Randomized trial of activated vitamin D for acute kidney injury prevention in critically ill patients.

Background: Active vitamin D metabolites, including 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D), have potent immunomodulatory effects that attenuate acute kidney injury (AKI) in animal models.

Methods: We conducted a phase 2, randomized, double-blind, multiple-dose, 3-arm clinical trial comparing oral calcifediol (25D), calcitriol (1,25D), and placebo among 150 critically ill adult patients at high-risk of moderate-to-severe AKI. The primary endpoint was a hierarchical composite of death, kidney replacement therapy (KRT), and kidney injury (baseline-adjusted mean change in serum creatinine), each assessed within 7 days following enrollment using a rank-based procedure.

RSV Vaccine Effectiveness Against Hospitalization Among US Adults Aged 60 Years or Older During 2 Seasons.

Importance: Respiratory syncytial virus (RSV) vaccines for adults aged 60 years or older became available in 2023. One dose is recommended for all adults aged 75 years or older and those aged 60 to 74 years at increased risk of severe RSV; however, duration of protection is unknown.

Objective: To evaluate RSV vaccine effectiveness against RSV-associated hospitalization among adults aged 60 years or older during 2 RSV seasons.

Circulating Interleukin-6 Levels and Timing of Acute Ischemic Stroke Onset.

Intravenous thrombolysis is the most widely available effective ischemic stroke treatment, but is approved only if given within 4.5 h from stroke onset. Many patients are not treated because stroke onset time is unknown.

Association Between Operator Experience and Procedural Outcomes of Tracheal Intubation in the Emergency Department and ICU.

Study Objectives: Complications are common during emergency tracheal intubation. Although graduate medical education in emergency medicine and critical care mandate competency in this procedure, thresholds for proficiency are poorly defined. We evaluated the relationship between the operator performing intubation and complications of emergency tracheal intubation.

Metformin on the Presence of COVID-19 Symptoms Over 6 Months: The ACTIV-6 Randomized Clinical Trial.

Background: The effect of metformin on preventing long-term COVID-19 symptoms among low-risk adults has not been studied. The objective of this study was to Assess metformin compared with placebo during acute SARS-CoV-2 infection on the presence of COVID-19 symptoms 180 days later.

Methods: The ACTIV-6 platform evaluated repurposed medications for mild to moderate COVID-19.

Multimorbidity Profiles and Severe In-Hospital Outcomes in Adults with Respiratory Syncytial Virus.

Background: Adults hospitalized with acute respiratory infections, including respiratory syncytial virus (RSV), often have multiple underlying conditions. Few data are available on the combined effect of conditions on risk of severe outcomes from RSV disease.

Methods: We enrolled adults hospitalized with RSV at 26 hospitals in 20 US states admitted January 2022-July 2024.

Metformin and Time to Sustained Recovery in Adults With COVID-19: The ACTIV-6 Randomized Clinical Trial.

Importance: The effect of metformin on reducing symptom duration among outpatient adults with COVID-19 has not been studied.

Objective: To assess metformin compared with placebo for symptom resolution during acute infection with SARS-CoV-2.

Design, Setting, And Participants: The Accelerating COVID-19 Therapeutic Interventions and Vaccines platform evaluated repurposed medications for mild to moderate COVID-19.

Effect of targeting normoxemia on supplemental oxygen-free days for adults with acute thermal burns: A stepped wedge cluster randomized clinical trial.

Background: Supplemental oxygen is essential in caring for adults with acute thermal burns but can expose patients to excess inspired oxygen. We sought to determine the safety and effectiveness of targeting normoxemia (peripheral oxygen saturation [SpO2] 90-96%) in adults with acute thermal burns admitted to a specialized burn unit. We hypothesized that targeting normoxemia would increase the number of supplemental oxygen-free days (SOFDs) and safely reduce exposure to hyperoxemia.

Implementation of an Online Drug-Drug Interaction Screener for the STRIVE Ensitrelvir Trial for COVID-19.

Background: Ensitrelvir is an antiviral agent against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with associated drug-drug interactions (DDIs) through CYP3A, -glycoprotein (-gp), breast cancer resistance protein (BCRP), and organic anion transporter-3 (OAT-3) inhibition. We present the development and implementation of an online DDI screener to assess interactions during the STRIVE ensitrelvir trial.

Methods: The STRIVE Network is conducting a randomized, double-blind, placebo-controlled trial evaluating ensitrelvir's efficacy and safety in hospitalized adults with coronavirus disease 2019 (COVID-19) and lower respiratory tract involvement.

Experiences of recently diagnosed urban COVID-19 outpatients: A survey on patient worries, provider-patient interactions, and neutralizing monoclonal antibody treatment.

Background: COVID-19 patients have experienced worry, altered provider-patient interactions, and options to use novel treatments, initially with neutralizing monoclonal antibodies (mAbs). Limited research has been performed on these aspects of the COVID-19 outpatient experience.

Objective: This study aimed to evaluate the experiences of outpatients recently diagnosed with COVID-19, who were eligible for use of mAbs, during the diagnosis and treatment process based on sociodemographic and clinical factors.

An End-user Assessment of the Novel i-view Video Laryngoscope After a Clinical Trial.

Introduction: Airway obstruction is a leading cause of potentially survivable death on the battlefield. Intubation remains the most frequently performed prehospital airway intervention. Unfortunately, survival is lower after prehospital intubation compared to the emergency department.

Identification of HIF1A as a therapeutic target during SARS-CoV-2-associated lung injury.

Hypoxia-inducible factors (HIFs) promote lung protection and pathogen eradication during acute lung injury. We, therefore, tested the theory that pharmacologic stabilization of HIFs dampens lung injury during SARS-CoV-2 pneumonia. Initial studies in murine SARS-CoV-2 models showed improved outcomes after treatment with the FDA-approved HIF stabilizer vadadustat.

Prochlorperazine maleate versus placebo for the prophylaxis of acute mountain sickness: a double-blind randomized controlled trial.

Background: Acute mountain sickness (AMS) is a debilitating condition that may occur on ascent to high altitude, with limited options for chemoprophylaxis. The pathophysiology of AMS is poorly understood, though it may be similar to migraine. This study aimed to determine the efficacy of prochlorperazine, a first-line agent for acute migraine, for AMS prophylaxis.

Impact of perioperative organ injury on morbidity and mortality in 28 million surgical patients.

Perioperative organ injury contributes to morbidity and mortality of surgical patients. This cohort study included all elective and emergent surgeries in Germany over 4 years to address the impact of perioperative organ injuries on outcomes. We analyzed 28,350,953 cases.

Vaccine Effectiveness Against Influenza A(H1N1), A(H3N2), and B-Associated Hospitalizations-United States, September 1, 2023-May 31, 2024.

Background: The 2023-2024 influenza season included sustained elevated activity from December 2023-February 2024 and continued activity through May 2024. Influenza A(H1N1), A(H3N2), and B viruses circulated during the season.

Methods: During September 1, 2023-May 31, 2024, a multistate sentinel surveillance network of 24 medical centers in 20 U.

Patient- and Community-Level Characteristics Associated With Respiratory Syncytial Virus Vaccination.

Importance: In 2023, the first respiratory syncytial virus (RSV) vaccines were recommended for US adults 60 years or older, but few data are available about which patients were most likely to receive vaccine to inform future RSV vaccine outreach efforts.

Objective: To assess patient- and community-level characteristics associated with RSV vaccine receipt and patient knowledge and attitudes related to RSV disease and RSV vaccines.

Design, Setting, And Participants: During the first season of RSV vaccine use from October 1, 2023, to April 30, 2024, adults 60 years or older hospitalized with RSV-negative acute respiratory illness were enrolled in this cross-sectional study from 26 hospitals in 20 US states.

Targeted Normoxemia and Supplemental Oxygen-Free Days in Critically Injured Adults: A Stepped-Wedge Cluster Randomized Clinical Trial.

Importance: Supplemental oxygen is fundamental to caring for critically injured adults but can expose them to excess inspired oxygen.

Objective: To determine the safety and effectiveness of targeting normoxemia in critically ill trauma patients.

Design, Setting, And Participants: This multicenter, stepped-wedge, cluster randomized clinical trial compared targeted normoxemia (defined as a peripheral oxygen saturation [Spo2] of 90% to 96%) with usual care among adult trauma patients admitted to an intensive care unit (ICU) at 8 level I trauma centers across the US.

Preoxygenation strategies for intubation of patients who are critically ill: a systematic review and network meta-analysis of randomised trials.

Background: Preoxygenation is a crucial preparatory step for intubation. Several strategies for preoxygenation exist, including facemask oxygen, high-flow nasal cannula (HFNC), and non-invasive positive pressure ventilation (NIPPV). However, the comparative efficacy of these strategies remains largely uncertain.

Interim Estimates of 2024-2025 COVID-19 Vaccine Effectiveness Among Adults Aged ≥18 Years - VISION and IVY Networks, September 2024-January 2025.

COVID-19 vaccination averted approximately 68,000 hospitalizations during the 2023-24 respiratory season. In June 2024, CDC and the Advisory Committee on Immunization Practices (ACIP) recommended that all persons aged ≥6 months receive a 2024-2025 COVID-19 vaccine, which targets Omicron JN.1 and JN.

Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of stratified aggregate data.

Background: A 2021 meta-analysis of 37 randomised controlled trials (RCTs) of vitamin D supplementation for prevention of acute respiratory infections (ARIs) revealed a statistically significant protective effect of the intervention (odds ratio [OR] 0·92 [95% CI 0·86 to 0·99]). Since then, six eligible RCTs have been completed, including one large trial (n=15 804). We aimed to re-examine the link between vitamin D supplementation and prevention of ARIs.

Long-term outcomes of passive immunotherapy for COVID-19: a pooled analysis of a large multinational platform randomized clinical trial.

Objectives: Passive immunotherapy, including monoclonal antibodies and neutralizing proteins, was used for the treatment of patients with COVID-19 during the pandemic. Accelerating COVID-19 Therapeutic Interventions and Vaccines-Therapeutics for Inpatients with COVID-19 (ACTIV-3/TICO) was a multinational, randomized placebo-controlled platform trial that evaluated the effectiveness of multiple passive immunotherapy agents in patients hospitalized with COVID-19. Given the long half-life of some agents studied, participants were followed for an extended period to assess the long-term efficacy and sustained safety of these agents.

COVID-19 and influenza vaccine Hesitancy among adults hospitalized in the United States, 2019-2022.

Background: Understanding similarities and differences between hesitancy for influenza and COVID-19 vaccines could facilitate strategies to improve public receptivity toward vaccination.

Methods: We compared hesitancy for COVID-19 vaccines during the first 13 months of availability (January 2021-January 2022) with hesitancy for influenza vaccines in the 15 months prior to COVID-19 vaccine availability (October 2019-December 2020) among adults hospitalized with acute respiratory illness at 21 hospitals in the United States. We interviewed patients regarding vaccination status, willingness to be vaccinated, and perceptions of vaccine safety and efficacy.

The circulating renin-angiotensin system and mortality among patients hospitalized for COVID-19: a mechanistic substudy of the ACTIV-4 Host Tissue trials.

SARS-CoV-2 targets angiotensin-converting enzyme-2 (ACE2), a key peptidase of the renin-angiotensin system (RAS), which regulates the balance of the vasoconstrictor/inflammatory peptide Ang II and the vasodilator/anti-inflammatory peptide Ang-(1-7). Few studies have quantified the circulating elements of the RAS longitudinally in SARS-CoV-2 infection and their association with COVID-19 outcomes. Thus, we evaluated the association of circulating RAS enzymes and peptides with mortality among patients with COVID-19.

Protocol and Statistical Analysis Plan for the Randomized Trial of Sedative Choice for Intubation (RSI).

Background: Emergency tracheal intubation is a common and high-risk procedure. Ketamine and etomidate are sedative medicines commonly used to induce anesthesia for emergency tracheal intubation, but whether the induction medication used affects patient outcomes is uncertain.

Research Question: Does the use of ketamine for induction of anesthesia decrease the incidence of death among adults undergoing emergency tracheal intubation, compared to the use of etomidate?

Study Design And Methods: The Randomized trial of Sedative choice for Intubation (RSI) is a pragmatic, multicenter, unblinded, parallel-group, randomized trial being conducted in 14 sites (6 emergency departments and 8 intensive care units) in the United States.

Video vs Direct Laryngoscopy for Tracheal Intubation After Cardiac Arrest: A Secondary Analysis of the Direct vs Video Laryngoscope Trial.

Background: Airway management is a critical component of the care of patients experiencing cardiac arrest, but data from randomized trials on the use of video vs direct laryngoscopy for intubation in the setting of cardiac arrest are limited. Current American Heart Association guidelines recommend placement of an endotracheal tube either during CPR or shortly after return of spontaneous circulation, but do not provide guidance around intubation methods, including the choice of laryngoscope.

Research Question: Does use of video laryngoscopy improve the incidence of successful intubation on the first attempt, compared with use of direct laryngoscopy, among adults undergoing tracheal intubation after experiencing cardiac arrest?

Study Design And Methods: This secondary analysis of the Direct vs Video Laryngoscope (DEVICE) trial compared video laryngoscopy vs direct laryngoscopy in the subgroup of patients who were intubated after cardiac arrest.