Use of augmented and virtual reality in resuscitation training: A systematic review.

Objectives: To evaluate the effectiveness of augmented reality (AR) and virtual reality (VR), compared with other instructional methods, for basic and advanced life support training. Methods: This systematic review was part of the continuous evidence evaluation process of the International Liaison Committee on Resuscitation (ILCOR) and reported based on the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) guidelines and registered with PROSPERO (CRD42023376751). MEDLINE, EMBASE, and SCOPUS were searched from inception to January 16, 2024. We included all published studies comparing virtual or augmented reality to other methods of resuscitation training evaluating knowledge acquisition and retention, skills acquisition and retention, skill performance in real resuscitation, willingness to help, bystander CPR rate, and patients' survival. Results: Our initial literature search identified 1807 citations. After removing duplicates, reviewing the titles and abstracts of the remaining 1301 articles, full text review of 74 articles and searching references lists of relevant articles, 19 studies were identified for analysis. AR was used in 4 studies to provide real-time feedback during CPR, demonstrating improved CPR performance compared to groups trained with no feedback, but no difference when compared to other sources of CPR feedback. VR use in resuscitation training was explored in 15 studies, with the majority of studies that assessed CPR skills favoring other interventions over VR, or showing no difference between groups. Conclusion: Augmented and virtual reality can be used to support resuscitation training of lay people and healthcare professionals, however current evidence does not clearly demonstrate a consistent benefit when compared to other methods of training.

Engagement in Distance Healthcare Simulation Debriefing: A Concept Development and Framework.

SUMMARY STATEMENT: Understanding distance health care simulation debriefing is crucial in light of the increased use of and emerging technology in remote education for reasons of accessibility, global collaboration, and continuous professional development. This article is a confluence of a number of previously published studies designed to serve as a foundation to develop the concept of "engagement in health care distance simulation debriefing" using the Schwartz-Barcott & Kim hybrid mixed methods model. The model uses 3 phases: theoretical (a realist systematic review of the literature), fieldwork (3 exploratory studies and 2 pilot experimental studies), and analytical (analysis of the theoretical and fieldwork findings through expert discussion). This study defines the concept of "engagement in health care simulation distance debriefing" through exploration of its uses and analysis in literature, interviews, and expert review. The hybrid approach to the analysis provided rigor to generate a new, reflective conceptual model. This conceptual model defines the complexity in engagement during distance debriefing and helps shape the development of simulationists and debriefers, leading to more effective distance simulations and debriefings.

The effect of scripted debriefing in resuscitation training: A scoping review.

Objectives: To evaluate the effectiveness of scripted debriefing relative to no use of script during debriefing in resuscitation training. Methods: This scoping review was undertaken as part of the continuous evidence evaluation process of the International Liaison Committee on Resuscitation (ILCOR) and based on the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) extension for scoping review. MEDLINE, EMBASE, and SCOPUS were searched from inception to January 2024. We included all published studies comparing scripted debriefing vs non-scripted debriefing evaluating patient outcomes, behaviour change of learners, learning outcomes for learners and cognitive load and teaching quality for instructors. Results: Our initial literature search identified 1238 citations. After removing 552 duplicates, reviewing the titles and abstracts of the remaining 686 articles yielded 11 for full-text review. Of these, six articles were selected for inclusion in the final analysis. The six studies described debriefing scripts varying in content, framework, scripted language and the integration of objective data. Scripted debriefing improved CPR performance, team leadership skills and knowledge acquisition, but showed no difference in teamwork performance compared to non-scripted debriefing. Scripted debriefing also improved debriefing quality and decreased cognitive load of the instructor during resuscitation training. Conclusion: The use of a debriefing script during resuscitation education can improve CPR performance, team leader performance, knowledge acquisition and reduce the debriefer's cognitive load. Future research should explore how debriefing scripts can be designed to optimize learning outcomes.

2023 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Pediatric Life Support; Neonatal Life Support; Education, Implementation, and Teams; and First Aid Task Forces.

The International Liaison Committee on Resuscitation engages in a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation and first aid science. Draft Consensus on Science With Treatment Recommendations are posted online throughout the year, and this annual summary provides more concise versions of the final Consensus on Science With Treatment Recommendations from all task forces for the year. Topics addressed by systematic reviews this year include resuscitation of cardiac arrest from drowning, extracorporeal cardiopulmonary resuscitation for adults and children, calcium during cardiac arrest, double sequential defibrillation, neuroprognostication after cardiac arrest for adults and children, maintaining normal temperature after preterm birth, heart rate monitoring methods for diagnostics in neonates, detection of exhaled carbon dioxide in neonates, family presence during resuscitation of adults, and a stepwise approach to resuscitation skills training. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, using Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces list priority knowledge gaps for further research. Additional topics are addressed with scoping reviews and evidence updates.

Completeness and accuracy of digital charting vs paper charting in simulated pediatric cardiac arrest: a randomized controlled trial.

OBJECTIVES: To determine if data collected through digital charting are more complete and more accurate compared to traditional paper-based charting during simulated pediatric cardiac arrest. METHODS: We performed a single-center simulation-based randomized controlled trial. Participants were randomized to a novel handheld digital charting device (intervention group) or to the standard resuscitation paper chart (control group). Participants documented two 15-min simulated pediatric cardiac arrest scenarios. We compared the charting completeness between the two groups. Completeness score (primary outcome) was established by calculating a completeness score for each group based on a list of pre-determined critical tasks. Charting accuracy (secondary outcome) was compared between the two groups, defined as the time interval between the real-time task performance and charted time. RESULTS: Charting data from 34 simulated cardiac arrest events were included in the analysis (n = 18 intervention; n = 16 control). The paper charting group had a higher completeness score (median (IQR) paper vs digital: 72.0% (66.4-76.9%) vs 65.0% (58.5-66.4%), p = 0.015). For accuracy, the digital charting group was superior to the paper charting group for all pre-established critical tasks. CONCLUSION: Compared to paper-based charting, digital charting group captured more critical tasks during pediatric simulated resuscitation and was more accurate in the time intervals between real-time tasks performance and charted time. For tasks charted, paper-based charting was significantly more complete and more detailed during simulated pediatric cardiac arrest.

RéSUMé: OBJECTIFS: Déterminer si les données recueillies au moyen de la cartographie numérique sont plus complètes et plus précises que celles recueillies sur papier lors d'un arrêt cardiaque pédiatrique simulé. MéTHODES: Nous avons réalisé un essai contrôlé randomisé basé sur une simulation à centre unique. Les participants ont été affectés par randomisation à un nouvel appareil de cartographie numérique portatif (groupe d'intervention) ou au tableau papier standard de réanimation (groupe témoin). Les participants ont documenté deux scénarios simulés d'arrêt cardiaque pédiatrique de 15 min. Nous avons comparé l'exhaustivité des dossiers entre les deux groupes. Le score d'exhaustivité (résultat principal) a été établi en calculant un score d'exhaustivité pour chaque groupe en fonction d'une liste de tâches critiques prédéterminées. La précision des graphiques (résultat secondaire) a été comparée entre les deux groupes, définie comme l'intervalle de temps entre la performance de la tâche en temps réel et le temps représenté sur la carte. RéSULTATS: Les données cartographiques de 34 arrêts cardiaques simulés ont été incluses dans l'analyse (n = 18 interventions; n = 16 contrôles). Le groupe de la cartographie papier avait un score d'exhaustivité plus élevé (papier médian (IQR) que numérique: 72,0% (66,4­76,9%) contre 65,0% (58,5­66,4%), p = 0,015). Pour des raisons de précision, le groupe de cartographie numérique était supérieur au groupe de cartographie papier pour toutes les tâches critiques préétablies. CONCLUSION: Par rapport à la cartographie sur papier, le groupe de cartographie numérique a capturé des tâches plus critiques lors de la réanimation pédiatrique simulée et était plus précis dans les intervalles de temps entre les performances des tâches en temps réel et le temps cartographié. Pour les tâches cartographiées, les dossiers papier étaient significativement plus complets et plus détaillés lors de l'arrêt cardiaque pédiatrique simulé.

2023 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Pediatric Life Support; Neonatal Life Support; Education, Implementation, and Teams; and First Aid Task Forces.

The International Liaison Committee on Resuscitation engages in a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation and first aid science. Draft Consensus on Science With Treatment Recommendations are posted online throughout the year, and this annual summary provides more concise versions of the final Consensus on Science With Treatment Recommendations from all task forces for the year. Topics addressed by systematic reviews this year include resuscitation of cardiac arrest from drowning, extracorporeal cardiopulmonary resuscitation for adults and children, calcium during cardiac arrest, double sequential defibrillation, neuroprognostication after cardiac arrest for adults and children, maintaining normal temperature after preterm birth, heart rate monitoring methods for diagnostics in neonates, detection of exhaled carbon dioxide in neonates, family presence during resuscitation of adults, and a stepwise approach to resuscitation skills training. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, using Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces list priority knowledge gaps for further research. Additional topics are addressed with scoping reviews and evidence updates.

Stepwise approach to skills teaching in resuscitation: A systematic review.

Aim: To compare the effectiveness of Peyton's four-step approach for teaching resuscitation skills with alternative approaches. Methods: For this systematic review, we followed the PICOST format (population, intervention, comparison, outcome, study design, timeframe) using Peyton's four-step approach as the standard. We included all studies analyzing skills training related to resuscitation and First Aid in any educational setting. Eligible were randomized controlled trials (RCTs) and non-randomized studies (non-randomized controlled trials, interrupted time series, controlled before-and-after studies, cohort studies, published conference abstracts, and case series where n ≥ 5). We excluded unpublished results (e.g. trial protocols), commentaries, editorials, reviews. Medline, Embase, PsycINFO, ERIC, CINAHL, and Cochrane were searched from inception until November 10, 2020 (updated November 25, 2022) for publications in all languages as long as there was an English abstract. Titles and abstracts of the papers retrieved were screened, and eligible publications were analysed in full text. From the final set of papers, data were extracted into a spreadsheet, subsequently risk of bias assessment was performed (using RoB2 and ROBINS-I), and the certainty of evidence (using GRADE) for each paper was assessed. Screening of studies, data extraction, risk-of-bias assessment, and assessment of certainty of evidence were all performed by two independent researchers. This review was conducted in adherence with PRISMA standards and was registered with PROSPERO (CRD42023377398). Results: Overall, the search identified 2,574 studies from which 17 were included in the final analysis (14 RCTs, and 3 non-RCTs). The studies involved a total of 2,906 participants from various populations (from lay persons to health care professionals) and analysed nine different resuscitation skills being taught (ranging from chest compressions to needle cricotomy). The alternative teaching approaches ranged from two-steps to five-steps with various modifications of single steps. High methodological and clinical heterogeneity precluded a meta-analysis from being conducted. The risk of bias assessment showed considerable variation between the studies ranging from 'low' to 'serious'. Across all studies, certainty of evidence was rated as very low due to imprecision and inconsistency. Overall, 14 out of 17 studies showed no difference in skill acquisition or retention when comparing Peyton's four steps to other stepwise approaches. Conclusions: Very low certainty evidence suggest that Peyton's four-step approach was not more effective in resuscitation skills training compared to alternative approaches. Funding: None.

Effectiveness of a Novel Tablet Application in Reducing Guideline Deviations During Pediatric Cardiac Arrest: A Randomized Clinical Trial.

Importance: Deviations from international resuscitation guidelines during the management of pediatric cardiac arrest are frequent and affect clinical outcomes. An interactive tablet application (app), PediAppRREST, was developed to reduce guideline deviations during pediatric cardiac arrest. Objective: To assess the effectiveness of PediAppRREST in improving the management of simulated in-hospital pediatric cardiac arrest. Design, Setting, and Participants: This multicenter 3-group simulation-based randomized clinical trial was conducted from September 2020 to December 2021 at 4 Italian university hospitals (Padua, Florence, Rome, Novara). Participants included residents in pediatrics, emergency medicine, and anesthesiology. Analyses were conducted as intention-to-treat. Data were analyzed from January to June 2022. Interventions: Teams were randomized to 1 of 3 study groups: an intervention group that used the PediAppRREST app; a control group that used a paper-based cognitive aid, the Pediatric Advanced Life Support (PALS) pocket card; and a control group that used no cognitive aids. All the teams managed the same standardized simulated scenario of nonshockable pediatric cardiac arrest. Main Outcomes and Measures: The primary outcome was the number of deviations from guidelines, measured by a 15-item checklist based on guideline recommendations. The main secondary outcomes were quality of chest compressions, team clinical performance (measured by the Clinical Performance Tool), and perceived team leader's workload. Study outcomes were assessed via video reviews of the scenarios. Results: Overall 100 teams of 300 participants (mean [SD] age, 29.0 [2.2] years; 195 [65%] female) were analyzed by intention-to-treat, including 32 teams randomized to the PediAppRREST group, 35 teams randomized to the PALS control group, and 33 teams randomized to the null control group. Participant characteristics (210 pediatric residents [70%]; 48 anesthesiology residents [16%]; 42 emergency medicine residents [14%]) were not statistically different among the study groups. The number of deviations from guidelines was significantly lower in the PediAppRREST group than in the control groups (mean difference vs PALS control, -3.0; 95% CI, -4.0 to -1.9; P < .001; mean difference vs null control, -2.6; 95% CI, -3.6 to -1.5; P < .001). Clinical Performance Tool scores were significantly higher in the PediAppRREST group than control groups (mean difference vs PALS control, 1.4; 95% CI, 0.4 to 2.3; P = .002; mean difference vs null control, 1.1; 95% CI, 0.2 to 2.1; P = .01). The other secondary outcomes did not significantly differ among the study groups. Conclusions and Relevance: In this randomized clinical trial, the use of the PediAppRREST app resulted in fewer deviations from guidelines and a better team clinical performance during the management of pediatric cardiac arrest. Trial Registration: ClinicalTrials.gov Identifier: NCT04619498.

Human cytomegalovirus mediates APOBEC3B relocalization early during infection through a ribonucleotide reductase-independent mechanism.

The APOBEC3 family of DNA cytosine deaminases comprises an important arm of the innate antiviral defense system. The gamma-herpesviruses Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus and the alpha-herpesviruses herpes simplex virus (HSV)-1 and HSV-2 have evolved an efficient mechanism to avoid APOBEC3 restriction by directly binding to APOBEC3B and facilitating its exclusion from the nuclear compartment. The only viral protein required for APOBEC3B relocalization is the large subunit of the ribonucleotide reductase (RNR). Here, we ask whether this APOBEC3B relocalization mechanism is conserved with the beta-herpesvirus human cytomegalovirus (HCMV). Although HCMV infection causes APOBEC3B relocalization from the nucleus to the cytoplasm in multiple cell types, the viral RNR (UL45) is not required. APOBEC3B relocalization occurs rapidly following infection suggesting the involvement of an immediate early or early (IE/E) viral protein. In support of this possibility, genetic (IE1 mutant) and pharmacologic (cycloheximide) strategies that prevent the expression of IE/E viral proteins also block APOBEC3B relocalization. In comparison, the treatment of infected cells with phosphonoacetic acid, which interferes with viral late protein expression, still permits A3B relocalization. These results combine to indicate that the beta-herpesvirus HCMV uses an RNR-independent, yet phenotypically similar, molecular mechanism to antagonize APOBEC3B. IMPORTANCE Human cytomegalovirus (HCMV) infections can range from asymptomatic to severe, particularly in neonates and immunocompromised patients. HCMV has evolved strategies to overcome host-encoded antiviral defenses to achieve lytic viral DNA replication and dissemination and, under some conditions, latency and long-term persistence. Here, we show that HCMV infection causes the antiviral factor, APOBEC3B, to relocalize from the nuclear compartment to the cytoplasm. This overall strategy resembles that used by related herpesviruses. However, the HCMV relocalization mechanism utilizes a different viral factor(s) and available evidence suggests the involvement of at least one protein expressed at the early stages of infection. This knowledge is important because a greater understanding of this mechanism could lead to novel antiviral strategies that enable APOBEC3B to naturally restrict HCMV infection.

APOBEC3 degradation is the primary function of HIV-1 Vif determining virion infectivity in the myeloid cell line THP-1.

HIV-1 must overcome multiple innate antiviral mechanisms to replicate in CD4+ T lymphocytes and macrophages. Previous studies have demonstrated that the apolipoprotein B mRNA editing enzyme polypeptide-like 3 (APOBEC3, A3) family of proteins (at least A3D, A3F, A3G, and stable A3H haplotypes) contribute to HIV-1 restriction in CD4+ T lymphocytes. Virus-encoded virion infectivity factor (Vif) counteracts this antiviral activity by degrading A3 enzymes allowing HIV-1 replication in infected cells. In addition to A3 proteins, Vif also targets other cellular proteins in CD4+ T lymphocytes, including PPP2R5 proteins. However, whether Vif primarily degrades only A3 proteins during viral replication is currently unknown. Herein, we describe the development and characterization of A3F-, A3F/A3G-, and A3A-to-A3G-null THP-1 cells. In comparison to Vif-proficient HIV-1, Vif-deficient viruses have substantially reduced infectivity in parental and A3F-null THP-1 cells, and a more modest decrease in infectivity in A3F/A3G-null cells. Remarkably, disruption of A3A-A3G protein expression completely restores the infectivity of Vif-deficient viruses in THP-1 cells. These results indicate that the primary function of Vif during infectious HIV-1 production from THP-1 cells is the targeting and degradation of A3 enzymes. IMPORTANCE HIV-1 Vif neutralizes the HIV-1 restriction activity of A3 proteins. However, it is currently unclear whether Vif has additional essential cellular targets. To address this question, we disrupted A3A to A3G genes in the THP-1 myeloid cell line using CRISPR and compared the infectivity of wild-type HIV-1 and Vif mutants with the selective A3 neutralization activities. Our results demonstrate that the infectivity of Vif-deficient HIV-1 and the other Vif mutants is fully restored by ablating the expression of cellular A3A to A3G proteins. These results indicate that A3 proteins are the only essential target of Vif that is required for fully infectious HIV-1 production from THP-1 cells.

Disparities in layperson resuscitation education: A scoping review.

BACKGROUND: The aim of this scoping review was to identify factors that would enable or hinder the opportunity for laypersons to undertake resuscitation education. METHODS: We searched PubMed, Ovid EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials (CENTRAL) to identify studies published from January 1, 1966 to December 31, 2022 including factors that could influence laypersons to undertake resuscitation education. Data regarding participant characteristics, interventions, and design and outcomes of included studies were extracted. RESULTS: Of the initially identified 6627 studies, 23 studies (20 cross-sectional and 3 cohort studies) were finally included. Among them, a wide variety of enablers and barriers were identified. High heterogeneity among studies was observed. We categorized factors into three themes: personal factors (age, sex, race, family status, language, prior experience of resuscitation, and immigration status), socioeconomic and educational factors (income, societal status, occupation and legislation, and educational attainment), and geographic factors (birthplace and habitancy). Several barriers were identified that affect laypersons from participating in resuscitation training, such as personal factors like advanced age, lower socioeconomic and educational status, as well as being part of marginalized groups due to race or language barriers. On the other hand, several enablers identified in the study included prior experiences of witnessing someone collapsing, awareness of automated external defibrillators in public locations, certain occupations, or legal requirements for training. CONCLUSIONS: Various barriers and enablers were found to influence laypersons to participate in resuscitation training. To enhance layperson response to cardiac arrest, targeted initiatives that aim to eliminate barriers need to be initiated, and further research is required to explore factors relating to populations with special needs.

Data-informed debriefing for cardiopulmonary arrest: A randomized controlled trial.

Aim: To determine if data-informed debriefing, compared to a traditional debriefing, improves the process of care provided by healthcare teams during a simulated pediatric cardiac arrest. Methods: We conducted a prospective, randomized trial. Participants were randomized to a traditional debriefing or a data-informed debriefing supported by a debriefing tool. Participant teams managed a 10-minute cardiac arrest simulation case, followed by a debriefing (i.e. traditional or data-informed), and then a second cardiac arrest case. The primary outcome was the percentage of overall excellent CPR. The secondary outcomes were compliance with AHA guidelines for depth and rate, chest compression (CC) fraction, peri-shock pause duration, and time to critical interventions. Results: A total of 21 teams (84 participants) were enrolled, with data from 20 teams (80 participants) analyzed. The data-informed debriefing group was significantly better in percentage of overall excellent CPR (control vs intervention: 53.8% vs 78.7%; MD 24.9%, 95%CI: 5.4 to 44.4%, p = 0.02), guideline-compliant depth (control vs. intervention: 60.4% vs 85.8%, MD 25.4%, 95%CI: 5.5 to 45.3%, p = 0.02), CC fraction (control vs intervention: 88.6% vs 92.6, MD 4.0%, 95%CI: 0.5 to 7.4%, p = 0.03), and peri-shock pause duration (control vs intervention: 5.8 s vs 3.7 s, MD -2.1 s, 95%CI: -3.5 to -0.8 s, p = 0.004) compared to the control group. There was no significant difference in time to critical interventions between groups. Conclusion: When compared with traditional debriefing, data-informed debriefing improves CPR quality and reduces pauses in CPR during simulated cardiac arrest, with no improvement in time to critical interventions.

Who is the real team leader? Comparing leadership performance of the team leader and CPR Coach during simulated cardiac arrest.

Purpose: To describe the leadership performance of team leaders and CPR Coaches, and to determine if there is a correlation between leadership scores and CPR performance during management of simulated pediatric cardiac arrest events. Methods: This is a secondary analysis of data from a prior randomized controlled trial. We observed the performance of both team leaders and CPR coaches during the management of an 18-minute simulated cardiac arrest scenario which was run for 20 resuscitation teams comprised of CPR-certified professionals from four pediatric tertiary care centers. CPR Coaches were responsible for providing real-time verbal feedback of CPR performance to compressors. Two raters were trained to use the Behavioral Assessment Tool (BAT) to assess leadership performance of the team leader and CPR Coach. BAT scores of team leaders and CPR coaches were compared and linked with objective CPR performance. Results: There was no significant difference between the BAT scores of team leaders and CPR coaches (median score 27/40 vs 28.8/40, p = 0.16). Higher BAT scores of team leaders were significantly associated with higher percentage of excellent CPR (r = 0.52, p = 0.02), while higher BAT scores of CPR coaches were significantly associated with higher chest compression fraction (r = 0.48, p = 0.03). Conclusions: Both team leaders and CPR coaches have similarly high leadership performance during the management of simulated cardiac arrest. Leadership behaviors were associated with quality of CPR performance.Clinical Trial Registration: Registration ID: NCT02539238; https://www.clinicaltrials.gov.

APOBEC3 degradation is the primary function of HIV-1 Vif for virus replication in the myeloid cell line THP-1.

HIV-1 must overcome multiple innate antiviral mechanisms to replicate in CD4 + T lymphocytes and macrophages. Previous studies have demonstrated that the APOBEC3 (A3) family of proteins (at least A3D, A3F, A3G, and stable A3H haplotypes) contribute to HIV-1 restriction in CD4 + T lymphocytes. Virus-encoded virion infectivity factor (Vif) counteracts this antiviral activity by degrading A3 enzymes allowing HIV-1 replication in infected cells. In addition to A3 proteins, Vif also targets other cellular proteins in CD4 + T lymphocytes, including PPP2R5 proteins. However, whether Vif primarily degrades only A3 proteins or has additional essential targets during viral replication is currently unknown. Herein, we describe the development and characterization of A3F -, A3F/A3G -, and A3A -to- A3G -null THP-1 cells. In comparison to Vif-proficient HIV-1, Vif-deficient viruses have substantially reduced infectivity in parental and A3F -null THP-1 cells, and a more modest decrease in infectivity in A3F/A3G -null cells. Remarkably, disruption of A3Aâ€"A3G protein expression completely restores the infectivity of Vif-deficient viruses in THP-1 cells. These results indicate that the primary function of Vif during HIV-1 replication in THP-1 cells is the targeting and degradation of A3 enzymes. Importance: HIV-1 Vif neutralizes the HIV-1 restriction activity of A3 proteins. However, it is currently unclear whether Vif has additional essential cellular targets. To address this question, we disrupted A3A to A3G genes in the THP-1 myeloid cell line using CRISPR and compared the infectivity of wildtype HIV-1 and Vif mutants with the selective A3 neutralization activities. Our results demonstrate that the infectivity of Vif-deficient HIV-1 and the other Vif mutants is fully restored by ablating the expression of cellular A3A to A3G proteins. These results indicate that A3 proteins are the only essential target of Vif that is required for HIV-1 replication in THP-1 cells.

Aerosol Box Use in Reducing Health Care Worker Contamination During Airway Procedures (AIRWAY Study): A Simulation-Based Randomized Clinical Trial.

Importance: The aerosol box has been used during the management of patients with COVID-19 to reduce health care practitioner (HCP) exposure during aerosol-generating medical procedures (AGMPs). Little is known about the effect of aerosol box use on HCP contamination and AGMP procedure time. Objective: To investigate whether use of an aerosol box during AGMPs reduces HCP contamination or influences the time to successful completion and first-pass success rate for endotracheal intubation (ETI) and laryngeal mask airway (LMA) insertion. Design, Setting, and Participants: This multicenter, simulation-based, randomized clinical trial was conducted from May to December 2021 at tertiary care pediatric hospitals. Participant teams performed 3 simulated patient scenarios: bag-valve-mask ventilation, ETI, and LMA insertion. During the scenarios, aerosols were generated using Glo Germ. Teams of 2 HCPs were randomly assigned to control (no aerosol box) or intervention groups (aerosol box). Statistical analysis was performed from July 2022 to February 2023. Interventions: The aerosol box (or SplashGuard CG) is a transparent, plastic barrier covering the patient's head and shoulders with access ports allowing HCPs to manage the airway. Main Outcomes and Measures: The primary outcome was surface area of contamination (AOC) on participants. Secondary outcomes were time to successful completion and first-pass success rates for ETI and LMA insertion. Results: A total of 64 teams (128 participants) were enrolled, with data from 61 teams (122 participants) analyzed. Among the 122 participants analyzed, 79 (64.8%) were female and 85 (69.7%) were physicians. Use of an aerosol box was associated with a 77.5% overall decreased AOC to the torso (95% CI, -86.3% to -62.9%; P < .001) and a 60.7% overall decreased AOC to the facial area (95% CI, -75.2% to -37.8%; P < .001) in airway HCPs. There was no statistically significant difference in surface contamination after doffing personal protective equipment between groups. Time to completing ETI was longer in the aerosol box group compared with the control group (mean difference: 10.2 seconds; 95% CI, 0.2 to 20.2 seconds; P = .04), but there was no difference between groups for LMA insertion (mean difference: 2.4 seconds; 95% CI, -8.7 to 13.5 seconds; P = .67). Conclusions and Relevance: In this randomized clinical trial of aerosol box use in AGMPs, use of an aerosol box reduced contamination deposition on HCPs' torso and face predoffing; the use of an aerosol box delayed time to successful intubation. These results suggest that the incremental benefits of reduced surface contamination from aerosol box use should be weighed against delayed time to complete intubation, which may negatively affect patient outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT04880668.

Human cytomegalovirus mediates APOBEC3B relocalization early during infection through a ribonucleotide reductase-independent mechanism.

The APOBEC3 family of DNA cytosine deaminases comprises an important arm of the innate antiviral defense system. The gamma-herpesviruses EBV and KSHV and the alpha-herpesviruses HSV-1 and HSV-2 have evolved an efficient mechanism to avoid APOBEC3 restriction by directly binding to APOBEC3B and facilitating its exclusion from the nuclear compartment. The only viral protein required for APOBEC3B relocalization is the large subunit of the ribonucleotide reductase (RNR). Here, we ask whether this APOBEC3B relocalization mechanism is conserved with the beta-herpesvirus human cytomegalovirus (HCMV). Although HCMV infection causes APOBEC3B relocalization from the nucleus to the cytoplasm in multiple cell types, the viral RNR (UL45) is not required. APOBEC3B relocalization occurs rapidly following infection suggesting involvement of an immediate early or early (IE-E) viral protein. In support of this mechanism, cycloheximide treatment of HCMV-infected cells prevents the expression of viral proteins and simultaneously blocks APOBEC3B relocalization. In comparison, the treatment of infected cells with phosphonoacetic acid, which is a viral DNA synthesis inhibitor affecting late protein expression, still permits A3B relocalization. These results combine to show that the beta-herpesvirus HCMV uses a fundamentally different, RNR-independent molecular mechanism to antagonize APOBEC3B. Importance: Human cytomegalovirus (HCMV) infections can range from asymptomatic to severe, particularly in neonates and immunocompromised patients. HCMV has evolved strategies to overcome host-encoded antiviral defenses in order to achieve lytic viral DNA replication and dissemination and, under some conditions, latency and long-term persistence. Here, we show that HCMV infection causes the antiviral factor, APOBEC3B, to relocalize from the nuclear compartment to the cytoplasm. This overall strategy resembles that used by related herpesviruses. However, the HCMV relocalization mechanism utilizes a different viral factor(s) and available evidence suggests the involvement of at least one protein expressed at the early stages of infection. This knowledge is important because a greater understanding of this mechanism could lead to novel antiviral strategies that enable APOBEC3B to naturally restrict HCMV infection.

Advanced neonatal procedural skills: a simulation-based workshop: impact and skill decay.

BACKGROUND: Trainees aiming to specialize in Neonatal Perinatal Medicine (NPM), must be competent in a wide range of procedural skills as per the Royal College of Canada. While common neonatal procedures are frequent in daily clinical practice with opportunity to acquire competence, there are substantial gaps in the acquisition of advanced neonatal procedural skills. With the advent of competency by design into NPM training, simulation offers a unique opportunity to acquire, practice and teach potentially life-saving procedural skills. Little is known on the effect of simulation training on different areas of competence, and on skill decay. METHODS: We designed a unique simulation-based 4-h workshop covering 6 advanced procedures chosen because of their rarity yet life-saving effect: chest tube insertion, defibrillation, exchange transfusion, intra-osseus (IO) access, ultrasound-guided paracentesis and pericardiocentesis. Direct observation of procedural skills (DOPS), self-perceived competence, comfort level and cognitive knowledge were measured before (1), directly after (2), for the same participants after 9-12 months (skill decay, 3), and directly after a second workshop (4) in a group of NPM and senior general pediatric volunteers. RESULTS: The DOPS for all six procedures combined for 23 participants increased from 3.83 to 4.59. Steepest DOPS increase pre versus post first workshop were seen for Defibrillation and chest tube insertion. Skill decay was evident for all procedures with largest decrease for Exchange Transfusion, followed by Pericardiocentesis, Defibrillation and Chest Tube. Self-perceived competence, comfort and cognitive knowledge increased for all six procedures over the four time points. Exchange Transfusion stood out without DOPS increase, largest skill decay and minimal impact on self-assessed competence and comfort. All skills were judged as better by the preceptor, compared to self-assessments. CONCLUSIONS: The simulation-based intervention advanced procedural skills day increased preceptor-assessed directly observed procedural skills for all skills examined, except exchange transfusion. Skill decay affected these skills after 9-12 months. Chest tube insertions and Defibrillations may benefit from reminder sessions, Pericardiocentesis may suffice by teaching once. Trainees' observed skills were better than their own assessment. The effect of a booster session was less than the first intervention, but the final scores were higher than pre-intervention. TRIAL REGISTRATION: Not applicable, not a health care intervention.

2022 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Pediatric Life Support; Neonatal Life Support; Education, Implementation, and Teams; and First Aid Task Forces.

This is the sixth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. This summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. Topics covered by systematic reviews include cardiopulmonary resuscitation during transport; approach to resuscitation after drowning; passive ventilation; minimizing pauses during cardiopulmonary resuscitation; temperature management after cardiac arrest; use of diagnostic point-of-care ultrasound during cardiac arrest; use of vasopressin and corticosteroids during cardiac arrest; coronary angiography after cardiac arrest; public-access defibrillation devices for children; pediatric early warning systems; maintaining normal temperature immediately after birth; suctioning of amniotic fluid at birth; tactile stimulation for resuscitation immediately after birth; use of continuous positive airway pressure for respiratory distress at term birth; respiratory and heart rate monitoring in the delivery room; supraglottic airway use in neonates; prearrest prediction of in-hospital cardiac arrest mortality; basic life support training for likely rescuers of high-risk populations; effect of resuscitation team training; blended learning for life support training; training and recertification for resuscitation instructors; and recovery position for maintenance of breathing and prevention of cardiac arrest. Members from 6 task forces have assessed, discussed, and debated the quality of the evidence using Grading of Recommendations Assessment, Development, and Evaluation criteria and generated consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections, and priority knowledge gaps for future research are listed.

Quantifying Simulated Contamination Deposition on Healthcare Providers Using Image Analysis.

INTRODUCTION: Simulation-based research has played an important role in improving care for communicable diseases. Unfortunately, few studies have attempted to quantify the level of contamination in these simulation activities. We aim to assess the feasibility and provide validity evidence for using integrated density values and area of contamination (AOC) to differentiate various levels of simulated contamination. METHODS: An increasing number of simulated contamination spots using fluorescent marker were applied on a manikin chest to simulate a contaminated healthcare provider. An ultraviolet light was used to illuminate the manikin to highlight the simulated contamination. Images of increasing contamination levels were captured using a camera with different exposure settings. Image processing software was used to measure 2 outcomes: (1) natural logarithm of integrated density; and (2) AOC. Mixed-effects linear regression models were used to assess the effect of contamination levels and exposure settings on both outcome measures. A standardized "proof-of-concept" exercise was set up to calibrate and formalize the process for human subjects. RESULTS: A total of 140 images were included in the analyses. Dose-response relationships were observed between contamination levels and both outcome measures. For each increment in the number of contaminated simulation spots (ie, simulated contaminated area increased by 38.5 mm 2 ), on average, log-integrated density increased by 0.009 (95% confidence interval, 0.006-0.012; P < 0.001) and measured AOC increased by 37.8 mm 2 (95% confidence interval, 36.7-38.8 mm 2 ; P < 0.001), which is very close to actual value (38.5 mm 2 ). The "proof-of-concept" demonstration further verified results. CONCLUSIONS: Integrated density and AOC measured by image processing can differentiate various levels of simulated, fluorescent contamination. The AOC measured highly agrees with the actual value. This method should be optimized and used in the future research to detect simulated contamination deposited on healthcare providers.