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Background Metformin has antiviral activity against RNA viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The mechanism appears to be suppression of protein translation via targeting the host mechanistic target of rapamycin pathway. In the COVID-OUT randomized trial for outpatient coronavirus disease 2019 (COVID-19), metformin reduced the odds of hospitalizations/death through 28 days by 58%, of emergency department visits/hospitalizations/death through 14 days by 42%, and of long COVID through 10 months by 42%. Methods COVID-OUT was a 2 × 3 randomized, placebo-controlled, double-blind trial that assessed metformin, fluvoxamine, and ivermectin; 999 participants self-collected anterior nasal swabs on day 1 (n = 945), day 5 (n = 871), and day 10 (n = 775). Viral load was quantified using reverse-transcription quantitative polymerase chain reaction. Results The mean SARS-CoV-2 viral load was reduced 3.6-fold with metformin relative to placebo (−0.56 log10 copies/mL; 95% confidence interval [CI], −1.05 to −.06; P =.027). Those who received metformin were less likely to have a detectable viral load than placebo at day 5 or day 10 (odds ratio [OR], 0.72; 95% CI,.55 to.94). Viral rebound, defined as a higher viral load at day 10 than day 5, was less frequent with metformin (3.28%) than placebo (5.95%; OR, 0.68; 95% CI,.36 to 1.29). The metformin effect was consistent across subgroups and increased over time. Neither ivermectin nor fluvoxamine showed effect over placebo. Conclusions In this randomized, placebo-controlled trial of outpatient treatment of SARS-CoV-2, metformin significantly reduced SARS-CoV-2 viral load, which may explain the clinical benefits in this trial. Metformin is pleiotropic with other actions that are relevant to COVID-19 pathophysiology. Clinical Trials Registration NCT04510194. [ABSTRACT FROM AUTHOR]

Objectives: The epidemic of opioid use disorder (OUD) remains pervasive in the United States. In an effort to increase the availability and timeliness of medications for opioid use disorder (MOUD), several agencies in the United States (US) offer buprenorphine by prehospital providers to selected patients, though published data remains limited. We describe the preliminary safety and feasibility of training all paramedics within a single agency to administer buprenorphine in the field without online medical control to simultaneously treat opioid withdrawal and initiate MOUD., Methods: Using data from an ongoing quality assurance (QA) database, cases were retrospectively reviewed. Inclusion criteria included administration of buprenorphine by paramedics; cases were excluded if administered prior to EMS arrival on scene (i.e., the patient was given buprenorphine by a bystander or took their own). Data were entered into a REDCap database as part of the ongoing QA process. The primary reported outcome was administration of buprenorphine without complications. Complications were defined as any adverse effects from the administration of medication, including but not limited to new or worsening opioid withdrawal symptoms., Results: In total, 121 patients met inclusion criteria, 82 were treated for naloxone-induced withdrawal and 39 for withdrawal due to opioid cessation. There were no cases of precipitated withdrawal or worsening of patient condition observed. Adverse effects were limited to three cases of nausea and vomiting post-administration, all of which were present prior to buprenorphine administration. No patients met the primary outcome of adverse effects from medication administration., Conclusions: In a single prehospital system, the use of buprenorphine appears to be a feasible and safe strategy for treating patients experiencing acute opioid withdrawal.

Background: Plasma dipeptidyl peptidase-3 (DPP3) and renin levels are associated with organ dysfunction and mortality. However, whether these biomarkers are associated with the subsequent onset of shock in at-risk patients is unknown., Methods: Using plasma samples collected from participants enrolled in the fourth Accelerating COVID-19 Therapeutic Interventions and Vaccines Host Tissue platform trial, we measured DPP3 and renin in 184 subjects hospitalized with acute hypoxemia from COVID-19 without baseline vasopressor requirement. We calculated the odds ratio of development of shock (defined as the initiation of vasopressor therapy) by Day 28 based on Day 0 DPP3 and renin levels., Results: Subjects with DPP3 above the median had a significantly higher incidence of vasopressor initiation within 28 days (28.4 % vs. 16.7 %, p = 0.031) and higher 28-day mortality (25.0 % vs. 6.7 %, p < 0.001). After adjusting for covariables, DPP3 above the median was associated with shorter time to vasopressor initiation, greater 28-day mortality, fewer vasopressor-free days, and greater odds of a hypotensive event over 7 days. Significant associations were not observed for renin., Conclusions: In patients hospitalized with COVID-19 and hypoxemia without baseline hypotension, higher baseline plasma levels of DPP3 but not renin were associated with increased risk of subsequent shock and death., Competing Interests: Declaration of competing interest All authors completed and submitted the ICMJE form for disclosure of potential conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Data suggest patients suffering acute coronary occlusion myocardial infarction (OMI) benefit from prompt primary percutaneous intervention (PPCI). Many emergency medical services (EMS) activate catheterization labs to reduce time to PPCI, but suffer a high burden of inappropriate activations. Artificial intelligence (AI) algorithms show promise to improve electrocardiogram (ECG) interpretation. The primary objective was to evaluate the potential of AI to reduce false positive activations without missing OMI., Methods: Electrocardiograms were categorized by (1) STEMI criteria, (2) ECG integrated device software and (3) a proprietary AI algorithm (Queen of Hearts (QOH), Powerful Medical). If multiple ECGs were obtained and any one tracing was positive for a given method, that diagnostic method was considered positive. The primary outcome was OMI defined as an angiographic culprit lesion with either TIMI 0-2 flow; or TIMI 3 flow with either peak high sensitivity troponin- I  > 5000 ng/L or new wall motion abnormality. The primary analysis was per-patient proportion of false positives., Results: A total of 140 patients were screened and 117 met criteria. Of these, 48 met the primary outcome criteria of OMI. There were 80 positives by STEMI criteria, 88 by device algorithm, and 77 by AI software. All approaches reduced false positives, 27% for STEMI, 22% for device software, and 34% for AI ( p  < 0.01 for all). The reduction in false positives did not significantly differ between STEMI criteria and AI software ( p  = 0.19) but STEMI criteria missed 6 (5%) OMIs, while AI missed none ( p  = 0.01)., Conclusions: In this single-center retrospective study, an AI-driven algorithm reduced false positive diagnoses of OMI compared to EMS clinician gestalt. Compared to AI (which missed no OMI), STEMI criteria also reduced false positives but missed 6 true OMI. External validation of these findings in prospective cohorts is indicated.