59 mmol/L) were significant independent predictors of 3-point MACE (P < 0.027) and all-cause death (P < 0.019) after adjustment for a full range of demographic, clinical and laboratory variables. In males, serum HDL-cholesterol quintile did not add to the most parsimonious model for 3-point MACE, but quintile 1 (< 0.90 mmol/L) was a significant predictor of death (P = 0.026 versus quintile 4 (1.15–1.31 mmol/L) as reference) after adjustment. Competing risk analyses for 3-point MACE showed similar results to the Cox models for both sexes.ConclusionThere was a significant U-shaped relationship between serum HDL-cholesterol and both 3-point MACE and all-cause death in females with type 2 diabetes after adjustment for confounders. There was no such relationship for 3-point MACE in males but a low HDL-cholesterol was associated with all-cause mortality. These data have sex-specific implications for assessment of serum lipid profiles in the clinical management of type 2 diabetes.

Testing Similarity of Parametric Competing Risks Models for Identifying Potentially Similar Pathways in Healthcare.

The identification of similar patient pathways is a crucial task in healthcare analytics. A flexible tool to address this issue are parametric competing risks models, where transition intensities may be specified by a variety of parametric distributions, thus in particular being possibly time-dependent. We assess the similarity between two such models by examining the transitions between different health states. This research introduces a method to measure the maximum differences in transition intensities over time, leading to the development of a test procedure for assessing similarity. We propose a parametric bootstrap approach for this purpose and provide a proof to confirm the validity of this procedure. The performance of our proposed method is evaluated through a simulation study, considering a range of sample sizes, differing amounts of censoring, and various thresholds for similarity. Finally, we demonstrate the practical application of our approach with a case study from urological clinical routine practice, which inspired this research.

Early deep-to-light sedation versus continuous light sedation for ICU patients with mechanical ventilation: A cohort study

BackgroundSedation strategies have not been well established for patients being treated with invasive mechanical ventilation (MV). This study aimed to compare the potential effects of alternative sedation strategies – including early deep-to-light sedation (DTLS), continuous deep sedation (CDS) and continuous light sedation (CLS, the currently recommended strategy) – on ventilator, intensive care unit (ICU) or hospital mortality. MethodsA cohort study was conducted using two large validated ICU databases, including the Registry of Healthcare-associated Infections in ICUs in China (ICU-HAI) and the Medical Information Mart for Intensive Care (MIMIC). Patients who received MV for more than 3 days with one of three sedation strategies were included. Multivariable survival analyses with inverse probability-weighted competing risk models were conducted separately for ICU-HAI and MIMIC cohorts. Adjusted estimates were pooled using fixed-effects models. ResultsIn total, 6700 patients (2627 ICU-HAI, 4073 MIMIC) were included in the cohort study, of whom 2689 received CLS, 2079 CDS and 1932 DTLS. Compared to CLS, DTLS was associated with lower ICU mortality (9.3% vs. 11.0%; pooled adjusted HR 0.78, 95% CI 0.66−0.94) and hospital mortality (16.0% vs. 14.1%; 0.86, CI 0.74–1.00); and CDS was associated with higher ventilator mortality (32.8% vs. 7.0%; 4.65, 3.91–5.53), ICU mortality (40.6% vs. 11.0%; 3.39, 2.95–3.90) and hospital mortality (46.8% vs. 14.1%; 3.27, 2.89–3.71) than CLS. All HRs were qualitatively consistent in both cohorts. ConclusionsCompared to the continuous light sedation, early deep-to-light sedation strategy was associated with improved patient outcomes, and continuous deep sedation was confirmed with poorer patient outcomes.

Analysis of dependent complementary competing risks data from a generalized inverted family of lifetime distributions under a maximum ranked set sampling procedure with unequal samples

This paper explores analysis of a dependent complementary competing risks model when the failure causes are distributed by the proposed generalized inverted family of lifetime distributions. Under maximum ranked set sampling with unequal samples (MRSSU), statistical inference of model parameters and reliability indices is discussed under classical frequentist and Bayesian approaches, respectively. Maximum likelihood estimators along with their existence and uniqueness are obtained for model parameters, and associated approximate confidence intervals are constructed in consequence. Bayesian estimation is also performed with respect to general flexible priors, and the Markov Chain Monte Carlo (MCMC) algorithm is proposed for complex posterior computation. The study further examines classical and Bayesian estimations with order restriction of parameters when additional historical information is available in the MRSSU scenario. Finally, the performance of different results is evaluated through numerical simulations and a real data example is presented for demonstrating the application of our methods.

Inactivated vaccine dosage and serum IgG levels correlate with persistent COVID-19 infections in hematologic malignancy patients during the Omicron Surge in China

PurposeThe essence of this scholarly work was to carefully outline the key factors intensifying the virulence and protracted contagion of COVID-19, particularly among individuals afflicted with hematologic malignancies (HM), in an epoch predominantly governed by the Omicron variant.MethodsAdults with HM diagnosed with COVID-19 from November 2022 to February 2023 were monitored in this retrospective study. Patient blood samples yielded biochemical data, and COVID-19 was confirmed through RNA or antigen testing. The factors affecting severity and infection duration were examined using both univariate and multivariate logistic regression analyses. For calculating the overall survival probabilities, the Kaplan–Meier product limit approach was employed.ResultsIn the examined cohort, 133 individuals diagnosed with HM and concomitantly infected with COVID-19 were scrutinized. Of the participants, 29.3% (39 patients) were classified as Severe/Critical, while the other 70.7% (94 patients) were categorized as Non-severe. A significant difference was observed in vaccination status: 61.7% of patients in the Non-severe group had received at least a two-dose vaccine regimen, whereas 61.5% of the Severe/Critical group had either minimal or only one dose of vaccination. The data analysis revealed that elevated C-reactive protein levels (≥ 100 mg/L) significantly raised the risk of severe/critical conditions in HM patients with COVID-19, as determined by advanced multivariate logistic regression. The odds ratio was 3.415 with a 95% confidence interval of 1.294–9.012 (p = 0.013). Patients who continued to have positive nucleic acid tests and ongoing symptoms beyond 30 days were categorized as having a persistent infection, whereas those who achieved infection control within this timeframe were categorized as having infection recovery. Of the HM cohort, 11 did not survive beyond 30 days after diagnosis. The results from a competing risk model revealed that increased interleukin-6 levels (HR: 2.626, 95% CI: 1.361–5.075; p = 0.004) was significantly associated with persistent infection. Conversely, receiving more than two vaccine doses (HR: 0.366, 95% CI: 0.158–0.846; p = 0.019), and having high IgG levels (≥ 1000 mg/dl) (HR: 0.364, 95% CI: 0.167–0.791; p = 0.011), were associated with infection recovery. There was a notable disparity in survival rates between patients with persistent infections and infection recovery, with those in the non-persistent group demonstrating superior survival outcomes (P < 0.001).ConclusionsIn conclusion, the study determined that HM patients with COVID-19 and increased C-reactive protein levels had a higher likelihood of severe health outcomes. Persistent infection tended to be more prevalent in those with vaccine dosages (< 2 doses), lower IgG levels, and higher interleukin-6 levels.

Changes in early HIV/AIDS mortality rates in people initiating antiretroviral treatment between 2013 and 2023: A 10-year multicenter survival study in Senegal

BackgroundHIV/AIDS-related early mortality has long been a significant challenge. Subsequent to recent policy changes and treatment advancements, we aimed to assess changes in early mortality rates in 2017–19 and 2020-23 compared to 2013–16. MethodsThis is a 10-year multicenter survival study in people living with human immunodeficiency virus having initiated ART between 2013 and 2023. We used frailty-based competing risk models to estimate adjusted early (6-month and one-year) mortality hazard ratios (HRs) in people living with HIV (PwHIV) having initiated ART in 2013–16 (comparator), 2017–19, and 2020–23. ResultsWe enrolled 4006 persons of whom 2281 (56.9 %) were female; median age was 40 years (IQR: 31–50); 635 (15.9 %) were at WHO clinical stage IV and 934 (23.3 %) had a CD4 count <200 cells/mm3. Median follow-up was 80.4 months (IQR: 48.6–106.7). All in all, 463 participants died (4.37 deaths per 100 person-years), including 296 at one year of follow-up (7.4 % [95 % CI: 6.6–8.2]). ART initiation in 2016–19 and 2020–23 was associated with 27 % (adjusted HR [aHR]: 0.73; 95 % CI: 0.55–0.98) and 63 % (aHR: 0.37; 95 % CI: 0.25–0.56) reductions in one-year mortality rates, respectively, compared to the 2013–16 period. ConclusionEarly mortality risk has significantly decreased over time in Senegal. However, the proportion of PwHIV with AIDS-defining conditions remains concerning. Continued efforts to ensure early diagnosis and prompt linkage to care are needed for more impact.

Dietary Restriction, Socioeconomic Factors, Access to Kidney Transplantation, and Waitlist Mortality.

Dietary restrictions for patients with end-stage kidney disease (ESKD) are burdensome. Kidney transplantation (KT) candidates who lack neighborhood resources and are burdened by dietary restrictions may have decreased access to KT. In our two-center prospective cohort study (2014-2023), 2471 ESKD patients who were evaluated for KT (candidates) reported their perceived burden of dietary restrictions (not at all, somewhat/moderately, or extremely bothered). Neighborhood-level socioeconomic factors were derived from residential ZIP codes. We quantified the association of perceived burden of the dietary restrictions with a chance of listing using Cox models and risk of waitlist mortality using competing risks models. Then we tested whether these associations differed by neighborhood-level socioeconomic factors. At evaluation, 18% of KT candidates felt extremely bothered by dietary restrictions. Those who felt extremely bothered were less likely to be listed for KT (adjusted hazard ratio [aHR]=0.75, 95% confidence interval [CI]: 0.64-0.87); this association did not differ by neighborhood-level socioeconomic factors. Overall, the burden of dietary restrictions was not associated with waitlist mortality (p=0.62). However, among candidates living in high food insecurity neighborhoods, those who felt extremely bothered had higher waitlist mortality (adjusted subhazard ratio [aSHR]=2.07, 95% CI: 1.14-3.75, p[interaction]=0.02). The association between dietary burden and waitlist mortality did not differ by neighborhood-level healthy food access. The perceived burden of dietary restrictions is associated with a lower chance of listing for KT, and higher waitlist mortality only among candidates residing in neighborhoods with high food insecurity. Transplant centers should identify vulnerable patients and support them with nutrition education and access to food assistance programs.

Outcomes of Left Atrioventricular Valve Operation following Atrioventricular Septal Defect Repair

Left atrioventricular valve (LAVV) operation following repair of atrioventricular septal defects (AVSD) can be challenging. We sought to describe characteristics and outcomes of patients requiring LAVV operation. Retrospective review of AVSDs requiring LAVV operation between 2000-2020. Patients who experienced adverse events (AEs; defined as the need for a LAVV reoperation (repair or replacement) or death) were compared to patients without AEs. Freedom from adverse events was displayed using the Kaplan-Meier method. Reoperation and death were characterized in terms of cumulative incidence function, estimated using competing risk models. Of 843 patients with AVSD repaired, 59 (7.3%) required a LAVV operation and 7 (9%) valve replacement. A simple repair (cleft closure and/or annuloplasty) occurred in 26 (48.1%) and complex repair using multiple techniques in 28 (51.8%) cases. Eleven patients (20%) required further LAVV reoperation; 3 replacement of mechanical valve, 6 new valve replacement (2 Melody, 4 Mechanical) and 2 re-repair. The cumulative incidence of freedom from AE was 84.1% (75.0%, 94.2%), 78.3% (68.2%, 90.0%), 73.4% (62.2%, 86.7%), 69.7% (57.5%, 84.7%) at 1, 5, 10 and 15 years respectively. Cox univariable regression showed smaller weight (p=0.027) and early need for LAVV operation (p=0.02) were associated with AEs while cleft closure (p = 0.003) was protective against AEs. The estimated cumulative incidence of reoperation was higher in complex repairs (17.3% (7.8%, 38.7%) vs 0.5% (NA, NA) at 1 year. Greys p = 0.02). In a comparison of eras (2000-2009, 2010- 2020) there was no difference in AE (Greys p = 0.96). Adverse outcomes following LAVV reoperation remain common. Smaller infants, those requiring earlier reoperation and complex type repairs are at highest risk. Future studies should focus on which high risk LAVVs are more suited to early LAVV replacement.

Role of Surgery in Potentially Resectable Small-Cell Lung Cancer Based on the Eighth Edition of the TNM Classification: A Population Study of the US SEER Database.

This study aimed to identify a specific SCLC population that would benefit from surgery. This study utilized patient data retrieved from the Surveillance, Epidemiology, and End Results (SEER) database spanning 2010 to 2017. To mitigate clinical biases, the propensity score matching (PSM) technique was employed. Separate cohorts were aligned using PSM according to the AJCC 8th edition TNM classification. The Kaplan-Meier method and a competing risk model were applied to evaluate overall survival (OS) and lung cancer-specific survival (LCSS), respectively. Among the 3394 patients with potentially resectable SCLC included in the study, 3062 underwent chemoradiotherapy and 332 underwent surgical treatment with adjuvant chemotherapy. Surgery was associated with better OS (median OS: 49 months; 95% CI: 35-63 months vs. 27 months; 95% CI: 21-33 months, p < 0.001) and LCSS (SHR, 0.578; 95% CI: 0.411-0.815, p < 0.001) in stage I patients after PSM. However, there was no significant difference in OS and LCSS between the surgery and nonsurgery groups in stage II and III patients after PSM. In the entire cohort, lobectomy was associated with improved OS (median OS: 48.6 vs. 28.7 months, p < 0.0001), but not LCSS (SHR, 0.696; 95% CI: 0.466-1.040, p = 0.078) compared with sublobar resection after PSM. Surgery with adjuvant chemotherapy significantly improved the survival prognosis of patients with early-stage SCLC. However, surgical treatment should be carefully considered in patients with stage II/III disease. Lobectomy is oncologically equal to sublobar resection.

Heart failure and major haemorrhage in people with atrial fibrillation

BackgroundHeart failure (HF) is not included in atrial fibrillation (AF) bleeding risk prediction scores, reflecting uncertainty regarding its importance as a risk factor for major haemorrhage. We aimed to report...

Application Value of Competing Risk Models in the Prevention of Preeclampsia

Preeclampsia is a common complication during pregnancy that severely impacts both maternal and fetal health. In recent years, competing risk models have emerged as a novel statistical method increasingly used to investigate the risk factors and prevention strategies associated with preeclampsia. This review summarizes the current applications of competing risk models in preeclampsia research, emphasizing their value in risk assessment, preventive interventions, and clinical decision-making. Additionally, it highlights future research directions that could further enhance the understanding and management of this condition.

Risk of Dementia Diagnosis After Injurious Falls in Older Adults

Emerging evidence suggests that mild cognitive impairment, which is a precursor to Alzheimer disease and related dementias (ADRD), places older adults at increased risk for falls. However, the risk that an older adult develops dementia after experiencing a fall is unknown. To determine the risk of new ADRD diagnosis after a fall in older adults. This retrospective cohort study examined Medicare Fee-for-Service data from 2014 to 2015, with follow-up data available for at least 1 year after the index encounter. Participants included adults aged 66 years and older who experienced a traumatic injury that resulted in an emergency department (ED) or inpatient encounter and did not have a preexisting diagnosis of dementia. Data analysis was performed from August 2023 to July 2024. Experiencing a fall compared with other mechanisms of injury, defined by International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 external cause of injury codes. The hazard of new ADRD diagnosis within 1 year of a fall, assessed by performing a Cox multivariable competing risk model that controlled for potential confounders while accounting for the competing risk of death. The study included 2 453 655 older adult patients who experienced a traumatic injury; 1 522 656 (62.1%) were female; 124 396 (5.1%) were Black and 2 232 102 (91.0%) were White; and the mean (SD) age was 78.1 (8.1) years. The mechanism of injury was a fall in 1 228 847 incidents (50.1%). ADRD was more frequently diagnosed within 1 year of a fall compared with other injury mechanisms (10.6% [129 910 of 1 228 847] vs 6.1% [74 799 of 1 224 808]; P < .001). The unadjusted hazard ratio (HR) of incident dementia diagnosis after a fall was 1.63 (95% CI, 1.61-1.64; P < .001). On multivariable Cox competing risk analysis, falling was independently associated with an increased risk of dementia diagnosis among older adults (HR, 1.21 [95% CI, 1.20-1.21]; P < .001) after controlling for patient demographics, medical comorbidities, and injury characteristics, while accounting for the competing risk of death. Among the subset of older adults without a recent skilled nursing facility admission, the HR was 1.27 (95% CI, 1.26-1.28; P < .001). In this cohort study, new ADRD diagnoses were more common after falls compared with other mechanisms of injury, with 10.6% of older adults being diagnosed with ADRD in the first year after a fall. To improve the early identification of ADRD, this study's findings suggest support for the implementation of cognitive screening in older adults who experience an injurious fall that results in an ED visit or hospital admission.