COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Simulating for Quality: A Centralized Quality Improvement and Patient Safety Simulation Curriculum for Residents and Fellows.

PROBLEM: Requirements for experiential education in quality improvement and patient safety (QI/PS) in graduate medical education (GME) have recently expanded. Major challenges to meeting these requirements include a lack of faculty with the needed expertise, paucity of standardized curricular models allowing for skill demonstration, and inconsistent access to data for iterative improvement. APPROACH: In October 2017, the authors began development of a centralized QI/PS flipped-classroom simulation-based medical education (SBME) curriculum for GME trainees across multiple disciplines at Oregon Health & Science University (OHSU). The curriculum development team included OHSU and Veterans Affairs faculty with experience in QI/PS and SBME, as well as house officers. The curriculum consisted of a pre-assessment and pre-work readings and videos (sent 3 weeks before the simulation day) and an 8-hour simulation day, with introductory activities, 4 linked simulation sessions, and concluding activities. The 4 linked simulation sessions followed the same medical error from disclosure and reporting to root cause analysis, iterative implementation of an action plan, and consolidation of lessons learned into routine operations with Lean huddles. OUTCOMES: In academic year 2018-2019, 71 residents and fellows of various postgraduate years from 23 training programs enrolled in 2 pilot sessions. Learners reacted favorably to the simulation curriculum. Learner attitudes, confidence, knowledge, and skills significantly increased across all QI/PS domains studied. NEXT STEPS: This approach focuses a small cadre of educators toward the creation of a centralized resource that, owing to its experiential SBME foundation, can accommodate many learners with data-driven practice-based learning and improvement cycles in a shorter timeframe than traditional QI initiatives. Next steps include the addition of a control group, assessment of the sustainability of learner outcomes, translation of learning to behavior change and improvements in patient and health system outcomes, and adapting the materials to include learners from different professions and levels

Increased alignment sensitivity improves the usage of genome alignments for comparative gene annotation

Genome alignments provide a powerful basis to transfer gene annotations from a well-annotated reference genome to many other aligned genomes. The completeness of these annotations crucially depends on the sensitivity of the underlying genome alignment. Here, we investigated the impact of the genome alignment parameters and found that parameters with a higher sensitivity allow the detection of thousands of novel alignments between orthologous exons that have been missed before. In particular, comparisons between species separated by an evolutionary distance of >0.75 substitutions per neutral site, like human and other non-placental vertebrates, benefit from increased sensitivity. To systematically test if increased sensitivity improves comparative gene annotations, we built a multiple alignment of 144 vertebrate genomes and used this alignment to map human genes to the other 143 vertebrates with CESAR. We found that higher alignment sensitivity substantially improves the completeness of comparative gene annotations by adding on average 2382 and 7440 novel exons and 117 and 317 novel genes for mammalian and non-mammalian species, respectively. Our results suggest a more sensitive alignment strategy that should generally be used for genome alignments between distantly-related species. Our 144-vertebrate genome alignment and the comparative gene annotations (https://bds.mpi-cbg.de/hillerlab/144VertebrateAlignment_CESAR/) are a valuable resource for comparative genomics

Creation of an International Interprofessional Simulation-enhanced Mechanical Ventilation Course

BACKGROUND: Evidence shows poor adherence to strategies for reducing morbidity and mortality in intensive care unit (ICU) patients receiving mechanical ventilation globally. Best practice management relies on training all members of the interprofessional ICU team, each with complementary roles in patient management. OBJECTIVES: To develop and evaluate a novel two-phase, train-the-trainer, interprofessional and multicultural "Best Practice Management of the Ventilated ICU Patient" multimodality, simulation-enhanced curriculum for Thai education leaders in critical care. METHODS: In phase 1 (Oregon Health and Science University cohort), two groups of nine ICU nurses and one critical care physician representing experts in critical care and education from a large hospital system in Thailand participated in a weeklong, immersive course consisting of didactic, simulation, and in situ immersive sessions focused on best practice management of mechanically ventilated ICU patients, as well as training in our educational techniques. Outcomes were assessed with pre- and postcourse knowledge assessments and overall course evaluation. In phase 2 (Thai cohort), participants from phase 1 returned to Thailand and implemented a lower fidelity curriculum in two hospitals, using the same pre- and posttest knowledge assessment in 41 participants, before the onset of the coronavirus disease (COVID-19) 6 pandemic. RESULTS: In the Oregon Health and Science University cohort, the mean pretest knowledge score was 58.4 +/- 13.2%, with a mean improvement to 82.5 +/- 11.6% after completion of the course (P < 0.05). The greatest improvements were seen in respiratory physiology and advanced/disease-specific concepts, which demonstrated absolute improvements of 30.4% and 30.6%, respectively (P < 0.05). Participants had a high degree of satisfaction, with 90% rating the course as "excellent" and .90% reporting that the course "greatly improved" their understanding of best practices and comfort in managing mechanical ventilation. The Thai cohort had a mean baseline score of 45.4 +/- 15.0% and a mean improvement to 70.3 +/- 19.1% after training (P < 0.05). This cohort also saw the greatest improvement in respiratory physiology and advanced/disease-specific concepts, with 26.2% and 26.3% absolute improvements, respectively (P < 0.05). CONCLUSION: A novel, two-phase, interprofessional, multicultural, simulation-enhanced train-the-trainer curriculum was feasible and effective in improving education in best practice management of mechanically ventilated patients and may be a useful model for improving the care of ICU patients across the world

Effects OxPAPC on barrier properties in macro- and microvascular pulmonary endothelial cells (ECs)

Human pulmonary artery (HPAEC) or microvascular (HLMVEC) ECs were plated on gold microelectrodes to measure transendothelial electrical resistance (TER) and were cultured to confluence. Growth medium was replaced with serum-free Opti-MEM (Invitrogen Corporation, Carlsbad, CA, USA). After equilibration and stabilization, measurements of TER were performed. At the time indicated by the arrow, ECs were treated with various concentrations of OxPAPC or cells were pretreated with OxPAPC (20 μg/mL) followed by thrombin (0.5 U/mL) stimulation (marked by second arrow) . Results are representative of three to six independent experiments. OxPAPC, oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine; Thr, thrombin.<p><b>Copyright information:</b></p><p>Taken from "Oxidized phospholipids reduce ventilator-induced vascular leak and inflammation "</p><p>http://ccforum.com/content/12/1/R27</p><p>Critical Care 2008;12(1):R27-R27.</p><p>Published online 24 Jan 2008</p><p>PMCID:PMC2374596.</p><p></p

Effects of Rho kinase inhibition on severity of high tidal volume (HTV)-induced lung injury

Mice received a single dose of Rho kinase inhibitor Y27632 (10 mg/kg, intraperitoneal) or TRAP-6 (3 × 10mol/mouse, intravenous) followed by mechanical ventilation (30 mL/kg, 4 hours) with or without OxPAPC injection (1.5 mg/kg, intravenous). Inhibition of the Rho pathway markedly attenuated HTV-induced bronchoalveolar lavage (BAL) cell count and protein content . TRAP-6 further enhanced HTV-induced increases in BAL cell count and protein content , whereas OxPAPC significantly reduced these effects. *< 0.05 (= 4 to 8 per group). Con, control; OxPAPC, oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine; TRAP-6, thrombin receptor activating peptide-6; Yinh, Y27632.<p><b>Copyright information:</b></p><p>Taken from "Oxidized phospholipids reduce ventilator-induced vascular leak and inflammation "</p><p>http://ccforum.com/content/12/1/R27</p><p>Critical Care 2008;12(1):R27-R27.</p><p>Published online 24 Jan 2008</p><p>PMCID:PMC2374596.</p><p></p

Cells subjected to pathologic cyclic stretch (CS) (18%, 2 hours) were pretreated with vehicle or OxPAPC (20 μg/mL) followed by thrombin (0

5 U/mL) stimulation for 30 or 50 minutes. F-actin was visualized by immunofluorescence staining with Texas-Red phalloidin. Cells subjected to CS and thrombins (30 or 50 minutes) demonstrate barrier disruption, with the formation of transcellular actin stress fibers resulting in increased tension, cellular contraction, and paracellular gap formation (arrows). OxPAPC enhanced monolayer integrity and peripheral actin cytoskeletal rearrangement in ECs exposed to 18% CS alone and dramatically attenuated thrombin-induced gap formation and disruption of monolayer integrity and accelerated EC barrier recovery. Representative results from three independent experiments are shown. Two wells from each experiment were observed for each stimulation. OxPAPC, oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine; Thr, thrombin.<p><b>Copyright information:</b></p><p>Taken from "Oxidized phospholipids reduce ventilator-induced vascular leak and inflammation "</p><p>http://ccforum.com/content/12/1/R27</p><p>Critical Care 2008;12(1):R27-R27.</p><p>Published online 24 Jan 2008</p><p>PMCID:PMC2374596.</p><p></p