UNASSIGNED: SARS-CoV2 can cause pulmonary failure requiring prolonged invasive mechanical ventilation (MV). Lung protective ventilation strategies are recommended in order to minimize ventilator induced lung injury. Whether patients with COVID-19 have the same risk for complications including barotrauma is still unknown. Therefore, we investigated barotrauma in patients with COVID-19 pneumonia requiring prolonged MV.
UNASSIGNED: All patients meeting diagnosis criteria for ARDS according to the Berlin Definition, with PCR positive SARS-CoV2 infection and prolonged mechanical ventilation, defined as ≥2 days, treated at our ARDS referral center between March and April 2020 were included in a retrospective registry analysis. Complications were detected by manual review of all patient data including respiratory data, imaging studies, and patient files.
UNASSIGNED: A total of 20 patients with severe COVID-19 pulmonary failure (Overall characteristics: median age: 61 years, female gender 6, median duration of MV 22 days) were analyzed. Eight patients (40%) developed severe barotrauma during MV (after median 18 days, range: 1-32) including pneumothorax (5/20), pneumomediastinum (5/20), pneumopericard (1/20), and extended subcutaneous emphysema (5/20). Median respirator settings 24 hours before barotrauma were: Peak inspiratory pressure (Ppeak) 29 cm H2O (range: 27-35), positive end-expiratory pressure (PEEP) 14 cm H2O (range: 5-24), tidal volume (VT) 5.4ml/kg predicted body weight (range 0.4-8.6), plateau pressure (Pplateau) 27 cm H2O (range: 19-30). Mechanical ventilation was significantly more invasive on several occasions in patients without barotrauma.
UNASSIGNED: Barotrauma in COVID-19 induced respiratory failure requiring mechanical ventilation was found in 40% of patients included in this registry. Our data suggest that barotrauma in COVID-19 may occur even when following recommendations for lung protective MV.

The burden of traumatic brain injury (TBI) poses a large public health and societal problem, but the characteristics of patients and their care pathways in Europe are poorly understood. We aimed to characterise patient case-mix, care pathways, and outcomes of TBI.
CENTER-TBI is a Europe-based, observational cohort study, consisting of a core study and a registry. Inclusion criteria for the core study were a clinical diagnosis of TBI, presentation fewer than 24 h after injury, and an indication for CT. Patients were differentiated by care pathway and assigned to the emergency room (ER) stratum (patients who were discharged from an emergency room), admission stratum (patients who were admitted to a hospital ward), or intensive care unit (ICU) stratum (patients who were admitted to the ICU). Neuroimages and biospecimens were stored in repositories and outcome was assessed at 6 months after injury. We used the IMPACT core model for estimating the expected mortality and proportion with unfavourable Glasgow Outcome Scale Extended (GOSE) outcomes in patients with moderate or severe TBI (Glasgow Coma Scale [GCS] score ≤12). The core study was registered with ClinicalTrials.gov, number NCT02210221, and with Resource Identification Portal (RRID: SCR_015582).
Data from 4509 patients from 18 countries, collected between Dec 9, 2014, and Dec 17, 2017, were analysed in the core study and from 22 782 patients in the registry. In the core study, 848 (19%) patients were in the ER stratum, 1523 (34%) in the admission stratum, and 2138 (47%) in the ICU stratum. In the ICU stratum, 720 (36%) patients had mild TBI (GCS score 13-15). Compared with the core cohort, the registry had a higher proportion of patients in the ER (9839 [43%]) and admission (8571 [38%]) strata, with more than 95% of patients classified as having mild TBI. Patients in the core study were older than those in previous studies (median age 50 years [IQR 30-66], 1254 [28%] aged >65 years), 462 (11%) had serious comorbidities, 772 (18%) were taking anticoagulant or antiplatelet medication, and alcohol was contributory in 1054 (25%) TBIs. MRI and blood biomarker measurement enhanced characterisation of injury severity and type. Substantial inter-country differences existed in care pathways and practice. Incomplete recovery at 6 months (GOSE <8) was found in 207 (30%) patients in the ER stratum, 665 (53%) in the admission stratum, and 1547 (84%) in the ICU stratum. Among patients with moderate-to-severe TBI in the ICU stratum, 623 (55%) patients had unfavourable outcome at 6 months (GOSE <5), similar to the proportion predicted by the IMPACT prognostic model (observed to expected ratio 1·06 [95% CI 0·97-1·14]), but mortality was lower than expected (0·70 [0·62-0·76]).
Patients with TBI who presented to European centres in the core study were older than were those in previous observational studies and often had comorbidities. Overall, most patients presented with mild TBI. The incomplete recovery of many patients should motivate precision medicine research and the identification of best practices to improve these outcomes.
European Union 7th Framework Programme, the Hannelore Kohl Stiftung, OneMind, and Integra LifeSciences Corporation.

BACKGROUND: After the sample size of a randomized clinical trial (RCT) is set by the power requirement of its primary endpoint, investigators select secondary endpoints while unable to further adjust sample size. How the sensitivity and specificity of an instrument used to measure these outcomes, together with their expected underlying event rates, affect an RCT\'s power to measure significant differences in these outcomes is poorly understood.
OBJECTIVE: Motivated by the design of an RCT of neuromuscular blockade in acute respiratory distress syndrome, we examined how power to detect a difference in secondary endpoints varies with the sensitivity and specificity of the instrument used to measure such outcomes.
METHODS: We derived a general formula and Stata code for calculating an RCT\'s power to detect differences in binary outcomes when such outcomes are measured with imperfect sensitivity and specificity. The formula informed the choice of instrument for measuring post-traumatic stress-like symptoms in the Reevaluation of Systemic Early Neuromuscular Blockade RCT ( www.clinicaltrials.gov identifier NCT02509078).
RESULTS: On the basis of published sensitivities and specificities, the Impact of Events Scale-Revised was predicted to measure a 36% symptom rate, whereas the Post-Traumatic Stress Symptoms instrument was predicted to measure a 23% rate, if the true underlying rate of post-traumatic stress symptoms were 25%. Despite its lower sensitivity, the briefer Post-Traumatic Stress Symptoms instrument provided superior power to detect a difference in rates between trial arms, owing to its higher specificity.
CONCLUSIONS: Examining instruments\' power to detect differences in outcomes may guide their selection when multiple instruments exist, each with different sensitivities and specificities.

Higher hospital case volume may produce local expertise (\"practice makes perfect\"), resulting in better patient outcomes. Associations between hospital noninvasive ventilation (NIV) case volume and outcomes for patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) are unclear.
To determine associations between total hospital NIV case volume for all indications and NIV failure and hospital mortality among patients with acute exacerbations of COPD.
Using the 2011 California State Inpatient Database and multivariable hierarchical logistic regression, we calculated hospital-level risk-adjusted rates for NIV failure (progression from NIV to invasive mechanical ventilation) and hospital mortality among patients with acute exacerbations of COPD.
We identified 37,516 hospitalizations for acute exacerbations of COPD in 252 California hospitals in 2011. Total hospital NIV use for all indications ranged from 2 to 565 cases (median, 64; interquartile range, 96). Hospital NIV failure rates for acute exacerbations of COPD ranged from 3.7 to 31.3% (median, 8.5%; interquartile range, 4.2). At the hospital level, higher total hospital NIV case volume was weakly associated with higher hospital NIV failure rates for acute exacerbations of COPD (r = 0.13; P = 0.03). Higher hospital NIV failure rates were weakly associated with higher hospital mortality rates for acute exacerbations of COPD (r = 0.15; P = 0.02), but higher total hospital NIV case volume was not associated with hospital mortality for exacerbations of COPD (r = -0.11; P = 0.08). At the patient level, patients admitted to high-NIV versus low-NIV case-volume hospitals had greater odds of NIV failure (quartile 4 vs. quartile 1 adjusted odds ratio [aOR], 1.95; 95% confidence interval [CI], 1.12-3.40). Compared with initial treatment with invasive mechanical ventilation, NIV failure was associated with higher odds of death (aOR, 1.81; 95% CI, 1.35-2.44). However, admission to high-NIV versus low-NIV case-volume hospitals was not significantly associated with patient in-hospital mortality (quartile 4 vs. quartile 1 aOR, 0.76; 95% CI, 0.57-1.02).
Despite strong evidence for use of NIV in the management of acute exacerbations of COPD, we observed no significant mortality benefit and higher rates of NIV failure in high-NIV case-volume hospitals. Further investigation of patient selection and hospital factors associated with NIV failure is needed to maximize favorable patient outcomes associated with use of NIV for acute exacerbations of COPD.