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Background: Staphylococcus aureus remains a common cause of ventilator-associated pneumonia, with little change in incidence over the past 15 years. We aimed to evaluate the efficacy of suvratoxumab, a monoclonal antibody targeting the α toxin, in reducing the incidence of S aureus pneumonia in patients in the intensive care unit (ICU) who are on mechanical ventilation.Methods: We did a multicentre, randomised, double-blind, placebo-controlled, parallel-group, phase 2 pilot trial at 31 hospitals in Belgium, the Czech Republic, France, Germany, Greece, Hungary, Portugal, Spain, and Switzerland. Eligible patients were in the ICU, aged ≥18 years, were intubated and on mechanical ventilation, were positive for S aureus colonisation of the lower respiratory tract, as assessed by quantitative PCR (qPCR) analysis of endotracheal aspirate, and had not been diagnosed with new-onset pneumonia. Patients were excluded if they had confirmed or suspected acute ongoing staphylococcal disease; had received antibiotics for S aureus infection for more than 48 h within 72 h of randomisation; had a Clinical Pulmonary Infection Score of 6 or higher; had an acute physiology and chronic health evaluation II score of 25 or higher with a Glasgow coma scale (GCS) score of more than 5, or an acute physiology and chronic health evaluation II score of at least 30 with a GCS score of 5 or less; had a Sequential Organ Failure Assessment score of 9 or higher; or had active pulmonary disease that would impair the ability to diagnose pneumonia. Colonised patients were randomly assigned (1:1:1), by use of an interactive voice or web response system, to receive either a single intravenous infusion of suvratoxumab 2000 mg, suvratoxumab 5000 mg, or placebo. Randomisation was done in blocks of size four, stratified by country and by whether patients had received systemic antibiotics for S aureus infection. Patients, investigators, and study staff involved in the treatment or clinical evaluation of patients were masked to patient assignment. The primary efficacy endpoint was the incidence of S aureus pneumonia at 30 days, as determined by a masked independent endpoint adjudication committee, in all patients who received their assigned treatment (modified intention-to-treat [ITT] population). Primary safety endpoints were the incidence of treatment-emergent adverse events at 30 days, 90 days, and 190 days after treatment, and the incidence of treatment-emergent serious adverse events, adverse events of special interest, and new-onset chronic disease at 190 days after treatment. All primary safety endpoints were assessed in the modified ITT population. This trial is registered with ClinicalTrials.gov (NCT02296320) and the EudraCT database (2014-001097-34).Findings: Between Oct 10, 2014, and April 1, 2018, 767 patients were screened, of whom 213 patients with confirmed S aureus colonisation of the lower respiratory tract were randomly assigned to the suvratoxumab 2000 mg group (n=15), the suvratoxumab 5000 mg group (n=96), or the placebo group (n=102). Two patients in the placebo group did not receive treatment after randomisation because their clinical conditions changed and they no longer met the eligibility criteria for dosing. As adjudicated by the data monitoring committee at an interim analysis, the suvratoxumab 2000 mg group was discontinued on the basis of predefined pharmacokinetic criteria. At 30 days after treatment, 17 (18%) of 96 patients in the suvratoxumab 5000 mg group and 26 (26%) of 100 patients in the placebo group had developed S aureus pneumonia (relative risk reduction 31·9% [90% CI -7·5 to 56·8], p=0·17). The incidence of treatment-emergent adverse events at 30 days were similar between the suvratoxumab 5000 mg group (87 [91%]) and the placebo group (90 [90%]). The incidence of treatment-emergent serious adverse events at 30 days were also similar between the suvratoxumab 5000 mg group (36 [38%]) and the placebo group (32 [32%]). No significant difference in the incidence of treatment-emergent adverse events between the two groups at 90 days (89 [93%] in the suvratoxumab 5000 mg group vs 92 [92%] in the placebo group) and at 190 days (93 [94%] vs 93 [93%]) was observed. 40 (40%) patients in the placebo group and 50 (52%) in the suvratoxumab 5000 mg group had a serious adverse event at 190 days. In the suvratoxumab 5000 mg group, one (1%) patient reported at least one treatment-emergent serious adverse event related to treatment, two (2%) patients reported an adverse event of special interest, and two (2%) reported a new-onset chronic disease.Interpretation: In patients in the ICU receiving mechanical ventilation with qPCR-confirmed S aureus colonisation of the lower respiratory tract, the incidence of S aureus pneumonia at 30 days was not significantly lower following treatment with 5000 mg suvratoxumab than with placebo. Despite these negative results, monoclonal antibodies still represent one promising therapeutic option to reduce antibiotic consumption that require further exploration and studies.Funding: AstraZeneca, with support from the Innovative Medicines Initiative Joint Undertaking. [ABSTRACT FROM AUTHOR]

Background: Few data are available on patients who have experienced anaphylaxis and were admitted to ICUs. The purpose of this observational study was to describe the epidemiology and management of these patients.Methods: This was a multicentre retrospective study carried out in 23 French ICUs between 2012 and 2017. All patients who suffered anaphylaxis and were transferred to an ICU were included. Data were collected using an electronic database after approval by an ethics committee.Results: A total of 339 patients were included, and 17 (5%) died secondary to anaphylaxis. The main triggers were drugs (77%), contrast media (11%), and food (7%). Epinephrine was administered before ICU admission in 88% of patients with Grade III anaphylaxis and 100% of patients with Grade IV anaphylaxis. Most patients with Grades III and IV anaphylaxes did not receive the recommended dose of i.v. fluid of 30 ml kg-1 within the first 4 h of ICU admission. The time to epinephrine administration was not statistically different between survivors and non-survivors, but non-survivors received a higher dose of epinephrine (median: 5 [3-10] vs 3 [2-7] mg; P<0.0001), which suggests that some forms of anaphylactic shock may be resistant to epinephrine. In multivariate analysis, only lactate concentration at ICU admission was a predictor of death (odds ratio: 1.47 [1.15-1.88]; P=0.002).Conclusions: Lactate concentration at ICU admission appeared to be the most reliable criterion for assessing prognosis. Epinephrine is widely used during anaphylaxis, but the volume of fluid resuscitation was consistently lower than recommended.Clinical Trial Registration: NCT04290507. [ABSTRACT FROM AUTHOR]

Fix data are available on the management of pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We conducted a retrospective study of 100 pregnant women with SARS-CoV-2 infection in 4 obstetric units in the Paris metropolitan area of France during March 12-April 13, 2020. Among patients, 52 (52%) were hospitalized, 10 (10%) in intensive care units (ICUs). Women with higher body mass indexes (BMIs; median 30.7 kg/m2) were more likely to be hospitalized in ICUs than other women (median BMI 26.2 kg/m2). Women hospitalized in ICUs had lower lymphocyte count at diagnosis (median 0.77 × 109 cells/L) than women not hospitalized in ICUs (median lymphocyte count 1.15 × 109 cells/L). All women requiring oxygen >5 L/min were intubated. Clinical and laboratory evaluation of SARS-CoV-2-positive pregnant women at the time of diagnosis can identify patients at risk for ICU hospitalization. [ABSTRACT FROM AUTHOR]

Purpose: Intensive care unit survivors suffer from prolonged impairment, reduced quality of life, and higher mortality rates after discharge compared to the general population. Socioeconomic status may play a partial but important role in mortality and recovery. Therefore, the detection of factors that are responsible for poor long-term outcomes would be beneficial in designing targeted interventions for at-risk populations.Methods: For an endpoint analysis, 1834 intensive care unit patients with known French Deprivation Index (FDep) scores were included from the French and euRopean Outcome reGistry in Intensive Care Units (FROG-ICU) study, which was a prospective, observational, multicenter cohort study performed in 20 French intensive care units in 13 different hospitals. Socioeconomic status was defined by using the FDep score [represented as quintiles when referring to the general French population, as quintiles when referring to the FROG-ICU cohort, or as dichotomized data (which was defined as a FDep ≤ 0 for nondeprived patients)] and by using a detailed social questionnaire that was completed 3 months after discharge. The primary outcome included an all-cause, 1-year mortality after ICU discharge when regarding socioeconomic status. The secondary outcomes included both ICU and hospital lengths of stay, both short- and medium-term mortality, and the quality of life, as assessed during the 1-year follow-up by using the Medical Outcome Survey Short Form-36 (SF-36). The Revised Impact of Event Scale (IES-R) was used to evaluate the symptoms of post-traumatic stress disorder, and the Hospital Anxiety and Depression Scale (HADS) was used to screen for anxiety and depression.Results: Of the 1447 patients who were discharged alive from the ICU, 19.2% died over the following year. No association was found between 1-year mortality and socioeconomic status, regardless of whether this association was analyzed in quintiles (p = 0.911 in the quintiles of the general French population; p = 0.589 in the quintiles of the FROG-ICU cohort itself) or as dichotomized data [nondeprived (n = 177; 1-year mortality of 18.2%) versus deprived (n = 97; 1-year mortality of 20.5%; p = 0.304)]. Moreover, no differences were found between the nondeprived and the deprived patients in the ICU and hospital lengths of stay, ICU mortalities, in-hospital mortalities, or 28-day mortalities. The SF-36 was below the score for the normal French population throughout the follow-up period. Socially deprived patients showed significantly lower median scores in the physical function subscale [55, interquartile range (IQR) (28.8-80) vs. 65, IQR (35-90); p = 0.014], the physical role subscale [25, IQR (0-75) vs. 33.3, IQR (0-100); p = 0.022], and the overall physical component scale [47.5, IQR (30-68.8) vs. 54.4, IQR (35-78.8); p = 0.010]. Up to 31.6% of survivors presented symptoms that indicated post-traumatic stress disorder, and up to 31.5% of survivors reported clinically meaningful symptoms of anxiety or depression.Conclusions: A lower socioeconomic status was associated with lower self-reported physical component scores in the nondeprived patients. Psychiatric symptoms are frequently reported after an ICU stay, and subsequent interventions should target those fields.Trial Registration: ClinicalTrials.gov NCT01367093; registered on June 6, 2011. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether ICUs caring for higher volumes of acute respiratory distress syndrome patients would be associated with lower ICU mortality.Design: A 9-year multicenter retrospective cohort study of prospectively collected data.Setting: French medical ICUs.Patients: From 2004 to 2012, acute respiratory distress syndrome cases were identified from a coding system through a regional database (Collège des Utilisateurs de Données en Réanimation).Interventions: None.Measurements and Main Results: Volume was calculated as the cumulative annual mean number of acute respiratory distress syndrome cases. Severity (Simplified Acute Physiology Score 2) and ICU mortality between categories (low, medium, and high) of acute respiratory distress syndrome cases volume were analyzed. Multivariable analysis using mixed effects models was performed to adjust for severity of illness and confounding factors. Over the study period, 8,383 acute respiratory distress syndrome patients among 31 ICUs met the study inclusion criteria. Overall, Simplified Acute Physiology Score 2 (median [interquartile]) was 58 (43-74), whereas ICU mortality was 53.7%. Severity as assessed by Simplified Acute Physiology Score 2 (median [interquartile]) was significantly higher in high-volume ICUs (> 65 acute respiratory distress syndrome per year) as compared to low (≤ 29 acute respiratory distress syndrome per year) and medium-volume ICUs (> 29-65 acute respiratory distress syndrome per year): 61 (46-77) versus 55 (41-72) and 55.0 (40-72), respectively (p < 0.01). ICU mortality was similar across the acute respiratory distress syndrome volume categories (53.6%, 54.1%, and 53.3% in low-, medium-, and high-volume categories ICUs, respectively). After adjustment for confounders, acute respiratory distress syndrome case volume was independently associated with ICU mortality (odds ratio for log-transformed volume: 0.77 [95% CI, 0.62-0.96]; p = 0.02).Conclusions: ICUs caring for higher volumes of acute respiratory distress syndrome cases were associated with lower ICU mortality. [ABSTRACT FROM AUTHOR]

Objectives: Family members of patients who die in the ICU often remain with unanswered questions and suffer from lack of closure. A letter of condolence may help bereaved relatives, but little is known about their experience of receiving such a letter. The objective of the study was to understand bereaved family members' experience of receiving a letter of condolence.Design: Qualitative study using interviews with bereaved family members who received a letter of condolence and letters written by these family members to the ICU team. This study was designed to provide insight into the results of a larger randomized, controlled, multicenter study.Setting: Twenty-two ICUs in France.Subjects: Family members who lost a loved one in the ICU and who received a letter of condolence.Measurements and Main Results: Thematic analysis was used and was based on 52 interviews and 26 letters. Six themes emerged: 1) a feeling of support, 2) humanization of the medical system, 3) an opportunity for reflection, 4) an opportunity to describe their loved one, 5) continuity and closure, and 6) doubts and ambivalence. Possible difficulties emerged, notably the re-experience of the trauma, highlighting the absence of further support.Conclusions: This study describes the benefits of receiving a letter of condolence; mainly, it humanizes the medical institution (feeling of support, confirmation of the role played by the relative, supplemental information). However, this study also shows a common ambivalence about the letter of condolence's benefit. Healthcare workers must strive to adapt bereavement follow-up to each individual situation. [ABSTRACT FROM AUTHOR]

Importance: The high mortality rate in critically ill elderly patients has led to questioning of the beneficial effect of intensive care unit (ICU) admission and to a variable ICU use among this population.Objective: To determine whether a recommendation for systematic ICU admission in critically ill elderly patients reduces 6-month mortality compared with usual practice.Design, Setting, and Participants: Multicenter, cluster-randomized clinical trial of 3037 critically ill patients aged 75 years or older, free of cancer, with preserved functional status (Index of Independence in Activities of Daily Living ≥4) and nutritional status (absence of cachexia) who arrived at the emergency department of one of 24 hospitals in France between January 2012 and April 2015 and were followed up until November 2015.Interventions: Centers were randomly assigned either to use a program to promote systematic ICU admission of patients (n=1519 participants) or to follow standard practice (n=1518 participants).Main Outcomes and Measures: The primary outcome was death at 6 months. Secondary outcomes included ICU admission rate, in-hospital death, functional status, and quality of life (12-Item Short Form Health Survey, ranging from 0 to 100, with higher score representing better self-reported health) at 6 months.Results: One patient withdrew consent, leaving 3036 patients included in the trial (median age, 85 [interquartile range, 81-89] years; 1361 [45%] men). Patients in the systematic strategy group had an increased risk of death at 6 months (45% vs 39%; relative risk [RR], 1.16; 95% CI, 1.07-1.26) despite an increased ICU admission rate (61% vs 34%; RR, 1.80; 95% CI, 1.66-1.95). After adjustments for baseline characteristics, patients in the systematic strategy group were more likely to be admitted to an ICU (RR, 1.68; 95% CI, 1.54-1.82) and had a higher risk of in-hospital death (RR, 1.18; 95% CI, 1.03-1.33) but had no significant increase in risk of death at 6 months (RR, 1.05; 95% CI, 0.96-1.14). Functional status and physical quality of life at 6 months were not significantly different between groups.Conclusions and Relevance: Among critically ill elderly patients in France, a program to promote systematic ICU admission increased ICU use but did not reduce 6-month mortality. Additional research is needed to understand the decision to admit elderly patients to the ICU.Trial Registration: clinicaltrials.gov Identifier: NCT01508819. [ABSTRACT FROM AUTHOR]

Purpose: Neurally adjusted ventilatory assist (NAVA) is a ventilatory mode that tailors the level of assistance delivered by the ventilator to the electromyographic activity of the diaphragm. The objective of this study was to compare NAVA and pressure support ventilation (PSV) in the early phase of weaning from mechanical ventilation.Methods: A multicentre randomized controlled trial of 128 intubated adults recovering from acute respiratory failure was conducted in 11 intensive care units. Patients were randomly assigned to NAVA or PSV. The primary outcome was the probability of remaining in a partial ventilatory mode (either NAVA or PSV) throughout the first 48 h without any return to assist-control ventilation. Secondary outcomes included asynchrony index, ventilator-free days and mortality.Results: In the NAVA and PSV groups respectively, the proportion of patients remaining in partial ventilatory mode throughout the first 48 h was 67.2 vs. 63.3 % (P = 0.66), the asynchrony index was 14.7 vs. 26.7 % (P < 0.001), the ventilator-free days at day 7 were 1.0 day [1.0-4.0] vs. 0.0 days [0.0-1.0] (P < 0.01), the ventilator-free days at day 28 were 21 days [4-25] vs. 17 days [0-23] (P = 0.12), the day-28 mortality rate was 15.0 vs. 22.7 % (P = 0.21) and the rate of use of post-extubation noninvasive mechanical ventilation was 43.5 vs. 66.6 % (P < 0.01).Conclusions: NAVA is safe and feasible over a prolonged period of time but does not increase the probability of remaining in a partial ventilatory mode. However, NAVA decreases patient-ventilator asynchrony and is associated with less frequent application of post-extubation noninvasive mechanical ventilation.Trial Registration: clinicaltrials.gov Identifier: NCT02018666. [ABSTRACT FROM AUTHOR]

Background: To our knowledge, there is no data on the epidemiology of patients hospitalized in intensive care unit (ICU) after a stay in Madagascar or other low-income countries. It is possible that such data may improve transfer delays and care quality for these patients.Methods: In a retrospective study, we reviewed the charts of all patients admitted to ICU of the Reunion Island Felix Guyon University Hospital from January 2011 through July 2013. We identified all patients who had stayed in Madagascar during the 6 months prior to ICU admission.Results: Of 1842 ICU patients, 62 (3.4%) had stayed in Madagascar during the 6 months prior to ICU admission. Patients were 76% male and the median age was 60.5 (48.25-64.75) years; patients were more frequently residents of Madagascar than travellers (56.5%). In most cases, patients were not hospitalized or given antibiotics in Madagascar. The most frequent causes of hospitalization were infections including malaria (21%) and lower respiratory infection (11%). Carriage and infection with multidrug resistant (MDR) bacteria on ICU admission were frequent (37% and 9.7%, respectively). The mortality rate in ICU was 21%, and severity acute physiological Score II was 53.5 (37-68).Conclusions: Patients admitted to ICU after a stay to Madagascar are mainly elderly patients with chronic illnesses, and often foreign residents. The admission causes are specific of the country like malaria, or specific to the population concerned such as cardiovascular accidents that could be prevented. [ABSTRACT FROM AUTHOR]

Purpose: To assess the prevalence of decisions to forgo life-sustaining treatment (DFLST), the patients characteristics, and to estimate the impact of DFLST stages on mortality.Methods: Observational study of a prospective database between 2005 and 2012 from 13 ICUs. DFLST were defined as follows: no escalation of treatment (stage 1), not to start or escalate treatment even if such treatment is considered in the future; withholding (stage 2), not to start or escalate necessary treatment; withdrawal (stage 3), to stop necessary treatment. The impact of daily DFLST stage on day-30 hospital mortality was tested with a discrete-time Cox's model and adjusted for admission severity and daily SOFA score.Results: Of 10,080 patients, 1290 (13%) made DFLST. The highest DFLST stage during the ICU stay was no escalation of treatment in 339 (26%) patients, withholding in 502 (39%) patients, and withdrawal in 449 (35%) patients. Older patients, patients with at least one chronic disease, and patients with greater ICU severity were significantly more numerous in the DFLST group. Day-30 mortality was 13% for non-DFLST patients, 35% for no escalation of treatment, 75% for withholding, 93% for withdrawal. After adjustment, an increase in day-30 mortality was associated with withholding and withdrawal (hazard ratio 95% CI 5.93 [4.95-7.12] and 20.05 [15.58-25.79], P < 0.0001), but not with no escalation of treatment (HR 1.14 [0.91-1.44], P = 0.25).Conclusions: DFLST were made in 13% of ICU patients. Withholding, withdrawal, older age, more comorbidities, and higher severity of illness were associated with higher mortality. No escalation of treatment was not associated with increased mortality. [ABSTRACT FROM AUTHOR]