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.

Differential Effect of Positive End-Expiratory Pressure Strategies in Patients With ARDS: A Bayesian Analysis of Clinical Subphenotypes.

BACKGROUND: ARDS is a heterogeneous condition with two subphenotypes identified by different methodologies. Our group similarly identified two ARDS subphenotypes using nine routinely available clinical variables. However, whether these are associated with differential response to treatment has yet to be explored. RESEARCH QUESTION: Are there differential responses to positive end-expiratory pressure (PEEP) strategies on 28-day mortality according to subphenotypes in adult patients with ARDS? STUDY DESIGN AND METHODS: We evaluated data from two prior ARDS trials (Higher vs Lower Positive End-Expiratory Pressures in Patients With the ARDS [ALVEOLI] and ARDS Trial [ART]) that compared different PEEP strategies. We classified patients into one of two subphenotypes as described previously. We assessed the differential effect of PEEP with a Bayesian hierarchical logistic model for the primary outcome of 28-day mortality. RESULTS: We analyzed data from 1,559 patients with ARDS. Compared with lower PEEP, a higher PEEP strategy resulted in higher 28-day mortality in patients with subphenotype A disease in the ALVEOLI study (OR, 1.61; 95% credible interval [CrI], 0.90-2.94) and ART (OR, 1.73; 95% CrI, 1.01-2.98), with a probability of harm resulting from higher PEEP in this subphenotype of 94.3% and 97.7% in the ALVEOLI and ART studies, respectively. Higher PEEP was not associated with mortality in patients with subphenotype B disease in each trial (OR, 0.95 [95% CrI, 0.51-1.73] and 1.00 [95% CrI, 0.63-1.55], respectively), with probability of benefit of 56.4% and 50.7% in the ALVEOLI and ART studies, respectively. These effects were not modified by Pao2 to Fio2 ratio, driving pressure, or the severity of illness for the cohorts. INTERPRETATION: We found evidence of differential response to PEEP strategies across two ARDS subphenotypes, suggesting possible harm with a higher PEEP strategy in one subphenotype. These observations may assist with predictive enrichment in future clinical trials.

Comparison of Central and Peripheral Arterial Blood Pressure Gradients in Critically Ill Patients: A Systematic Review and Meta-Analysis.

OBJECTIVES: Measurement of blood pressure taken from different anatomical sites, are often perceived as interchangeable, despite them representing different parts of the systemic circulation. We aimed to perform a systematic review and meta-analysis on blood pressure differences between central and peripheral arterial cannulation in critically ill patients. DATA SOURCES: We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase from inception to December 26, 2023, using Medical Subject Headings (MeSH) terms and keywords. STUDY SELECTION: Observation study of adult patients in ICUs and operating rooms who underwent simultaneous central (femoral, axillary, or subclavian artery) and peripheral (radial, brachial, or dorsalis pedis artery) arterial catheter placement in ICUs and operating rooms. DATA EXTRACTION: We screened and extracted studies independently and in duplicate. We assessed risk of bias using the revised Quality Assessment for Studies of Diagnostic Accuracy tool. DATA SYNTHESIS: Twenty-four studies that enrolled 1598 patients in total were included. Central pressures (mean arterial pressure [MAP] and systolic blood pressure [SBP]) were found to be significantly higher than their peripheral counterparts, with mean gradients of 3.5 and 8.0 mm Hg, respectively. However, there was no statistically significant difference in central or peripheral diastolic blood pressure (DBP). Subgroup analysis further highlighted a higher MAP gradient during the on-cardiopulmonary bypass stage of cardiac surgery, reperfusion stage of liver transplant, and in nonsurgical critically ill patients. SBP or DBP gradient did not demonstrate any subgroup specific changes. CONCLUSIONS: SBP and MAP obtained by central arterial cannulation were higher than peripheral arterial cannulation; however, clinical implication of a difference of 8.0 mm Hg in SBP and 3.5 mm Hg in MAP remains unclear. Our current clinical practices preferring peripheral arterial lines need not change.

Validity of International Classification of Diseases, Tenth Revision, Codes for Atrial Fibrillation/Flutter in Critically Ill Patients with Sepsis.

BACKGROUND: Atrial fibrillation (AF) and atrial flutter (AFL) are frequently seen in critically ill sepsis patients and are associated with poor outcomes. There is a need for further research, however, studies are limited due to challenges in identifying patient cohorts. Administrative data using the International Classification of Diseases, Tenth Revision (ICD-10) are routinely used for identifying disease cohorts in large datasets. However, the validity of ICD-10 for AF/AFL remains unexplored in these populations. METHODS: This validation study included 6,554 adults with sepsis and septic shock admitted to the intensive care unit. We sought to determine whether ICD-10 coding could accurately identify patients with and without AF/AFL compared to manual chart review. We also evaluated whether the date of ICD-10 code entry could distinguish prevalent from incident AF/AFL, presuming codes dated during the index admission to be incident AF/AFL. A manual chart review was performed on 400 randomly selected patients for confirmation of AF/AFL, and validity was measured using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: Among the 400 randomly selected patients, 293 lacked ICD-10 codes for AF/AFL. The manual chart review confirmed the absence of AF/AFL in 286 patients (NPV 97.3%, specificity 99.7%). Among the 107 patients with ICD-10 codes for AF/AFL, 106 were confirmed to have AF/AFL by manual chart review (PPV 99.1%, sensitivity 93.0%). Out of the 114 patients with confirmed AF/AFL, 44 had ICD-10 codes dated during the index admission. All 44 were confirmed to have AF/AFL, however, 18 patients had prior documentation of AF/AFL (incident AF/AFL: PPV 59.1%). Specificity for incident (95.1%) and prevalent (99.7%) AF/AFL were high; however, sensitivity was 76.5% and 77.5%, respectively. DISCUSSION/CONCLUSION: ICD-10 codes perform well in identifying clinical AF/AFL in critically ill sepsis. However, their temporal specificity in distinguishing incidents from prevalent AF/AFL is limited.

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.

Research trends and hotspots in the field of electrical impedance tomography for mechanical ventilation: a bibliometric analysis.

Background: Electrical impedance tomography (EIT) is a relatively recent functional imaging technique that is both noninvasive and radiation free. EIT measures the associated voltage when a weak current is applied to the surface of the human body to determine the distribution of electrical resistance within tissues. We performed a bibliometrics-based review to explore the geographic hotspots of current research and future trends developing in the field of EIT for mechanical ventilation. Methods: The Web of Science database was searched from its inception to June 25, 2023. CiteSpace software was used to visualize and analyze the relevant literature and identify the most impactful literature, trends, and hotspots. Results: 363 articles describing EIT use in mechanical ventilation were identified. A fluctuating growth in the number of publications was observed from 1998 to 2023. Germany had the highest number of articles (n=154), followed by Italy (n=53) and China (n=52). A cluster analysis of keyword co-occurrence revealed that "titration", "ventilator-related lung injury", and "oxygenation" were the most actively researched terms associated with the use of EIT in mechanically ventilated patients. Conclusions: Significant progress has been made in EIT research for mechanical ventilation. EIT research is limited to a small number of countries with a present research focus on the prevention and treatment of ventilator-related lung injury, oxygenation status, and prone ventilation. These topics are expected to remain research hotspots in the future.

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.

Prevalence and prognosis of hyperdynamic left ventricular systolic function in septic patients: a systematic review and meta-analysis.

PURPOSE: The prevalence of hyperdynamic left ventricular (LV) systolic function in septic patients and its impact on mortality remain controversial. In this systematic review and meta-analysis, we investigated the prevalence and association of hyperdynamic LV systolic function with mortality in patients with sepsis. METHODS: We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase. Primary outcomes were the prevalence of hyperdynamic LV systolic function in adult septic patients and the associated short-term mortality as compared to normal LV systolic function. Hyperdynamic LV systolic function was defined using LV ejection fraction (LVEF) of 70% as cutoff. Secondary outcomes were heart rate, LV end-diastolic diameter (LVEDD), and E/e' ratio. RESULTS: Four studies were included, and the pooled prevalence of hyperdynamic LV systolic function was 18.2% ([95% confidence interval (CI) 12.5, 25.8]; I2 = 7.0%, P < 0.0001). Hyperdynamic LV systolic function was associated with higher mortality: odds ratio of 2.37 [95%CI 1.47, 3.80]; I2 = 79%, P < 0.01. No difference was found in E/e' (P = 0.43) between normal and hyperdynamic LV systolic function, while higher values of heart rate (mean difference: 6.14 beats/min [95%CI 3.59, 8.69]; I2 = 51%, P < 0.0001) and LVEDD (mean difference: - 0.21 cm [95%CI - 0.33, - 0.09]; I2 = 73%, P < 0.001) were detected in patients with hyperdynamic LV systolic function. CONCLUSION: The prevalence of hyperdynamic LV systolic function is not negligible in septic patients. Such a finding is associated with significantly higher short-term mortality as compared to normal LV systolic function.

Forecasting disease trajectories in critical illness: comparison of probabilistic dynamic systems to static models to predict patient status in the intensive care unit.

OBJECTIVE: Conventional prediction models fail to integrate the constantly evolving nature of critical illness. Alternative modelling approaches to study dynamic changes in critical illness progression are needed. We compare static risk prediction models to dynamic probabilistic models in early critical illness. DESIGN: We developed models to simulate disease trajectories of critically ill COVID-19 patients across different disease states. Eighty per cent of cases were randomly assigned to a training and 20% of the cases were used as a validation cohort. Conventional risk prediction models were developed to analyse different disease states for critically ill patients for the first 7 days of intensive care unit (ICU) stay. Daily disease state transitions were modelled using a series of multivariable, multinomial logistic regression models. A probabilistic dynamic systems modelling approach was used to predict disease trajectory over the first 7 days of an ICU admission. Forecast accuracy was assessed and simulated patient clinical trajectories were developed through our algorithm. SETTING AND PARTICIPANTS: We retrospectively studied patients admitted to a Cleveland Clinic Healthcare System in Ohio, for the treatment of COVID-19 from March 2020 to December 2022. RESULTS: 5241 patients were included in the analysis. For ICU days 2-7, the static (conventional) modelling approach, the accuracy of the models steadily decreased as a function of time, with area under the curve (AUC) for each health state below 0.8. But the dynamic forecasting approach improved its ability to predict as a function of time. AUC for the dynamic forecasting approach were all above 0.90 for ICU days 4-7 for all states. CONCLUSION: We demonstrated that modelling critical care outcomes as a dynamic system improved the forecasting accuracy of the disease state. Our model accurately identified different disease conditions and trajectories, with a <10% misclassification rate over the first week of critical illness.

Hemodynamic profile of cirrhotic patients with sepsis and septic shock: A propensity score matched case-control study.

PURPOSE: Our understanding of hemodynamics in cirrhotic patients with sepsis remains limited. Our study aims to investigate differences in hemodynamic profiles using echocardiography between septic patients with and without cirrhosis. MATERIALS AND METHODS: This is a single-center, retrospective study of septic patients with echocardiogram within 3 days of ICU admission. We compared baseline characteristics, echocardiographic markers of LV systolic function arterial load between patients with and without cirrhosis. A propensity score-matched case-control model was developed to describe the differences in those echocardiography derived parameters between the groups. RESULTS: 3151 patients with sepsis were included of which 422 (13%) had cirrhosis. In the propensity score matched group with 828 patients, cirrhotic patients had significantly higher left ventricular ejection fraction (64 vs.56%, p < 0.001) and stroke volume (72 vs.48 ml, p < 0.001) along with lower arterial elastance (Ea) (1.35 1vs.20.3, p < 0.001) and systemic vascular resistance (SVR) (851 vs.1209 dynes/s/m-5, p = 0.001). The left ventricular elastance (Ees) (2.83 vs 2.45, p = 0.002) was higher and ventricular-arterial coupling (Ea/Ees) (0.48 vs. 0.86, p < 0.001) lower in cirrhotic compared to non-cirrhotic. CONCLUSIONS: Septic patients with cirrhosis had higher LVEF with lower Ea and SVR with higher Ees and significantly lower Ea/Ees suggesting vasodilation as the principal driver of the hyperdynamic profile in cirrhosis.

Extracorporeal Carbon Dioxide Removal to Avoid Invasive Ventilation During Exacerbations of Chronic Obstructive Pulmonary Disease: VENT-AVOID Trial - A Randomized Clinical Trial.

Rationale: It is unclear whether extracorporeal CO2 removal (ECCO2R) can reduce the rate of intubation or the total time on invasive mechanical ventilation (IMV) in adults experiencing an exacerbation of chronic obstructive pulmonary disease (COPD). Objectives: To determine whether ECCO2R increases the number of ventilator-free days within the first 5 days postrandomization (VFD-5) in exacerbation of COPD in patients who are either failing noninvasive ventilation (NIV) or who are failing to wean from IMV. Methods: This randomized clinical trial was conducted in 41 U.S. institutions (2018-2022) (ClinicalTrials.gov ID: NCT03255057). Subjects were randomized to receive either standard care with venovenous ECCO2R (NIV stratum: n = 26; IMV stratum: n = 32) or standard care alone (NIV stratum: n = 22; IMV stratum: n = 33). Measurements and Main Results: The trial was stopped early because of slow enrollment and enrolled 113 subjects of the planned sample size of 180. There was no significant difference in the median VFD-5 between the arms controlled by strata (P = 0.36). In the NIV stratum, the median VFD-5 for both arms was 5 days (median shift = 0.0; 95% confidence interval [CI]: 0.0-0.0). In the IMV stratum, the median VFD-5 in the standard care and ECCO2R arms were 0.25 and 2 days, respectively; median shift = 0.00 (95% confidence interval: 0.00-1.25). In the NIV stratum, all-cause in-hospital mortality was significantly higher in the ECCO2R arm (22% vs. 0%, P = 0.02) with no difference in the IMV stratum (17% vs. 15%, P = 0.73). Conclusions: In subjects with exacerbation of COPD, the use of ECCO2R compared with standard care did not improve VFD-5. Clinical trial registered with www.clinicaltrials.gov (NCT03255057).

Impact of Sedation Practices on Mortality in COVID-19-Associated Adult Respiratory Distress Syndrome Patients: A Multicenter Retrospective Descriptive Study.

Background: Reduction in sedation exposure is an important metric in intensive care unit (ICU) patients. However, challenges arose during the coronavirus disease-2019 (COVID-19) pandemic in adhering to this practice, driven by concerns on transmission and disease severity issues. Accordingly, diverse sedation approaches emerged, although the effect on mortality has not been studied thoroughly. Methods: Retrospective cohort study in the medical ICU of seven hospitals within a major Health System in Northeast Ohio. We included all adult patients admitted with COVID-19 requiring invasive mechanical ventilation (IMV) from March 2020 to December 2021. Results: Study included 2394 COVID-19 patients requiring IMV. Across waves, sample included 55-63% male subjects, with an average age of 61-68 years (P < 0.001), Acute Physiologic and Chronic Health Evaluation (APACHE)-III score 65.8-68.9 (P = 0.37), median IMV duration 8-10 days (P = 0.14), and median ICU duration 9.8-11.6 days (P = 0.084). Propofol remained the primary sedative (84-92%; P = 0.089). Ketamine use increased from the first (9.7%) to fourth (19%) wave (P = 0.002). Midazolam use decreased from the first (27.4%) to third (9.4%) wave (P = 0.001). Dexmedetomidine use declined from 35% to 27-28% (P = 0.002) after the first wave. A multivariable regression analysis indicated clinical variables explained 34% of the variation in hospital mortality (R2). Factors associated with higher mortality included age [aOR = 1.059 (95% CI 1.049-1.069); P < 0.001], COVID-19 wave, especially fourth wave [aOR = 2.147, (95% CI 1.370-3.365); P = 0.001], and higher number of vasopressors [aOR = 31.636, (95% CI 17.603-56.856); P < 0.001]. Addition of sedative medications to a second model led to an increase in the R2 by only 1.6% to 35.6% [aOR = 1 (95% CI 1-1); P > 0.05] for propofol, ketamine, and midazolam. Dexmedetomidine demonstrated a decrease in the odds of mortality [aOR = 0.96 (95% CI 0.94-0.97); P < 0.001]. Conclusion: Mortality in critical COVID-19 patients was mostly driven by illness severity, and the choice of sedation might have minimal impact when other factors are controlled.

Structural Brain Injury on Brain Magnetic Resonance Imaging in Acute Respiratory Distress Syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is an acute inflammatory respiratory failure condition that may be associated with brain injury. We aimed to describe the types of structural brain injuries detected by brain magnetic resonance imaging (MRI) among patients with ARDS. METHODS: We retrospectively reviewed and collected data on brain injuries as detected by brain MRI during index hospitalization of all patients with ARDS at a single tertiary center in the United States from January 2010 to October 2018 (pre-COVID era). Structural brain injuries were classified as cerebral ischemia (ischemic infarct and hypoxic-ischemic brain injury) or cerebral hemorrhage (intraparenchymal hemorrhage, cerebral microbleeds, subarachnoid hemorrhage, and subdural hematoma). Descriptive statistics were conducted. RESULTS: Of the 678 patients with ARDS, 66 (9.7%) underwent brain MRI during their ARDS illness. The most common indication for brain MRI was encephalopathy (45.4%), and the median time from hospital admission to MRI was 10 days (interquartile range 4-17). Of 66 patients, 29 (44%) had MRI evidence of brain injury, including cerebral ischemia in 33% (22 of 66) and cerebral hemorrhage in 21% (14 of 66). Among those with cerebral ischemia, common findings were bilateral globus pallidus infarcts (n = 7, 32%), multifocal infarcts (n = 5, 23%), and diffuse hypoxic-ischemic brain injury (n = 3, 14%). Of those with cerebral hemorrhage, common findings were cerebral microbleeds (n = 12, 86%) and intraparenchymal hemorrhage (n = 2, 14%). Patients with ARDS with cerebral hemorrhage had significantly greater use of rescue therapies, including prone positioning (28.6% vs. 5.8%, p = 0.03), inhaled vasodilator (35.7% vs. 11.5%, p = 0.046), and recruitment maneuver (14.3% vs. 0%, p = 0.04). CONCLUSIONS: Structural brain injury was not uncommon among selected patients with ARDS who underwent brain MRI. The majority of brain injuries seen were bilateral globus pallidus infarcts and cerebral microbleeds.

Baricitinib versus tocilizumab in critically ill COVID-19 patients: A retrospective cohort study.

OBJECTIVES: The immunomodulators tocilizumab and baricitinib improve outcomes in severely ill patients with coronavirus disease 2019 (COVID-19); however, comparative analyses of clinical outcomes related to these agents are lacking. A tocilizumab national shortage shifted treatment to baricitinib in critically ill patients, allowing for an outcome comparison in a similar population. The purpose of this study is to compare clinical outcomes in critically ill COVID-19 patients who received tocilizumab and those who received baricitinib. DESIGN: Retrospective, observational cohort study using generalized estimating equation models, accounting for clustering by hospital and known confounders, to estimate the proportional odds of the ordinal World Health Organization Clinical Progression Scale (WHO-CPS) score at day 14, the primary outcome. Secondary outcomes included WHO-CPS score at day 7. SETTING: Multiple hospitals within the Cleveland Clinic Health System. PATIENTS: Adult patients admitted for COVID-19 between January 2021 and November 2021. INTERVENTIONS: Receipt of tocilizumab, before its shortage, or baricitinib, during shortage. MEASUREMENTS AND MAIN RESULTS: In total, 507 patients were included; 217 received tocilizumab and 290 received baricitinib. Over 96% of patients required ICU admission and 98% received concomitant dexamethasone. Tocilizumab recipients had higher (worse) baseline WHO-CPS scores. After adjustment, tocilizumab use was associated with higher odds of a worse day 14 WHO-CPS score compared with baricitinib (adjusted odds ratio [OR] 1.65 [95% confidence interval (CI) 1.10-2.48]). Similarly, after adjustment, tocilizumab use was associated with higher odds of a worse day 7 WHO-CPS score (adjusted OR 1.65 [95% CI 1.22-2.24]). CONCLUSIONS: Baricitinib use was associated with better WHO-CPS scores at day 14 and day 7 compared with tocilizumab in a cohort of critically ill patients with COVID-19. The odds of having a one unit increase in WHO-CPS score at day 14 was 71% higher with tocilizumab than baricitinib. No difference in mortality or adverse effects was noted.

Physical and Chemical Compatibility of Medications Commonly Used in Critically Ill Patients With Balanced Crystalloids: A Systematic Review.

OBJECTIVE: Evaluate available evidence of physical and/or chemical compatibility of commonly used medications in critically ill patients with balanced crystalloids. DATA SOURCES: Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews were queried from inception to September 2022. STUDY SELECTION AND DATA EXTRACTION: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. English-language studies reporting physical and/or chemical compatibility data between 50 selected medications and balanced crystalloids were included. A previously designed tool to assess risk of bias was adapted for use. DATA SYNTHESIS: Twenty-nine studies encompassing 39 (78%) medications and 188 unique combinations with balanced crystalloids were included. Combinations included 35 (70%) medications with lactated Ringer's, 26 (52%) medications with Plasma-Lyte, 10 (20%) medications with Normosol, and one (2%) medication with Isolyte. Studies commonly evaluated physical and chemical compatibility (55.2%). More medications were evaluated via Y-site than admixture. Incompatibilities were identified in 18% of combinations comprising 13 individual drugs. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This systematic review evaluates the compatibility of select critical care medications with balanced crystalloid solutions. Results may be used as a tool to guide clinicians on balanced crystalloid compatibility, potentially increasing ubiquitous use and reducing patient exposure to normal saline. CONCLUSION AND RELEVANCE: Data are limited regarding chemical/physical compatibility of commonly used medications in critically ill patients with balanced crystalloids. Additional compatibility studies are warranted, particularly methodologically rigorous studies assessing Plasma-Lyte, Normosol, and Isolyte. Of the evaluated medications, there was a low frequency of incompatibilities with balanced crystalloids.

Vaccine Effectiveness Against Influenza A-Associated Hospitalization, Organ Failure, and Death: United States, 2022-2023.

BACKGROUND: Influenza circulation during the 2022-2023 season in the United States largely returned to pre-coronavirus disease 2019 (COVID-19)-pandemic patterns and levels. Influenza A(H3N2) viruses were detected most frequently this season, predominately clade 3C.2a1b.2a, a close antigenic match to the vaccine strain. METHODS: To understand effectiveness of the 2022-2023 influenza vaccine against influenza-associated hospitalization, organ failure, and death, a multicenter sentinel surveillance network in the United States prospectively enrolled adults hospitalized with acute respiratory illness between 1 October 2022, and 28 February 2023. Using the test-negative design, vaccine effectiveness (VE) estimates against influenza-associated hospitalization, organ failures, and death were measured by comparing the odds of current-season influenza vaccination in influenza-positive case-patients and influenza-negative, SARS-CoV-2-negative control-patients. RESULTS: A total of 3707 patients, including 714 influenza cases (33% vaccinated) and 2993 influenza- and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative controls (49% vaccinated) were analyzed. VE against influenza-associated hospitalization was 37% (95% confidence interval [CI]: 27%-46%) and varied by age (18-64 years: 47% [30%-60%]; ≥65 years: 28% [10%-43%]), and virus (A[H3N2]: 29% [6%-46%], A[H1N1]: 47% [23%-64%]). VE against more severe influenza-associated outcomes included: 41% (29%-50%) against influenza with hypoxemia treated with supplemental oxygen; 65% (56%-72%) against influenza with respiratory, cardiovascular, or renal failure treated with organ support; and 66% (40%-81%) against influenza with respiratory failure treated with invasive mechanical ventilation. CONCLUSIONS: During an early 2022-2023 influenza season with a well-matched influenza vaccine, vaccination was associated with reduced risk of influenza-associated hospitalization and organ failure.

Antipsychotic Use for ICU Delirium and Associated Inflammatory Markers.

Purpose: We sought to evaluate critically ill patients with delirium to evaluate inflammatory cytokine production and delirium progression and the role of antipsychotics. Materials and Methods: Adult critically ill patients with confirmed delirium according to a positive CAM-ICU score were included and IL-6 and IL-8 levels were trended for 24 h in this single-center, prospective, observational cohort study. Results: A total of 23 patients were consented and had blood samples drawn for inclusion. There was no difference in IL-6 and IL-8 levels at baseline, 4 to 8 h, and 22 to 28 h after enrollment when comparing patients based on antipsychotic exposure. We identified 2 patient clusters based on age, APACHE III, need for mechanical ventilation, and concomitant infection. In cluster 1, 5 (33.3%) patients received antipsychotics versus 5 (62.5%) patients in cluster 2 (P = .18). Patients in cluster 1 had more co-inflammatory conditions (P < .0001), yet numerically lower baseline IL-6 (P = .18) and IL-8 levels (P = .80) compared to cluster 2. Patients in cluster 1 had a greater median number of delirium-free days compared to cluster 2 (17.0 vs 6.0 days; P = .05). Conclusions: In critically ill patients with delirium, IL-6 and IL-8 levels were variable and antipsychotics were not associated with improvements in delirium or inflammatory markers.