The Time to Offer Treatments for COVID-19

Introduction: COVID-19 has several overlapping phases. Treatment has focused on the late stage of the disease in hospital. Yet, the continuation of the pandemic is by propagation of the disease in outpatients. The current public health strategy relies solely on vaccines to prevent disease. Areas Covered: We searched the major national registries, pubmed.org, and the preprint servers for all ongoing, completed and published trial results with subject numbers of 100 or more on, and used a targeted search to find announcements of unpublished trial results. As of 2/15/2021, we found 111 publications reporting findings in human studies on 14 classes of agents, and on 9 vaccines. There were 62 randomized controlled studies, the rest retrospective observational analyses. Only 21 publications dealt with outpatient care, the rest all in hospitalized patients. Remdesivir and convalescent plasma have emergency use authorization for hospitalized patients in the U.S.A. There is also support for glucocorticoid treatment of the COVID-19 respiratory distress syndrome. Monoclonal antibodies are authorized for outpatients, but the supply is inadequate to treat all at time of diagnosis. Favipiravir, ivermectin, and interferons are approved in certain countries Expert Opinion: Worldwide vaccination is now underway. Vaccines and antibodies are highly antigen specific and new variants are appearing. There is a need for treatment of outpatients who contract the disease, in addition to mass immunization. We call on public health authorities to authorize treatments with known low risk and potential benefit for use in parallel with mass immunization

Effects of eight neuropsychiatric copy number variants on human brain structure

Many copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 (n = 39/28), 16p11.2 (n = 87/78), 22q11.2 (n = 75/30), and 15q11.2 (n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen’s d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions

Lung ultrasound artifact findings in pediatric patients admitted to the intensive care unit for acute respiratory failure

Purpose: To describe point-of-care lung ultrasound (POC-LUS) artifact findings in children admitted to the pediatric intensive care unit (PICU) for acute respiratory failure (ARF). Methods: This is a secondary analysis of a prospective observational study completed in a 21-bed PICU. Children \u3e 37 weeks gestational age and ≤ 18 years were enrolled from December 2018 to February 2020. POC-LUS was completed and interpreted by separate physicians blinded to all clinical information. POC-LUS was evaluated for the presence of lung sliding, pleural line characteristics, ultrasound artifacts, and the ultrasound diagnosis. Results: Eighty-seven subjects were included. A-lines were the most frequent artifact, occurring in 58% of lung zones (163/281) in those with bronchiolitis, 39% of lung zones (64/164) in those with pneumonia, and 81% of lung zones (48/59) in those with status asthmaticus. Sub-pleural consolidation was second most common, occurring in 28% (80/281), 30% (50/164), and 12% (7/59) of those with bronchiolitis, pneumonia, and status asthmaticus, respectively. The pattern a priori defined as bronchiolitis, pneumonia, and status asthmaticus was demonstrated in 31% (15/48), 10% (3/29), and 40% (4/10) of subjects with bronchiolitis, pneumonia, and status asthmaticus, respectively. Conclusion: We found significant heterogeneity and overlap of POC-LUS artifacts across the most common etiologies of ARF in children admitted to the PICU. We have described the POC-LUS artifact findings in pediatric ARF to support clinicians using POC-LUS and to guide future pediatric POC-LUS studies. Determining the optimal role of POC-LUS as an adjunct in the care of pediatric patients requires further study

The Assessment of Competency in Thoracic Sonography (ACTS) scale: validation of a tool for point-of-care ultrasound

Abstract Background The rapid adoption of point-of-care ultrasound (POCUS) has created a need to develop assessment tools to ensure that learners can competently use these technologies. In this study, the authors developed and tested a rating scale to assess the quality of point-of-care thoracic ultrasound studies performed by novices. In Phase 1, the Assessment of Competency in Thoracic Sonography (ACTS) scale was developed based on structured interviews with subject matter experts. The tool was then piloted on a small series of ultrasound studies in Phase 2. In Phase 3 the tool was applied to a sample of 150 POCUS studies performed by ten learners; performance was then assessed by two independent raters. Results Evidence for the content validity of the ACTS scale was provided by a consensus exercise wherein experts agreed on the general principles and specific items that make up the scale. The tool demonstrated reasonable inter-rater reliability despite minimal requirements for evaluator training and displayed evidence of good internal structure, with related scale items correlating well with each other. Analysis of the aggregate learning curves suggested a rapid early improvement in learner performance with slower improvement after approximately 25–30 studies. Conclusions The ACTS scale provides a straightforward means to assess learner performance. Our results support the conclusion that the tool is an effective means of making valid judgments regarding competency in point-of-care thoracic ultrasound, and that the majority of learner improvement occurs during their first 25–30 practice studies

Comparison of chest radiograph and lung ultrasound in children with acute respiratory failure

Purpose:Chest x-ray (CXR) is the standard imaging used to evaluate children in acute respiratory distress and failure. Our objective was to compare the lung-imaging techniques of CXR and lung ultrasound (LUS) in the evaluation of children with acute respiratory failure (ARF) to quantify agreement and to determine which technique identified a higher frequency of pulmonary abnormalities. Methods:This was a secondary analysis of a prospective observational study evaluating the sensitivity and specificity of LUS in children with ARF from 12/2018 to 02/2020 completed at the University of Wisconsin-Madison (USA). Children \u3e 37.0 weeks corrected gestational age and ≤ 18 years of age admitted to the PICU with ARF were evaluated with LUS. We compared CXR and LUS completed within 6 h of each other. Kappa statistics (k) adjusted for maximum attainable agreement (k/kmax) were used to quantify agreement between imaging techniques and descriptive statistics were used to describe the frequency of abnormalities. Results:Eighty-eight children had LUS completed, 32 with concomitant imaging completed within 6 h are included. There was fair agreement between LUS and CXR derived diagnoses with 58% agreement (k/kmax = 0.36). Evaluation of imaging patterns included: normal, 57% agreement (k = 0.032); interstitial pattern, 47% agreement (k = 0.003); and consolidation, 65% agreement (k = 0.29). CXR identified more imaging abnormalities than LUS. Conclusions:There is fair agreement between CXR and LUS-derived diagnoses in children with ARF. Given this, clinicians should consider the benefits and limitations of specific imaging modalities when evaluating children with ARF. Additional studies are necessary to further define the role of LUS in pediatric ARF given the small sample size of our study

Outcomes from extensive training in critical care echocardiography: Identifying the optimal number of practice studies required to achieve competency

Purpose Optimal instruction and assessment of critical care ultrasound (CCUS) skills requires an assessment tool to measure learner competency and changes over time. In this study, a previously published tool was used to monitor the development of critical care echocardiography (CCE) competencies, the attainment of performance plateaus, and the extent to which previous experience influenced learning. Materials and methods A group of experts used the Rapid Assessment of Competency in Echocardiography (RACE) scale to rate a large pool of CCE studies performed by novices in a longitudinal design. A total of 380 studies performed by twelve learners were assessed; each study was independently rated by two experts. Results Learners demonstrated improvement