Abstract Background Randomized trials evaluating emergency treatments may be conducted with Exception from Informed Consent (EFIC) when informed consent is infeasible. In EFIC trials, a period of community consultation and public disclosure precedes initiation of enrollment. The Randomized Trial of Sedative Choice for Intubation (RSI) was a 2,365-patient randomized trial conducted with EFIC in 14 emergency departments and intensive care units across the United States. This manuscript reports the approach to community consultation and public disclosure in the RSI trial. Methods Community consultation and public disclosure were conducted locally in each region of enrolling sites. The coordinating center provided sites with templates and access to an engagement coordinator to assist with developing and executing site plans. Results Community consultation and public disclosure occurred at the coordinating center from February 2021-January 2022 and in the regions of the five additional enrolling sites from September 2023-June 2024. Community consultation included in-person surveys with 789 patients or family members in emergency department or intensive care unit waiting rooms and invitation of more than 200 local groups to town halls or Community Engagement Studios. Public disclosure included (i) social media advertisements viewed more than 1.2 million times, (ii) a trial website with more than 16,000 unique visitors, (iii) informational flyers in hospitals and public settings, and (iv) featured information in traditional media. Completing local community consultation and public disclosure required an average of 139 h of research personnel time and approximately $18,822 at each site, in addition to coordinating center effort and costs. Conclusions Pre-trial community consultation activities in the RSI trial engaged over 1,000 patients, families, and community members and public disclosure reached over 1.2 million community members. While the total cost and duration of activities at sites were substantially lower than reported in prior EFIC trials, these costs remained significant. Trial registration ClinicalTrials.gov; No.: NCT05277896; URL: www.clinicaltrials.gov

BACKGROUND:To enhance biological understanding of ARDS, pneumonia, and sepsis and to accelerate therapeutic development in these areas, the National Institutes of Health developed the ARDS, Pneumonia, and Sepsis (APS) Consortium. RESEARCH QUESTION:Is the APS Consortium study rapidly generating data and biospecimens from a large cohort of critically ill adults with ARDS, pneumonia, and sepsis that will facilitate phenotyping of these syndromes? STUDY DESIGN AND METHODS:The APS Consortium Phenotyping Study is a multicenter, longitudinal, prospective, observational cohort study aimed at enrolling 4,000 critically ill adults with ARDS, pneumonia, sepsis, or a combination thereof over 4 years. Data and biospecimens are collected to characterize many aspects of each participant's chronic health, acute illness, and long-term recovery to facilitate phenotyping, that is, subclassifying ARDS, pneumonia, and sepsis into precise biologically based subsets with shared pathophysiologic characteristics. Feasibility of the study was assessed by evaluating the first 1,000 participants in terms of recruitment pace, participant characteristics, biospecimen collection, and proportion with confirmed ARDS, pneumonia, and sepsis based on expert adjudication. RESULTS:The first 1,000 participants were recruited ahead of schedule in < 13 months. Median age was 64 years, 75% received vasopressors, 50% received invasive mechanical ventilation, and 25% died in the hospital within 4 weeks of enrollment. Biospecimen collection rates were high, with 99% of participants with blood samples, 98% with upper respiratory swabs, 37% with lower respiratory samples, 80% with urine samples, and 65% with gastrointestinal samples. Expert adjudication resulted in 40% classified with ARDS, 52% classified with pneumonia, and 89% classified with sepsis. INTERPRETATION:The APS Consortium Phenotyping Study is producing a cohort of critically ill adults with ARDS, pneumonia, and sepsis with high severity of disease and a rich set of data and biospecimens. The study will continue to full enrollment of 4,000 participants. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov; No.: NCT06521502; URL: www. CLINICALTRIALS:gov.

RATIONALE:Empiric anti-pseudomonal coverage is an important part of treatment of sepsis, but there is limited data to guide antibiotic selection. The antibiotic choice on renal outcomes (ACORN) randomized trial found no difference in mortality when comparing cefepime and piperacillin-tazobactam, while an Instrumental Variable (IV) study found improved mortality with cefepime. OBJECTIVE:To determine if white blood cell (WBC) count modifies the effect of antibiotic choice on mortality. METHODS:We conducted post-hoc sub-group analyses of the ACORN trial and the IV study comparing cefepime to piperacillin-tazobactam. We performed regression modeling of interaction between treatment group and WBC on 28-day mortality with adjustment for relevant covariates, with evaluation for heterogeneity of treatment effect through likelihood ratio testing. MEASUREMENTS:The main outcome was 28-day mortality in both cohorts. Secondary outcomes in the secondary analysis of the ACORN trial included highest stage of acute kidney injury on an ordinal scale, a composite outcome of major adverse kidney events, and incidence of coma or delirium within 14 days. MAIN RESULTS:There was a significant interaction between WBC and treatment group in predicting 28-day mortality in both the ACORN trial and the IV study (odds ratio [OR] 0.95, 95% confidence interval [CI] 0.92-0.98, p = <0.01 and OR 0,95, CI 0.94-0.96, P < .01, respectively), with likelihood ratio testing revealing better model fit with inclusion of the interaction term (F = 8.17, p = <0.01 and F = 42.9, P < .01, respectively). In the ACORN cohort, patients with a baseline WBC count of 16 or higher had significantly lower odds of mortality when treated with piperacillin-tazobactam compared to cefepime (OR 0.51, CI 0.29-0.90). CONCLUSIONS:WBC modified the effect of antibiotic choice on mortality in two large clinical studies. Further research is needed to confirm this effect in prospective studies and to determine if WBC count could be used for predictive enrichment in future trials of anti-pseudomonal antibiotics.

INTRODUCTION:Statins are a cornerstone of cardiovascular disease prevention yet remain underused among eligible patients. Clinical decision support systems embedded in electronic health records (EHRs) are commonly used to encourage guideline-concordant prescribing. Interruptive reminders (eg, pop-ups) may be effective but interfere with clinical workflows and contribute to alert fatigue. Non-interruptive alerts are less intrusive, but their effectiveness remains unclear. The Interruptive versus Non-Interruptive Reminders for Statin tHerApy in Primary Care (INIRSHA-PC) trial is designed to evaluate the comparative effectiveness of interruptive and non-interruptive reminders on statin-prescribing rates. METHODS AND ANALYSIS:INIRSHA-PC is a single-centre, pragmatic, three-arm, parallel-group randomised controlled trial embedded in the EHR at Vanderbilt University Medical Center. The trial will enrol adults aged 18-74 seen in primary care who are eligible for, but not currently prescribed, statin therapy. The planned sample size is 3000 patients (1000 per arm). Enrolled patients will be randomised 1:1:1 to (1) interruptive reminder, (2) non-interruptive reminder or (3) no reminder (usual care). The primary outcome is statin prescription within 24 hours of enrolment. Secondary outcomes are statin prescribing within 12 months and low-density lipoprotein cholesterol levels measured between 30 days and 12 months after enrolment. Enrolment began on 14 August 2024. The study is expected to be completed on 19 November 2025. ETHICS AND DISSEMINATION:The trial has been approved by the Vanderbilt University Medical Center Institutional Review Board with waiver of patient informed consent (IRB number: 240419). Results will be disseminated through peer-reviewed publication and presentation at scientific conferences. TRIAL REGISTRATION NUMBER:NCT06456658.

BACKGROUND:Fear of methicillin-resistant Staphylococcus aureus (MRSA) as a cause of community-acquired pneumonia (CAP) frequently leads to empiric vancomycin coverage. Data evaluating the use of MRSA polymerase chain reaction (PCR) nasal swab testing to guide vancomycin de-escalation is limited for patients in the intensive care unit (ICU). METHODS:Swab Testing to Optimize Pneumonia Treatment With Empiric Vancomycin (STOP-Vanc) is a pragmatic, prospective, single-center, non-blinded randomized trial in which adult ICU patients with suspicion of CAP were randomized 1:1 to receive usual care either with (intervention) or without (control) the addition of MRSA nares PCR testing following ICU admission. The primary outcome was vancomycin-free hours alive, defined as the expected number of hours alive and free of vancomycin use within the first 7 days of trial enrollment as estimated using a longitudinal proportional odds state transition model adjusted for baseline covariates. RESULTS:A total of 277 adult ICU patients were randomized. Methicillin-resistant Staphylococcus aureus PCR nasal swab testing had a negative predictive value (NPV) of 98.9% in the intervention arm. The primary endpoint, vancomycin-free hours alive, was 105.7 in the control arm and 109.7 in the intervention arm (adjusted difference, 4 hours; 95% CI, -9.5-18.2; P = .458). CONCLUSIONS:Despite MRSA PCR nasal swab testing demonstrating a high NPV in this critically ill population, MRSA PCR nasal swab testing did not decrease the duration of vancomycin use or 30-day mortality among ICU patients with suspected CAP. Additional clinician education and antimicrobial stewardship interventions might be needed to reduce vancomycin use in this patient population. CLINICAL TRIALS REGISTRATION:ClinicalTrials.gov NCT06272994 (STOP-Vanc).

RATIONALE:For critically ill adults receiving invasive mechanical ventilation, randomized trials have found no significant average treatment effect of a higher (96-100%) versus lower (88-92%) peripheral oxygen saturation (SpO2) target. The effect of SpO2 targets on outcomes, however, may differ for patients with different characteristics. Machine learning methods have been used recently to derive and validate a statistical model capable of predicting which SpO2 target will result in lower mortality for an individual patient, as a personalized SpO2 target. Personalized targets can only improve patient outcomes, however, if the SpO2 target predicted to be best for them differs from the SpO2 values they are already experiencing in care. Whether the SpO2 values experienced in clinical care differ for patients predicted to benefit from a higher vs a lower SpO2 target is unknown. METHODS:Among consecutive patients receiving invasive mechanical ventilation in an intensive care unit, we used the previously validated machine learning model to calculate a personalized SpO2 target (predicted to benefit from a higher SpO2 target (96-100%) vs predicted to benefit from a lower SpO2 target (88-92%)) from baseline characteristics for each patient. We compared the personalized SpO2 target as the primary exposure to the observed SpO2 values experienced in clinical care as the primary outcome using a proportional odds model accounting for within-subject correlation. FiO2 values received in clinical care were analyzed as the secondary outcome. MEASUREMENTS AND MAIN RESULTS:Among 615 patients (median age, 58 years; 41% female), 325 (53%) were predicted by the machine learning model to benefit from a higher SpO2 target and 290 (47%) were predicted to benefit from a lower SpO2 target. Patients predicted to benefit from higher and lower targets experienced similar SpO2 values (mean 96.2% vs 95.6%; median 97% vs 96%; adjusted median difference 0.3%; 95%CI: -0.1% to 0.6%; P = 0.18) and FiO2 values (mean 0.45 vs 0.47; median 0.40 vs 0.40; adjusted median difference -0.02; 95%CI: -0.07 to 0.03; P = 0.38) in clinical care. In subgroups of interest, differences in the SpO2 or FiO2 values between groups were found only among patients with shock. CONCLUSIONS:In current clinical care, patients do not experience SpO2 values consistent with those predicted to result in the best outcomes for them, based on a machine learning model derived and validated in data from prior clinical trials. This lack of difference in care suggests that using evidence-based personalized oxygen saturation targets to guide oxygen administration in clinical care has the potential to improve outcomes.

Background:COPD is a leading diagnosis for hospital readmissions and a focus of the Centers for Medicare & Medicaid Services Hospital Readmission Reduction Program, which penalizes hospitals for avoidable readmissions. Research Question:Does a pharmacist-led evaluation and recommendation of chronic inhaler therapy before hospital discharge impact time to hospital readmission and emergency department (ED) visit? Study Design and Methods:A single-center randomized controlled trial at a large academic medical center enrolled admitted patients prescribed a long-acting inhaler. Patients received usual care or the intervention wherein a pharmacist reviewed inhaler therapy and provided recommendations for those with inappropriate therapy based on insurance formulary preference or clinical guidelines before discharge. The primary outcome was the combined time (days) to either hospital readmission or ED visit after hospitalization measured 6 months postdischarge. Similar analyses were performed for patients with and without COPD. Results:The study included 914 patients on long-acting inhaler therapy (56% with COPD and 33% with asthma). Fifty percent of patients were identified to have inappropriate inhaler therapy. The mean time to readmission/ED visit ± SD was 121 ± 71 days for the intervention arm and 117 ± 73 days for the usual care arm (hazard ratio [HR], 0.97; 95% CI, 0.79-1.18). Patients with COPD in the intervention arm had a lower risk of readmission/ED visit at both 30 days (HR, 0.63; 95% CI, 0.42-0.93) and 6 months (HR, 0.42; 95% CI, 0.28-0.64) compared with usual care; however, no difference was seen for patients without COPD at 30 days (HR, 1.18; 95% CI, 0.75-1.86; P = .468) and 6 months (HR, 1.5; 95% CI, 1.11-2.04; P = .009). Interpretation:In a group of patients receiving long-acting inhaler therapy for various indications, a significant reduction in risk of time to readmission/ED visit was not seen between the intervention and usual care groups. However, a significant reduction in risk of time to readmission/ED visit was observed for patients with COPD in the intervention group, suggesting an opportunity for pharmacist inhaler therapy review for financial and clinical appropriateness to reduce avoidable readmissions. Clinical Trial Registration:ClinicalTrials.gov; No.NCT03927820; URL: www.clinicaltrials.gov.

BACKGROUND: Laryngoscope blade size may affect successful intubation on the first attempt, but evidence to inform the optimal blade size for standard-geometry curved video laryngoscopes (VLs) in critically ill adults is limited. RESEARCH QUESTION: Does the use of a size 3 vs size 4 standard-geometry curved VL blade affect outcomes of tracheal intubation in critically ill adults? STUDY DESIGN AND METHODS: We performed a secondary analysis of data from 2 multicenter randomized trials conducted in ICUs and emergency departments (EDs) in the United States. We included adult patients who, on the first intubation attempt, received a standard-geometry curved VL blade of size 3 or 4. The primary outcome was the incidence of successful intubation on the first attempt. Secondary outcomes included the duration of the procedure, the lowest oxygen saturation, the incidence of severe hypoxemia, glottic view, and exploratory clinical outcomes. We used propensity score-based inverse probability of treatment weighting (IPTW) to adjust for baseline differences between groups. RESULTS: Of 1,220 patients, 517 patients (42%) were intubated with a size 3 blade and 703 patients (58%) were intubated with a size 4 blade. After IPTW adjustment, patients intubated with a size 3 blade and a size 4 blade did not differ regarding the incidence of successful intubation on the first attempt (84.6% vs 87.6%, respectively; adjusted OR, 0.78; 95% CI, 0.54-1.14). Procedure duration was similar (38.4 seconds vs 39.1 seconds; aHR, 0.97; 95% CI, 0.85-1.10). Complications and exploratory outcomes were comparable between groups. INTERPRETATION: Our results show that among critically ill adults undergoing emergency tracheal intubation with standard-geometry VLs, blade size (3 vs 4) was not associated with first-pass success or other major procedural and clinical outcomes.

OBJECTIVES:. Understanding the mechanistic impact of fostamatinib, a spleen tyrosine kinase inhibitor, in severe COVID-19 using biomarkers associated with disease severity is crucial for the development of host-directed therapeutics. We analyzed samples from a randomized clinical trial to investigate the impact of fostamatinib on multiple inflammatory biomarkers associated with COVID-19 disease severity. DESIGN:. Secondary analyses of biomarkers from a randomized clinical trial. SETTING:. Multicenter randomized clinical trial. PATIENTS:. A total of 400 adults hospitalized with COVID-19 were enrolled in a phase 3 randomized clinical trial. Absolute neutrophil counts (ANCs) were analyzed across 392 patients and biomarkers were measured in 190 patients with available plasma samples. INTERVENTIONS:. Adults hospitalized with COVID-19 were randomized to receive either fostamatinib (150 mg bid) or placebo. ANCs and 24 biomarkers were assessed at day 0 and over time using a multiplexed Meso Scale Discovery assay (Meso Scale Diagnostics LLC, Rockville, MD). MEASUREMENTS AND MAIN RESULTS:. At day 0, participants with World Health Organization ordinal scale 5–7 had elevated ANC counts, compared with ordinal scale 4. In addition, the levels of neutrophil-associated biomarkers, inflammatory cytokines, and mediators of endothelial dysfunction at day 0 were increased in the participants who were ordinal scale 5–7 vs. ordinal scale 4. Randomization to fostamatinib compared with placebo resulted in a decrease in ANC and several neutrophil-associated biomarkers, pro-inflammatory cytokines, and mediators of endothelial dysfunction/tissue damage. This differential finding was also demonstrated in a subgroup of patients (n = 85) with a hypoinflammatory phenotype. LIMITATIONS:. Missing plasma samples and neutral phase 3 trial results. CONCLUSIONS:. Randomization to fostamatinib resulted in lower neutrophil counts and levels of circulating biomarkers in hospitalized patients with COVID-19; however, the observed impact of fostamatinib was modest compared with prior studies.

For many of the decisions made in the clinical care setting, clinicians lack evidence to inform which treatment would result in the best patient outcomes. This problem is particularly common in emergency care, a field in which the condition of the patient and the urgent nature of the treatment often preclude research conducted using prospective informed consent. Large-scale comparative effectiveness clinical trials could address the evidence gaps in clinical medicine and improve patient outcomes but are hindered by the lack of a clear regulatory framework in the United States for low-to-minimal risk trials comparing commonly used treatments. In this paper, we summarize a presentation and discussion that took place at a workshop held by the National Institutes of Health that focused on the issue of informed consent and the appropriate regulatory pathway for comparative effectiveness trials conducted in the emergency care setting. A key insight of this workshop is that generating the comparative effectiveness data needed to improve clinical care will require revising ethical and regulatory oversight practices and related guidance to support the conduct of this socially valuable research.

Pragmatic trials can efficiently generate comparative effectiveness evidence by embedding delivery of interventions assigned by the trial with the people and systems of clinical care. Delivering assigned treatments with high fidelity is essential to generating informative trial results, but which factors affect clinicians’ adherence to assigned treatments in pragmatic trials is not known. Observational study assessing clinician perceptions of trial rationale, conduct, and interventions during a pragmatic, randomized trial of three ventilator modes (volume control vs. pressure control vs. adaptive pressure control) in a single intensive care unit. Clinicians were surveyed before and monthly during the 9-month trial. Survey instruments assessed readiness for the trial using the Hospital Change Readiness Questionnaire (scored from 7 to 49), Proctor’s Implementation Outcomes, and comfort with each mode on a Likert scale of 1–7. We hypothesized that perceptions would differ by ventilator mode, clinician type (respiratory therapists, advanced practice providers, fellow physicians, attending physicians) and over time. Comparisons between groups were performed by chi-squared and ANOVA tests, and tests for change over time were performed by generalized estimating equations. Overall, 82 of 120 clinicians (68

Importance:As SARS-CoV-2 JN.1 lineage descendants continue to evolve, evaluating COVID-19 vaccine effectiveness (VE) against severe COVID-19 remains important to guide vaccination strategies. Objective:To estimate the VE of the 2024-2025 COVID-19 vaccines against COVID-19-associated hospitalization and severe in-hospital outcomes overall and by time since dose (7-89, 90-179, and ≥180 days), JN.1 descendant lineage (KP.3.1.1, XEC, LP.8.1), and spike protein mutations associated with immune evasion. Design, Setting, and Participants:This multicenter, test-negative, case-control study conducted by the Investigating Respiratory Viruses in the Acutely Ill Network included adult patients (aged ≥18 years) hospitalized between September 1, 2024, and April 30, 2025, at 26 hospitals in 20 US states. Case patients presented with COVID-19-like illness and positive SARS-CoV-2 nucleic acid or antigen test results; control patients had COVID-19-like illness but tested negative for SARS-CoV-2. Exposure:Receipt of a 2024-2025 COVID-19 vaccine at least 7 days before illness onset. Main Outcomes and Measures:Main outcomes were COVID-19-associated hospitalization and severe in-hospital outcomes (supplemental oxygen therapy, acute respiratory failure, intensive care unit admission, and invasive mechanical ventilation or death). Logistic regression was used to estimate the odds of vaccination in case and control patients, adjusting for demographics, clinical characteristics, and enrollment region. The VE was estimated as (1 - adjusted odds ratio) × 100%. Results:A total of 8493 patients (median [IQR] age, 66 [54-76] years; 4338 female [51.1%]), including 1888 case patients with COVID-19 (among whom 951 [50.4%] had successful whole-genome sequencing, including 348 [36.6%] with KP.3.1.1, 218 [22.9%] with XEC, and 134 [14.1%] with LP.8.1 infections) and 6605 control patients were enrolled. Vaccine effectiveness against COVID-19-associated hospitalization was 40% (95% CI, 27%-51%), and protection was sustained through 90 to 179 days after vaccination. Vaccine effectiveness was higher against the most severe outcome of invasive mechanical ventilation or death at 79% (95% CI, 55%-92%). It was 49% (95% CI, 25%-67%) against hospitalization with KP.3.1.1, 34% (95% CI, 4%-56%) against XEC, and 24% (95% CI, -19% to 53%) against LP.8.1, with increasing median time since dose receipt among vaccinated case patients due to sequential circulation patterns (60, 89, and 141 days, respectively). The VE was similar against lineages with spike protein S31 deletion (41% [95% CI, 22%-56%]) and T22N and F59S substitutions (37% [95% CI, 9%-57%]). Conclusions and Relevance:In this multicenter, case-control analysis of VE, 2024-2025 COVID-19 vaccines may have provided protection against hospitalizations and severe in-hospital outcomes as multiple JN.1 descendant lineages circulated. Monitoring COVID-19 VE, including stratifying by SARS-CoV-2 lineage and spike protein mutations, remains important to guide COVID-19 vaccine composition and recommendations.

Introduction Due to widespread availability and familiarity, unfractionated heparin (UFH) is the most used intravenous anticoagulant for many indications in hospitalised patients. UFH, however, is a high-risk medication with complex pharmacokinetics and pharmacodynamics that are highly variable between different patients and within the same patients over time. The traditional titration and monitoring approach uses a clot-based assay, the activated partial thromboplastin time (aPTT), titrated to one and a half to two and a half times the upper limit of the normal range. Alternate assays indirectly measuring the anti-Xa level have not been compared with the aPTT for the monitoring of heparin in a prospective study. The optimal laboratory test for monitoring and adjusting heparin is not known. Our pragmatic study developed within the learning healthcare infrastructure is designed to answer this clinical question by comparing two established protocols for monitoring heparin in our hospital through a pragmatic randomised clinical trial. Methods and analysis The Comparison of Heparin Assay Monitoring Protocols (CHAMP) Trial is a single-centre, pragmatic, randomised trial conducted at Vanderbilt University Medical Centre (VUMC) beginning 26 June 2024. The CHAMP trial compares the aPTT protocol to the anti-Xa protocol for monitoring and titration of intravenous UFH for systemic anticoagulation in hospitalised adult patients. Admitted patients initiated on UFH protocols are assigned to either the aPTT or anti-Xa protocol in a randomised fashion. The primary outcome is time to reach the therapeutic anticoagulation range by coagulation assay. Secondary outcomes include the percent of measurements in the therapeutic range, the number of coagulation laboratory measurements over time, frequency of heparin rate changes while on the protocol and the incidence of thrombotic and clinically relevant bleeding events. Ethics, waiver of informed consent and dissemination The CHAMP trial is an ongoing pragmatic trial embedded into the current existing clinical workflow for heparin administration. The two protocols are considered clinically equivalent and already used in clinical practice, allowing for a waiver of consent approval (VUMC Institutional Review Board #232192). This waiver is critical to the implementation of the study due to the nature of scenarios and time constraints in which UFH is typically initiated. Partnering with nursing, pharmacy and clinical providers has been key to launching this study, which provides the first prospective, randomised, direct comparison of the two heparin laboratory protocols available for the monitoring and titration of intravenous UFH in hospitalised patients. After trial completion and data analysis, the findings of the CHAMP trial will be submitted to a peer-reviewed journal for consideration of publication for distribution to a broad clinical audience. Trial registration number The CHAMP study was registered on ClinicalTrials.gov (NCT identifier: NCT06329921 ) on 19 March 2024. The first patient was enrolled in the study on 26 June 2024, with enrolment of the planned 700 participants expected to occur over two years.

BACKGROUND:Assessing variant-specific coronavirus disease 2019 (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 US states admitted 18 October 2023-9 March 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:A total of 585 case-patients with XBB lineages, 397 case-patients with JN lineages, and 4580 control patients were included. VE in the first 7-89 days after receipt of an updated dose was 54.2% (95% confidence interval [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], .80; 95% CI, .46-1.38) and IMV or death (aOR, .69; 95% CI, .34-1.40) were not significantly different among JN compared with 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.