Time-dependent Variables Research Articles

Respective impact of bleeding and ischemic complications of mortality after percutaneous coronary interventions: substudy from the FRANCE-PCI registry

Abstract Background Patients undergoing percutaneous coronary interventions (PCI) remain at high risk of both bleeding and ischemic events, both burdened with high morbimortality. The respective impact of both type of complications in contemporary PCI, however, remains unclear. Purpose To evaluate and compare the respective impact of ischemic and bleeding complications on mortality after PCI Methods The FRANCE PCI is an ongoing registry of consecutive French patients undergoing PCI and monitored for one year thereafter. Patients presenting with complications after the index PCI were categorized as ischemic complications in case of stent thrombosis, myocardial infarction, stroke or unplanned revascularization, as hemorrhagic complications in case of bleeding BARC ≥3 or as ischemic and hemorrhagic when both types of events occurred in the same patients. The impact of ischemic and hemorrhagic complications on mortality was evaluated separately for the index hospitalization and the 12-months follow-up after hospital discharge, using multivariate logistic model and Cox proportional hazards model, respectively. The multivariate Cox model was developed using complications as time-dependent variables and estimating the hazard ratios (HRs) over 3 periods of time (0 to 8 weeks, 8 to 24 weeks, and 24 to 52 weeks). Consequently, the proportional hazard assumption, tested using the Schoenfeld test, was met for each period. Multiple imputations were performed for missing data on covariates. Results A total of 54,599 patients, with a median age of 69 [60.0-78.0] years, 75.0% male, underwent PCI in 30 centers between 2014 and 2020, in an elective setting for 47% of the cases. During the index hospitalization, an ischemic and hemorrhagic complications occurred in 610 (1.1% 95%CI 1.0-1.2) and 531 (1.0% 95%CI 0.9-1.1) patients, respectively, while the mortality rate was 2.1% 95%CI 2.0-2.2. The association between ischemic, hemorrhagic and ischemic and hemorrhagic events with mortality was aOR 8.4 95%CI 6.4-10.9, aOR 10.3 95%CI 8.1-13.2 and aOR 13.2 95%CI 7.0-24.7, respectively. Among the 51,738 patients alive and not lost-to-follow-up after discharge, an ischemic and hemorrhagic complications occurred in 2,727 (5.3% 95%CI 5.1-5.5) and 1,022 (2.0% 95%CI 1.9-2.1) patients, respectively, while the mortality incidence was 3.8% 95%CI 3.6-4.0. The associations between ischemic, hemorrhagic and ischemic and hemorrhagic events with mortality according to the periods of time are detailed in Table 1 and Figure 1. Conclusion Both ischemic and hemorrhagic complications after PCI are associated with increased risk of mortality. The risk is particularly increased during the early period after the index PCI and diminishes over time, albeit faster after ischemic complications alone, compared to hemorrhagic events alone or the association of ischemic and hemorrhagic complications.

Atrial Fibrillation (AF) detected by repeat handheld ECG screening and the risk of heart failure hospitalization

Abstract Purpose Heart failure and atrial fibrillation (AF) frequently complicate one another. Risk of heart failure in screen-detected patients was not investigated. We aimed to compare risk of hospitalization for heart failure (HHF) between screen-detected and clinically-diagnosed AF, and to evaluate the impact of AF burden. Methods Consecutive patients aged over 65 attending outpatient clinics were prospectively recruited for AF screening, using handheld single-lead ECG (AliveCor) during December 2014 and December 2017. Patients who had >1 visits received repeat screening. All participants were divided into 5 cohorts: (i) previously known AF at enrolment; (ii) initial screen-detected AF; (iii) subsequent screen-detected AF; (iv) clinically-diagnosed AF during follow-up (FU); (v) No AF. Risk of HHF was estimated by adjusted sub-distribution hazard ratios (aSHR) derived from Fine and Gray regression, accounting for death as competing risk, adjusting for CHA2DS2VASC components and chronic kidney disease, AF diagnosis being handled as time-dependent variable. Patients who participated in repeat screening and previously known AF formed a sub-cohort. Patients with previously known AF who were in AF in the initial screening and those with repeat screen-positivity were defined probably persistent AF, otherwise paroxysmal AF (single screen-positivity) or no AF (never screen-positive). Risk of HHF was compared between groups stratified by AF burden (persistent vs. paroxysmal) and scenario of AF diagnosis (screen-detected vs. clinically-diagnosed). Results Of 11,972 subjects (mean age 76.6±7.8, female 49.2%), 18.7% (n=2,236) had known AF, 1.9% (n=223) initial screen-detected AF, 0.6% (n=71) subsequent screen-detected AF, 7.3% (n=867) clinically-diagnosed AF during FU, and 71.6% (n=8,559) no AF. During a median FU of 6.7 (IQR:4.4-8.0) years, risk of HHF was highest in patients with clinically-diagnosed AF (aSHR=3.5(2.7-4.5)), followed by subsequent screen-detected AF (aSHR=2.8(1.6-5.0)), previously known AF (aSHR=1.9(1.6-2.2)), and initial screen-detected AF (aSHR=1.7(1.1-2.4)) (Figure 1a). Sensitivity analysis excluded those with known heart failure at baseline, after which risk of HHF became comparable between previously known and initial screen-detected AF (Figure 1b). Sub-analysis for participants (32.2% (n=3,853), mean age 76.7±7.3, female 47.5%) of repeat screening showed screen-detected persistent AF (aSHR=3.7(1.9-7.2)) was at highest risk of HHF, followed by clinically-diagnosed AF (AF burden unassessed) (aSHR=3.3(2.2-5.0)), previously known persistent AF (aSHR=3.1(2.5-3.8)), screen-detected paroxysmal AF (aSHR=2.1(1.4-3.4)), previously known paroxysmal AF (aSHR=1.8(1.3-2.4) (Figure 1c). Conclusion Higher AF burden and FU new AF diagnosed by either screening or clinic visit was associated with higher risk of HHF. Screening facilitating early AF diagnosis and early downstream intervention, warranted further study.

A Million Person Study Innovation: Evaluating Cognitive Impairment and other Morbidity Outcomes from Chronic Radiation Exposure Through Linkages with the Centers for Medicaid and Medicare Services Assessment and Claims Data.

The study of One Million U.S. Radiation Workers and Veterans, the Million Person Study (MPS), examines the health consequences, both cancer and non-cancer, of exposure to ionizing radiation received gradually over time. Recently the MPS has focused on mortality patterns from neurological and behavioral conditions, e.g., Parkinson's disease, Alzheimer's disease, dementia, and motor neuron disease such as amyotrophic lateral sclerosis. A fuller picture of radiation-related late effects comes from studying both mortality and the occurrence (incidence) of conditions not leading to death. Accordingly, the MPS is identifying neurocognitive diagnoses from fee-for-service insurance claims from the Centers for Medicare and Medicaid Services (CMS), among Medicare beneficiaries beginning in 1999 (the earliest date claims data are available). Linkages to date have identified ∼540,000 workers with available health information. Such linkages provide individual information on important co-factor and confounding variables such as smoking, alcohol consumption, blood pressure, obesity, diabetes and many other health and demographic characteristics. The total person-level set of time-dependent variables, outcomes, organ-specific dose measures, co-factors, and demographics will be massive and much too large to be evaluated with standard software. Thus, development of specialized open-source software designed for large datasets (Colossus) is nearly complete. The wealth of information available from CMS claims data, coupled with individual dose reconstructions, will thus greatly enhance the quality and precision of health evaluations for this new field of low-dose radiation and neurocognitive effects.

Determinants of Length of Stay for Medical Inpatients Using Survival Analysis

With the increase in insured patients and an aging population, managing the length of stay (LOS) for inpatients has become crucial for controlling medical costs. Analyzing the factors influencing LOS is necessary for effective management. Previous studies often used multiple or logistic regression analyses, which have limitations such as unmet assumptions and the inability to handle time-dependent variables. To address these issues, this study applied survival analysis to examine the factors affecting LOS using the National Health Insurance Service (NHIS) sample cohort data from 2016 to 2019, covering over 4 million records. We used Kaplan–Meier survival estimation to assess LOS probabilities based on sociodemographic, patient, health checkup, and institutional characteristics. Additionally, the Cox proportional hazards model controlled for confounding factors, providing more robust validation. Key findings include the influence of age, gender, type of insurance, and hospital type on LOS. For instance, older patients and medical aid recipients had longer LOS, while general hospitals showed shorter stays. This study is the first in Korea to use survival analysis with a large cohort database to identify LOS determinants. The results provide valuable insights for shaping healthcare policies aimed at optimizing inpatient care and managing hospital resources more efficiently.

Treatment of Subclinical Hyperthyroidism and Incident Atrial Fibrillation.

Treating overt hyperthyroidism prevents atrial fibrillation (AF). Though subclinical hyperthyroidism (SH) has been associated with AF, it is unknown whether treating SH prevents AF. We aimed to identify the association between treating SH and incident AF. In a pharmacoepidemiologic retrospective cohort study, patients diagnosed with SH between 2000 and 2021 were followed. Outpatients ≥ 18 years with biochemical SH and without prior AF, hypothyroidism, thyroid cancer, pituitary disease, or pregnancy were included. The primary outcome was incident AF. Secondary outcomes were ECG and echocardiographic features associated with AF. Of 2169 patients screened, 360 (131 treated and 229 untreated) were followed up for a mean of 4.27 years. In the treated and untreated groups, AF occurred in 4 (3.1%) and 15 (6.6%) patients (p = 0.15), and AF incidence was 0.8% and 1.4%/year (p = 0.31), respectively. The hazard ratio (HR) for treatment as a time-dependent variable was 0.60 (95% CI 0.19-1.92; p = 0.39). As some cases of AF were documented nearly simultaneously with SH treatment, a sensitivity analysis was performed reassigning two patients diagnosed with AF < 30 days after starting SH treatment to the untreated group. Here, in the treated and untreated groups, AF occurred in 1.6% and 7.4% (p = 0.02), and AF incidence was 0.4% and 1.8%/year (p = 0.02), respectively. The HR was 0.25 (0.06-1.13; p = 0.07). There were no differences in ECG or echocardiographic features. There was an overall trend towards lower incidence and prevalence of AF following treatment of SH, supporting the need for larger scale studies.

Dynamic control of cardboard-blank picking by using reinforcement learning

Abstract Standard packaging lines with high output rates often struggle when dealing with uncertainties in the conditions of the handled materials. This paper focuses on a piece of machinery in an automatic packaging line, namely an automated apparatus that extracts cardboard blanks from a buffer and transfers them to the next section through suction cups. In this context, the success of the operation depends on various controllable parameters, disturbances, and time-dependent variables, whose mutual relationships are not easily identifiable and whose understanding has so far been entrusted to the experiential knowledge of human operators. Currently, drops in picking success rates require the machine to be stopped and operators to intervene on-site, making use of their expertise to identify the issue and recalibrate the machine. To address the problem, this paper presents an artificial-intelligence-enabled controller, capable of continuously and autonomously recalibrating the apparatus and compensating for disturbances, in order to avoid missed or incorrectly picked cardboard blanks. In particular, this work exploits experimental data to build a model of the system, on which a reinforcement-learning algorithm is trained. The controller is tasked with regulating the controllable parameters while monitoring process variables. The developed agent is tested on the real apparatus to assess its performance.

Clinical characteristics and survival outcomes of patients with primary central nervous system lymphoma treated with high-dose methotrexate-based polychemotherapy and consolidation therapies

Given the rarity of primary central nervous system lymphoma (PCNSL), evaluations of different high-dose methotrexate-(HD-MTX)-based treatment regimens is sparse. This retrospective, multicenter study evaluates clinical characteristics and outcomes (progression-free, overall and disease-specific survival) after five HD-MTX-based polychemotherapeutic regimens and two consolidation therapies. 346 patients with histologically confirmed PCNSL, treated with ≥ 1 cycle HD-MTX-based strategies (≥3g/m2/cycle) were included. The regimens included MATRIX (HD-MTX, HD-AraC, thiotepa, and rituximab), (R)MBVP±HD-AraC (HD-MTX, teniposide/etoposide, carmustine, prednisolone, ± HD-AraC, ± rituximab), (R)MP (HD-MTX, procarbazine, ± rituximab), and a combination of HD-MTX and HD-AraC. The overall response rate after induction was 69 %, 28 % complete remission and progressive disease was observed in 100 (29 %) patients. 126 (36 %) patients received consolidation, including high-dose-BCNU-thiotepa with autologous stem cell transplantation (HD-BCNU-TT/ASCT, n = 59 (17 %)) or whole brain radiotherapy (WBRT, n = 67 (19 %)). Clinical characteristics associated with adverse mortality risk by multivariable prognostication contained age > 60 years (HR 1.61, p = 0.011), elevated LDH (HR 1.75, p = 0.004) and WHO status ≥ 2 (HR 1.56, p = 0.010). Independently, induction regimens containing HD-AraC demonstrated survival benefit compared to induction regimens without HD-AraC (HR 0.59, p = 0.002). Without preference for HD-BCNU-TT/ASCT or WBRT, a favorable effect of consolidation (HR 0.44 and HR 0.42, p < 0.001) was confirmed, also with consolidation as time-dependent variable. Competing risk analysis showed similar low incidence of lymphoma-unrelated deaths in consolidated and unconsolidated patients. This study confirms that age, elevated LDH and WHO status increase the mortality risk. HD-AraC containing treatment regimens and consolidation with HD-BCU-TT/ASCT or WBRT were associated with superior survival, including a favorable low incidence of lymphoma-unrelated deaths.

A frequency-domain finite element model for simulating high temperature superconductors using the J-A and T-A formulations

Abstract The AC losses, the current density and the magnetic field are important variables to design devices made of High Temperature Superconductors (HTS). These variables are often numerically computed using a transient finite element analysis even though the interest may lay in the steady-state regime of the device. The need for solving time-dependent variables has led to improve the computation time with efficient finite element models (FEM) relying on different formulations. These transient FEM are computationally slow and demanding in terms of resources. In the present work, an alternative path is taken with the development of a frequency-domain FEM using a phasor representation to alleviate the computation burden. This model does not have the versatility of the transient models. However, it can generate the initial steady-state conditions for a subsequent transient analysis. It is perfectly adapted to study the steady-state regime of HTS devices operated in AC conditions. In this phasor modelling approach, the Root Mean Square (RMS) resistivity of the superconductor is introduced. It is subsequently approximated by an exponential function introducing a factor to ease its implementation in the commercial software COMSOL Multiphysics with the most recent and fastest formulations T-A and J-A. The case studies encompass single BSCCO and REBCO tapes as well as a CORC cable or specifically, in the present work, a CORT (Conductor on Round Tube). The results of the time- and frequency-domain FEM simulations are compared against experimental data. The comparison of the models' results is carried out comparing the current density distributions as well as the AC losses. The comparison against experimental data is only conducted on the AC losses. In the present case, it is used to quantify thoroughly the accuracy of the numerical results compared to the measurements. A reasonable agreement between those results and the experimental data was found. &amp;#xD;

8527 The Role Of SGLT2 Inhibitors In Outcomes After LVAD Implantation

Abstract Disclosure: L. Carafone: None. S. McNitt: None. I. Goldenberg: None. J. Alexis: None. Introduction: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are important medications in the treatment of diabetes mellitus, however they offer several additional benefits, including improved heart failure outcomes in patients with and without diabetes. The role of SGLT2i in heart failure outcomes for patients who receive left ventricular assist device (LVAD) implantation is not known. Right heart failure, in particular, is a frequent complication and major contributor to morbidity and mortality after LVAD implantation. SGLT2i have been increasingly used in patients who undergo LVAD implantation, however it is unknown whether right heart failure events post-LVAD implantation are meaningfully impacted by SGLT2i use. Objective: The purpose of this study was to evaluate the role of SGLT2i in outcomes after LVAD implantation. The primary endpoint was the onset of a first right heart failure (RHF) event following LVAD implantation. Secondary endpoints included recurrent RHF, first and recurrent hospitalization for RHF, and all-cause mortality. Methods: The study population comprised all consecutive patients who received a HeartMate 3 LVAD implantation at the medical center from 9/25/2015 through 9/1/2023 who are included in the institution’s LVAD Database. Both patients who received and did not receive a SGLT2i were included. A time-dependent model was used to evaluate treatment with SGLT2i as a time-dependent variable. Multivariable propensity score matching was used in the analysis of outcomes. Results: A total of 399 patients were analyzed, which included 175 patients who received SGLT2i and 224 patients who did not receive SGLT2i. Cox proportional hazards regression, employing propensity score stratification, demonstrated SGLT2i use was not associated with a statistical significant effect in the primary endpoint of a first occurrence of RHF event (HR = 1.41, 95% CI = 0.77-2.61, p = 0.268). Similarly, SGLT2i use was not associated with secondary outcomes, including recurrent RHF (HR = 1.28, 95% CI = 0.76-2.16, p = 0.360), first or recurrent hospitalization for RHF (HR = 0.38, 95% CI = 0.11-1.33, p = 0.131 and HR = 0.63, 95% CI = 0.27-1.46, p = 0.285, respectively), and all-cause mortality (HR = 0.90, 95% CI = 0.44-1.83, p = 0.771). Presence or absence of diabetes diagnosis did not significantly impact outcomes. Conclusions: The observational data in this study suggest no incremental benefit of SGLT2i for right heart failure or mortality outcomes after LVAD implantation, however large-scale prospective studies are needed to evaluate the role of SGLT2i in this setting. Further elucidating the role of these medications in LVAD outcomes will be critical in clinical decision-making regarding use of SGLT2i in this population. Presentation: 6/1/2024

Oligotrophic state reduces the time dependence of the observed survival fraction for heavy ion beam-irradiated Saccharomyces cerevisiae and provides new insights into DNA repair.

Heavy ion beam (HIB) irradiation is widely utilized in studies of cosmic rays-induced cellular effects and microbial breeding. Establishing an accurate dose-survival relationship is crucial for selecting the optimal irradiation dose. Typically, after irradiating logarithmic-phase cell suspensions with HIB, the survival fraction (SF) is determined by the ratio of clonal-forming units in irradiated versus control groups. However, our findings indicated that SF measurements were time sensitive. For the Saccharomyces cerevisiae model, the observed SF initially declined and subsequently increased in a eutrophic state; conversely, in an oligotrophic state, it remained relatively stable within 120 minutes. This time effect of SF observations in the eutrophic state can be ascribed to HIB-exposed cells experiencing cell cycle arrest, whereas the control proliferated rapidly, resulting in an over-time disproportionate change in viable cell count. Therefore, an alternative involves irradiating oligotrophic cells, determining SF thereafter, and transferring cells to the eutrophic state to facilitate DNA repair-mutation. Transcriptomic comparisons under these two trophic states yield valuable insights into the DNA damage response. Although DNA repair was postponed in an oligotrophic state, cells proactively mobilized specific repair pathways to advance this process. Effective nutritional supplementation should occur within 120 minutes, beyond this window, a decline in SF indicates an irreversible loss of repair capability. Upon transition to the eutrophic state, S. cerevisiae swiftly adapted and completed the repair. This study helps to minimize time-dependent variability in SF observations and to ensure effective damage repair and mutation in microbial breeding using HIB or other mutagens. It also promotes the understanding of microbial responses to complex environments.IMPORTANCEMutation breeding is a vital means of developing excellent microbial resources. Consequently, understanding the mechanisms through which microorganisms respond to complex environments characterized by mutagens and specific physiological-biochemical states holds significant theoretical and practical values. This study utilized Saccharomyces cerevisiae as a microbial model and highly efficient heavy ion beam (HIB) radiation as a mutagen, it revealed the time dependence of observations of survival fractions (SF) in response to HIB radiation and proposed an alternative to avoid the indeterminacy that this variable brings. Meanwhile, by incorporating an oligotrophic state into the alternative, this study constructed a dynamic map of gene expression during the fast-repair and slow-repair stages. It also highlighted the influence of trophic states on DNA repair. The findings apply to the survival-damage repair-mutation effects of single-celled microorganisms in response to various mutagens and contribute to elucidating the biological mechanisms underlying microbial survival in complex environments.

Effect of the COVID-19 pandemic on malnutrition in socially vulnerable children in Brazil.

This article aims to evaluate the effect of the COVID-19 pandemic on malnutrition among children under two years of age enrolled in the Bolsa Família Program (BFP). Ecological study of interrupted time series (ITS), with low weight for age, stunting, and overweight as time-dependent variables of malnutrition, extracted monthly (Jan/2008 to June/2021) from the Food and Nutrition Surveillance System. The COVID-19 pandemic was the exposure, dichotomized into pre-pandemic and pandemic. In RStudio, the trend was obtained by Prais-Winsten regression, and the effect of the pandemic on the time-dependent variables was determined by SARIMA modeling, estimating the regression coefficients (RC) adjusted for trend and seasonality (α = 5%). The pandemic was associated with an increase in: i) low weight for age in the South (RC = 0.94; p < 0.001) and Southeast (RC = 1.97; p < 0.001); ii) height deficit in the Midwest (RC = 2.4; p = 0.01), South (RC = 2.15; p < 0.001) and Southeast (RC = 2.96; p < 0.001); and iii) and overweight in the North (RC = 1.51; p = 0.04), Midwest (RC = 2.29; p = 0.01), South (RC = 2.83; p < 0.001), and Southeast (RC = 0.72; p = 0.04). The pandemic increased underweight in the South and Southeast, and the double burden of malnutrition in the Midwest, South, and Southeast. In the Northeast and North, higher rates of malnutrition still persist.

Dynamic analysis of Hashimoto’s Thyroiditis bio-mathematical model using artificial neural network

This article establishes an efficient solution scheme for a mathematical model of Hashimoto’s Thyroiditis (HT) employing artificial neural networks. HT is an auto-immune disorder hostile to the thyroid follicle cells, effectuating hypothyroid or hyperthyroidism. Under this condition, the thyroid-stimulating hormone (TSH) alters incomparably to the free thyroxine (FT4) interrupts the functioning of the hypothalamus-pituitary-thyroid (HPT) axis, implicating the thyroid follicle cells getting destroyed. We primarily focus on utilizing artificial neural network (ANN) to perform numerical simulations for the system of ordinary differential equations describing the dynamics of an existing 4D model of HT. The presented model comprises four time-dependent variables: TSH, FT4, anti-thyroid antibodies (Ab), and size of the thyroid gland (T). We utilize ND-Solver and ANN scheme in the Mathematica software to acquire the computational data and illustrate thus retrieved results with essential performance plots. Further, mean square error has been considered in validating the proposed ANN-based approach accurately. The plot for training and validation loss exhibits the effectiveness of the proposed methodology, and substantiate that the suggested ANN approach is a good fit for the solving the mathematical model of HT.

Associations Among Circle-Based Kidney Allocation, Center Waiting Time, and Likelihood of Deceased-Donor Kidney Transplantation

The kidney allocation system (KAS250), using circle-based distribution, attempts to address geographic disparities through broader sharing of deceased-donor kidney allografts. This study sought to evaluate the association between KAS250 and likelihood of deceased-donor kidney transplantation (DDKT) among waitlisted candidates, and whether the policy has differentially affected centers with shorter vs. longer waiting time. Retrospective cohort study. & Participants: 160,941 candidates waitlisted at 176 transplant centers between 3/2017-3/2024. KAS250 allocation policy. Rate of DDKT. Multivariable Cox regression, modeling KAS250 as a time-dependent variable. KAS250 was not independently associated with likelihood of DDKT overall (HR=1.01 vs. pre-KAS250, 95% C.I. 0.97-1.04). KAS250's association with likelihood of DDKT varied across centers from HR=0.18 (DDKT less likely after KAS250) to HR=17.12 (DDKT more likely) and varied even among neighboring centers. KAS250 was associated with decreased DDKT at 25.6% and increased DDKT at 18.2% of centers. Centers with previously long median waiting times (57+ months) experienced increased likelihood of DDKT after KAS250 (HR=1.20, 95% C.I. 1.15-1.26), whereas centers with previously short median waiting times (6-24mo.; HR=0.88, 0.84-0.92) experienced decreased likelihood of DDKT. Retrospective study of allocation policy changes, confounded by multiple changes over the study timeframe. Association between KAS250 and DDKT varied across centers. For one-in-four centers, DDKT was less likely after KAS250 relative to pre-KAS250 trends. Candidates at centers with previously long waiting times experienced increased likelihood of DDKT after KAS250. Thus, broader distribution of kidneys may be associated with improved equity in access to DDKT, but additional strategies may be needed to minimize disparities between centers.

Some minutes matter more: Groin-to-recanalization is the main time-related predictor of outcome in acute ischemic stroke

Introduction Endovascular thrombectomy (EVT) is the standard of care for selected patients with acute ischemic stroke (AIS) and large vessel occlusion (LVO), associated with intravenous thrombolysis, when indicated. While many studies focused on pre-hospital and in-hospital pathways, only few analyzed the relationship between groin-to-recanalization (GTR) time and functional outcome. Aim To explore whether GTR time is an independent predictor of outcome in patients undergoing EVT. Methods All patients with anterior circulation stroke treated with EVT at a high-volume center from January 2021 to December 2023 were included. The cohort was divided into two groups according to GTR time shorter or longer than 30 min. Regression analysis assessed the association between GTR time and 3-month good outcome, defined as modified Rankin Scale 0–2. Results The study included 419 patients. The groups had similar baseline characteristics and similar onset to recanalization (OTR) time. Regression analysis showed shorter GTR time is an independent predictor of favorable outcome (OR 2.49 [95% CI 1.26–4.94]). Age, baseline NIHSS, ASPECT score and bridging IVT were also found to be independently associated with outcome. Discussion and conclusions Our study showed GTR time is an independent predictor of good outcome in patients undergoing EVT with similar OTR time, emphasizing procedural time as a key prognostic factor, even greater than other well-known pre-hospital and in-hospital time-dependent variables. These findings may raise the issue of developing alternative approaches or early “rescue” strategies for complicated procedures.

Classical and quantum thermodynamics in a non-equilibrium regime: Application to thermostatic Stirling engine

We have developed a thermodynamic theory in the non-equilibrium regime, which we describe as a thermodynamic system–bath model [Koyanagi and Tanimura, J. Chem. Phys. 160, 234112 (2024)]. Based on the dimensionless (DL) minimum work principle, non-equilibrium thermodynamic potentials are expressed in terms of non-equilibrium extensive and intensive variables in time derivative form. This is made possible by incorporating the entropy production rate into the definition of non-equilibrium thermodynamic potentials. These potentials can be evaluated from the DL non-equilibrium-to-equilibrium minimum work principle, which is derived from the principle of DL minimum work and is equivalent to the second law of thermodynamics. We thus obtain the non-equilibrium Massieu–Planck potentials as entropic potentials and the non-equilibrium Helmholtz–Gibbs potentials as free energies. Unlike the fluctuation theorem and stochastic thermodynamics theory, this theory does not require the assumption of a factorized initial condition and is valid in the full quantum regime, where the system and bath are quantum mechanically entangled. Our results are numerically verified by simulating a thermostatic Stirling engine consisting of two isothermal processes and two thermostatic processes using the quantum hierarchical Fokker–Planck equations and the classical Kramers equation derived from the thermodynamic system–bath model. We then show that, from weak to strong system–bath interactions, the thermodynamic process can be analyzed using a non-equilibrium work diagram analogous to the equilibrium one for given time-dependent intensive variables. The results can be used to develop efficient heat machines in non-equilibrium regimes.

COVID-19 Diagnosis, Oral Anticoagulation, and Stroke Risk in Patients with Atrial Fibrillation.

Coronavirus disease 2019 (COVID-19) has been associated with an increased risk of stroke. It remains unclear whether the risk of stroke associated with a diagnosis of COVID-19 differed with oral anticoagulation (OAC) use. The aim of this study was to evaluate the association between COVID-19 infection, OAC use, and stroke in patients with atrial fibrillation (AF). A retrospective cohort study was conducted in individuals with established AF using data from Optum's deidentified Clinformatics® Data Mart Database. Cox proportional hazard models with time-dependent variables were employed to assess the association between possession of OAC, COVID-19 diagnosis in both inpatient and outpatient setting, and time to ischemic stroke. A total of 561,758 individuals aged 77 ± 10 were included in the study, with a mean follow up time of 1.3 years. OAC use was associated with a reduced stroke risk [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.82-0.88]. COVID-19 infection was associated with an increased risk of stroke (HR 2.11, 95% CI 1.87-2.38); this increased risk was particularly pronounced for patients diagnosed with an inpatient diagnosis of COVID-19 (HR 3.95, 95% CI 3.33-4.68). There was no significant interaction between OAC use and COVID-19 diagnosis (p value = 0.96). As a result, the relative increase in stroke risk associated with COVID-19 did not differ between patients on OAC (HR 2.12; 95% CI 1.71-2.62) and those not on OAC (HR 2.11; 95% CI 1.83-2.43). In a nationwide sample of patients with established AF, we found the relative increase in stroke risk associated with COVID-19 was independent of OAC use.

Effects of aircraft noise exposure on self-reported health through aircraft noise annoyance: Causal mediation analysis in the DEBATS longitudinal study in France.

Previous studies reported an association between transportation noise and self-reported health status (SRHS). They also suggested a mediating role of noise annoyance using conventional statistical methods. These methods are subject to bias in longitudinal studies with time-dependent exposure, mediator and confounding factors. This study aims to investigate the mediating role of aircraft noise annoyance in the effect of aircraft noise on SRHS using a causal inference approach to address time-dependent variables issues. We used data from 881 participants in all three visits in the DEBATS longitudinal study conducted around three French airports. Participants over 18 years of age reported their self-perceived health status, aircraft noise annoyance, and noise sensitivity by completing a questionnaire at three visits in 2013, 2015 and 2017. Noise maps were used to estimate aircraft noise levels outside their homes. Marginal structural models with inverse probability weighting were used to estimate the total effect of aircraft noise levels on SRHS and its decomposition into direct and indirect effect through aircraft noise annoyance. This study showed a deleterious effect of aircraft noise on SRHS. The odds ratio (OR) corresponding to the total effect and comparing the highest aircraft noise category (≥60 dBA) to the reference category (<50 dBA) was significant (ORpoor/fair_SHRS = 1.25 (95%CI: 1.06 to 2.08)). It also showed no direct effect of aircraft noise levels on SRHS, but an indirect effect through annoyance. This indirect effect increased as aircraft noise levels increased, with a statistically significant OR when comparing the highest noise category (≥60 dBA) to the lowest (<50 dBA) (ORpoor/fair_SHRS = 1.16 (95%CI: 1.03 to 1.52)). Nearly 66% of aircraft noise's effect on SRHS was mediated by aircraft noise annoyance. This study supports the deleterious causal effect of aircraft noise on SRHS. The results highlight the important mediating role of aircraft noise annoyance in the causal pathway from exposure to aircraft noise to poor/fair SRHS.

Probabilistic pre-estimation of life-cycle costs of road bridges using dynamic Bayesian networks

Proper life-cycle cost (LCC) estimation of vital transportation network assets, such as road bridges, is crucial for cost-efficient projects. This study presents a probabilistic framework for the LCC estimation of concrete bridges based on Dynamic Bayesian Network (DBN) modelling that stakeholders can consult in projects’ preliminary stages for suitable decision-making. The proposed model consists of two separate modules. The first accounts for the probabilistic estimation of material quantities and their relative costs during the construction phase, specifically for the bridge’s superstructure and foundation. The second one refers to the operational phase of the bridge’s components. For illustrative purposes, the maintenance costs of deck expansion joints are presented, as they are regarded as vulnerable bridge components with regular repairs. The suggested DBN includes time-dependent and continuous variables thoroughly documented over multiple time stages. The DBN is formulated using actual records of 78 concrete bridges’ construction, deterioration, inspections and maintenance from the Egnatia Odos motorway in Greece. The presented approach is an effective tool for bridge management enhancement owing to stochastic dynamic interdependencies among parameters and continuous information updating.

Energy-stable auxiliary variable viscosity splitting (AVVS) method for the incompressible Navier–Stokes equations and turbidity current system

In this work, we develop a novel energy-stable linear approach, which we name as auxiliary variable viscosity splitting (AVVS) method, to efficiently solve the incompressible fluid flows. Different from the projection-type methods with pressure correction, the AVVS method adopts the viscosity splitting strategy to split the original momentum equation into an intermediate momentum equation without divergence-free constraint and an advection-free momentum equation. A time-dependent auxiliary variable which has exact value 1 is introduced to construct a supplementary equation. The new model not only inherits the same dynamics of original incompressible Navier–Stokes equations, but also facilitates us to design linearly decoupled and energy-stable time-marching scheme. Comparing with the conventional projection-type schemes, the present method leads to an energy dissipation law with respect to kinetic energy instead of a modified energy including velocity and pressure gradient. In each time step, only two parabolic equations with constant coefficients and one Poisson equation need to be solved. Therefore, the numerical implementation is highly efficient. Moreover, the proposed AVVS method can be directly extended to construct linear, decoupled, and energy-stable scheme for the turbidity current system with slight modifications on the right-hand side of supplementary equation. Extensive numerical experiments are implemented to validate the accuracy, energy stability, and capability in complex fluid simulations.

Continuous Kidney replacement Therapy Dosage and Mortality in Critically Ill Patients: a Retrospective Cohort Study using Marginal Structural Model.

Continuous kidney replacement therapy (CKRT) is a crucial intervention for hemodynamically unstable patients with acute kidney injury (AKI). Despite the recommendations to offer a CKRT dose of 20-25 mL/kg/h, the optimal CKRT dose remains uncertain, especially whether low-dose CKRT is associated with poor outcomes. This study investigated the association between low CKRT dosage and 90-day mortality using a marginal structural model (MSM). Using the MIMIC-IV database, adult patients who received CKRT for more than 24 hours were included. Data on time-fixed and time-dependent variables were collected. Patients were categorized based on CKRT dose thresholds of 13 and 20 ml/kg/h. Among the 1,329 patients, the 90-day mortality rate was 49.6%. The median age of the patients was 62 years (IQR: 52-72). Changes in CKRT dosing during treatment were frequent. Patients with a reduced delivered CKRT dose (<20 and < 13 ml/kg/h) generally exhibited low values during the initial days of CKRT, with an increase in the delivered CKRT dose. After adjusting only for baseline variables (traditional Cox regression model), patients receiving CKRT doses <13 ml/kg/h had significantly greater 90-day mortality (HR: 1.70, 95% CI 1.16-2.49) than those receiving CKRT doses ≥13 ml/kg/h. However, after adjusting for time-dependent variables, the CKRT dose was not significantly associated with mortality at either the 13 or 20 ml/kg/h threshold. Additionally, there were no significant associations between the delivered CKRT dose and 90-day mortality within the range of 5 to 40 ml/kg/h. This study highlights the impact of methodological approaches on the association between CKRT dose and mortality and that with personalized adjustments, there may not be a lower limit of the unsafe CKRT dose. However, lower CKRT doses were initially associated with higher mortality, and adjusting for time-dependent variables nullified this association.