Bedside ONSD measurement, performed by neurointensivists, is an accurate, non-invasive method to identify ICP > 20 mmHg in a heterogeneous group of patients with acute brain injury. ONSD ≥0.48 cm has the greatest accuracy, however, internal validation of ONSD criteria may be required.

IMPORTANCEAcutely ill inpatients with COVID-19 typically receive antithrombotic therapy, although the risks and benefits of this intervention among outpatients with COVID-19 have not been established. OBJECTIVE To assess whether anticoagulant or antiplatelet therapy can safely reduce major adverse cardiopulmonary outcomes among symptomatic but clinically stable outpatients with COVID-19. DESIGN, SETTING, AND PARTICIPANTSThe ACTIV-4B Outpatient Thrombosis Prevention Trial was designed as a minimal-contact, adaptive, randomized, double-blind, placebo-controlled trial to compare anticoagulant and antiplatelet therapy among 7000 symptomatic but clinically stable outpatients with COVID-19. The trial was conducted at 52 US sites between September 2020 and June 2021; final follow-up was August 5, 2021. Prior to initiating treatment, participants were required to have platelet count greater than 100 000/mm 3 and estimated glomerular filtration rate greater than 30 mL/min/1.73 m 2 .INTERVENTIONS Random allocation in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days. MAIN OUTCOMES AND MEASURESThe primary end point was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause. The primary analyses for efficacy and bleeding events were limited to participants who took at least 1 dose of trial medication. RESULTSOn June 18, 2021, the trial data and safety monitoring board recommended early terminationbecauseoflowerthananticipatedeventrates;atthattime,657symptomaticoutpatients with COVID-19 had been randomized (median age, 54 years [IQR,[46][47][48][49][50][51][52][53][54][55][56][57][58][59]; 59% women). The median times from diagnosis to randomization and from randomization to initiation of study treatment were 7 days and 3 days, respectively. Twenty-two randomized participants (3.3%) were hospitalized for COVID-19 prior to initiating treatment. Among the 558 patients who initiated treatment, the adjudicated primary composite end point occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5-mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group. The risk differences compared with placebo for the primary end point were 0.0% (95% CI not calculable) in the aspirin group, 0.7% (95% CI, -2.1% to 4.1%) in the 2.5-mg apixaban group, and 1.4% (95% CI, -1.5% to 5.0%) in the 5-mg apixaban group. Risk differences compared with placebo for bleeding events were 2.0% (95% CI, -2.7% to 6.8%), 4.5% (95% CI, -0.7% to 10.2%), and 6.9% (95% CI, 1.4% to 12.9%) among participants who initiated therapy in the aspirin, prophylactic apixaban, and therapeutic apixaban groups, respectively, although none were major. Findings inclusive of all randomized patients were similar.CONCLUSIONS AND RELEV...

IntroductionUltrasound (US) performed prior to percutaneous tracheostomy (PT) may be useful in avoiding injury to pretracheal vascular structures and in avoiding high placement of the tube. Bedside real-time US guidance with visualization of needle path is routinely utilized for other procedures such as central venous catheterization, and may enhance the safety and accuracy of PT without causing airway occlusion or hypercarbia. Our objective was to demonstrate that PT performed under real-time US guidance with visualization of needle path during tracheal puncture is feasible, including in patients with features that increase the technical difficulty of PT.MethodsMechanically ventilated patients with acute brain injury requiring tracheostomy underwent US guided PT. The orotracheal tube was withdrawn using direct laryngoscopy. The trachea was punctured under real-time US guidance (with visualization of the needle path) while using the acoustic shadows of the cricoid and the tracheal rings to identify the level of puncture. After guidewire passage the site and level of entry was verified using the bronchoscope, which was then withdrawn. Following dilatation and tube placement, placement in the airway was confirmed using auscultation and the "lung sliding" sign on US. Bronchoscopy and chest X-ray were then performed to identify any complications.ResultsThirteen patients successfully underwent US guided PT. Three patients were morbidly obese, two were in cervical spine precautions and one had a previous tracheostomy. In all 13 patients bronchoscopy confirmed that guidewire entry was through the anterior wall and between the first and fifth tracheal rings. There was no case of tube misplacement, pneumothorax, posterior wall injury, significant bleeding or other complication during the procedure.ConclusionsPercutaneous tracheostomy performed under real-time ultrasound guidance is feasible and appears accurate and safe, including in patients with morbid obesity and cervical spine precautions. Larger studies are required to further define the safety and relative benefits of this technique.Trial registrationUMIN Clinical Trials Registry, UMIN000005023.

IntroductionOptic nerve sheath diameter (ONSD) measurement with bedside ultrasound has been shown in many studies to accurately detect high intracranial pressure (ICP). The accuracy of point-in-time ONSD measurement in the presence of ongoing fluctuation of ICP between high and normal is not known. Recent laboratory investigation suggests that reversal of optic nerve sheath distension may be impaired following bouts of intracranial hypertension. Our objective was to compare the accuracy of ONSD measurement in the setting of fluctuating versus stable ICP.MethodsThis was a retrospective analysis of data from prospective study comparing ONSD to invasive ICP. Patients with invasive ICP monitors in the ICU underwent ONSD measurement with simultaneous blinded recording of ICP from the invasive monitor. Three measurements were made in each eye. Significant acute ICP fluctuation (SAIF) was defined in two different ways; as the presence of ICP both above and below 20 mmHg within a cluster of six measurements (Definition 1) and as a magnitude of fluctuation >10 mmHg within the cluster (Definition 2). The accuracy of point-in-time ONSD measurements for the detection of concurrent ICP >20 mmHg within clusters fulfilling a specific definition of SAIF was compared to the accuracy of ONSD measurements within clusters not fulfilling the particular definition by comparison of independent receiver operating characteristic (ROC) curves.ResultsA total of 613 concurrent ONSD-ICP measurements in 109 clusters were made in 73 patients. Twenty-three (21%) clusters fulfilled SAIF Definition 1 and 17 (16%) SAIF Definition 2. For Definition 1, the difference in the area under the curve (AUC) of ROC curves for groups with and without fluctuation was 0.10 (P = 0.0001). There was a fall in the specificity from 98% (95% CI 96 to 99%) to 74% (63 to 83%) and in the positive predictive value from 89% (80 to 95%) to 76% (66 to 84%) with fluctuation. For Definition 2, also, there was a significant difference between the AUC of ROC curves of groups with fluctuation-magnitude >10 mmHg and those with fluctuation-magnitude 5 to 10 mmHg (0.06, P = 0.04) as well as <5 mmHg (0.07, P = 0.01).ConclusionsSpecificity and PPV of ONSD for ICP >20 mmHg are substantially decreased in patients demonstrating acute fluctuation of ICP between high and normal. This may be because of delayed reversal of nerve sheath distension.