Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccination Against SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 Lineage Hospitalization and a Comparison of Clinical Severity-IVY Network, 26 Hospitals, October 18, 2023-March 9, 2024.

BACKGROUND: Assessing variant-specific COVID-19 vaccine effectiveness (VE) and severity can inform public health risk assessments and decisions about vaccine composition. BA.2.86 and its descendants, including JN.1 (referred to collectively as "JN lineages"), emerged in late 2023 and exhibited substantial divergence from co-circulating XBB lineages. METHODS: We analyzed patients hospitalized with COVID-19-like illness at 26 hospitals in 20 U.S. states admitted October 18, 2023-March 9, 2024. Using a test-negative, case-control design, we estimated effectiveness of an updated 2023-2024 (Monovalent XBB.1.5) COVID-19 vaccine dose against sequence-confirmed XBB and JN lineage hospitalization using logistic regression. Odds of severe outcomes, including intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) or death, were compared for JN versus XBB lineage hospitalizations using logistic regression. RESULTS: 585 case-patients with XBB lineages, 397 case-patients with JN lineages, and 4,580 control-patients were included. VE in the first 7-89 days after receipt of an updated dose was 54.2% (95% CI = 36.1%-67.1%) against XBB lineage hospitalization and 32.7% (95% CI = 1.9%-53.8%) against JN lineage hospitalization. Odds of ICU admission (adjusted odds ratio [aOR] 0.80; 95% CI = 0.46-1.38) and IMV or death (aOR 0.69; 95% CI = 0.34-1.40) were not significantly different among JN compared to XBB lineage hospitalizations. CONCLUSIONS: Updated 2023-2024 COVID-19 vaccination provided protection against both XBB and JN lineage hospitalization, but protection against the latter may be attenuated by immune escape. Clinical severity of JN lineage hospitalizations was not higher relative to XBB.

ICU Utilization After Implementation of Minor Severe Pneumonia Criteria in Real-Time Electronic Clinical Decision Support.

OBJECTIVES: To determine if the implementation of automated clinical decision support (CDS) with embedded minor severe community-acquired pneumonia (sCAP) criteria was associated with improved ICU utilization among emergency department (ED) patients with pneumonia who did not require vasopressors or positive pressure ventilation at admission. DESIGN: Planned secondary analysis of a stepped-wedge, cluster-controlled CDS implementation trial. SETTING: Sixteen hospitals in six geographic clusters from Intermountain Health; a large, integrated, nonprofit health system in Utah and Idaho. PATIENTS: Adults admitted to the hospital from the ED with pneumonia identified by: 1) discharge International Classification of Diseases , 10th Revision codes for pneumonia or sepsis/respiratory failure and 2) ED chest imaging consistent with pneumonia, who did not require vasopressors or positive pressure ventilation at admission. INTERVENTIONS: After implementation, patients were exposed to automated, open-loop, comprehensive CDS that aided disposition decision (ward vs. ICU), based on objective severity scores (sCAP). MEASUREMENTS AND MAIN RESULTS: The analysis included 2747 patients, 1814 before and 933 after implementation. The median age was 71, median Elixhauser index was 17, 48% were female, and 95% were Caucasian. A mixed-effects regression model with cluster as the random effect estimated that implementation of CDS utilizing sCAP increased 30-day ICU-free days by 1.04 days (95% CI, 0.48-1.59; p < 0.001). Among secondary outcomes, the odds of being admitted to the ward, transferring to the ICU within 72 hours, and receiving a critical therapy decreased by 57% (odds ratio [OR], 0.43; 95% CI, 0.26-0.68; p < 0.001) post-implementation; mortality within 72 hours of admission was unchanged (OR, 1.08; 95% CI, 0.56-2.01; p = 0.82) while 30-day all-cause mortality was lower post-implementation (OR, 0.71; 95% CI, 0.52-0.96; p = 0.03). CONCLUSIONS: Implementation of electronic CDS using minor sCAP criteria to guide disposition of patients with pneumonia from the ED was associated with safe reduction in ICU utilization.

Interim Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccines Against COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalization Among Immunocompetent Adults Aged ≥18 Years - VISION and IVY Networks, September 2023-January 2024.

In September 2023, CDC's Advisory Committee on Immunization Practices recommended updated 2023-2024 (monovalent XBB.1.5) COVID-19 vaccination for all persons aged ≥6 months to prevent COVID-19, including severe disease. However, few estimates of updated vaccine effectiveness (VE) against medically attended illness are available. This analysis evaluated VE of an updated COVID-19 vaccine dose against COVID-19-associated emergency department (ED) or urgent care (UC) encounters and hospitalization among immunocompetent adults aged ≥18 years during September 2023-January 2024 using a test-negative, case-control design with data from two CDC VE networks. VE against COVID-19-associated ED/UC encounters was 51% (95% CI = 47%-54%) during the first 7-59 days after an updated dose and 39% (95% CI = 33%-45%) during the 60-119 days after an updated dose. VE estimates against COVID-19-associated hospitalization from two CDC VE networks were 52% (95% CI = 47%-57%) and 43% (95% CI = 27%-56%), with a median interval from updated dose of 42 and 47 days, respectively. Updated COVID-19 vaccine provided increased protection against COVID-19-associated ED/UC encounters and hospitalization among immunocompetent adults. These results support CDC recommendations for updated 2023-2024 COVID-19 vaccination. All persons aged ≥6 months should receive updated 2023-2024 COVID-19 vaccine.

Prescription of potentially inappropriate medications after an intensive care unit stay for acute respiratory failure.

BACKGROUND: Among survivors of critical illness, prescription of potentially inappropriate medications (PIM) at hospital discharge is thought to be an important, modifiable patient safety concern. To date, there are little empirical data evaluating this issue. RESEARCH QUESTION: The objective of this study was to determine the frequency of PIM prescribed to survivors of acute respiratory failure (ARF) at hospital discharge and explore their association with readmissions or death within 90 days of hospital discharge. STUDY DESIGN AND METHODS: Prospective multicenter cohort study of ARF survivors admitted to ICUs and discharged home. Prospective of new PIMs with a high-adverse-effect profile ("high impact") at discharge was the primary exposure. Potential inappropriateness was determined by a structured consensus process using Screening Tool of Older Persons' Prescriptions-Screening Tool to Alert to Right Treatment, Beers' criteria, and clinical context of prescriptions by a multidisciplinary team. Covariate balancing propensity score was used for the primary analysis. RESULTS: Of the 195 Addressing Post Intensive Care Syndrome-01 (APICS-01) patients, 169 (87%) had ≥1 new medications prescribed at discharge, with 154 (91.1%) prescribed with one or more high-impact (HI) medications. Patients were prescribed a median of 5 [3-7] medications, of which 3 [1-4] were HI. Twenty percent of HI medications were potentially inappropriate. Medications with significant central nervous system side-effects were most prescribed potentially inappropriately. Forty-six (30%) patients experienced readmission or death within 90 days of hospital discharge. After adjusting for prespecified covariates, the association between prescription of potentially inappropriate HI medications and the composite primary outcome did not meet the prespecified threshold for statistical significance (risk ratio: 0.54; 0.26-1.13; p = 0.095) or with the constituent endpoints: readmission (risk ratio: 0.57, 0.27-1.11) or death (0.7, 0.05-9.32). CONCLUSION: At hospital discharge, most ARF survivors are prescribed medications with a high-adverse-effect profile and approximately one-fifth are potentially inappropriate. Although prescription of such medications was not associated with 90-day readmissions and mortality, these results highlight an area for additional investigation.

Relationship Between Resuscitation Team Members' Self-Efficacy and Team Competence During In-Hospital Cardiac Arrest.

OBJECTIVES: Inadequate self-efficacy of resuscitation team members may impair team performance, but high self-efficacy does not guarantee competence. We evaluated the relationship between individual self-efficacy and resuscitation team competence. DESIGN: Secondary analysis of a randomized controlled trial. SETTING: High-fidelity in situ in-hospital cardiac arrest simulations at seven hospitals in Utah. SUBJECTS: Multidisciplinary cardiac arrest resuscitation team members. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Resuscitation team members completed surveys evaluating resuscitation self-efficacy (confidence in resuscitation role, difficulty thinking clearly, and concerns about committing errors) after each simulation. The primary outcome was event-level chest compression hands-on fraction greater than 75%. Secondary outcomes included other measures of resuscitation quality, advanced cardiac life support protocol adherence, and nontechnical team performance. Analyses employed the Datta-Satten rank-sum method to account for response clustering within simulation events. Of 923 participants in 76 analyzable simulations, 612 (66%) submitted complete surveys and 33 (43%) resuscitation teams achieved hands-on fraction greater than 75%. Event-level chest compression hands-on fraction greater than 75% versus less than or equal to 75% was not associated with the percentage of resuscitation team members reporting confidence in their team role (n = 213 [74%] vs. n = 251 [77%], respectively, p = 0.18), lack of difficulty thinking clearly (n = 186 [65%] vs. n = 214 [66%], p = 0.92), or lack of worry about making errors (n = 155 [54%] vs. n = 180 [55%], p = 0.41). Team members' confidence was also not associated with secondary outcomes, except that teams with confident members had better values for composite (3.55 [interquartile range, IQR 3.00-3.82] vs. 3.18 [IQR 2.57-3.64], p = 0.024) and global (8 [7-9] vs. 8 [6-8], p = 0.029) scales measuring nontechnical team performance. CONCLUSIONS: Team members' self-efficacy was not associated with most team-level competence metrics during simulated cardiac arrest resuscitation. These data suggest that self-efficacy should have a limited role for evaluation of resuscitation training programs and for initial certification and monitoring of individual resuscitation team members' competence.

Identifying predictors and determining mortality rates of septic cardiomyopathy and sepsis-related cardiogenic shock: A retrospective, observational study.

INTRODUCTION: Septic shock is a severe form of sepsis that has a high mortality rate, and a substantial proportion of these patients will develop cardiac dysfunction, often termed septic cardiomyopathy (SCM). Some SCM patients may develop frank cardiac failure, termed sepsis-related cardiogenic shock (SeRCS). Little is known of SeRCS. This study describes baseline characteristics of patients with SCM and SeRCS compared to patients with septic shock without cardiac dysfunction. We compare clinical outcomes among SCM, SeRCS, and septic shock, and identify risk factors for the development of SCM and SeRCS. METHODS: Septic patients admitted to the ICU with an echocardiogram obtained within 72 hours were included. Left ventricular ejection fraction of ≤55% was used to define SCM, and cardiac index ≤2.1 L/min/m2 among patients with SCM defined SeRCS. Machine learning was used to identify risk factors for development of SCM and SeRCS. Logistic regression was used to compare mortality among groups. RESULTS: Among 1229 patients, 977 patients had septic shock without cardiac dysfunction, 207 had SCM, and 45 had SeRCS. In patients with septic shock, the strongest predictor for developing SCM and SeRCs was a prior history of cardiac dysfunction. Mortality did not significantly differ among the three groups. CONCLUSIONS: SCM and SeRCS affect a minority of patients with septic shock, disproportionately affecting individuals with a history of cardiac disease. We did not identify a mortality difference associated with SCM or SeRCS. Additional work is needed to define further subtypes and treatment options for this patient population.

Predicting stroke risk after sepsis hospitalization with new-onset atrial fibrillation.

BACKGROUND: New-onset atrial fibrillation (AF) during sepsis is common, but models designed to stratify stroke risk excluded patients with secondary AF. We assessed the predictive validity of CHA2DS2VASc scores among patients with new-onset AF during sepsis and developed a novel stroke prediction model incorporating presepsis and intrasepsis characteristics. METHODS: We included patients ≥40 years old who survived hospitalizations with sepsis and new-onset AF across 21 Kaiser Permanente Northern California hospitals from January 1, 2011 to September 30, 2017. We calculated the area under the receiver operating curve (AUC) for CHA2DS2VASc scores to predict stroke or transient ischemic attack (TIA) within 1 year after a hospitalization with new-onset AF during sepsis using Fine-Gray models with death as competing risk. We similarly derived and validated a novel model using presepsis and intrasepsis characteristics associated with 1-year stroke/TIA risk. RESULTS: Among 82,748 adults hospitalized with sepsis, 3992 with new-onset AF (median age: 80 years, median CHA2DS2VASc of 4) survived to discharge, among whom 70 (2.1%) experienced stroke or TIA outcome and 1393 (41.0%) died within 1 year of sepsis. The CHA2DS2VASc score was not predictive of stroke risk after sepsis (AUC: 0.50, 95% confidence interval [CI]: 0.48-0.52). A newly derived model among 2555 (64%) patients in the derivation set and 1437 (36%) in the validation set included 13 variables and produced an AUC of 0.61 (0.49-0.73) in derivation and 0.54 (0.43-0.65) in validation. CONCLUSION: Current models do not accurately stratify risk of stroke following new-onset AF secondary to sepsis. New tools are required to guide anticoagulation decisions following new-onset AF in sepsis.

Effectiveness and Safety of an Emergency Department Code Sepsis Protocol: A Pragmatic Clinical Trial.

RATIONALE: Sepsis care delivery - including initiation of prompt, appropriate antimicrobials - remains suboptimal. OBJECTIVE: Determine direct and off-target effects of emergency department (ED) sepsis care reorganization. METHODS: This pragmatic pilot trial enrolled adult patients presenting November 2019 to February 2021 to an ED in Utah before and after implementation of a multimodal, team-based "Code Sepsis" protocol. Patients presenting to two other EDs where usual care was continued served as contemporaneous controls. The primary outcome was door-to-antimicrobial time among patients meeting Sepsis-3 criteria before ED departure. Secondary and safety outcomes included all-cause 30-day mortality, antimicrobial utilization and overtreatment, and antimicrobial-associated adverse events. Multivariable regression analyses employed difference-in-differences methods to account for trends in outcomes unrelated to the studied intervention. RESULTS: Code Sepsis protocol activation (N=307) exhibited 8.5% sensitivity and 66% positive predictive value for patients meeting sepsis criteria before ED departure. Among 10,151 patients meeting sepsis criteria during the study, adjusted difference-in-differences analysis demonstrated a 13-minute (95% CI 7-19-minute) decrease in door-to-antimicrobial time associated with Code Sepsis implementation (p<0.001). Mortality and clinical safety outcomes were unchanged, but Code Sepsis implementation was associated with increased false-positive presumptive infection diagnosis among patients meeting sepsis criteria in the ED and increased antimicrobial utilization. CONCLUSIONS: Implementation of a team-based protocol for rapid sepsis evaluation and treatment during the COVID-19 pandemic's first year was associated with decreased ED door-to-antimicrobial time but also increased antimicrobial utilization. Measurement of both patient-centered and off-target effects of sepsis care improvement interventions is essential to comprehensive assessment of their value. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT04148989) This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Severity of Respiratory Syncytial Virus vs COVID-19 and Influenza Among Hospitalized US Adults.

Importance: On June 21, 2023, the Centers for Disease Control and Prevention recommended the first respiratory syncytial virus (RSV) vaccines for adults aged 60 years and older using shared clinical decision-making. Understanding the severity of RSV disease in adults can help guide this clinical decision-making. Objective: To describe disease severity among adults hospitalized with RSV and compare it with the severity of COVID-19 and influenza disease by vaccination status. Design, Setting, and Participants: In this cohort study, adults aged 18 years and older admitted to the hospital with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively enrolled from 25 hospitals in 20 US states from February 1, 2022, to May 31, 2023. Clinical data during each patient's hospitalization were collected using standardized forms. Data were analyzed from August to October 2023. Exposures: RSV, SARS-CoV-2, or influenza infection. Main Outcomes and Measures: Using multivariable logistic regression, severity of RSV disease was compared with COVID-19 and influenza severity, by COVID-19 and influenza vaccination status, for a range of clinical outcomes, including the composite of invasive mechanical ventilation (IMV) and in-hospital death. Results: Of 7998 adults (median [IQR] age, 67 [54-78] years; 4047 [50.6%] female) included, 484 (6.1%) were hospitalized with RSV, 6422 (80.3%) were hospitalized with COVID-19, and 1092 (13.7%) were hospitalized with influenza. Among patients with RSV, 58 (12.0%) experienced IMV or death, compared with 201 of 1422 unvaccinated patients with COVID-19 (14.1%) and 458 of 5000 vaccinated patients with COVID-19 (9.2%), as well as 72 of 699 unvaccinated patients with influenza (10.3%) and 20 of 393 vaccinated patients with influenza (5.1%). In adjusted analyses, the odds of IMV or in-hospital death were not significantly different among patients hospitalized with RSV and unvaccinated patients hospitalized with COVID-19 (adjusted odds ratio [aOR], 0.82; 95% CI, 0.59-1.13; P = .22) or influenza (aOR, 1.20; 95% CI, 0.82-1.76; P = .35); however, the odds of IMV or death were significantly higher among patients hospitalized with RSV compared with vaccinated patients hospitalized with COVID-19 (aOR, 1.38; 95% CI, 1.02-1.86; P = .03) or influenza disease (aOR, 2.81; 95% CI, 1.62-4.86; P < .001). Conclusions and Relevance: Among adults hospitalized in this US cohort during the 16 months before the first RSV vaccine recommendations, RSV disease was less common but similar in severity compared with COVID-19 or influenza disease among unvaccinated patients and more severe than COVID-19 or influenza disease among vaccinated patients for the most serious outcomes of IMV or death.

Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccination Against SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 Lineage Hospitalization and a Comparison of Clinical Severity - IVY Network, 26 Hospitals, October 18, 2023-March 9, 2024.

Background: Assessing COVID-19 vaccine effectiveness (VE) and severity of SARS-CoV-2 variants can inform public health risk assessments and decisions about vaccine composition. BA.2.86 and its descendants, including JN.1 (referred to collectively as "JN lineages"), emerged in late 2023 and exhibited substantial genomic divergence from co-circulating XBB lineages. Methods: We analyzed patients hospitalized with COVID-19-like illness at 26 hospitals in 20 U.S. states admitted October 18, 2023-March 9, 2024. Using a test-negative, case-control design, we estimated the effectiveness of an updated 2023-2024 (Monovalent XBB.1.5) COVID-19 vaccine dose against sequence-confirmed XBB and JN lineage hospitalization using logistic regression. Odds of severe outcomes, including intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) or death, were compared for JN versus XBB lineage hospitalizations using logistic regression. Results: 585 case-patients with XBB lineages, 397 case-patients with JN lineages, and 4,580 control-patients were included. VE in the first 7-89 days after receipt of an updated dose was 54.2% (95% CI = 36.1%-67.1%) against XBB lineage hospitalization and 32.7% (95% CI = 1.9%-53.8%) against JN lineage hospitalization. Odds of ICU admission (adjusted odds ratio [aOR] 0.80; 95% CI = 0.46-1.38) and IMV or death (aOR 0.69; 95% CI = 0.34-1.40) were not significantly different among JN compared to XBB lineage hospitalizations. Conclusions: Updated 2023-2024 COVID-19 vaccination provided protection against both XBB and JN lineage hospitalization, but protection against the latter may be attenuated by immune escape. Clinical severity of JN lineage hospitalizations was not higher relative to XBB lineage hospitalizations.

What Next? New Drugs, Old Drugs, and New Challenges in Choosing Treatments for Covid-19.

Much has changed since March 2020, when the World Health Organization declared Covid-19 a pandemic and clinicians around the world began desperately searching for therapies that could help afflicted patients. Barely 2.5 years after SARS-CoV-2 was discovered, we have solid evidence for the efficacy and safety of repurposed and novel agents for pre- and postexposure prophylaxis and for mild and severe disease, not to mention highly effective vaccines.