Granulocyte colony-stimulating factor for stem cell mobilisation in acute myocardial infarction: a randomised controlled trial.

BACKGROUND: To determine whether granulocyte colony-stimulating factor (G-CSF) improves clinical outcomes after large ST-elevation myocardial infarction (STEMI) when administered early in patients with left ventricular (LV) dysfunction after successful percutaneous coronary intervention (PCI). METHODS: STEM-AMI OUTCOME was designed as a prospective, multicentre, nationwide, randomised, open-label, phase III trial (ClinicalTrials.gov ID: NCT01969890) to demonstrate the efficacy and safety of early G-CSF administration in reducing 2-year cardiac mortality and morbidity in patients with STEMI with LV ejection fraction ≤45% after PCI. The primary outcome was a composite of all-cause death, recurrence of myocardial infarction and hospitalisation for heart failure. Due to low recruitment and event rates, the study was discontinued and did not achieve adequate statistical power to verify the hypothesis. RESULTS: Patients were randomly allocated to G-CSF (n=260) or standard of care (SOC; n=261). No difference was found in the composite primary outcome between study groups (HR 1.20; 95% CI 0.63 to 2.28). The 2-year mortality was 2.31% in the G-CSF and 2.68% in the control group (HR 0.88; 95% CI 0.29 to 2.60). Adverse events did not differ between the G-CSF (n=65) and SOC groups (n=58; OR 1.17; 95% CI 0.78 to 1.75). In post hoc analyses on the intervention group, we observed a trend towards fewer composite primary outcomes in patients with low bone marrow (BM) cell mobilisation (n=108) versus those with high mobilisation (n=152, with peak leucocyte count >50×109/L; HR 2.86; 95% CI 0.96 to 8.56). Primary outcomes were lower in patients with severe LV systolic dysfunction at discharge treated with G-CSF than in controls (interaction ß±SE, -0.08±0.04; p=0.034). CONCLUSIONS: Although inconclusive, this is the largest trial in the field of cell-based cardiac repair after STEMI providing evidence of the tolerability and long-term safety of G-CSF treatment. The results prompt further studies to understand which patient can benefit most from BM cell mobilisation. TRIAL REGISTRATION NUMBER: NCT01969890.

Pathophysiological Markers of Acute Respiratory Distress Syndrome Severity Are Correlated With Ventilation-Perfusion Mismatch Measured by Electrical Impedance Tomography.

OBJECTIVES: Pulmonary ventilation/perfusion (V/Q) mismatch measured by electrical impedance tomography (EIT) is associated with the outcome of patients with the acute respiratory distress syndrome (ARDS), but the underlying pathophysiological mechanisms have not been fully elucidated. The present study aimed to verify the correlation between relevant pathophysiological markers of ARDS severity and V/Q mismatch. DESIGN: Prospective observational study. SETTING: General ICU of a university-affiliated hospital. PATIENTS: Deeply sedated intubated adult patients with ARDS under controlled mechanical ventilation. INTERVENTIONS: Measures of V/Q mismatch by EIT, respiratory mechanics, gas exchange, lung imaging, and plasma biomarkers. MEASUREMENTS AND MAIN RESULTS: Unmatched V/Q units were assessed by EIT as the fraction of ventilated nonperfused plus perfused nonventilated lung units. At the same time, plasma biomarkers with proven prognostic and mechanistic significance for ARDS (carbonic anhydrase 9 [CA9], hypoxia-inducible factor 1 [HIF1], receptor for advanced glycation endproducts [RAGE], angiopoietin 2 [ANG2], gas exchange, respiratory mechanics, and quantitative chest CT scans were measured. Twenty-five intubated ARDS patients were included with median unmatched V/Q units of 37.1% (29.2-49.2%). Unmatched V/Q units were correlated with plasma levels of CA9 (rho = 0.47; p = 0.01), HIF1 (rho = 0.40; p = 0.05), RAGE (rho = 0.46; p = 0.02), and ANG2 (rho = 0.42; p = 0.03). Additionally, unmatched V/Q units correlated with plateau pressure (r = 0.38; p = 0.05) and with the number of quadrants involved on chest radiograph (r = 0.73; p < 0.01). Regional unmatched V/Q units were correlated with the corresponding fraction of poorly aerated lung tissue (r = 0.62; p = 0.01) and of lung tissue weight (rho: 0.51; p = 0.04) measured by CT scan. CONCLUSIONS: In ARDS patients, unmatched V/Q units are correlated with pathophysiological markers of lung epithelial and endothelial dysfunction, increased lung stress, and lung edema. Unmatched V/Q units could represent a comprehensive marker of ARDS severity, reflecting the complex organ pathophysiology and reinforcing their prognostic significance.

Association of non-cardiac comorbidities and sex with long-term Re-hospitalization for heart failure.

Heart failure (HF) often coexists with non-cardiac comorbidities (NCC), but their association with long-term HF re-hospitalizations is not defined. Using the Lombardy Regional Health Database, that includes >10 million residents, we assessed the risk of re-hospitalization for HF after first HF discharge as a function of NCC, employing age- and sex-adjusted Cox proportional-hazard models. Kaplan Meier curves for HF re-hospitalizations were stratified for number of NCC. End of follow-up was June 30th 2021. Between January 1st 2015 to December 31st 2019, 88,528 consecutive patients were discharged from hospital with a primary diagnosis of HF; over 42.8 ± 18.3 months follow-up, 79,533 HF re-hospitalizations occurred (32.94/100 patient/year). Number of NCC, age, and male sex were significantly associated with re-hospitalization risk. Compared to those without NCC, females and males with >4 NCC had a 3.08 (CI 2.73-3.47) and a 2.62 (CI 2.39-2.87) fold higher risk, respectively. Risk of all-cause death increased with number of NCC (hazard ratio (HR): 1.42 (1.38-1.46) for HF patients with 1-2 NCC, HR: 1.90 (1.82-1.98) for patients with 3-4 NCC, HR: 2.20 (2.01-2.40) for those with HF and >4 NCC), as it did the number of days spent in hospital because of HF (from 19.91±19.25 for patients without NCC to 45.35±33.00 days for those with >4 NCC, p < 0.0001). In conclusion, this study shows that in patients hospitalized with HF, HF re-hospitalizations, all-cause mortality, and time spent in hospital increased with number of NCC. NCC associates with a worse clinical trajectory in patients with HF.

Pain Management in Knee Osteoarthritis: Insights from an Exploratory Online Survey of Italian Patients and Physicians.

BACKGROUND: In Italy, knee osteoarthritis (KOA) accounts for over 5 million prevalent cases and requires long-term multidisciplinary management. The most frequent KOA symptom is pain. The aim of the survey is to provide a national overview of the current management of moderate-to-severe pain associated with KOA from both clinicians' and patients' perspectives. METHODS: An exploratory qualitative survey was conducted in Italy between July and October 2023. The survey participants were members of four national scientific societies and two patient associations who were invited to participate via email and given an online questionnaire. Questions included a mix of single and multiple responses and scalar items. RESULTS: In total, 1473 clinicians and 150 patients with KOA completed the questionnaire. Patients rated knee pain as both the most burdensome symptom and the most frequent reason for treatment dissatisfaction and seeking consultation. One in two patients declared that they were unsatisfied/little satisfied with the current prescribed analgesic treatments. The clinicians surveyed preferentially prescribed intra-articular hyaluronic acid, oral non-steroidal anti-inflammatory drugs/paracetamol, non-pharmacological intervention, and intra-articular corticosteroids. The clinicians' selection of analgesic therapy often failed to adequately meet patients' expectations for pain relief. CONCLUSIONS: Our findings highlight the current unmet needs of patients with KOA in Italy and call for new approaches to effectively optimize the management of KOA-associated pain.

A tidal volume of 7 mL/kg PBW or higher may be safe for COVID-19 patients.

PURPOSE: The novel coronavirus disease (COVID-19) has revived the debate on the optimal tidal volume during acute respiratory distress syndrome (ARDS). Some experts recommend 6 mL/kg of predicted body weight (PBW) for all patients, while others suggest 7-9 mL/kg PBW for those with compliance >50 mL/cmH2O. We investigated whether a tidal volume ≥ 7 ml/kg PBW may be safe in COVID-19 patients, particularly those with compliance >50 mL/cmH2O. MATERIALS AND METHODS: This secondary analysis of a multicenter study compares the Intensive Care Unit (ICU) mortality among 600 patients ventilated with <7 or ≥ 7 mL/kg PBW. Compliance was categorized as <40, 40-50, or > 50 mL/cmH2O. RESULTS: 346 patients were ventilated with <7 (6.2 ± 0.5) mL/kg PBW and 254 with ≥7 (7.9 ± 0.9) mL/kg PBW. ICU mortality was 33 % and 29 % in the two groups (p = 0.272). At multivariable regression analysis, tidal volume ≥ 7 mL/kg PBW was associated with lower ICU mortality in the overall population (odds ratio: 0.62 [95 %-confidence interval: 0.40-0.95]) and in each compliance category. CONCLUSIONS: A tidal volume ≥ 7 (up to 9) mL/kg PBW was associated with lower ICU mortality in these COVID-19 patients, including those with compliance <40 mL/cmH2O. This finding should be interpreted cautiously due to the retrospective study design. TRIAL REGISTRATION: ClinicalTrails.govNCT04388670.

Medical occurrence and safety of SARS-CoV-2 vaccination outside of the hospital setting.

During COVID-19 pandemic, vaccination has been strongly recommended and advocated to prevent COVID-19 infection and adverse outcomes, particularly among at-risk populations. The vaccination against SARS-CoV-2 (COVAC) occurred at off-site locations capable of accommodating large crowds, distinct from the hospital setting, where a team of intensivists, emergency physicians, and nurses, ensuring prompt medical attention (medical occurrences, MO) in cases of adverse event following immunization. Our aims were to estimate the incidence of MO, and to assess its association with demographics, and vaccine characteristics. Our retrospective cohort study included all subject aged 12 years and older who received vaccinations at two large out-of-hospital vaccination hubs (Fiera Milano City, Palazzo delle Scintille), between April 12th and August 31st, 2021. Nine hundred and ninety-five thousand and twenty-eight vaccinations were administrated. MOs incidence rate was 278/100,000 doses (95% confidence interval (CI) 268-289). Most MOs were mild (86.27%) and mainly observed in subjects who received the Comirnaty vaccine; 92 MOs (3.32%) were severe and mostly occurred in recipients of the Vaxzeria vaccine. The incidence rate for hospital transfers following vaccination was 4.7/100,000 doses (95% CI 3.5-6.2) and any level of anaphylaxis occurred in 0.4 cases per 100,000 administrated doses (95% CI 0.3.-0.7). Sex, age, type of vaccine and first dose were associated with incidence of MO. Our results showed a low incidence rate in MOs after COVAC, mainly mild and support the feasibility, effectiveness and safety of vaccinations administered in hubs with a dedicated SEU located outside of the hospital setting.

Corrigendum: Time-Trends in Air Pollution Impact on Health in Italy, 1990-2019: An Analysis from the Global Burden of Disease Study 2019.

[This corrects the article DOI: 10.3389/ijph.2023.1605959.].

Treatment with inhaled Argon: a systematic review of pre-clinical and clinical studies with meta-analysis on neuroprotective effect.

BACKGROUND: Argon (Ar) has been proposed as a potential therapeutic agent in multiple clinical conditions, specifically in organ protection. However, conflicting data on pre-clinical models, together with a great variability in Ar administration protocols and outcome assessments, have been reported. The aim of this study was to review evidence on treatment with Ar, with an extensive investigation on its neuroprotective effect, and to summarise all tested administration protocols. METHODS: Using the PubMed database, all existing pre-clinical and clinical studies on the treatment with Ar were systematically reviewed (registration: https://doi.org/10.17605/OSF.IO/7983D). Study titles and abstracts were screened, extracting data from relevant studies post full-text review. Exclusion criteria included absence of full text and non-English language. Furthermore, meta-analysis was also performed to assess Ar potential as neuroprotectant agent in different clinical conditions: cardiac arrest, traumatic brain injury, ischemic stroke, perinatal hypoxic-ischemic encephalopathy, subarachnoid haemorrhage. Standardised mean differences for neurological, cognitive and locomotor, histological, and physiological measures were evaluated, through appropriate tests, clinical, and laboratory variables. In vivo studies were evaluated for risk of bias using the Systematic Review Center for Laboratory Animal Experimentation tool, while in vitro studies underwent assessment with a tool developed by the Office of Health Assessment and Translation. FINDINGS: The systematic review detected 60 experimental studies (16 in vitro, 7 ex vivo, 31 in vivo, 6 with both in vitro and in vivo) investigating the role of Ar. Only one clinical study was found. Data from six in vitro and nineteen in vivo studies were included in the meta-analyses. In pre-clinical models, Ar administration resulted in improved neurological, cognitive and locomotor, and histological outcomes without any change in physiological parameters (i.e., absence of adverse events). INTERPRETATION: This systematic review and meta-analysis based on experimental studies supports the neuroprotective effect of Ar, thus providing a rationale for potential translation of Ar treatment in humans. Despite adherence to established guidelines and methodologies, limitations in data availability prevented further analyses to investigate potential sources of heterogeneity due to study design. FUNDING: This study was funded in part by Italian Ministry of Health-Current researchIRCCS and by Ministero della Salute Italiano, Ricerca Finalizzata, project no. RF 2019-12371416.

Continuous vs intermittent Non-Invasive blood pressure MONitoring in preventing postoperative organ failure (niMON): study protocol for an open-label, multicenter randomized trial.

BACKGROUND: Blood pressure has become one of the most important vital signs to monitor in the perioperative setting. Recently, the Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care (SIAARTI) recommended, with low level of evidence, continuous monitoring of blood pressure during the intraoperative period. Continuous monitoring allows for early detection of hypotension, which may potentially lead to a timely treatment. Whether the ability to detect more hypotension events by continuous noninvasive blood pressure (C-NiBP) monitoring can improve patient outcomes is still unclear. Here, we report the rationale, study design, and statistical analysis plan of the niMON trial, which aims to evaluate the effect of intraoperative C-NiBP compared with intermittent (I-NiBP) monitoring on postoperative myocardial and renal injury. METHODS: The niMon trial is an investigator-initiated, multicenter, international, open-label, parallel-group, randomized clinical trial. Eligible patients will be randomized in a 1:1 ratio to receive C-NiBP or I-NiBP as an intraoperative monitoring strategy. The proportion of patients who develop myocardial injury in the first postoperative week is the primary outcome; the secondary outcomes are the proportions of patients who develop postoperative AKI, in-hospital mortality rate, and 30 and 90 postoperative days events. A sample size of 1265 patients will provide a power of 80% to detect a 4% absolute reduction in the rate of the primary outcome. CONCLUSIONS: The niMON data will provide evidence to guide the choice of the most appropriate intraoperative blood pressure monitoring strategy. CLINICAL TRIAL REGISTRATION: Clinical Trial Registration: NCT05496322, registered on the 5th of August 2023.

A non-invasive continuous and real-time volumetric monitoring in spontaneous breathing subjects based on bioimpedance-ExSpiron®Xi: a validation study in healthy volunteers.

Tidal volume (TV) monitoring breath-by-breath is not available at bedside in non-intubated patients. However, TV monitoring may be useful to evaluate the work of breathing. A non-invasive device based on bioimpedance provides continuous and real-time volumetric tidal estimation during spontaneous breathing. We performed a prospective study in healthy volunteers aimed at evaluating the accuracy, the precision and the trending ability of measurements of ExSpiron®Xi as compared with the gold standard (i.e. spirometry). Further, we explored whether the differences between the 2 devices would be improved by the calibration of ExSpiron®Xi with a pre-determined tidal volume. Analysis accounted for the repeated nature of measurements within each subject. We enrolled 13 healthy volunteers, including 5 men and 8 women. Tidal volume, TV/ideal body weight (IBW) and respiratory rate (RR) measured with spirometer (TVSpirometer) and with ExSpiron®Xi (TVExSpiron) showed a robust correlation, while minute ventilation (MV) showed a weak correlation, in both non/calibrated and calibrated steps. The analysis of the agreement showed that non-calibrated TVExSpiron underestimated TVspirometer, while in the calibrated steps, TVExSpiron overestimated TVspirometer. The calibration procedure did not reduce the average absolute difference (error) between TVSpirometer and TVExSpiron. This happened similarly for TV/IBW and MV, while RR showed high accuracy and precision. The trending ability was excellent for TV, TV/IBW and RR. The concordance rate (CR) was >95% in both calibrated and non-calibrated measurements. The trending ability of minute ventilation was limited. Absolute error for both calibrated and not calibrated values of TV, TV/IBW and MV accounting for repeated measurements was variably associated with BMI, height and smoking status. Conclusions: Non-invasive TV, TV/IBW and RR estimation by ExSpiron®Xi was strongly correlated with tidal ventilation according to the gold standard spirometer technique. This data was not confirmed for MV. The calibration of the device did not improve its performance. Although the accuracy of ExSpiron®Xi was mild and the precision was limited for TV, TV/IBW and MV, the trending ability of the device was strong specifically for TV, TV/IBW and RR. This makes ExSpiron®Xi a non-invasive monitoring system that may detect real-time tidal volume ventilation changes and then suggest the need to better optimize the patient ventilatory support.

Hemodynamic failure and graft dysfunction after lung transplant: A possible clinical continuum with immediate and long-term consequences.

INTRODUCTION: The postoperative hemodynamic management after lung transplant (LUTX) is guided by limited evidence. We aimed to describe and evaluate risk factors and outcomes of postoperative vasoactive support of LUTX recipients. METHODS: In a single-center retrospective analysis of consecutive adult LUTX, two cohorts were identified: (1) patients needing prolonged vasoactive support (>12 h from ICU admission) (VASO+); (2) or not (VASO-). Postoperative hemodynamic characteristics were thoroughly analyzed. Risk factors and outcomes of VASO+ versus VASO- cohorts were assessed by multivariate logistic regression and propensity score matching. RESULTS: One hundred and thirty-eight patients were included (86 (62%) VASO+ versus 52 (38%) VASO-). Vasopressors (epinephrine, norepinephrine, dopamine) were used in the first postoperative days (vasoactive inotropic score at 12 h: 6 [4-12]), while inodilators (dobutamine, levosimendan) later. Length of vasoactive support was 3 [2-4] days. Independent predictors of vasoactive use were: LUTX indication different from cystic fibrosis (p = .003), higher Oto score (p = .020), longer cold ischemia time (p = .031), but not preoperative cardiac catheterization. VASO+ patients showed concomitant hemodynamic and graft impairment, with longer mechanical ventilation (p = .010), higher primary graft dysfunction (PGD) grade at 72 h (PGD grade > 0 65% vs. 31%, p = .004, OR 4.2 [1.54-11.2]), longer ICU (p < .001) and hospital stay (p = .013). Levosimendan as a second-line inodilator appeared safe. CONCLUSIONS: Vasoactive support is frequently necessary after LUTX, especially in recipients of grafts of lesser quality. Postoperative hemodynamic dysfunction requiring vasopressor support and graft dysfunction may represent a clinical continuum with immediate and long-term consequences. Further studies may elucidate if this represents a possible treatable condition.

Validation of a tool for estimating clinician recognition of ARDS using data from the international LUNG SAFE study.

Under-recognition of acute respiratory distress syndrome (ARDS) by clinicians is an important barrier to adoption of evidence-based practices such as low tidal volume ventilation. The burden created by the COVID-19 pandemic makes it even more critical to develop scalable data-driven tools to improve ARDS recognition. The objective of this study was to validate a tool for accurately estimating clinician ARDS recognition rates using discrete clinical characteristics easily available in electronic health records. We conducted a secondary analysis of 2,705 ARDS and 1,261 non-ARDS hypoxemic patients in the international LUNG SAFE cohort. The primary outcome was validation of a tool that estimates clinician ARDS recognition rates from health record data. Secondary outcomes included the relative impact of clinical characteristics on tidal volume delivery and clinician documentation of ARDS. In both ARDS and non-ARDS patients, greater height was associated with lower standardized tidal volume (mL/kg PBW) (ARDS: adjusted ß = -4.1, 95% CI -4.5 --3.6; non-ARDS: ß = -7.7, 95% CI -8.8 --6.7, P<0.00009 [where α = 0.01/111 with the Bonferroni correction]). Standardized tidal volume has already been normalized for patient height, and furthermore, height was not associated with clinician documentation of ARDS. Worsening hypoxemia was associated with both increased clinician documentation of ARDS (ß = -0.074, 95% CI -0.093 --0.056, P<0.00009) and lower standardized tidal volume (ß = 1.3, 95% CI 0.94-1.6, P<0.00009) in ARDS patients. Increasing chest imaging opacities, plateau pressure, and clinician documentation of ARDS also were associated with lower tidal volume in ARDS patients. Our EHR-based data-driven approach using height, gender, ARDS documentation, and lowest standardized tidal volume yielded estimates of clinician ARDS recognition rates of 54% for mild, 63% for moderate, and 73% for severe ARDS. Our tool replicated clinician-reported ARDS recognition in the LUNG SAFE study, enabling the identification of ARDS patients at high risk of being unrecognized. Our approach can be generalized to other conditions for which there is a need to increase adoption of evidence-based care.

Time-Trends in Air Pollution Impact on Health in Italy, 1990-2019: An Analysis From the Global Burden of Disease Study 2019.

Objectives: We explored temporal variations in disease burden of ambient particulate matter 2.5 µm or less in diameter (PM2.5) and ozone in Italy using estimates from the Global Burden of Disease Study 2019. Methods: We compared temporal changes and percent variations (95% Uncertainty Intervals [95% UI]) in rates of disability adjusted life years (DALYs), years of life lost, years lived with disability and mortality from 1990 to 2019, and variations in pollutant-attributable burden with those in the overall burden of each PM2.5- and ozone-related disease. Results: In 2019, 467,000 DALYs (95% UI: 371,000, 570,000) were attributable to PM2.5 and 39,600 (95% UI: 18,300, 61,500) to ozone. The crude DALY rate attributable to PM2.5 decreased by 47.9% (95% UI: 10.3, 65.4) from 1990 to 2019. For ozone, it declined by 37.0% (95% UI: 28.9, 44.5) during 1990-2010, but it increased by 44.8% (95% UI: 35.5, 56.3) during 2010-2019. Age-standardized rates declined more than crude ones. Conclusion: In Italy, the burden of ambient PM2.5 (but not of ozone) significantly decreased, even in concurrence with population ageing. Results suggest a positive impact of air quality regulations, fostering further regulatory efforts.

Weaning from mechanical ventilation in intensive care units across 50 countries (WEAN SAFE): a multicentre, prospective, observational cohort study.

BACKGROUND: Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. METHODS: WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. FINDINGS: Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0-4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2-6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. INTERPRETATION: In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates. FUNDING: European Society of Intensive Care Medicine, European Respiratory Society.