scholarly journals Effect of tocilizumab in hospitalized patients with severe pneumonia COVID-19: a cohort study

Author(s):  
Benjamin Rossi ◽  
Lee S Nguyen ◽  
Philippe Zimmermann ◽  
Faiza Boucenna ◽  
Louise Baucher ◽  
...  

Background. Tocilizumab, a drug targeting interleukin-6 administrated in the right timeframe may be beneficial in coronavirus-disease-2019 (COVID-19). We aimed to assess its benefit, drawing from observations in compassionately treated patients. Methods: In a retrospective case-control study, treatment effect (tocilizumab 400mg, single-dose) was assessed using three statistical methods: propensity-score matching, Cox multivariable survival and inverse probability score weighting (IPSW) analyses. Were included all patients hospitalized with COVID-19, who presented severity criteria with SpO2<96% despite O2-support >6L/min for more than 6 hours. Were excluded patients in critical care medicine department and those under invasive mechanical ventilation. Primary outcome was a composite of mortality and ventilation, with a maximum follow-up of 28 days. Results: 246 patients were included (106 treated by tocilizumab). They were 67.6 +/-15.3 years-old, with 95 (38.5%) women. Delay between first symptoms and inclusion was 8.4 +/-4.5 days. Overall, 105 (42.7%) patients presented the primary outcome, with 71 (28.9%) deaths during the 28-days follow-up. Propensity-score-matched 84 pairs of comparable patients. In the matched cohort (n=168), tocilizumab was associated with fewer primary outcomes (hazard ratio (HR)=0.49 (95% confidence interval (95CI)=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 (95CI=0.135-0.51, p=0.0001), confirmed by IPSW analysis (p<0.0001). Analyses on mortality with 28-days follow-up yielded similar results. Conclusion: In this retrospective study, tocilizumab single-dose was associated with improved survival without mechanical ventilation in patients with severe COVID-19.

2020 ◽  
Vol 13 (10) ◽  
pp. 317 ◽  
Author(s):  
Benjamin Rossi ◽  
Lee S. Nguyen ◽  
Philippe Zimmermann ◽  
Faiza Boucenna ◽  
Louis Dubret ◽  
...  

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.


2021 ◽  
Author(s):  
Angela McLigeyo ◽  
Jamilla Rajab ◽  
Peter Oyiro ◽  
Mohammed Ezzi ◽  
Yatich Bett ◽  
...  

Abstract Background Imatinib is the gold standard for the treatment of all phases of Philadelphia positive Chronic Myeloid Leukemia (CML). During treatment, patients may develop cytopenia. We aimed to study the baseline characteristics and factors associated with cytopenia at a Nairobi Hospital. Methods This was a retrospective case-control study of patients aged ≥ 18 years on follow-up at the Glivec International Patient Access Program (GIPAP) clinic from 2007–2015. The cases consisted of CML patients on imatinib who developed cytopenia. The controls were CML patients on imatinib who did not develop cytopenia. Baseline socio – demographic, clinical, hematologic, and molecular data were retrieved from patients’ files. Chi square or fishers’ exact tests were used to analyze for differences between cytopenia and no cytopenia. Binary logistic regressions were employed to identify relationships. Univariate and multivariate analyses were done to identify independent predictors of cytopenia. Odds ratios (OR) were presented including the 95% confidence intervals and respective p values. Results A total of 201 patients were studied. Males were 52%, 42% were aged 36–50 years, 70% had symptoms for > 12 months before diagnosis, 78.6% had B symptoms at baseline, 80% had a moderate splenomegaly at baseline, 40% and 37.4% developed cytopenia within 3 months and 3–6 months respectively after imatinib initiation. Baseline neutrophilia, neutropenia, anaemia, thrombocytosis, thrombocytopenia was found in 68%, 11%, 11%, 23.5% and 11% respectively. Baseline hemoglobin, neutrophil and platelet level were significantly different between the cytopenia and the no cytopenia group. On univariable analysis, baseline anemia with hb < 7.9g/dL (p = 0.002), neutropenia (p = 0.001), neutrophilia > 100,000/mm3 (p = 0.002) and thrombocytopenia (p = 0.001) increased the odds of developing cytopenia. On multivariable analysis, baseline anaemia (p value < 0.002), neutropenia (p value < 0.001), thrombocytopenia (p value, < 0.001) and thrombocytosis (p value, 0.033) increased the odds of developing cytopenia. Conclusion Odds of cytopenia were higher in presence of baseline cytopenia and thrombocytosis. Clinicians should have a high index of suspicion for these patients.


2021 ◽  
Author(s):  
Jiandong Zhou ◽  
Sharen Lee ◽  
Ishan Lakhani ◽  
Lei Yang ◽  
Tong Liu ◽  
...  

Abstract Background: Programmed death-1 (PD-1) and programmed death- ligand 1 (PD-L1) inhibitors, such as pembrolizumab, nivolumab and atezolizumab, are major classes of immune checkpoint inhibitors that are increasingly used for cancer treatment. However, their use is associated with adverse cardiovascular events. We examined the incidence of new-onset cardiac complications in patients receiving PD-1 or PD-L1 inhibitors.Methods: Patients receiving PD-1 or PD-L1 inhibitors since their launch up to 31st December 2019 at the Hospital Authority of Hong Kong, without pre-existing cardiac complications were included. The primary outcome was a composite of incident heart failure, acute myocardial infarction, atrial fibrillation or atrial flutter with the last follow-up date of 31st December 2020. Propensity score matching between PD-L1 inhibitor use and PD-1 inhibitor use with a 1:2 ratio for patient demographics, past comorbidities and non-PD-1/PD-L1 medications was performed.Results: A total of 1959 patients were included. Over a median follow-up of 247 days (interquartile range [IQR]: 72-506), 320 (incidence rate [IR]: 16.31%) patients met the primary outcome after PD-1/PD-L1 treatment: 244 (IR: 12.57%) with heart failure, 38 (IR: 1.93%) with acute myocardial infarction, 54 (IR: 2.75%) with atrial fibrillation, 6 (IR: 0.31%) with atrial flutter. Compared with PD-1 inhibitor treatment, PD-L1 inhibitor treatment was significantly associated with a lower risk of composite outcome both before (hazard ratio [HR]: 0.32, 95% CI: [0.18-0.59], P value=0.0002) and after matching (HR: 0.34, 95% CI: [0.18-0.65], P value=0.001), and lower all-cause mortality risk before matching (HR: 0.77, 95% CI: [0.64-0.93], P value=0.0078) and after matching (HR: 0.80, 95% CI: [0.65-1.00], P value=0.0463). Patients who developed cardiac complications had shorter average readmission intervals and a higher number of hospitalizations after treatment with PD-1/PD-L1 inhibitors both before and after matching (P value<0.0001). Competing risk analysis with cause-specific hazard and subdistribution hazard models, and multiple approaches based on the propensity score all confirmed these observations. Conclusions: Compared with PD-1 treatment, PD-L1 treatment was significantly associated with lower risk of new onset cardiac composite outcome and all-cause mortality both before and after propensity score matching.


Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
A. Ceccato ◽  
A. Russo ◽  
E. Barbeta ◽  
P. Oscanoa ◽  
G. Tiseo ◽  
...  

Abstract Background Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality worldwide despite correct antibiotic use. Corticosteroids have long been evaluated as a treatment option, but heterogeneous effects on survival have precluded their widespread implementation. We aimed to evaluate whether corticosteroids might improve clinical outcomes in patients with severe CAP and high inflammatory responses. Study design and methods We analyzed two prospective observational cohorts of patients with CAP in Barcelona and Rome who were admitted to intensive care with a high inflammatory response. Propensity score (PS) matching was used to obtain balance among the baseline variables in both groups, and we excluded patients with viral pneumonia or who received hydrocortisone. Results Of the 610 patients admitted with severe CAP, 198 (32%) received corticosteroids and 387 had major criteria for severe CAP. All patients had a baseline serum C-reactive protein above 15 mg/dL. Patients who received corticosteroids were more commonly male, had more comorbidities (e.g., cancer or chronic obstructive pulmonary disease), and presented with significantly higher sequential organ failure assessment scores. Eighty-nine patients met major severity criteria (invasive mechanical ventilation and/or septic shock) and were matched per group. Twenty-eight-day mortality was lower among patients receiving corticosteroids (16 patients, 18%) than among those not receiving them (28 patients, 31%; p = 0.037). After PS matching, corticosteroid therapy reduced the 28-day mortality risk in patients who met major severity criteria (hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.29–0.98) (p = 0.043). In patients who did not meet major severity criteria, no benefits were observed with corticosteroid use (HR 0.88 (95%CI 0.32–2.36). Conclusions Corticosteroid treatment may be of benefit for patients with CAP who have septic shock and/or a high inflammatory response and requirement for invasive mechanical ventilation. Corticosteroids appear to have no impact on mortality when these features are not present.


Neonatology ◽  
2021 ◽  
pp. 1-7
Author(s):  
Xingwang Zhu ◽  
Zhichun Feng ◽  
Chengjun Liu ◽  
Liping Shi ◽  
Yuan Shi ◽  
...  

<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.


2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Bo Yu ◽  
Victor Perez Gutierrez ◽  
Alex Carlos ◽  
Gregory Hoge ◽  
Anjana Pillai ◽  
...  

Abstract Background Hospitalized patients with COVID-19 demonstrate a higher risk of developing thromboembolism. Anticoagulation (AC) has been proposed for high-risk patients, even without confirmed thromboembolism. However, benefits and risks of AC are not well assessed due to insufficient clinical data. We performed a retrospective analysis of outcomes from AC in a large population of COVID-19 patients. Methods We retrospectively reviewed 1189 patients hospitalized for COVID-19 between March 5 and May 15, 2020, with primary outcomes of mortality, invasive mechanical ventilation, and major bleeding. Patients who received therapeutic AC for known indications were excluded. Propensity score matching of baseline characteristics and admission parameters was performed to minimize bias between cohorts. Results The analysis cohort included 973 patients. Forty-four patients who received therapeutic AC for confirmed thromboembolic events and atrial fibrillation were excluded. After propensity score matching, 133 patients received empiric therapeutic AC while 215 received low dose prophylactic AC. Overall, there was no difference in the rate of invasive mechanical ventilation (73.7% versus 65.6%, p = 0.133) or mortality (60.2% versus 60.9%, p = 0.885). However, among patients requiring invasive mechanical ventilation, empiric therapeutic AC was an independent predictor of lower mortality (hazard ratio [HR] 0.476, 95% confidence interval [CI] 0.345–0.657, p < 0.001) with longer median survival (14 days vs 8 days, p < 0.001), but these associations were not observed in the overall cohort (p = 0.063). Additionally, no significant difference in mortality was found between patients receiving empiric therapeutic AC versus prophylactic AC in various subgroups with different D-dimer level cutoffs. Patients who received therapeutic AC showed a higher incidence of major bleeding (13.8% vs 3.9%, p < 0.001). Furthermore, patients with a HAS-BLED score of ≥2 had a higher risk of mortality (HR 1.482, 95% CI 1.110–1.980, p = 0.008), while those with a score of ≥3 had a higher risk of major bleeding (Odds ratio: 1.883, CI: 1.114–3.729, p = 0.016). Conclusion Empiric use of therapeutic AC conferred survival benefit to patients requiring invasive mechanical ventilation, but did not show benefit in non-critically ill patients hospitalized for COVID-19. Careful bleeding risk estimation should be pursued before considering escalation of AC intensity.


PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0238552
Author(s):  
Ana C. Monteiro ◽  
Rajat Suri ◽  
Iheanacho O. Emeruwa ◽  
Robert J. Stretch ◽  
Roxana Y. Cortes-Lopez ◽  
...  

Purpose To describe the trajectory of respiratory failure in COVID-19 and explore factors associated with risk of invasive mechanical ventilation (IMV). Materials and methods A retrospective, observational cohort study of 112 inpatient adults diagnosed with COVID-19 between March 12 and April 16, 2020. Data were manually extracted from electronic medical records. Multivariable and Univariable regression were used to evaluate association between baseline characteristics, initial serum markers and the outcome of IMV. Results Our cohort had median age of 61 (IQR 45–74) and was 66% male. In-hospital mortality was 6% (7/112). ICU mortality was 12.8% (6/47), and 18% (5/28) for those requiring IMV. Obesity (OR 5.82, CI 1.74–19.48), former (OR 8.06, CI 1.51–43.06) and current smoking status (OR 10.33, CI 1.43–74.67) were associated with IMV after adjusting for age, sex, and high prevalence comorbidities by multivariable analysis. Initial absolute lymphocyte count (OR 0.33, CI 0.11–0.96), procalcitonin (OR 1.27, CI 1.02–1.57), IL-6 (OR 1.17, CI 1.03–1.33), ferritin (OR 1.05, CI 1.005–1.11), LDH (OR 1.57, 95% CI 1.13–2.17) and CRP (OR 1.13, CI 1.06–1.21), were associated with IMV by univariate analysis. Conclusions Obesity, smoking history, and elevated inflammatory markers were associated with increased need for IMV in patients with COVID-19.


PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252388
Author(s):  
Anis Saib ◽  
Walid Amara ◽  
Pascal Wang ◽  
Simon Cattan ◽  
Azeddine Dellal ◽  
...  

Background Hydroxychloroquine combined with azithromycin (HCQ/AZI) has initially been used against coronavirus disease-2019 (COVID-19). In this retrospective study, we assessed the clinical effects of HCQ/AZI, with a 28-days follow-up. Methods In a registry-study which included patients hospitalized for COVID-19 between March 15 and April 2, 2020, we compared patients who received HCQ/AZI to those who did not, regarding a composite outcome of mortality and mechanical ventilation with a 28-days follow-up. QT was monitored for patients treated with HCQ/AZI. Were excluded patients in intensive care units, palliative care and ventilated within 24 hours of admission. Three analyses were performed to adjust for selection bias: propensity score matching, multivariable survival, and inverse probability score weighting (IPSW) analyses. Results Overall, 203 patients were included: 60 patients treated by HCQ/AZI and 143 control patients. During the 28-days follow-up, 32 (16.3%) patients presented the primary outcome and 23 (12.3%) patients died. Propensity-score matching identified 52 unique pairs of patients with similar characteristics. In the matched cohort (n = 104), HCQ/AZI was not associated with the primary composite outcome (log-rank p-value = 0.16). In the overall cohort (n = 203), survival and IPSW analyses also found no benefit from HCQ/AZI. In the HCQ/AZI group, 11 (18.3%) patients prolonged QT interval duration, requiring treatment cessation. Conclusions HCQ/AZI combination therapy was not associated with lower in-hospital mortality and mechanical ventilation rate, with a 28-days follow-up. In the HCQ/AZI group, 18.3% of patients presented a prolonged QT interval requiring treatment cessation, however, control group was not monitored for this adverse event, making comparison impossible.


Author(s):  
Nicolás Merchante ◽  
Sheila Cárcel ◽  
José Carlos Garrido-Gracia ◽  
Marta Trigo-Rodríguez ◽  
María Ángeles Esteban Moreno ◽  
...  

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.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Dong Geum Shin ◽  
Hye-Jeong Lee ◽  
Junbeom Park ◽  
Young Jin Kim ◽  
Jae-Sun Uhm ◽  
...  

Background: Late gadolinium enhancement (LGE) by cardiac MR (CMR) has been related to adverse clinical outcomes in patients with nonischemic dilated cardiomyopathy (NIDC). But, a statistically significant association between LGE and arrhythmic risk in NIDC has not been demonstrated consistently. This study evaluated the impact of the presence, location and pattern of LGE on arrhythmic risk prediction in NICM. Methods: This study included 365 patients (54±15years) with NICM who underwent CMR. The extent, location and pattern of LGE were categorized. We analyzed for the primary outcome of ventricular arrhythmia (VA) including sustained or nonsustained ventricular tachycardia (VT), appropriate implantable cardioverter-defibrillator (ICD) intervention and ventricular fibrillation (VF). Cardiac death and hospitalization for heart failure (HF) were evaluated as secondary outcomes. Results: LGE was seen in 267 (73 %) patients. During median follow-up of 44±36 months, patients with LGE had higher incidence of cardiac death (15 % vs. 2 %, p<0.001), hospitalization for HF (40 % vs. 15 %, p<0.001) and VA (14% vs. 6%, p=0.03). In multivariable analysis, the presence of LGE (HR 2.78; 95% CI 1.10-7.02; p=0.03) was the independent predictor of arrhythmias. Patients with extensive LGE had higher VA (32% vs. 10%, p<0.001) with lower cumulative survival free of VA than those without extensive LGE (p=0.001). The frequent LGE location was as follows: LV septum 64%, LV-RV junction 42% and inferior 10%. VA was lower in patients with than without localized LGE limited to LV-RV junction (21% vs. 46%, p=0.005). Interestingly, while the incidence of ventricular arrhythmia was higher in patients with transmural LGE (29% vs. 10%, p=0.003), it was lower in those with patch LGE (2% vs. 16%, p=0.02) than the other patients. Conclusions: In patients with NICM, the LGE was an independent prognostic predictor of VA. Extensive LGE and specific location of LGE was related with the arrhythmic events.


Sign in / Sign up

Export Citation Format

Share Document