Utility of point of care ultrasound for identifying dental abscesses in emergency department patients presenting with dental pain

Introduction: Computed tomography (CT) is the current gold standard for diagnosing dental abscesses in the Emergency Department (ED). There are limitations to using CT, including high cost, radiation exposure, and lengthy time to diagnosis. Point of Care Ultrasound (POCUS) is an alternative imaging modality that does not have these limitations, and is already used to diagnose other soft tissue abscesses. The efficacy of POCUS for diagnosing suspected dental abscesses has never been investigated. The purpose of this project is to compare the utility of POCUS to CT in diagnosing suspected dental abscesses in the ED. Methods: A convenience sample of patients presenting to the ED with dental pain were enrolled into a prospective observational cohort study design, when trained providers were available. Patients were eligible for enrollment after a CT was ordered. The ability of POCUS to identify dental abscesses was compared to CT in each patient. Data was collected using REDCap, and analyzed testing for non-inferiority. Results: Preliminary results indicate that POCUS is non-inferior to CT at diagnosing dental abscesses (p=0.002, n=31). Additionally, the time to diagnosis is significantly shorter for POCUS compared to CT (p\u3c0.0001). Conclusions: These results suggest that POCUS may be an adequate tool for evaluating suspected dental abscesses in the ED. Due to decreased time to diagnosis, patients with suspected dental abscesses receiving POCUS instead of CT as an initial diagnostic imaging study may receive treatment and disposition significantly earlier. This could potentially lead to improved outcomes in patients

The Clicker Study

Purpose: A recent study in orthopedics showed that clicker-based learning was more effective than traditional feedback when teaching procedures. We sought to determine whether this principle is applicable to ultrasound skills. Methods: Our prospective randomized control trial used a population of new ultrasound learners. Exclusion criteria included previous ultrasound experience of more than one hour. Students were shown an instructional video on the Focused Assessment with Sonography in Trauma (FAST) exam and randomized to receive clicker or scripted feedback. Each student performed the FAST exam once without feedback, then with either scripted or clicker-based feedback. They were timed and scored on 18 microskills. Results and Conclusions: 45 students were enrolled in the study, with 6 excluded from analysis. This included 24 premedical and 15 medical students. No significant differences were observed between groups for time or accuracy on the FAST exam. Among medical students, there was a trend toward faster results in the clicker group (mean=83 seconds) than the script group (mean=103 seconds) (p=0.22). Among undergraduates, there was a trend toward higher accuracy in the script group (mean=100%) than the clicker group (mean=95%) (p=0.068) and towards faster performance (mean=103 seconds) than the clicker group (mean=121 seconds) (p=0.38). Although no significant differences were observed, there seemed to be a trend toward faster performance with clicker feedback among medical students and faster and more accurate performance with scripted feedback among premedical students. This may be an area for future study

Cholera Toxin B Subunits Assemble into Pentamers - Proposition of a Fly-Casting Mechanism

The cholera toxin B pentamer (CtxB5), which belongs to the AB5 toxin family, is used as a model study for protein assembly. The effect of the pH on the reassembly of the toxin was investigated using immunochemical, electrophoretic and spectroscopic methods. Three pH-dependent steps were identified during the toxin reassembly: (i) acquisition of a fully assembly-competent fold by the CtxB monomer, (ii) association of CtxB monomer into oligomers, (iii) acquisition of the native fold by the CtxB pentamer. The results show that CtxB5 and the related heat labile enterotoxin LTB5 have distinct mechanisms of assembly despite sharing high sequence identity (84%) and almost identical atomic structures. The difference can be pinpointed to four histidines which are spread along the protein sequence and may act together. Thus, most of the toxin B amino acids appear negligible for the assembly, raising the possibility that assembly is driven by a small network of amino acids instead of involving all of them

The accuracy of self-performed ultrasound tele-guidance image acquisition among laypeople

Background: The recent events of COVID-19 has expedited an evolving interest in furthering telemedicine technology to maximize the quality of remote healthcare provided to patients. Studies that assessed the quality of lung and cardiac tele-ultrasound images performed by patients under supervision to be of satisfactory quality for diagnosis and management.2,3 Objectives: We set out to investigate the practical feasibility, performance, and acceptability of tele-ultrasound performed under real-time supervision. Curricular Design: A consensus group of patients over 18 years of age and without any fever, skin rash, pregnancy, and incarceration. This is a single-center prospective trial performed at Jefferson Internal Medicine Associates (JIMA). Participants will have an instruction sheet on how to turn on the device. Through tele-communication participants will be instructed to use the Philips Lumify® ultrasound transducer. The participant will apply the transducer on their antecubital fossa. The image will be saved with no identifier. The quality of all images will be assessed by a certified Ultrasound physician. Applicability: Successful results at the conclusion of this study will demonstrate the feasibility for patients to self-obtain tele-ultrasound images under proper instruction that are both accurate and diagnostically helpful. This imaging technique can possibly empower patients to have a direct role in managing their health and provide clinicians valuable diagnostic information that would have otherwise been obtained at bedside or in the office. A new depth to telemedicine can help establish this arm of medicine as more independent, and thus reducing the need for patients to physically meet with a provider

GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19

Data availability: Downloadable summary data are available through the GenOMICC data site (https://genomicc.org/data). Summary statistics are available, but without the 23andMe summary statistics, except for the 10,000 most significant hits, for which full summary statistics are available. The full GWAS summary statistics for the 23andMe discovery dataset will be made available through 23andMe to qualified researchers under an agreement with 23andMe that protects the privacy of the 23andMe participants. For further information and to apply for access to the data, see the 23andMe website (https://research.23andMe.com/dataset-access/). All individual-level genotype and whole-genome sequencing data (for both academic and commercial uses) can be accessed through the UKRI/HDR UK Outbreak Data Analysis Platform (https://odap.ac.uk). A restricted dataset for a subset of GenOMICC participants is also available through the Genomics England data service. Monocyte RNA-seq data are available under the title ‘Monocyte gene expression data’ within the Oxford University Research Archives (https://doi.org/10.5287/ora-ko7q2nq66). Sequencing data will be made freely available to organizations and researchers to conduct research in accordance with the UK Policy Framework for Health and Social Care Research through a data access agreement. Sequencing data have been deposited at the European Genome–Phenome Archive (EGA), which is hosted by the EBI and the CRG, under accession number EGAS00001007111.Extended data figures and tables are available online at https://www.nature.com/articles/s41586-023-06034-3#Sec21 .Supplementary information is available online at https://www.nature.com/articles/s41586-023-06034-3#Sec22 .Code availability: Code to calculate the imputation of P values on the basis of SNPs in linkage disequilibrium is available at GitHub (https://github.com/baillielab/GenOMICC_GWAS).Acknowledgements: We thank the members of the Banco Nacional de ADN and the GRA@CE cohort group; and the research participants and employees of 23andMe for making this work possible. A full list of contributors who have provided data that were collated in the HGI project, including previous iterations, is available online (https://www.covid19hg.org/acknowledgements).Change history: 11 July 2023: A Correction to this paper has been published at: https://doi.org/10.1038/s41586-023-06383-z. -- In the version of this article initially published, the name of Ana Margarita Baldión-Elorza, of the SCOURGE Consortium, appeared incorrectly (as Ana María Baldion) and has now been amended in the HTML and PDF versions of the article.Copyright © The Author(s) 2023, Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).GenOMICC was funded by Sepsis Research (the Fiona Elizabeth Agnew Trust), the Intensive Care Society, a Wellcome Trust Senior Research Fellowship (to J.K.B., 223164/Z/21/Z), the Department of Health and Social Care (DHSC), Illumina, LifeArc, the Medical Research Council, UKRI, a BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070 and BBS/E/D/30002275) and UKRI grants MC_PC_20004, MC_PC_19025, MC_PC_1905 and MRNO2995X/1. A.D.B. acknowledges funding from the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z), the Edinburgh Clinical Academic Track (ECAT) programme. This research is supported in part by the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant MC_PC_20029). Laboratory work was funded by a Wellcome Intermediate Clinical Fellowship to B.F. (201488/Z/16/Z). We acknowledge the staff at NHS Digital, Public Health England and the Intensive Care National Audit and Research Centre who provided clinical data on the participants; and the National Institute for Healthcare Research Clinical Research Network (NIHR CRN) and the Chief Scientist’s Office (Scotland), who facilitate recruitment into research studies in NHS hospitals, and to the global ISARIC and InFACT consortia. GenOMICC genotype controls were obtained using UK Biobank Resource under project 788 funded by Roslin Institute Strategic Programme Grants from the BBSRC (BBS/E/D/10002070 and BBS/E/D/30002275) and Health Data Research UK (HDR-9004 and HDR-9003). UK Biobank data were used in the GSMR analyses presented here under project 66982. The UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government, British Heart Foundation and Diabetes UK. The work of L.K. was supported by an RCUK Innovation Fellowship from the National Productivity Investment Fund (MR/R026408/1). J.Y. is supported by the Westlake Education Foundation. SCOURGE is funded by the Instituto de Salud Carlos III (COV20_00622 to A.C., PI20/00876 to C.F.), European Union (ERDF) ‘A way of making Europe’, Fundación Amancio Ortega, Banco de Santander (to A.C.), Cabildo Insular de Tenerife (CGIEU0000219140 ‘Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19’ to C.F.) and Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC20/57 to C.F.). We also acknowledge the contribution of the Centro National de Genotipado (CEGEN) and Centro de Supercomputación de Galicia (CESGA) for funding this project by providing supercomputing infrastructures. A.D.L. is a recipient of fellowships from the National Council for Scientific and Technological Development (CNPq)-Brazil (309173/2019-1 and 201527/2020-0)

Mapping the human genetic architecture of COVID-19

The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases3,4,5,6,7. They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease