; for the CORIMUNO-19 Collaborative Group IMPORTANCE Severe pneumonia with hyperinflammation and elevated interleukin-6 is a common presentation of coronavirus disease 2019 (COVID-19). OBJECTIVE To determine whether tocilizumab (TCZ) improves outcomes of patients hospitalized with moderate-to-severe COVID-19 pneumonia. DESIGN, SETTING, AND PARTICPANTS This cohort-embedded, investigator-initiated, multicenter, open-label, bayesian randomized clinical trial investigating patients with COVID-19 and moderate or severe pneumonia requiring at least 3 L/min of oxygen but without ventilation or admission to the intensive care unit was conducted between March 31, 2020, to April 18, 2020, with follow-up through 28 days. Patients were recruited from 9 university hospitals in France. Analyses were performed on an intention-to-treat basis with no correction for multiplicity for secondary outcomes. INTERVENTIONS Patients were randomly assigned to receive TCZ, 8 mg/kg, intravenously plus usual care on day 1 and on day 3 if clinically indicated (TCZ group) or to receive usual care alone (UC group). Usual care included antibiotic agents, antiviral agents, corticosteroids, vasopressor support, and anticoagulants. MAIN OUTCOMES AND MEASURES Primary outcomes were scores higher than 5 on the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) on day 4 and survival without need of ventilation (including noninvasive ventilation) at day 14. Secondary outcomes were clinical status assessed with the WHO-CPS scores at day 7 and day 14, overall survival, time to discharge, time to oxygen supply independency, biological factors such as C-reactive protein level, and adverse events. RESULTS Of 131 patients, 64 patients were randomly assigned to the TCZ group and 67 to UC group; 1 patient in the TCZ group withdrew consent and was not included in the analysis. Of the 130 patients, 42 were women (32%), and median (interquartile range) age was 64 (57.1-74.3) years. In the TCZ group, 12 patients had a WHO-CPS score greater than 5 at day 4 vs 19 in the UC group (median posterior absolute risk difference [ARD] −9.0%; 90% credible interval [CrI], −21.0 to 3.1), with a posterior probability of negative ARD of 89.0% not achieving the 95% predefined efficacy threshold. At day 14, 12% (95% CI −28% to 4%) fewer patients needed noninvasive ventilation (NIV) or mechanical ventilation (MV) or died in the TCZ group than in the UC group (24% vs 36%, median posterior hazard ratio [HR] 0.58; 90% CrI, 0.33-1.00), with a posterior probability of HR less than 1 of 95.0%, achieving the predefined efficacy threshold. The HR for MV or death was 0.58 (90% CrI, 0.30 to 1.09). At day 28, 7 patients had died in the TCZ group and 8 in the UC group (adjusted HR, 0.92; 95% CI 0.33-2.53). Serious adverse events occurred in 20 (32%) patients in the TCZ group and 29 (43%) in the UC group (P = .21). CONCLUSIONS AND RELEVANCE In this randomized clinical trial of patients with COVID-19 and pneumonia requiring oxygen support but not admitted to the intensive care...
Idiopathic acute eosinophilic pneumonia (IAEP) is characterized by acute febrile respiratory failure associated with diffuse radiographic infiltrates and pulmonary eosinophilia. We conducted a multicenter retrospective study to characterize this rare clinical entity further and to improve its diagnostic criteria. A total of 13 male and 9 female patients (mean age: 29 +/- 15.8 years) presented with severe hypoxemia (Pa(O2)/fraction of inspired oxygen ratio = 156 +/- 74.1) requiring mechanical ventilation in 14 cases. Bronchoalveolar lavage was performed on all patients and showed 54.4 +/- 19.2% eosinophils on differential cell count, but no open-lung biopsies were done. No clinical differences were found between patients seen at less than 7 days (n = 15) or at 7 to 31 days (n = 7) from the onset of IAEP. A total of 12 patients met the clinical criteria of acute lung injury, and eight of these patients met the criteria for acute respiratory distress syndrome. All patients recovered, either spontaneously (6) or on corticosteroid treatment (16). No relapses occurred. We conclude that: (1) diagnostic criteria of IAEP are compatible with a duration of symptoms for up to 1 month, but the response to corticosteroid treatment is not diagnostic because of possible spontaneous recovery; (2) IAEP should be considered as differential diagnosis of acute lung injury or acute respiratory distress syndrome; (3) bronchoalveolar lavage eosinophilia obviates the need for lung biopsy in IAEP.
Comprehension and satisfaction are relevant criteria for evaluating the effectiveness of information provided to family members of intensive care unit (ICU) patients. We performed a prospective randomized trial in 34 French ICUs to compare comprehension of diagnosis, prognosis, treatment, and satisfaction with information provided by ICU caregivers, in ICU patient family representatives who did (n = 87) or did not (n = 88) receive a family information leaflet (FIL) in addition to standard information. An FIL designed specifically for this study was delivered at the first visit of the family representative: it provided general information on the ICU and hospital, the name of the ICU physician caring for the patient, a diagram of a typical ICU room with the names of all the devices, and a glossary of 12 terms commonly used in ICUs. Characteristics of the ICUs, patients, and family representatives were similar in the two groups. The FIL reduced the proportion of family members with poor comprehension from 40.9% to 11.5% (p < 0.0001). In the representatives with good comprehension, the FIL was associated with significantly better satisfaction (21 [18 to 24, quartiles] versus 27 [24 to 29, quartiles], p = 0.01). These results indicate that ICU caregivers should consider using an FIL to improve the effectiveness of the information they impart to families.
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