Association between combination antibiotic therapy as opposed as monotherapy and outcomes of ICU patients with Pseudomonas aeruginosa ventilator-associated pneumonia: an ancillary study of the iDIAPASON trial.

BACKGROUND: The optimal treatment duration and the nature of regimen of antibiotics (monotherapy or combination therapy) for Pseudomonas aeruginosa ventilator­associated pneumonia (PA-VAP) remain debated. The aim of this study was to evaluate whether a combination antibiotic therapy is superior to a monotherapy in patients with PA-VAP in terms of reduction in recurrence and death, based on the 186 patients included in the iDIAPASON trial, a multicenter, randomized controlled trial comparing 8 versus 15 days of antibiotic therapy for PA-VAP. METHODS: Patients with PA-VAP randomized in the iDIAPASON trial (short-duration-8 days vs. long-duration-15 days) and who received appropriate antibiotic therapy were eligible in the present study. The main objective is to compare mortality at day 90 according to the antibiotic therapy received by the patient: monotherapy versus combination therapy. The primary outcome was the mortality rate at day 90. The primary outcome was compared between groups using a Chi-square test. Time from appropriate antibiotic therapy to death in ICU or to censure at day 90 was represented using Kaplan-Meier survival curves and compared between groups using a Log-rank test. RESULTS: A total of 169 patients were included in the analysis. The median duration of appropriate antibiotic therapy was 14 days. At day 90, among 37 patients (21.9%) who died, 17 received monotherapy and 20 received a combination therapy (P = 0.180). Monotherapy and combination antibiotic therapy were similar for the recurrence rate of VAP, the number of extra pulmonary infections, or the acquisition of multidrug-resistant (MDR) bacteria during the ICU stay. Patients in combination therapy were exposed to mechanical ventilation for 28 ± 12 days, as compared with 23 ± 11 days for those receiving monotherapy (P = 0.0243). Results remain similar after adjustment for randomization arm of iDIAPASON trial and SOFA score at ICU admission. CONCLUSIONS: Except longer durations of antibiotic therapy and mechanical ventilation, potentially related to increased difficulty in achieving clinical cure, the patients in the combination therapy group had similar outcomes to those in the monotherapy group. TRIAL REGISTRATION: NCT02634411 , Registered 15 December 2015.

Multiple spatial representations interact to increase reach accuracy when coordinating a saccade with a reach.

Reaching is an essential behavior that allows primates to interact with the environment. Precise reaching to visual targets depends on our ability to localize and foveate the target. Despite this, how the saccade system contributes to improvements in reach accuracy remains poorly understood. To assess spatial contributions of eye movements to reach accuracy, we performed a series of behavioral psychophysics experiments in nonhuman primates (Macaca mulatta). We found that a coordinated saccade with a reach to a remembered target location increases reach accuracy without target foveation. The improvement in reach accuracy was similar to that obtained when the subject had visual information about the location of the current target in the visual periphery and executed the reach while maintaining central fixation. Moreover, we found that the increase in reach accuracy elicited by a coordinated movement involved a spatial coupling mechanism between the saccade and reach movements. We observed significant correlations between the saccade and reach errors for coordinated movements. In contrast, when the eye and arm movements were made to targets in different spatial locations, the magnitude of the error and the degree of correlation between the saccade and reach direction were determined by the spatial location of the eye and the hand targets. Hence, we propose that coordinated movements improve reach accuracy without target foveation due to spatial coupling between the reach and saccade systems. Spatial coupling could arise from a neural mechanism for coordinated visual behavior that involves interacting spatial representations.NEW & NOTEWORTHY How visual spatial representations guiding reach movements involve coordinated saccadic eye movements is unknown. Temporal coupling between the reach and saccade system during coordinated movements improves reach performance. However, the role of spatial coupling is unclear. Using behavioral psychophysics, we found that spatial coupling increases reach accuracy in addition to temporal coupling and visual acuity. These results suggest that a spatial mechanism to couple the reach and saccade systems increases the accuracy of coordinated movements.

Association of socioeconomic deprivation with outcomes in critically ill adult patients: an observational prospective multicenter cohort study.

BACKGROUND: The influence of socioeconomic deprivation on health inequalities is established, but its effect on critically ill patients remains unclear, due to inconsistent definitions in previous studies. METHODS: Prospective multicenter cohort study conducted from March to June 2018 in eight ICUs in the Greater Paris area. All admitted patients aged ≥ 18 years were enrolled. Socioeconomic phenotypes were identified using hierarchical clustering, based on education, health insurance, income, and housing. Association of phenotypes with 180-day mortality was assessed using Cox proportional hazards models. RESULTS: A total of 1,748 patients were included. Median age was 62.9 [47.4-74.5] years, 654 (37.4%) patients were female, and median SOFA score was 3 [1-6]. Study population was clustered in five phenotypes with increasing socioeconomic deprivation. Patients from phenotype A (n = 958/1,748, 54.8%) were without socioeconomic deprivation, patients from phenotype B (n = 273/1,748, 15.6%) had only lower education levels, phenotype C patients (n = 117/1,748, 6.7%) had a cumulative burden of 1[1-2] deprivations and all had housing deprivation, phenotype D patients had 2 [1-2] deprivations, all of them with income deprivation, and phenotype E patients (n = 93/1,748, 5.3%) included patients with 3 [2-4] deprivations and included all patients with health insurance deprivation. Patients from phenotypes D and E were younger, had fewer comorbidities, more alcohol and opiate use, and were more frequently admitted due to self-harm diagnoses. Patients from phenotype C (predominant housing deprivation), were more frequently admitted with diagnoses related to chronic respiratory diseases and received more non-invasive positive pressure ventilation. Following adjustment for age, sex, alcohol and opiate use, socioeconomic phenotypes were not associated with increased 180-day mortality: phenotype A (reference); phenotype B (hazard ratio [HR], 0.85; 95% confidence interval CI 0.65-1.12); phenotype C (HR, 0.56; 95% CI 0.34-0.93); phenotype D (HR, 1.09; 95% CI 0.78-1.51); phenotype E (HR, 1.20; 95% CI 0.73-1.96). CONCLUSIONS: In a universal health care system, the most deprived socioeconomic phenotypes were not associated with increased 180-day mortality. The most disadvantaged populations exhibit distinct characteristics and medical conditions that may be addressed through targeted public health interventions.

Oxygen therapy in acute hypoxemic respiratory failure: guidelines from the SRLF-SFMU consensus conference.

INTRODUCTION: Although largely used, the place of oxygen therapy and its devices in patients with acute hypoxemic respiratory failure (ARF) deserves to be clarified. The French Intensive Care Society (Société de Réanimation de Langue Française, SRLF) and the French Emergency Medicine Society (Société Française de Médecine d'Urgence, SFMU) organized a consensus conference on oxygen therapy in ARF (excluding acute cardiogenic pulmonary oedema and hypercapnic exacerbation of chronic obstructive diseases) in December 2023. METHODS: A committee without any conflict of interest (CoI) with the subject defined 7 generic questions and drew up a list of sub questions according to the population, intervention, comparison and outcomes (PICO) model. An independent work group reviewed the literature using predefined keywords. The quality of the data was assessed using the GRADE methodology. Fifteen experts in the field from both societies proposed their own answers in a public session and answered questions from the jury (a panel of 16 critical-care and emergency medicine physicians, nurses and physiotherapists without any CoI) and the public. The jury then met alone for 48 h to write its recommendations. RESULTS: The jury provided 22 statements answering 11 questions: in patients with ARF (1) What are the criteria for initiating oxygen therapy? (2) What are the targets of oxygen saturation? (3) What is the role of blood gas analysis? (4) When should an arterial catheter be inserted? (5) Should standard oxygen therapy, high-flow nasal cannula oxygen therapy (HFNC) or continuous positive airway pressure (CPAP) be preferred? (6) What are the indications for non-invasive ventilation (NIV)? (7) What are the indications for invasive mechanical ventilation? (8) Should awake prone position be used? (9) What is the role of physiotherapy? (10) Which criteria necessarily lead to ICU admission? (11) Which oxygenation device should be preferred for patients for whom a do-not-intubate decision has been made? CONCLUSION: These recommendations should optimize the use of oxygen during ARF.

Influence of socio-economic status on functional recovery after ARDS caused by SARS-CoV-2: the multicentre, observational RECOVIDS study.

PURPOSE: Survivors after acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) are at high risk of developing respiratory sequelae and functional impairment. The healthcare crisis caused by the pandemic hit socially disadvantaged populations. We aimed to evaluate the influence of socio-economic status on respiratory sequelae after COVID-19 ARDS. METHODS: We carried out a prospective multicenter study in 30 French intensive care units (ICUs), where ARDS survivors were pre-enrolled if they fulfilled the Berlin ARDS criteria. For patients receiving high flow oxygen therapy, a flow ≥ 50 l/min and an FiO2 ≥ 50% were required for enrollment. Socio-economic deprivation was defined by an EPICES (Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examens de Santé - Evaluation of Deprivation and Inequalities in Health Examination Centres) score ≥ 30.17 and patients were included if they performed the 6-month evaluation. The primary outcome was respiratory sequelae 6 months after ICU discharge, defined by at least one of the following criteria: forced vital capacity < 80% of theoretical value, diffusing capacity of the lung for carbon monoxide < 80% of theoretical value, oxygen desaturation during a 6-min walk test and fibrotic-like findings on chest computed tomography. RESULTS: Among 401 analyzable patients, 160 (40%) were socio-economically deprived and 241 (60%) non-deprived; 319 (80%) patients had respiratory sequelae 6 months after ICU discharge (81% vs 78%, deprived vs non-deprived, respectively). No significant effect of socio-economic status was identified on lung sequelae (odds ratio (OR), 1.19 [95% confidence interval (CI), 0.72-1.97]), even after adjustment for age, sex, most invasive respiratory support, obesity, most severe P/F ratio (adjusted OR, 1.02 [95% CI 0.57-1.83]). CONCLUSIONS: In COVID-19 ARDS survivors, socio-economic status had no significant influence on respiratory sequelae 6 months after ICU discharge.

Cold agglutinin disease secondary to severe SARS-CoV-2 treated with eculizumab.

Impaired immune response with uncontrolled inflammation and various immunological disorders have been reported during SARS-CoV-2 infection. Here, we report a case of cold agglutinin disease occurring during a severe coronavirus disease 2019 (COVID-19) in a French intensive care unit. A patient was presented with acute respiratory distress syndrome, acute renal failure and haemolytic anaemia. Direct antiglobulin test was positive with a cold agglutinin titre of 1/512. No other cause than COVID-19 explained the occurrence of cold agglutinin disease; however, causality could not be formally established. Persistent anaemia despite transfusion therapy and the short-term life-threatening, prompted the infusion of a monoclonal anti-C5 antibody (eculizumab). Eculizumab therapy quasi-fully resolved haemolysis within a few days, but ultimately the patient died from his severe COVID-19 infection. Data regarding the specific treatment of cold agglutinin disease during COVID-19 are rare. Although additional studies are warranted, eculizumab may be considered in critical situations.

Comparison of 8 versus 15 days of antibiotic therapy for Pseudomonas aeruginosa ventilator-associated pneumonia in adults: a randomized, controlled, open-label trial.

PURPOSE: Duration of antibiotic therapy for ventilator-associated pneumonia (VAP) due to non-fermenting Gram-negative bacilli (NF-GNB), including Pseudomonas aeruginosa (PA) remains uncertain. We aimed to assess the non-inferiority of a short duration of antibiotics (8 days) vs. prolonged antibiotic therapy (15 days) in VAP due to PA (PA-VAP). METHODS: We conducted a nationwide, randomized, open-labeled, multicenter, non-inferiority trial to evaluate optimal duration of antibiotic treatment in PA-VAP. Eligible patients were adults with diagnosis of PA-VAP and randomly assigned in 1:1 ratio to receive a short-duration treatment (8 days) or a long-duration treatment (15 days). A pre-specified analysis was used to assess a composite endpoint combining mortality and PA-VAP recurrence rate during hospitalization in the intensive care unit (ICU) within 90 days. RESULTS: The study was stopped after 24 months due to slow inclusion rate. In intention-to-treat population (n = 186), the percentage of patients who reached the composite endpoint was 25.5% (N = 25/98) in the 15-day group versus 35.2% (N = 31/88) in the 8-day group (difference 9.7%, 90% confidence interval (CI) -1.9%-21.2%). The percentage of recurrence of PA-VAP during the ICU stay was 9.2% in the 15-day group versus 17% in the 8-day group. The two groups had similar median days of mechanical ventilation, of ICU stay, number of extra pulmonary infections and acquisition of multidrug-resistant (MDR) pathogens during ICU stay. CONCLUSIONS: Our study failed to show the non-inferiority of a short duration of antibiotics in the treatment of PA-VAP, compared to a long duration. The short duration strategy may be associated to an increase of PA-VAP recurrence. However, the lack of power limits the interpretation of this study.

Influence of socioeconomic status on functional recovery after ARDS caused by SARS-CoV-2: a multicentre, observational study.

INTRODUCTION: Prognosis of patients with COVID-19 depends on the severity of the pulmonary affection. The most severe cases may progress to acute respiratory distress syndrome (ARDS), which is associated with a risk of long-term repercussions on respiratory function and neuromuscular outcomes. The functional repercussions of severe forms of COVID-19 may have a major impact on quality of life, and impair the ability to return to work or exercise. Social inequalities in healthcare may influence prognosis, with socially vulnerable individuals more likely to develop severe forms of disease. We describe here the protocol for a prospective, multicentre study that aims to investigate the influence of social vulnerability on functional recovery in patients who were hospitalised in intensive care for ARDS caused by COVID-19. This study will also include an embedded qualitative study that aims to describe facilitators and barriers to compliance with rehabilitation, describe patients' health practices and identify social representations of health, disease and care. METHODS AND ANALYSIS: The "Functional Recovery From Acute Respiratory Distress Syndrome (ARDS) Due to COVID-19: Influence of Socio-Economic Status" (RECOVIDS) study is a mixed-methods, observational, multicentre cohort study performed during the routine follow-up of post-intensive care unit (ICU) functional recovery after ARDS. All patients admitted to a participating ICU for PCR-proven SARS-CoV-2 infection and who underwent chest CT scan at the initial phase AND who received respiratory support (mechanical or not) or high-flow nasal oxygen, AND had ARDS diagnosed by the Berlin criteria will be eligible. The primary outcome is the presence of lung sequelae at 6 months after ICU discharge, defined either by alterations on pulmonary function tests, oxygen desaturation during a standardised 6 min walk test or fibrosis-like pulmonary findings on chest CT. Patients will be considered to be socially disadvantaged if they have an "Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examen de Santé" (EPICES) score ≥30.17 at inclusion. ETHICS AND DISSEMINATION: The study protocol and the informed consent form were approved by an independent ethics committee (Comité de Protection des Personnes Sud Méditerranée II) on 10 July 2020 (2020-A02014-35). All patients will provide informed consent before participation. Findings will be published in peer-reviewed journals and presented at national and international congresses. TRIAL REGISTRATION NUMBER: NCT04556513.

Comparison of high-flow nasal oxygen therapy and non-invasive ventilation in ICU patients with acute respiratory failure and a do-not-intubate orders: a multicentre prospective study OXYPAL.

INTRODUCTION: A palliative approach to intensive care unit (ICU) patients with acute respiratory failure and a do-not-intubate order corresponds to a poorly evaluated target for non-invasive oxygenation treatments. Survival alone should not be the only target; it also matters to avoid discomfort and to restore the patient's quality of life. We aim to conduct a prospective multicentre observational study to analyse clinical practices and their impact on outcomes of palliative high-flow nasal oxygen therapy (HFOT) and non-invasive ventilation (NIV) in ICU patients with do-not-intubate orders. METHODS AND ANALYSIS: This is an investigator-initiated, multicentre prospective observational cohort study comparing the three following strategies of oxygenation: HFOT alone, NIV alternating with HFOT and NIV alternating with standard oxygen in patients admitted in the ICU for acute respiratory failure with a do-not-intubate order. The primary outcome is the hospital survival within 14 days after ICU admission in patients weaned from NIV and HFOT. The sample size was estimated at a minimum of 330 patients divided into three groups according to the oxygenation strategy applied. The analysis takes into account confounding factors by modelling a propensity score. ETHICS AND DISSEMINATION: The study has been approved by the ethics committee and patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03673631.

Successful continuation of pregnancy in a patient with COVID-19-related ARDS.

A 33-year-old pregnant woman was hospitalised with fever, cough, myalgia and dyspnoea at 23.5 weeks of gestation (WG). Development of acute respiratory distress syndrome (ARDS) mandated invasive mechanical ventilation. A nasopharyngeal swab proved positive for severe acute respiratory syndrome coronavirus 2 by reverse transcription-PCR. The patient developed hypertension and biological disorders suggesting pre-eclampsia and HELLP (haemolysis, elevated liver enzyme levels and low platelet levels) syndrome. Pre-eclampsia was subsequently ruled out by a low ratio of serum soluble fms-like tyrosine kinase-1 to placental growth factor. Given the severity of ARDS, delivery by caesarean section was contemplated. Because the ratio was normal and the patient's respiratory condition stabilised, delivery was postponed. She recovered after 10 days of mechanical ventilation. She spontaneously delivered a healthy boy at 33.4 WG. Clinical and laboratory manifestations of COVID-19 infection can mimic HELLP syndrome. Fetal extraction should not be systematic in the absence of fetal distress or intractable maternal disease. Successful evolution was the result of a multidisciplinary teamwork.