scholarly journals Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: results of the CHIC study

2020 ◽  
Vol 79 (9) ◽  
pp. 1143-1151 ◽  
Author(s):  
Sofia Ramiro ◽  
Rémy L M Mostard ◽  
César Magro-Checa ◽  
Christel M P van Dongen ◽  
Tom Dormans ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Hospital Mortality ◽  
Supportive Care ◽  
Primary Outcome ◽  
Invasive Mechanical Ventilation ◽  
Sensitivity Analyses ◽  
Control Group ◽  
High Dose ◽  
Cytokine Storm ◽  
Interleukin 6 Receptor

ObjectivesTo prospectively investigate in patients with severe COVID-19-associated cytokine storm syndrome (CSS) whether an intensive course of glucocorticoids with or without tocilizumab accelerates clinical improvement, reduces mortality and prevents invasive mechanical ventilation, in comparison with a historic control group of patients who received supportive care only.MethodsFrom 1 April 2020, patients with COVID-19-associated CSS, defined as rapid respiratory deterioration plus at least two out of three biomarkers with important elevations (C-reactive protein >100 mg/L; ferritin >900 µg/L; D-dimer >1500 µg/L), received high-dose intravenous methylprednisolone for 5 consecutive days (250 mg on day 1 followed by 80 mg on days 2–5). If the respiratory condition had not improved sufficiently (in 43%), the interleukin-6 receptor blocker tocilizumab (8 mg/kg body weight, single infusion) was added on or after day 2. Control patients with COVID-19-associated CSS (same definition) were retrospectively sampled from the pool of patients (n=350) admitted between 7 March and 31 March, and matched one to one to treated patients on sex and age. The primary outcome was ≥2 stages of improvement on a 7-item WHO-endorsed scale for trials in patients with severe influenza pneumonia, or discharge from the hospital. Secondary outcomes were hospital mortality and mechanical ventilation.ResultsAt baseline all patients with COVID-19 in the treatment group (n=86) and control group (n=86) had symptoms of CSS and faced acute respiratory failure. Treated patients had 79% higher likelihood on reaching the primary outcome (HR: 1.8; 95% CI 1.2 to 2.7) (7 days earlier), 65% less mortality (HR: 0.35; 95% CI 0.19 to 0.65) and 71% less invasive mechanical ventilation (HR: 0.29; 95% CI 0.14 to 0.65). Treatment effects remained constant in confounding and sensitivity analyses.ConclusionsA strategy involving a course of high-dose methylprednisolone, followed by tocilizumab if needed, may accelerate respiratory recovery, lower hospital mortality and reduce the likelihood of invasive mechanical ventilation in COVID-19-associated CSS.

Early Use of Sarilumab in Patients Hospitalised with COVID-19 Pneumonia and Features of Systemic Inflammation.

2021 ◽  
Author(s):  
Nicolás Merchante ◽  
Sheila Cárcel ◽  
José Carlos Garrido-Gracia ◽  
Marta Trigo-Rodríguez ◽  
María Ángeles Esteban Moreno ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Systemic Inflammation ◽  
Primary Outcome ◽  
Invasive Mechanical Ventilation ◽  
Control Group ◽  
Controlled Clinical Trial ◽  
Open Label ◽  
Randomized Controlled ◽  
Subcutaneous Dose ◽  
Early Use

In this phase II, open-label, randomized, controlled clinical trial of 115 patients hospitalized with COVID-19 and systemic inflammation, early use of sarilumab was associated with a low risk of acute respiratory distress syndrome requiring high-flow devices or mechanical ventilation. Objective: To investigate the efficacy and safety of early treatment with sarilumab, added to standard of care (SOC), in hospitalised adults with COVID-19. Methods: Phase II, open-label, randomized, controlled clinical trial of hospitalised patients with COVID-19 pneumonia and interleukin (IL)-6 levels ≥ 40 pg/mL and/or D-dimer > 1500 ng/mL. Participants were randomized (1:1:1) to receive SOC (control group), SOC plus a single subcutaneous dose of sarilumab 200 mg (Sarilumab-200) or SOC plus a single subcutaneous dose of sarilumab 400 mg (Sarilumab-400). The primary outcome variable was the development of acute respiratory distress syndrome (ARDS) requiring high-flow nasal oxygenation (HFNO), non-invasive mechanical ventilation (NIMV) or invasive mechanical ventilation (IMV) at day 28. Results: One-hundred and fifteen participants (control group, n = 39; Sarilumab-200, n = 37; Sarilumab-400, n = 39) were included. At randomization, 104 (90%) patients had supplemental oxygen and 103 (90%) received corticosteroids. Eleven (28%) patients in the control group, ten (27%) in Sarilumab-200 and five (13%) in Sarilumab-400 developed the primary outcome (hazard ratio [95% CI] of Sarilumab-400 vs control group: 0.41 [0.14-1.18]; p=0.09). Seven (6%) patients died: three in the control group and four in Sarilumab-200. There were no deaths in Sarilumab-400 (p = 0.079, log-rank test for comparisons with the control group). Conclusion: In patients recently hospitalised with COVID-19 pneumonia and features of systemic inflammation, early IL-6 blockade with a single dose of sarilumab 400 mg was safe and associated with a trend for better outcomes.

scholarly journals Effect of Tocilizumab in Hospitalized Patients with Severe COVID-19 Pneumonia: A Case-Control Cohort Study

2020 ◽  
Vol 13 (10) ◽  
pp. 317 ◽  
Author(s):  
Benjamin Rossi ◽  
Lee S. Nguyen ◽  
Philippe Zimmermann ◽  
Faiza Boucenna ◽  
Louis Dubret ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Cohort Study ◽  
Single Dose ◽  
Primary Outcome ◽  
Invasive Mechanical Ventilation ◽  
Multivariable Analysis ◽  
Control Group ◽  
Care Hospital ◽  
Primary Care Hospital

Tocilizumab, an anti-interleukin-6 receptor, administrated during the right timeframe may be beneficial against coronavirus-disease-2019 (COVID-19) pneumonia. All patients admitted for severe COVID-19 pneumonia (SpO2 ≤ 96% despite O2-support ≥ 6 L/min) without invasive mechanical ventilation were included in a retrospective cohort study in a primary care hospital. The treatment effect of a single-dose, 400 mg, of tocilizumab was assessed by comparing those who received tocilizumab to those who did not. Selection bias was mitigated using three statistical methods. Primary outcome measure was a composite of mortality and ventilation at day 28. A total of 246 patients were included (106 were treated with tocilizumab). Overall, 105 (42.7%) patients presented the primary outcome, with 71 (28.9%) deaths during the 28-day follow-up. Propensity-score-matched 84 pairs of comparable patients. In the matched cohort (n = 168), tocilizumab was associated with fewer primary outcomes than the control group (hazard ratio (HR) = 0.49 (95% confidence interval (95%CI) = 0.3–0.81), p-value = 0.005). These results were similar in the overall cohort (n = 246), with Cox multivariable analysis yielding a protective association between tocilizumab and primary outcome (adjusted HR = 0.26 (95%CI = 0.135–0.51, p = 0.0001), confirmed by inverse probability score weighting (IPSW) analysis (p < 0.0001). Analyses on mortality only, with 28 days of follow-up, yielded similar results. In this study, tocilizumab 400 mg in a single-dose was associated with improved survival without mechanical ventilation in patients with severe COVID-19.

Nasal High-Frequency Oscillatory Ventilation in Preterm Infants with Moderate Respiratory Distress Syndrome: A Multicenter Randomized Clinical Trial

Neonatology ◽  
2021 ◽  
pp. 1-7
Author(s):  
Xingwang Zhu ◽  
Zhichun Feng ◽  
Chengjun Liu ◽  
Liping Shi ◽  
Yuan Shi ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Respiratory Distress Syndrome ◽  
Preterm Infants ◽  
High Frequency ◽  
Primary Outcome ◽  
Distress Syndrome ◽  
Invasive Mechanical Ventilation ◽  
Risk Difference ◽  
High Frequency Oscillatory Ventilation ◽  
High Frequency Oscillatory

<b><i>Objective:</i></b> To determine whether nasal high-frequency oscillatory ventilation (NHFOV) as a primary mode of respiratory support as compared with nasal continuous airway pressure (NCPAP) will reduce the need for invasive mechanical ventilation in preterm infants (26<sup>0/7</sup>–33<sup>6/7</sup> weeks of gestational age [GA]) with respiratory distress syndrome (RDS). <b><i>Methods:</i></b> This multicenter randomized controlled trial was conducted in 18 tertiary neonatal intensive care units in China. A total of 302 preterm infants born at a GA of 26<sup>0/7</sup>–33<sup>6/7</sup> weeks with a diagnosis of RDS were randomly assigned to either the NCPAP (<i>n</i> = 150) or the NHFOV (<i>n</i> = 152) group. The primary outcome was the need for invasive mechanical ventilation during the first 7 days after birth. <b><i>Results:</i></b> Treatment failure occurred in 15 of 152 infants (9.9%) in the ­NHFOV group and in 26 of 150 infants (17.3%) in the NCPAP group (95% CI of risk difference: −15.2 to 0.4, <i>p =</i> 0.06). In the subgroup analysis, NHFOV resulted in a significantly lower rate of treatment failure than did NCPAP in the strata of 26<sup>+0/7</sup>–29<sup>+6/7</sup>weeks of GA (11.9 vs. 32.4%, 95% CI of risk difference: −39.3 to −1.7, <i>p =</i> 0.03) and birth weight &#x3c;1,500 g (10.4 vs. 29.6%, 95% CI of risk difference: −33.8 to −4.6, <i>p =</i> 0.01). The rate of thick secretions causing an airway obstruction was higher in the NHFOV group than in the NCPAP group (13.8 vs. 5.3%, 95% CI of risk difference: 1.9–15.1, <i>p =</i> 0.01). No significant differences in other secondary outcomes were found between the NHFOV and NCPAP groups. <b><i>Conclusions:</i></b> NHFOV was not superior to NCPAP with regard to the primary outcome when applied as the primary respiratory support for RDS in infants between 26<sup>+0/7</sup> and 33<sup>+6/7</sup> weeks of GA. In the subgroup analysis, NHFOV seemed to improve effectiveness than NCPAP in preterm infants &#x3c;30 weeks of GA.

scholarly journals 562. Tocilizumab for the Treatment of Severe COVID-19: A Retrospective, Multi-Center, Case-Matched Series

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S346-S346
Author(s):  
Sarah Norman ◽  
Sara Jones ◽  
David Reeves ◽  
Christian Cheatham
Keyword(s):  
Mechanical Ventilation ◽  
Length Of Stay ◽  
Hospital Mortality ◽  
Primary Outcome ◽  
Fungal Infections ◽  
Hospital Length ◽  
Hospitalized Patients ◽  
Hospital Length Of Stay ◽  
Matched Design ◽  
Median Hospital

Abstract Background At the time of this writing, there is no FDA approved medication for the treatment of COVID-19. One medication currently under investigation for COVID-19 treatment is tocilizumab, an interleukin-6 (IL-6) inhibitor. It has been shown there are increased levels of cytokines including IL-6 in severe COVID-19 hospitalized patients attributed to cytokine release syndrome (CRS). Therefore, inhibition of IL-6 receptors may lead to a reduction in cytokines and prevent progression of CRS. The purpose of this retrospective study is to utilize a case-matched design to investigate clinical outcomes associated with the use of tocilizumab in severe COVID-19 hospitalized patients. Methods This was a retrospective, multi-center, case-matched series matched 1:1 on age, BMI, and days since symptom onset. Inclusion criteria included ≥ 18 years of age, laboratory confirmed positive SARS-CoV-2 result, admitted to a community hospital from March 1st – May 8th, 2020, and received tocilizumab while admitted. The primary outcome was in-hospital mortality. Secondary outcomes included hospital length of stay, total mechanical ventilation days, mechanical ventilation mortality, and incidence of secondary bacterial or fungal infections. Results The following results are presented as tocilizumab vs control respectively. The primary outcome of in-hospital mortality for tocilizumab (n=26) vs control (n=26) was 10 (38%) vs 11 (42%) patients, p=0.777. The median hospital length of stay for tocilizumab vs control was 14 vs 11 days, p=0.275. The median days of mechanical ventilation for tocilizumab (n=21) vs control (n=15) was 8 vs 7 days, p=0.139, and the mechanical ventilation mortality was 10 (48%) vs 9 (60%) patients, p=0.463. In the tocilizumab group, for those expired (n=10) vs alive (n=16), 10 (100%) vs 7 (50%) patients respectively had a peak ferritin &gt; 600 ng/mL, and 6 (60%) vs 8 (50%) patients had a peak D-dimer &gt; 2,000 ng/mL. The incidence of secondary bacterial or fungal infections within 7 days of tocilizumab administration occurred in 5 (19%) patients. Conclusion These findings suggest that tocilizumab may be a beneficial treatment modality for severe COVID-19 patients. Larger, prospective, placebo-controlled trials are needed to further validate results. Disclosures Christian Cheatham, PharmD, BCIDP, Antimicrobial Resistance Solutions (Shareholder)

scholarly journals Association between the level of plasma B-type natriuretic peptide and in-hospital mortality in patients with acute exacerbation of COPD without a history of coronary ischemic heart disease: a retrospective study

2021 ◽  
Author(s):  
Jiyun Cui ◽  
Jie Liu ◽  
Jing Wang ◽  
Meng Lv ◽  
Chunyan Xing ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Heart Disease ◽  
Hospital Mortality ◽  
Ischemic Heart Disease ◽  
Natriuretic Peptide ◽  
Invasive Mechanical Ventilation ◽  
Ischemic Heart ◽  
Composite Outcome ◽  
History Of ◽  
Secondary Outcomes

Abstract Background: Previous studies suggested that plasma B-type natriuretic peptide (BNP) level was often elevated in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and was associated with increased mortality. However, most studies did not consider the fact that conditions such as coronary ischemic heart disease can also increase BNP level. Therefore, we aimed to explore the association between BNP level and in-hospital mortality in patients with AECOPD without a history of coronary ischemic heart disease.Methods: In this retrospective cohort study, patients who were diagnosed with AECOPD using International Statistical Classification of Diseases and Related Health Problems, Nineth Revision (ICD-9 codes) between January 2017 and December 2019. All data were obtained from electronic patient files and medical data intelligence platform of Jinan Central Hospital. BNP level was determined within 24 hours after admission, and the value was log2 transformed. The primary outcome was in-hospital mortality, and the secondary outcome was a composite outcome of in-hospital mortality or invasive mechanical ventilation.Results: A total of 300 patients were included in this study. Univariate cox regression analysis showed that the unadjusted HRs of the primary and secondary outcomes were 1.85 (95% CI, 1.39-2.47) and 1.45 (95% CI, 1.20-1.75), respectively. After adjustment for age, sex, past medical history, smoking status, drinking status, CURB65 (Confusion, Urea > 7mmol/L, Respiratory rate≥30/min, Blood pressure systolic < 90 mmHg or diastolic <60 mmHg and age > 65 years), arterial partial pressure of O2(PaO2), the adjusted HRs of the primary and secondary outcomes were 3.65 (95% CI, 2.54-5.26) and 1.43 (95% CI, 1.14-1.97), respectively. The results of subgroup analysis by age, sex, and lung function were robust. This study was retrospective, so there was no clinical trial registration.Conclusions: The plasma log2BNP level was significantly associated with in-hospital mortality and a composite outcome of in-hospital mortality or invasive mechanical ventilation.

Abstract 17292: Does Morbid Obesity Worsens Outcomes in COVID-19?

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sohaib Roomi ◽  
Waqas Ullah ◽  
Nayab Nadeem ◽  
Rehan Saeed ◽  
Donald Haas ◽  
...  
Keyword(s):  
Morbid Obesity ◽  
Mechanical Ventilation ◽  
Hospital Mortality ◽  
Invasive Mechanical Ventilation ◽  
Multivariate Logistic Regression Analysis ◽  
Odds Ratios ◽  
Increased Risk ◽  
Significant Difference ◽  
The Mean ◽  
Mean Differences

Introduction: Given the high prevalence of obesity around the globe, patients with coronavirus disease 2019 (COVID-19) are at an increased risk of devastating complications. Hypothesis: We hypothesize that morbid obesity is independently associated with increased risk of in-hospital mortality, upgrade to intensive care unit, invasive mechanical ventilation(IVM), and acute renal failure necessitating dialysis. Methods: A retrospective cohort study was performed to determine the association of basal metabolic index (BMI) with the above-mentioned outcomes. Independent t-test and multivariate logistic regression analysis were performed to calculate mean differences and adjusted odds ratios (aOR) with its 95% confidence interval (CI), respectively. Results: A total of 176 patients with confirmed COVID-19 diagnosis were included. The mean age was 62.2 years, with 51% of male patients. The mean BMI for non-surviving patients was significantly higher compared to patients surviving on the 7th day of hospitalization (35 vs. 30 kg/m2, p=0.022) and patients with a higher BMI had higher in-hospital mortality (21% vs. 9%, OR 3.2, 95% CI 1.3-8.2, p=0.01) compared to patients with a normal BMI. Similarly, patients requiring IMV had a higher BMI (33 vs. 29, p=0.002) compared to non-intubated patients. aOR of patients needing IMV (56% vs. 28%, OR 3.3, 95% CI 1.6-7.0, p=0.002) and upgrade to ICU (46% vs. 28%, OR 2.2, 1.07-4.6, p=0.04) were significantly higher compared to patients with a lower BMI. There was no significant difference between the two groups in terms of the need for dialysis (5% vs. 13%, OR 3.8, 13% vs. 4%, 1.1-14.1, p=0.07). Adjusted odds ratios controlled for baseline comorbidities and medications mirrored the overall results, except for the need to upgrade to ICU. Conclusions: In patients with confirmed COVID-19, morbid obesity serves as an independent risk factor of high in-hospital mortality and the need for invasive mechanical ventilation.

scholarly journals Effect of high-dose vitamin C therapy on severe burn patients: a nationwide cohort study

Critical Care ◽  
2019 ◽  
Vol 23 (1) ◽  
Author(s):  
Mikio Nakajima ◽  
Morita Kojiro ◽  
Shotaro Aso ◽  
Hiroki Matsui ◽  
Kiyohide Fushimi ◽  
...  
Keyword(s):  
Propensity Score ◽  
Vitamin C ◽  
Confidence Interval ◽  
Hospital Mortality ◽  
Control Group ◽  
High Dose ◽  
Burn Patients ◽  
Severe Burn ◽  
Severe Burns ◽  
High Dose Vitamin

Abstract Background Vitamin C is a well-documented antioxidant that reduces oxidative stress and fluid infusion in high doses; however, the association between high-dose vitamin C and reduced mortality remains unclear. This study evaluates the effect of high-dose vitamin C in severe burn patients under two varying thresholds. Methods We enrolled adult patients with severe burns (burn index ≥ 15) who were registered in the Japanese Diagnosis Procedure Combination national inpatient database from 2010 to 2016. Propensity score matching was performed between patients who received high-dose vitamin C within 1 day of admission (vitamin C group) and those who did not (control group). High-dose vitamin C was defined as a dosage in excess of 10 g or 24 g within 2 days of admission. The primary outcome was in-hospital mortality. Results Eligible patients (n = 2713) were categorized into the vitamin C group (n = 157) or control group (n = 2556). After 1:4 propensity score matching, we compared 157 and 628 patients who were administered high-dose vitamin C (> 10-g threshold) and controls, respectively. Under this particular threshold, high-dose vitamin C therapy was associated with reduced in-hospital mortality (risk ratio, 0.79; 95% confidence interval, 0.66–0.95; p = 0.006). In contrast, in-hospital mortality did not differ between the control and high-dose vitamin C group under the > 24-g threshold (risk ratio, 0.83; 95% confidence interval, 0.68–1.02; p = 0.068). Conclusions High-dose vitamin C therapy was associated with reduced mortality in patients with severe burns when used under a minimum threshold of 10 g within the first 2 days of admission. While “high-dose” vitamin C therapy lacks a universal definition, the present study reveals that different “high-dose” regimens may yield improved outcomes.

scholarly journals Clinical and paraclinical predictive factors for in-hospital mortality in adult patients with COVID-19

2021 ◽  
Author(s):  
Seyed Alireza Mousavi ◽  
Reyhaneh Sadat Mousavi-Roknabadi ◽  
Fateme Nemati ◽  
Somaye Pourteimoori ◽  
Arefeh Ghorbani ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Hospital Mortality ◽  
Ct Scan ◽  
Predictive Factors ◽  
Invasive Mechanical Ventilation ◽  
Cross Sectional Study ◽  
Study Data ◽  
Cross Sectional ◽  
Factors Affecting ◽  
Non Invasive

Abstract Background Since December 2019, a type of coronavirus has emerged in Wuhan, China, which has become the focus of global attention due to an epidemic of pneumonia of unknown cause, called COVID-19. This study aimed to investigate the factors affecting in-hospital mortality of patients with COVID-19 hospitalized in one of the main hospital in central Iran. Methods This retrospective cross-sectional study (February 2019-May 2020) was conducted on patients with confirmed diagnosis COVID-19, who were admitted in Yazd Shahid Sadoughi Hospital, in middle of Iran. The patients with uncompleted or missed medical files were excluded from the study. Data were extracted from the patients' medical files and then analyzed. The patients were categorized as survivors and non-survivors groups, and they were compared. Results Totally, 573 patients were enrolled, that 356 (62.2%) were male. The mean ± SD of age was 56.29 ± 17.53 years, and 93 (16.23%) were died. All the complications were more in non-survivors. Intensive care unit (ICU) admission was in 20.5% of the patients which was more in non-survivors (P < 0.001). The results of multivariate logistic regression test showed that plural effusion in lung computed tomography (CT) scan (OR = 0.055, P = 0.009), white blood cell (WBC) (OR = 1.417, P = 0.022), serum albumin (OR = 0.009, P < 0.001), non-invasive mechanical ventilation (OR = 34.315, P < 0.001), and acute respiratory distress syndrome (ARDS) (OR = 66.039, P = 0.001) were achieved as the predictive factors for in-hospital mortality were the predictive factors for in-hospital mortality. Conclusion In-hospital mortality in patients with COVID-19 was about 16%. Plural effusion in lung CT scan, WBC, albumin, non-invasive mechanical ventilation, and ARDS were obtained as the predictive factors for in-hospital mortality.

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