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Background: COVID-19 vaccination has become a pivotal global strategy in managing the pandemic. Despite COVID-19 no longer being classified as a Public Health Emergency of International Concern, the virus continues affecting people worldwide. This study aimed to evaluate risk factors and vaccine effectiveness on COVID-19-related hospital admissions, intensive care unit (ICU) admission and mortality within the Andalusian population throughout the pandemic., Methods: From March 2020 to April 2022, 671,229 individuals, out of 9,283,485 with electronic health records in Andalusia, experienced SARS-CoV-2 infection and were included in the analysis. Data on demographics, medical history, vaccine administration, and hospitalization records were collected. Associations between medical history, COVID-19 vaccines, and COVID-19 outcomes were assessed., Results: Our study identified 48,196 hospital admissions, 5,057 ICU admissions, and 11,289 deaths linked to COVID-19. Age, male sex, and chronic diseases were identified as risk factors, while the COVID-19 vaccine demonstrated protective effects, although with reduced effectiveness during the omicron variant period. However, the risk for these outcomes increased over time after receiving the last vaccine dose, particularly after six months, especially among those aged 60 or older., Conclusion: The global health challenge of COVID-19 persists, marked by emerging variants with higher virulence and severity, particularly among the unvaccinated and those beyond six months post-vaccination, especially those aged 60 and above. These findings highlight the need for robust surveillance systems targeting new variants and administering booster doses, particularly for individuals aged 60 or older with underlying health conditions, to mitigate the global burden of COVID-19., Competing Interests: Declarations. Ethics Approval: The Clinical Research Ethics Committee of Andalusia (CCEIBA in Spanish) approved the research protocol for this study (010722 (Act 07/22), FPS-VAC-2022-01). This study was an epidemiological study including anonymized data, and the analysis was performed in Andalusian servers of the public healthcare system, and was not required to obtain informed consent from the patients. We conducted this study in accordance with the Declaration of Helsinki and the Spanish Law on the Protection of Personal Data and Guarantee of Digital Rights (3/2018 of December 5). Consent to Participate: Not applicable. Competing Interests: The authors have no competing interests to declare that are relevant to the content of this article., (© 2024. The Author(s).)

Background: The global COVID-19 pandemic, caused by the SARS-CoV-2 virus, has presented significant challenges to healthcare systems worldwide., Objective: This study, based on an analysis of a cohort from the Public Health System of Andalusia (Spain), aims to evaluate how vaccination affects case-fatality rate in patients hospitalized due to COVID-19 infection in Andalusia., Methods: The cohort consists of 37,274 individuals after applying the inclusion criteria. We conducted survival analyses employing the Cox proportional hazards models and generated adjusted survival curves to examine the outcomes. The analyses were performed from three perspectives: vaccinated vs. unvaccinated patients, vaccinated and unvaccinated patients grouped by age, and stratified by vaccination status., Results: Results indicate a substantial correlation between vaccination and a 20% reduction in the risk of case-fatality. Age-specific effects reveal varying degrees of protection across different age groups., Conclusion: These findings emphasize the pivotal role of vaccination status in COVID-19 risk assessment, supporting the development of a clinical decision support system for accurate predictions and optimizing healthcare management at admission., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 González Rodríguez, Oprescu, Muñoz Lezcano, Cordero Ramos, Romero Cabrera, Armengol de la Hoz and Estella.)

Competing Interests: Leo Anthony Celi is the Editor-in-Chief of PLOS Digital Health and Miguel Ángel Armengol de la Hoz is a Section Editor of PLOS Digital Health. AR, CMJ, JLG, JCR, PH, ET, IT and MAA are associated with the Andalusian Regional Ministry of Health and Consumer Affairs.

Objective: To determine if potential predictors for invasive mechanical ventilation (IMV) are also determinants for mortality in COVID-19-associated acute respiratory distress syndrome (C-ARDS)., Design: Single center highly detailed longitudinal observational study., Setting: Tertiary hospital ICU: two first COVID-19 pandemic waves, Madrid, Spain., Patients or Participants: 280 patients with C-ARDS, not requiring IMV on admission., Interventions: None., Main Variables of Interest: Target: endotracheal intubation and IMV, mortality., Predictors: demographics, hourly evolution of oxygenation, clinical data, and laboratory results., Results: The time between symptom onset and ICU admission, the APACHE II score, the ROX index, and procalcitonin levels in blood were potential predictors related to both IMV and mortality. The ROX index was the most significant predictor associated with IMV, while APACHE II, LDH, and DaysSympICU were the most with mortality., Conclusions: According to the results of the analysis, there are significant predictors linked with IMV and mortality in C-ARDS patients, including the time between symptom onset and ICU admission, the severity of the COVID-19 waves, and several clinical and laboratory measures. These findings may help clinicians to better identify patients at risk for IMV and mortality and improve their management., (Copyright © 2023 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.)

Background: Evidence regarding acute kidney injury associated with concomitant administration of vancomycin and piperacillin-tazobactam is conflicting, particularly in patients in the ICU., Research Question: Does a difference exist in the association between commonly prescribed empiric antibiotics on ICU admission (vancomycin and piperacillin-tazobactam, vancomycin and cefepime, and vancomycin and meropenem) and acute kidney injury?, Study Design and Methods: This was a retrospective cohort study using data from the eICU Research Institute, which contains records for ICU stays between 2010 and 2015 across 335 hospitals. Patients were enrolled if they received vancomycin and piperacillin-tazobactam, vancomycin and cefepime, or vancomycin and meropenem exclusively. Patients initially admitted to the ED were included. Patients with hospital stay duration of < 1 h, receiving dialysis, or with missing data were excluded. Acute kidney injury was defined as Kidney Disease: Improving Global Outcomes stage 2 or 3 based on serum creatinine component. Propensity score matching was used to match patients in the control (vancomycin and meropenem or vancomycin and cefepime) and treatment (vancomycin and piperacillin-tazobactam) groups, and ORs were calculated. Sensitivity analyses were performed to study the effect of longer courses of combination therapy and patients with renal insufficiency on admission., Results: Thirty-five thousand six hundred fifty-four patients met inclusion criteria (vancomycin and piperacillin-tazobactam, n = 27,459; vancomycin and cefepime, n = 6,371; vancomycin and meropenem, n = 1,824). Vancomycin and piperacillin-tazobactam was associated with a higher risk of acute kidney injury and initiation of dialysis when compared with that of both vancomycin and cefepime (Acute kidney injury: OR, 1.37 [95% CI, 1.25-1.49]; dialysis: OR, 1.28 [95% CI, 1.14-1.45]) and vancomycin and meropenem (Acute kidney injury: OR, 1.27 [95%, 1.06-1.52]; dialysis: OR, 1.56 [95% CI, 1.23-2.00]). The odds of acute kidney injury developing was especially pronounced in patients without renal insufficiency receiving a longer duration of vancomycin and piperacillin-tazobactam therapy compared with vancomycin and meropenem therapy., Interpretation: VPT is associated with a higher risk of acute kidney injury than both vancomycin and cefepime and vancomycin and meropenem in patients in the ICU, especially for patients with normal initial kidney function requiring longer durations of therapy. Clinicians should consider vancomycin and meropenem or vancomycin and cefepime to reduce the risk of nephrotoxicity for patients in the ICU., (Published by Elsevier Inc.)

High resolution clinical databases from electronic health records are increasingly being used in the field of health data science. Compared to traditional administrative databases and disease registries, these newer highly granular clinical datasets offer several advantages, including availability of detailed clinical information for machine learning and the ability to adjust for potential confounders in statistical models. The purpose of this study is to compare the analysis of the same clinical research question using an administrative database and an electronic health record database. The Nationwide Inpatient Sample (NIS) was used for the low-resolution model, and the eICU Collaborative Research Database (eICU) was used for the high-resolution model. A parallel cohort of patients admitted to the intensive care unit (ICU) with sepsis and requiring mechanical ventilation was extracted from each database. The primary outcome was mortality and the exposure of interest was the use of dialysis. In the low resolution model, after controlling for the covariates that are available, dialysis use was associated with an increased mortality (eICU: OR 2.07, 95% CI 1.75-2.44, p<0.01; NIS: OR 1.40, 95% CI 1.36-1.45, p<0.01). In the high-resolution model, after the addition of the clinical covariates, the harmful effect of dialysis on mortality was no longer significant (OR 1.04, 95% 0.85-1.28, p = 0.64). The results of this experiment show that the addition of high resolution clinical variables to statistical models significantly improves the ability to control for important confounders that are not available in administrative datasets. This suggests that the results from prior studies using low resolution data may be inaccurate and may need to be repeated using detailed clinical data., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Leo Anthony Celi is the Editor-in Chief of PLOS Digital Health., (Copyright: © 2022 Ziegler et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Importance: Heart failure with preserved ejection fraction (HFpEF) is a joint metabolic and cardiovascular disorder with significant noncardiac contributions., Objective: To define and quantify the metabolic cost of initiating exercise in individuals with and without HFpEF and its functional consequences., Design, Setting, and Participants: This prospective cohort study included individuals with hemodynamically confirmed HFpEF from the Massachusetts General Hospital Exercise Study (MGH-ExS) and community-dwelling participants from the Framingham Heart Study (FHS). Analysis began April 2016 and ended November 2020., Exposures: Internal work (IW), a measure of work equivalents required to initiate movement., Main Outcomes and Measures: Using breath-by-breath oxygen uptake (V̇o2) measurements and V̇o2-work rate associations, cost of initiating exercise (IW) in patients with HFpEF (MGH-ExS) and in community-dwelling individuals (FHS) was quantified. Linear regression was used to estimate associations between IW and clinical/hemodynamic measures., Results: Of 3231 patients, 184 (5.7%) had HFpEF and were from MGH-ExS, and 3047 (94.3%) were community-dwelling individuals from FHS. In the MGH-ExS cohort, 86 (47%) were women, the median (interquartile range) age was 63 (53-72) years, and the median (interquartile range) peak V̇o2 level was 13.33 (11.77-15.62) mL/kg/min. In the FHS cohort, 1620 (53%) were women, the median (interquartile range) age was 54 (48-60) years, and the median (interquartile range) peak V̇o2 level was 22.2 (17.85-27.35) mL/kg/min. IW was higher in patients with HFpEF and accounted for 27% (interquartile range, 21%-39%) of the total work (IW + measured external workload on the cycle), compared with 15% (interquartile range, 12%-20%) of that in FHS participants. Body mass index accounted for greatest explained variance in patients with HFpEF from MGH-ExS and FHS participants (22% and 18%, respectively), while resting cardiac output and biventricular filling pressures were not significantly associated with variance in IW in patients with HFpEF. A higher IW in patients with HFpEF was associated with a greater increase in left- and right-sided cardiac filing pressure during unloaded exercise, despite similar resting hemodynamic measures across IW., Conclusions and Relevance: This study found that internal work, a new body mass index-related measure reflecting the metabolic cost of initiating movement, is higher in individuals with HFpEF compared with middle-aged adults in the community and is associated with steep, early increases in cardiac filling pressures. These findings highlight the importance of quantifying heterogeneous responses to exercise initiation when evaluating functional intolerance in individuals at risk for or with HFpEF.

Illness severity scores are regularly employed for quality improvement and benchmarking in the intensive care unit, but poor generalization performance, particularly with respect to probability calibration, has limited their use for decision support. These models tend to perform worse in patients at a high risk for mortality. We hypothesized that a sequential modeling approach wherein an initial regression model assigns risk and all patients deemed high risk then have their risk quantified by a second, high-risk-specific, regression model would result in a model with superior calibration across the risk spectrum. We compared this approach to a logistic regression model and a sophisticated machine learning approach, the gradient boosting machine. The sequential approach did not have an effect on the receiver operating characteristic curve or the precision-recall curve but resulted in improved reliability curves. The gradient boosting machine achieved a small improvement in discrimination performance and was similarly calibrated to the sequential models., Competing Interests: Competing interestsO.B. is employed by Philips Healthcare. The other authors declare no competing interests.