Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Mechanistic-Based Procedure for the Early Opening of Concrete Pavements

Determining the opening time for a concrete pavement is a critical decision. Longer construction time may negatively affect the contractor and funding government agency by increasing construction cost and the travelling public by increasing the time lost to drivers due to congestion or detours. However, opening early can be detrimental to short- and long-term pavement performance. If a pavement has not had the time to reach the strength needed to carry the expected traffic load, performance issues are possible and the chance of failure or damage increases the earlier a pavement is opened. Current criteria for opening a concrete pavement to traffic are empirically derived and often outdated with most transportation agencies using an age and strength requirement. The existing criteria do not account for time of construction, design features, early age traffic load conditions, climate conditions, edge support conditions, and other factors that affect early age pavement performance. The current methods also ignore the effect early opening has on the long-term performance. This limits the accuracy of cost-benefit decisions for the life of the pavement when considering when to open to traffic and causes conservative opening times that unnecessarily extend construction and road closure. To address these limitations, this study aimed to improve flexibility and efficiency in traffic opening criteria without compromising pavement performance. The accurate determination and prediction of in-place concrete strength during early-age development until it achieves design strength is a crucial element of the early opening process. To achieve this, a procedure was proposed that combines nondestructive maturity and ultrasound tomography methods to improve early-age concrete strength evaluation. This approach leverages the predictive capabilities of the maturity method along with the accuracy and efficiency of ultrasonic testing to obtain maximum information on in-situ concrete strength development during early ages. The combined nondestructive test procedure involves evaluating the shear wave velocity and using the maturity method to predict concrete strength development for a specific location and construction month, enabling users to make informed decisions on when to perform early-age procedures. A mechanistic-based model for prediction of pavement damage due to early pavement opening was also proposed. The procedure accounts for site conditions and pavement characteristics creating a simplified but accurate model for stress estimations. Web tools were published to implement the developed procedures for easy public use. This provides users with the probability of damage occurring for an alternative opening strength beyond the conservative, generalized state criteria. Users can move forward with procedures based on the conditions of their individual project and increase their allowable construction efficiency. The results of the recently conducted full scale and laboratory tests conducted by the Minnesota Department of Transportation as well as the University of Pittsburgh Impactful Resilient Infrastructure Science and Engineering (IRISE) public/private research consortium were used to calibrate and validate the methods developed in this study

Evaluation of Early Age Concrete Pavement Strength by Combined Nondestructive Tests

During concrete pavement construction, comprehensive information on concrete strength development is necessary for knowledgeable scheduling decisions. To improve in situ strength estimation, nondestructive tests can be combined to maximize available information and increase collection efficiency. Ultrasonic testing has a higher accuracy in strength estimation for early age concrete and the external device allows for more data to be easily collected, while maturity testing can use temperature models to predict strength development. A procedure was created that combines these methods and their strength models in the laboratory for improved and increased field strength data. Using the procedure allows more data to be collected with greater accuracy and provides an adjustable, predicted strength development. This improves the efficiency of fast-track construction projects without resorting to costly alternatives by providing more information on strength development of in situ concrete than traditional strength testing or nondestructive methods individually

Operator-Induced Variability Caused by Hand Mixing of Cement Paste-Effects on Fresh and Hardened Properties

Laboratories typically adapt ASTM C305-14, Standard Practice for Mechanical Mixing of Hydraulic Cement Pastes and Mortars of Plastic Consistency, ASTM C1738-19, Standard Practice for High-Shear Mixing of Hydraulic Cement Pastes, and other standardized mixing methods to prepare cement paste and mortar specimens for testing. Hand mixing is adapted when small amounts of material are available (for example, pure phases) or necessary for testing (for example, isothermal calorimetry testing). Although a majority of past research has focused on studying the dependence of cement paste rheology on mixing, relatively fewer studies have focused on hydration and hardened properties of cement pastes. In this study, fresh and hardened cement paste properties were tested at two water-to-cement ratios (w/c): 0.36 and 0.45. The following tests were performed: flow test, set time, isothermal calorimetry, thermogravimetric analysis (TGA), apparent density, and entrapped air. Results from hand mixing were compared to those from mechanical mixing (ASTM C305-14). Operator-induced variability that was due to hand mixing was assessed by comparing results obtained by three operators. Data were quantitatively evaluated using the coefficient of variation (CV) values for hand-mixing results, and the percentage difference (PD) between the mechanical mixing result and the average hand-mixing result. For most results from the tests conducted, CV and PD were below 5 %, and hence, they may be considered insignificant. A few measured parameters (certain flow diameters, set times, peak heat time) showed CV and PD values ranging from 5 to 10 % and could be potentially significant. The highest values of CV and PD were found for entrapped air, likely because values of entrapped air were low. These results suggest that for carrying out certain tests on cement pastes in the lab such as isothermal calorimetry and TGA, hand mixing could potentially be used instead of ASTM C305-14 without altering results

Onsite strength determination for early-opening decision making of high early strength concrete pavement

High early strength (HES) concrete pavements are commonly opened to traffic within the first 24 h after construction, making early-opening decisions critical for pavement quality and traffic operations. Currently, most state departments of transportation rely on compressive strength testing for early-opening decision making. However, there laboratory tests are labor intensive, costly and not always representative of field strength development. In this study, non-destructive testing (maturity and ultrasonic tomography) was explored for faster and reliable in-situ strength estimations. An experimental section constructed using HES concrete was routinely monitored using compressive testing, maturity, and ultrasonic tomography in the first 24 h after construction. The shear wave velocity, measured using ultrasonic tomography, was able to capture the strength-gain variability within a single slab and between different slabs due to the ability to monitor several locations in a short period of time. Maturity results were consistently conservative in the first 24 h of monitoring. Results show that both maturity testing and ultrasonic tomography are able to replace or add to conventional strength testing for HES concrete pavements to facilitate making the opening decision within the first 24 h. Ultrasonic tomography proved more beneficial as a result of the device's portability, increased speed of testing, and accurate estimations of HES concrete strength for the entire pavement length

Evaluation of Long-Term Impacts of Early Opening of Concrete Pavements

(c) 1003327 (wo) 3Due to an increase in demand to shorten construction time as much as possible, the purpose of this project was to determine the optimum strength for concrete pavement before opening it to traffic and without jeopardizing long-term performance. Six test cells in MnDOT\u2019s MnROAD project were constructed in 2017 with varying degrees of early loading. Various tests were performed during and immediately following construction and, four years later, ride quality and load transfer efficiency were used to quantify long-term damage. A finite element analysis was then performed using ISLAB2000 to determine the effects of load location and temperature gradient on the Portland cement concrete (PCC) longitudinal stresses to explain the absence of premature failure. A mechanistic-based early opening damage analysis procedure was created to determine the optimum timing for opening of a concrete pavement to traffic. The procedure accounts for the effect of site conditions and pavement characteristics. A web-based tool was developed to facilitate implementation of this procedure

Faulting Model Improvements for MEPDG

Accurate joint transverse faulting prediction is essential for proper pavement design. Departments of transportation are encouraged to evaluate, recalibrate, and even modify the faulting model if discrepancies between predicted and field measured faulting are observed. The Pennsylvania Department of Transportation (PennDOT) identified a series of problems with Pavement ME faulting prediction for jointed plain concrete pavements (JPCP). Moreover, the current design of bonded concrete overlays on asphalt (BCOA) lacks a faulting model that simulates the different aspects of the BCOA structure. To address these issues, this project had two main objectives: reevaluate and modify Pavement ME faulting model for JPCP and develop a singular faulting model for BCOA

Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19

International audienc