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      Threshold of increase in oxygen demand to predict mechanical ventilation use in novel coronavirus disease 2019: A retrospective cohort study incorporating restricted cubic spline regression

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          Abstract

          Background

          Rapid deterioration of oxygenation occurs in novel coronavirus disease 2019 (COVID-19), and prediction of mechanical ventilation (MV) is needed for allocation of patients to intensive care unit. Since intubation is usually decided based on varying clinical conditions, such as required oxygen changes, we aimed to elucidate thresholds of increase in oxygen demand to predict MV use within 12 h.

          Methods

          A single-center retrospective cohort study using data between January 2020 and January 2021was conducted. Data were retrieved from the hospital data warehouse. Adult patients diagnosed with COVID-19 with a positive polymerase chain reaction (PCR) who needed oxygen during admission were included. Hourly increments in oxygen demand were calculated using two consecutive oxygen values. Covariates were selected from measurements at the closest time points of oxygen data. Prediction of MV use within 12 h by required oxygen changes was evaluated with the area under the receiver operating curves (AUCs). A threshold for increased MV use risk was obtained from restricted cubic spline curves.

          Results

          Among 66 eligible patients, 1835 oxygen data were analyzed. The AUC was 0.756 for predicting MV by oxygen demand changes, 0.888 by both amounts and changes in oxygen, and 0.933 by the model adjusted with respiratory rate, PCR quantification cycle (Ct), and days from PCR. The threshold of increments of required oxygen was identified as 0.44 L/min/h and the probability of MV use linearly increased afterward. In subgroup analyses, the threshold was lower (0.25 L/min/h) when tachypnea or frequent respiratory distress existed, whereas it was higher (1.00 L/min/h) when viral load is low (Ct ≥20 or days from PCR >7 days).

          Conclusions

          Hourly changes in oxygen demand predicted MV use within 12 h, with a threshold of 0.44 L/min/h. This threshold was lower with an unstable respiratory condition and higher with a low viral load.

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          Most cited references29

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          Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report

          Abstract Background Coronavirus disease 2019 (Covid-19) is associated with diffuse lung damage. Glucocorticoids may modulate inflammation-mediated lung injury and thereby reduce progression to respiratory failure and death. Methods In this controlled, open-label trial comparing a range of possible treatments in patients who were hospitalized with Covid-19, we randomly assigned patients to receive oral or intravenous dexamethasone (at a dose of 6 mg once daily) for up to 10 days or to receive usual care alone. The primary outcome was 28-day mortality. Here, we report the preliminary results of this comparison. Results A total of 2104 patients were assigned to receive dexamethasone and 4321 to receive usual care. Overall, 482 patients (22.9%) in the dexamethasone group and 1110 patients (25.7%) in the usual care group died within 28 days after randomization (age-adjusted rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93; P<0.001). The proportional and absolute between-group differences in mortality varied considerably according to the level of respiratory support that the patients were receiving at the time of randomization. In the dexamethasone group, the incidence of death was lower than that in the usual care group among patients receiving invasive mechanical ventilation (29.3% vs. 41.4%; rate ratio, 0.64; 95% CI, 0.51 to 0.81) and among those receiving oxygen without invasive mechanical ventilation (23.3% vs. 26.2%; rate ratio, 0.82; 95% CI, 0.72 to 0.94) but not among those who were receiving no respiratory support at randomization (17.8% vs. 14.0%; rate ratio, 1.19; 95% CI, 0.91 to 1.55). Conclusions In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. (Funded by the Medical Research Council and National Institute for Health Research and others; RECOVERY ClinicalTrials.gov number, NCT04381936; ISRCTN number, 50189673.)
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            Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area

            There is limited information describing the presenting characteristics and outcomes of US patients requiring hospitalization for coronavirus disease 2019 (COVID-19).
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              Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial

              Summary Background No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models. Methods We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2–10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir–ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656. Findings Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87–1·75]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95–2·43]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early. Interpretation In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies. Funding Chinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: Project administrationRole: Writing – review & editing
                Role: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: MethodologyRole: Writing – review & editing
                Role: SupervisionRole: ValidationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                14 July 2022
                2022
                : 17
                : 7
                : e0269876
                Affiliations
                [1 ] Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Tokyo, Japan
                [2 ] Clinical and Translational Research Center, Keio University Hospital, Tokyo, Japan
                Tanta University Faculty of Medicine, EGYPT
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                ¶ Membership of the Keio Donner Project is listed in the Acknowledgments.

                Author information
                https://orcid.org/0000-0001-8772-9600
                https://orcid.org/0000-0002-3733-7411
                https://orcid.org/0000-0002-5190-8524
                Article
                PONE-D-22-06778
                10.1371/journal.pone.0269876
                9282654
                35834478
                635fe56f-2558-43a3-b564-2f94bc3098ec
                © 2022 Yamamoto et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 7 March 2022
                : 29 May 2022
                Page count
                Figures: 3, Tables: 4, Pages: 14
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Physical Sciences
                Chemistry
                Chemical Elements
                Oxygen
                Medicine and Health Sciences
                Medical Conditions
                Infectious Diseases
                Viral Diseases
                Covid 19
                Biology and Life Sciences
                Molecular Biology
                Molecular Biology Techniques
                Artificial Gene Amplification and Extension
                Polymerase Chain Reaction
                Research and Analysis Methods
                Molecular Biology Techniques
                Artificial Gene Amplification and Extension
                Polymerase Chain Reaction
                Biology and Life Sciences
                Physiology
                Physiological Processes
                Respiration
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Intubation
                Biology and life sciences
                Organisms
                Viruses
                RNA viruses
                Coronaviruses
                SARS coronavirus
                SARS CoV 2
                Biology and life sciences
                Microbiology
                Medical microbiology
                Microbial pathogens
                Viral pathogens
                Coronaviruses
                SARS coronavirus
                SARS CoV 2
                Medicine and health sciences
                Pathology and laboratory medicine
                Pathogens
                Microbial pathogens
                Viral pathogens
                Coronaviruses
                SARS coronavirus
                SARS CoV 2
                Biology and life sciences
                Organisms
                Viruses
                Viral pathogens
                Coronaviruses
                SARS coronavirus
                SARS CoV 2
                Medicine and Health Sciences
                Epidemiology
                Medical Risk Factors
                Biology and Life Sciences
                Microbiology
                Virology
                Viral Transmission and Infection
                Viral Load
                Custom metadata
                The data of this study are available from the Donner Registry of the Keio Donner Project; however, restrictions apply to the availability of these data, which were used under a license for the current study, so they are not publicly available. However, data are available from the Keio Donner Project at Keio University School of Medicine (contact via email: sayuri.z2@ 123456keio.jp ) for researchers who meet the criteria for access to confidential data.

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