Hydrocortisone in Severe Community-Acquired Pneumonia.

BACKGROUND: Whether the antiinflammatory and immunomodulatory effects of glucocorticoids may decrease mortality among patients with severe community-acquired pneumonia is unclear. METHODS: In this phase 3, multicenter, double-blind, randomized, controlled trial, we assigned adults who had been admitted to the intensive care unit (ICU) for severe community-acquired pneumonia to receive intravenous hydrocortisone (200 mg daily for either 4 or 7 days as determined by clinical improvement, followed by tapering for a total of 8 or 14 days) or to receive placebo. All the patients received standard therapy, including antibiotics and supportive care. The primary outcome was death at 28 days. RESULTS: A total of 800 patients had undergone randomization when the trial was stopped after the second planned interim analysis. Data from 795 patients were analyzed. By day 28, death had occurred in 25 of 400 patients (6.2%; 95% confidence interval [CI], 3.9 to 8.6) in the hydrocortisone group and in 47 of 395 patients (11.9%; 95% CI, 8.7 to 15.1) in the placebo group (absolute difference, -5.6 percentage points; 95% CI, -9.6 to -1.7; P = 0.006). Among the patients who were not undergoing mechanical ventilation at baseline, endotracheal intubation was performed in 40 of 222 (18.0%) in the hydrocortisone group and in 65 of 220 (29.5%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.40 to 0.86). Among the patients who were not receiving vasopressors at baseline, such therapy was initiated by day 28 in 55 of 359 (15.3%) of the hydrocortisone group and in 86 of 344 (25.0%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.43 to 0.82). The frequencies of hospital-acquired infections and gastrointestinal bleeding were similar in the two groups; patients in the hydrocortisone group received higher daily doses of insulin during the first week of treatment. CONCLUSIONS: Among patients with severe community-acquired pneumonia being treated in the ICU, those who received hydrocortisone had a lower risk of death by day 28 than those who received placebo. (Funded by the French Ministry of Health; CAPE COD ClinicalTrials.gov number, NCT02517489.).

[ECRIN standard requirements for good clinical practices-compliant data management in multinational clinical trials]. / Référentiel ECRIN pour la conformité aux bonnes pratiques de gestion des données des essais cliniques multinationaux.

CONTEXT: Clinical studies involve an increasing amount of data collection and management. However, there is no specific quality standard sufficiently practical, in free access, and open for data management and the underlying IT-infrastructure in academic units. European Clinical Research Infrastructures Network (ECRIN) published standard requirements for certified data management units. We present a French version of these standards. METHODS: A group of experts produced the standards, by consensus. The first version was revised after two pilot audits for data centre certification were performed. RESULTS: The revised version includes 21 lists of five to ten standards, in three groups: information technologies, data management (DM) and "general". CONCLUSIONS: These standards offer a clear description of DM and IT requirements for clinical studies. Initially created for ECRIN certification purposes, they offer a very useful reference for academic DM structures.

Effect of Hydrocortisone on 21-Day Mortality or Respiratory Support Among Critically Ill Patients With COVID-19: A Randomized Clinical Trial.

Importance: Coronavirus disease 2019 (COVID-19) is associated with severe lung damage. Corticosteroids are a possible therapeutic option. Objective: To determine the effect of hydrocortisone on treatment failure on day 21 in critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute respiratory failure. Design, Setting, and Participants: Multicenter randomized double-blind sequential trial conducted in France, with interim analyses planned every 50 patients. Patients admitted to the intensive care unit (ICU) for COVID-19-related acute respiratory failure were enrolled from March 7 to June 1, 2020, with last follow-up on June 29, 2020. The study intended to enroll 290 patients but was stopped early following the recommendation of the data and safety monitoring board. Interventions: Patients were randomized to receive low-dose hydrocortisone (n = 76) or placebo (n = 73). Main Outcomes and Measures: The primary outcome, treatment failure on day 21, was defined as death or persistent dependency on mechanical ventilation or high-flow oxygen therapy. Prespecified secondary outcomes included the need for tracheal intubation (among patients not intubated at baseline); cumulative incidences (until day 21) of prone position sessions, extracorporeal membrane oxygenation, and inhaled nitric oxide; Pao2:Fio2 ratio measured daily from day 1 to day 7, then on days 14 and 21; and the proportion of patients with secondary infections during their ICU stay. Results: The study was stopped after 149 patients (mean age, 62.2 years; 30.2% women; 81.2% mechanically ventilated) were enrolled. One hundred forty-eight patients (99.3%) completed the study, and there were 69 treatment failure events, including 11 deaths in the hydrocortisone group and 20 deaths in the placebo group. The primary outcome, treatment failure on day 21, occurred in 32 of 76 patients (42.1%) in the hydrocortisone group compared with 37 of 73 (50.7%) in the placebo group (difference of proportions, -8.6% [95.48% CI, -24.9% to 7.7%]; P = .29). Of the 4 prespecified secondary outcomes, none showed a significant difference. No serious adverse events were related to the study treatment. Conclusions and Relevance: In this study of critically ill patients with COVID-19 and acute respiratory failure, low-dose hydrocortisone, compared with placebo, did not significantly reduce treatment failure (defined as death or persistent respiratory support) at day 21. However, the study was stopped early and likely was underpowered to find a statistically and clinically important difference in the primary outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT02517489.

Evaluation of 16S rRNA gene PCR sensitivity and specificity for diagnosis of prosthetic joint infection: a prospective multicenter cross-sectional study.

There is no standard method for the diagnosis of prosthetic joint infection (PJI). The contribution of 16S rRNA gene PCR sequencing on a routine basis remains to be defined. We performed a prospective multicenter study to assess the contributions of 16S rRNA gene assays in PJI diagnosis. Over a 2-year period, all patients suspected to have PJIs and a few uninfected patients undergoing primary arthroplasty (control group) were included. Five perioperative samples per patient were collected for culture and 16S rRNA gene PCR sequencing and one for histological examination. Three multicenter quality control assays were performed with both DNA extracts and crushed samples. The diagnosis of PJI was based on clinical, bacteriological, and histological criteria, according to Infectious Diseases Society of America guidelines. A molecular diagnosis was modeled on the bacteriological criterion (≥ 1 positive sample for strict pathogens and ≥ 2 for commensal skin flora). Molecular data were analyzed according to the diagnosis of PJI. Between December 2010 and March 2012, 264 suspected cases of PJI and 35 control cases were included. PJI was confirmed in 215/264 suspected cases, 192 (89%) with a bacteriological criterion. The PJIs were monomicrobial (163 cases [85%]; staphylococci, n = 108; streptococci, n = 22; Gram-negative bacilli, n = 16; anaerobes, n = 13; others, n = 4) or polymicrobial (29 cases [15%]). The molecular diagnosis was positive in 151/215 confirmed cases of PJI (143 cases with bacteriological PJI documentation and 8 treated cases without bacteriological documentation) and in 2/49 cases without confirmed PJI (sensitivity, 73.3%; specificity, 95.5%). The 16S rRNA gene PCR assay showed a lack of sensitivity in the diagnosis of PJI on a multicenter routine basis.