Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Comprehensive Cleft Care Delivery in Developing Countries: Impact of Geographic and Demographic Factors

INTRODUCTION: The authors analyzed the insights of participants and faculty members of Global Smile Foundation's Comprehensive Cleft Care Workshops concerning the barriers and interventions to multidisciplinary cleft care delivery, after stratification based on demographic and geographic factors. METHODS: During 2 simulation-based Comprehensive Cleft Care Workshops organized by Global Smile Foundation, participants and faculty members filled a survey. Surveys included demographic and geographic data and investigated the most relevant barrier to multidisciplinary cleft care and the most significant intervention to deliver comprehensive cleft care in outreach settings, as perceived by participants. RESULTS: The total response rate was 57.8%. Respondents reported that the greatest barrier to comprehensive cleft care was financial, and the most relevant intervention to deliver multidisciplinary cleft care was building multidisciplinary teams. Stratification by age, gender, and geographical area showed no statistical difference in reporting that the greatest barrier to cleft care was financial. However, lack of multidisciplinary teams was the most important barrier according to respondents with less than 5 years of experience (P = 0.03). Stratification by gender, years in practice, specialty, and geographical area showed no statistical difference, with building multidisciplinary teams reported as the most significant intervention. However, increased training was reported as the main intervention to cleft care for those aged less than 30 years old (P = 0.04). CONCLUSIONS: Our study delivers an assessment for barriers facing multidisciplinary cleft care delivery and interventions required to improve cleft care delivery. The authors are hoping that stratification by demographic and geographic factors will help them delineate community-specific road maps to refine cleft care delivery

Simulation-Based Comprehensive Cleft Care Workshops: A Reproducible Model for Sustainable Education

Objective: Evaluate simulation-based comprehensive cleft care workshops as a reproducible model for education with sustained impact. Design: Cross-sectional survey-based evaluation. Setting: Simulation-based comprehensive cleft care workshop. Participants: Total of 180 participants. Interventions: Three-day simulation-based comprehensive cleft care workshop. Main Outcome Measures: Number of workshop participants stratified by specialty, satisfaction with the workshop, satisfaction with simulation-based workshops as educational tools, impact on cleft surgery procedural confidence, short-term impact on clinical practice, medium-term impact on clinical practice. Results: The workshop included 180 participants from 5 continents. The response rate was 54.5%, with participants reporting high satisfaction with all aspects of the workshop and with simulation-based workshops as educational tools. Participants reported a significant improvement in cleft lip (33.3 ± 5.7 vs 25.7 ± 7.6; P <.001) and palate (32.4 ± 7.1 vs 23.7 ± 6.6; P <.001) surgery procedural confidence following the simulation sessions. Participants also reported a positive short-term and medium-term impact on their clinical practices. Conclusion: Simulation-based comprehensive cleft care workshops are well received by participants, lead to improved cleft surgery procedural confidence, and have a sustained positive impact on participants’ clinical practices. Future efforts should focus on evaluating and quantifying this perceived positive impact, as well reproducing these efforts in other areas of need

The First Hybrid International Educational Comprehensive Cleft Care Workshop.

OBJECTIVE Describe the first hybrid global simulation-based comprehensive cleft care workshop, evaluate impact on participants, and compare experiences based on in-person versus virtual attendance. DESIGN Cross-sectional survey-based evaluation. SETTING International comprehensive cleft care workshop. PARTICIPANTS Total of 489 participants. INTERVENTIONS Three-day simulation-based hybrid comprehensive cleft care workshop. MAIN OUTCOME MEASURES Participant demographic data, perceived barriers and interventions needed for global comprehensive cleft care delivery, participant workshop satisfaction, and perceived short-term impact on practice stratified by in-person versus virtual attendance. RESULTS The workshop included 489 participants from 5 continents. The response rate was 39.9%. Participants perceived financial factors (30.3%) the most significant barrier and improvement in training (39.8%) as the most important intervention to overcome barriers facing cleft care delivery in low to middle-income countries. All participants reported a high level of satisfaction with the workshop and a strong positive perceived short-term impact on their practice. Importantly, while this was true for both in-person and virtual attendees, in-person attendees reported a significantly higher satisfaction with the workshop (28.63 ± 3.08 vs 27.63 ± 3.93; P = .04) and perceived impact on their clinical practice (22.37 ± 3.42 vs 21.02 ± 3.45 P = .01). CONCLUSION Hybrid simulation-based educational comprehensive cleft care workshops are overall well received by participants and have a positive perceived impact on their clinical practices. In-person attendance is associated with significantly higher satisfaction and perceived impact on practice. Considering that financial and health constraints may limit live meeting attendance, future efforts will focus on making in-person and virtual attendance more comparable