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Study Objective: The real-world effectiveness and safety of a 0/1-hour accelerated protocol using high-sensitivity cardiac troponin (hs-cTn) to exclude myocardial infarction (MI) compared to routine care in the United States is uncertain. The objective was to compare a 0/1-hour accelerated protocol for evaluation of MI to a 0/3-hour standard care protocol., Methods: The RACE-IT trial was a stepped-wedge, randomized trial across 9 emergency departments (EDs) that enrolled 32,609 patients evaluated for possible MI from July 2020 through April 2021. Patients undergoing high-sensitivity cardiac troponin I testing with concentrations less than or equal to 99th percentile were included. Patients who had MI excluded by the 0/1-hour protocol could be discharged from the ED. Patients in the standard care protocol had 0- and 3-hour troponin testing and application of a modified HEART score to be eligible for discharge. The primary endpoint was the proportion of patients discharged from the ED without 30-day death or MI., Results: There were 13,505 and 19,104 patients evaluated in the standard care and accelerated protocol groups, respectively, of whom 19,152 (58.7%) were discharged directly from the ED. There was no significant difference in safe discharges between standard care and the accelerated protocol (59.5% vs 57.8%; adjusted odds ratio (aOR)=1.05, 95% confidence interval [CI] 0.95 to 1.16). At 30 days, there were 90 deaths or MIs with 38 (0.4%) in the standard care group and 52 (0.4%) in the accelerated protocol group (aOR=0.84, 95% CI 0.43 to 1.68)., Conclusion: A 0/1-hour accelerated protocol using high-sensitivity cardiac troponin I did not lead to more safe ED discharges compared with standard care., (Copyright © 2024 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Introduction: Obstructive sleep apnea (OSA) and atrial fibrillation (AF) are disorders that have increased in the United States during recent years. Earlier investigations have shown that underlying undiagnosed and unmanaged OSA plays a significant role in high rates and also as a trigger for newly diagnosed AF. Since the introduction of continuous positive airway pressure (CPAP) as a main therapy for OSA, more studies have evaluated the effect of CPAP on the development or recurrence of AF in OSA patients. However, sample sizes in a limited number of studies have been too small to conclude whether CPAP therapy has a significant effect on the development of AF in patients with OSA. The authors report results of their systematic review and meta-analysis summarizing what is currently known about the efficacy of CPAP for mitigating AF in patients with OSA., Method: The authors systematically reviewed the published reports on CPAP use and the incidence of AF from PubMed, Google Scholar, EMBASE, Web of Science, meeting abstracts, and Cochrane databases published between January 2015 and November 2021. Study data were extracted by two reviewers and a random-effects meta-analysis was performed using RevMan version 5.4., Results: A total of 17 studies that met inclusion criteria were identified Studies included a total of 6,523 patients, 3,248 (49.8%) who used CPAP and 3,275 (50.2%) who did not use CPAP. In a random effects model, patients treated with CPAP showed a decrease in the incidence of AF (OR, 0.51; 95% CI; 0.27; 0.97, p = 0.04). High heterogeneity among the included studies was also observed (I2 = 97%)., Conclusion: Our results add to the increasing evidence that CPAP therapy may reduce the incidence of development of AF in patients with OSA. Prospective future studies and clinical trials are needed to refine our understanding of the relationship between OSA and AF and how CPAP may reduce cardiovascular disease development.

In Staphylococcus aureus, the agr locus is responsible for controlling virulence gene expression via quorum sensing. As the blockade of quorum sensing offers a novel strategy for attenuating infection, we sought to gain novel insights into the structure, activity and turnover of the secreted staphylococcal autoinducing peptide (AIP) signal molecules. A series of analogues (including the L-alanine and D-amino acid scanned peptides) was synthesized to determine the functionally critical residues within the S. aureus group I AIP. As a consequence, we established that (i) the group I AIP is inactivated in culture supernatants by the formation of the corresponding methionyl sulphoxide; and (ii) the group I AIP lactam analogue retains the capacity to activate agr, suggesting that covalent modification of the AgrC receptor is not a necessary prerequisite for agr activation. Although each of the D-amino acid scanned AIP analogues retained activity, replacement of the endocyclic amino acid residue (aspartate) located C-terminally to the central cysteine with alanine converted the group I AIP from an activator to a potent inhibitor. The screening of clinical S. aureus isolates for novel AIP groups revealed a variant that differed from the group I AIP by a single amino acid residue (aspartate to tyrosine) in the same position defined as critical by alanine scanning. Although this AIP inhibits group I S. aureus strains, the producer strains possess a functional agr locus dependent on the endogenous peptide and, as such, constitute a fourth S. aureus AIP pheromone group (group IV). The addition of exogenous synthetic AIPs to S. aureus inhibited the production of toxic shock syndrome toxin (TSST-1) and enterotoxin C3, confirming the potential of quorum-sensing blockade as a therapeutic strategy.